Biomimetic materials for medical applications.

Introduction

Biomimetic materials are advanced functional materials derived from or inspired by natural biological systems. They possess exceptional biocompatibility and biosimilarity to emulate the microstructure and physiological functions of native human tissues. Biomimetic materials have been extensively used in tissue engineering, drug delivery systems, and medical device fabrication within the broader context of the medical field. [ 1 – 3 ] Their design, which is informed by the complexity of relevant theoretical relationships, predominantly follows two strategic paradigms: (1) direct utilization of naturally sourced components to leverage their intrinsic biological properties and structural advantages (e.g., natural polysaccharides); and (2) rational engineering of synthetic materials to replicate the structure–function relationships observed in natural systems (e.g., synthetic biomimetic membrane). These advancements have facilitated substantial integration between materials science and clinical medicine, yielding novel solutions to longstanding medical challenges. This is evidenced by their potential to achieve breakthroughs in tissue regeneration, targeted drug delivery, and biocompatible implants. [ 4 – 7 ] Collectively, these developments underscore the growing convergence of biological principles and materials engineering in therapeutic applications.

The emergence of natural biomimetic materials has inaugurated a new era in precision medicine for the management of systemic diseases. Biomimetic collagen matrix materials facilitate bone regeneration in motor system diseases (e.g., fractures and osteoporosis). Their structure closely mimics that of natural bone, and they have excellent biocompatibility and regenerative effects. [ 8 ] Nanocarriers based on natural polysaccharides are used to deliver anti-inflammatory drugs to target sites in digestive system disorders (e.g., gastrointestinal inflammation) to minimize systemic side effects. [ 9 ] Biomimetic nanoparticles leverage the properties of cell membranes to facilitate efficient drug delivery and tumor targeting in respiratory disorders (e.g., lung cancer). [ 10 ] Natural biomimetic materials have been used to develop artificial glomeruli that replicate the filtering function of the natural glomeruli in kidney diseases (e.g., nephrotic syndrome). [ 11 ] Biomimetic nanocarriers derived from red blood cell membranes facilitate intelligent insulin delivery and help maintain stable blood glucose concentrations in endocrine system disorders (e.g., diabetes). [ 12 ] Biomimetic nanoparticles can cross the blood–brain barrier and deliver neuroprotective drugs for Alzheimer’s disease (AD). [ 13 ] Biomimetic materials are used to engineer tissue-based skin substitutes and promote wound healing in skin-related diseases (e.g., chronic wounds). Natural biomimetic materials facilitate the targeted delivery of chemotherapeutic agents for hematological disorders (e.g., leukemia) and help reduce damage to normal hematopoietic cells. Biomimetic nanoparticles also facilitate the targeted delivery of anticoagulant drugs in circulatory system diseases (e.g., cardiovascular disease) and help reduce the risk of thrombosis. [ 14 ] These natural biomimetic materials enhance drug efficacy and markedly reduce treatment-related side effects, highlighting their broad application potential.

Natural biomimetic materials offer transformative solutions for systemic disease intervention through their unique bioinspired designs. Their efficacy has been demonstrated across a broad range of physiological systems, highlighting their advantages over conventional therapies and their role in advancing biomedical research and clinical translation. This integration of materials innovation and medical science carries profound implications for academic discovery and patient care.

Biomimetic Materials in Musculoskeletal Applications

Osteoarthritis

Osteoarthritis (OA), the most disabling degenerative joint disease globally, is driven by an imbalance between cartilage matrix degradation and synthesis. Abnormal biomechanics, subchondral bone sclerosis, and synovial inflammation cause joint space narrowing and osteophyte formation, leading to severe pain and loss of function. Conventional treatments, ranging from non-steroidal anti-inflammatory drugs to joint replacement, primarily offer symptomatic relief but are frequently associated with long-term complications including drug dependence and prosthesis loosening. As shown in Figure 1 and Table 1 , bioinspired materials have recently been developed as biological solutions to slow the progression of OA by facilitating cartilage repair through structural reconstruction, lubrication, and anti-inflammatory regulation.

Biomimetic materials derived from natural products

Reconstructing the natural gradient heterogeneity of the meniscus and osteochondral tissue is key to repairing damage and restoring function. Du et al [ 15 ] used a gradient-sized diamond pore scaffold (GSDP-TEM) to induce mesenchymal stem cell gradient differentiation, recreate meniscus-like extracellular matrix (ECM), and reduce joint degeneration. Liu et al [ 16 ] applied a 3D-printed multilayer scaffold (hyaluronic acid methacrylate/protein-polycaprolactone [PCL]) to enhance collagen II expression, suppress IL-1β, and promote chondrogenesis in osteochondral defects. Joint lubrication failure is a key driver of OA progression. Deng et al [ 17 ] reported the efficacy of natural lubricant mimics developed with chitosan-block-poly (sulfobetaine methacrylate) (CS-b-pSBMA) copolymers, which have lower friction than hyaluronic acid. The biomimetic materials had antibacterial, biocompatible, and stable properties and reduced cartilage degradation in mice with OA. Gong et al [ 18 ] developed a mussel-adhesive, synovial-fluid-mimicking system with durable lubrication and photothermal response capabilities. This system maintained its performance for 7200 friction cycles. Inflammatory microenvironment imbalance is a central feature of OA. Tong et al [ 19 ] designed a thermosensitive chondroitin sulfate nanoparticle–hydrogel system that inhibits IL-1β-driven chondrocyte inflammation and promotes M2 macrophage polarization to improve synovitis and slow cartilage loss.

Biomimetic materials inspired by the structure and function of natural products

Li et al [ 20 ] developed apoptotic T-cell membrane nanovesicles carrying miR-124 to target synovial M1 macrophages. These nanovesicles inhibited proinflammatory factor release via the TLR4/NF-κB pathway, induced M2 macrophage polarization, regulated FOXO1 signaling, reduced chondrocyte apoptosis, alleviate synovial inflammation and protect cartilage tissue from degeneration in OA mice. They were further used to encapsulate tannic acid (TA)-loaded poly (lactic-co-glycolic acid) (PLGA) nanoparticles based on microvesicles derived from CD90 + synovial mesenchymal stem cells (MSCs). These microvesicles bound strongly to chondrocyte membranes via surface integrins, enabling targeted TA delivery to the damaged sites and promoting M2 polarization. In a rabbit OA model, 8 weeks of TA-loaded PLGA nanoparticle treatment increased cartilage thickness by approximately 45% and reduced the proportion of apoptotic cells by approximately 60%. [ 21 ]

Biomimetic strategies for OA have demonstrated efficacy in cartilage repair, lubrication, and inflammation control. However, concerns regarding the immunogenicity of naturally derived scaffolds, long-term toxicity of the degradation products, and mechanical mismatch with native tissue persist. Evidence has also predominantly originated from short-term studies involving small animals. Therefore, the durability and safety of these interventions have not been established in large animals or humans. Future work would prioritize long-term in vivo safety assessment, standardized evaluation methods, and scalable manufacturing processes to facilitate clinical translation.

Rheumatoid arthritis

Rheumatoid arthritis (RA) is an autoimmune disease characterized by synovial pannus proliferation. This proliferation results in articular cartilage erosion and leads to joint destruction and disability. [ 22 ] Current disease-modifying antirheumatic drugs (DMARDs) can suppress inflammatory responses, but they have limited ability to repair existing bone erosion. New targeted biologics can slow disease progression, but they are associated with high infection risks and low response rates in many patients. Biomimetic materials have been shown to reduce inflammation, promote osteoblast differentiation and enable precise spatiotemporal “anti-inflammation–bone repair” effects.

Biomimetic materials derived from natural products

The application of natural products to the treatment of RA involves overcoming drug delivery limitations through biomimetic designs that integrate anti-inflammatory, antioxidant, and immune-regulatory properties. For example, sinomenine hydrochloride (SIN) can inhibit the IL-1β/NF-κB pathway. However, its short half-life (~2.1 h) and dose-dependent liver toxicity limit its clinical use. Lin et al [ 23 ] reported the development of Prussian blue nanoparticle complexes that scavenge joint reactive oxygen species (ROS) with 78% efficiency via catalase (CAT)-like activity and achieve immune evasion through macrophage membrane camouflage. These complexes increased the accumulation of SIN in the joints of rats with adjuvant-induced arthritis by 3.2-fold and reduced TNF-α secretion by 62%. Hua et al [ 24 ] developed a dual-functional nanocomplex coated with human serum albumin (HSA), and combined it with a soluble hyaluronic acid microneedle system. This platform targets synovial cells via the HSA-CD44 receptor, increases the bioavailability of SIN by 4.5-fold in mice with collagen-induced arthritis (CIA), and reduces the proportion of M1 macrophages from 45% to 18% by blocking NF-κB phosphorylation. Inspired by the lubricating property of chondroitin sulfate, Yang et al [ 25 ] grafted chondroitin sulfate onto chitosan nanoparticles (reducing the friction coefficient to 0.08) and loaded them with diclofenac sodium (DS). The complex accumulated at the inflamed sites and DS was released to block the COX-2/PGE2 pathway. This reduced the concentrations of IL-6 and TNF-α in rats with CIA by 54% and 67%, respectively.

Biomimetic materials inspired by the structure and function of natural products

RA is characterized by macrophage accumulation, excessive ROS production, and abnormal osteoclast activation. These features guide the design of targeted and synergistic biomimetic treatments. Cell membrane-coated biomimetic nanoplatforms have recently attracted attention for their immune evasion and lesion targeting. Xu et al [ 26 ] developed macrophage membrane-coated mesoporous dopamine nanoparticles (M-M@I) coated with macrophage membranes and loaded with iguratimod. These nanoparticles target inflamed joints, scavenge ROS, and inhibit NF-κB signaling to reduce TNF-α, IL-6, and osteoclast markers. M-M@I reduced bone destruction in CIA mice by 68% via extended joint retention. Song et al [ 27 ] used macrophage membranes to encapsulate epigallocatechin gallate-cerium nanoparticles. Cerium ions mimic natural enzyme active sites and scavenge ROS and reactive nitrogen species with efficiency exceeding 90%. The IL-1β binding domain targets synovial inflammatory cells and reduces cartilage erosion scores by 2.5-fold in mice with CIA. Genetic engineering has further enhanced the precise control of biomimetic therapies. Chen et al [ 28 ] developed a gene-engineered macrophage membrane-coated mRNA carrier (MR@P-mPTEN) that binds inflammatory factors and delivers PTEN mRNA to synovial tissue by overexpressing TNF-α receptor decoys. It activates the PTEN/PI3K/Akt pathway, suppresses synovial proliferation, reduces matrix metalloproteinase (MMP)3 and COX-2 expression, and alleviates synovitis in rats with RA (by ~55%). These strategies integrate the functions of natural membrane proteins with programmable synthetic materials to achieve “biomimetic structure–targeted delivery–multi-mechanism synergy” and enhance therapeutic efficacy.

Biomimetic strategies for RA enable targeted anti-inflammation and bone repair. However, their limitations include immune sensitization from xenogeneic cell membranes, disruption of physiological redox balance, and unclear biodistribution or clearance. Donor variability affects targeting uniformity, and the current findings were primarily obtained from studies involving early-stage animal models. Future research would focus on chronic safety and integration of these strategies with existing DMARDs in translational studies.

Osteoporosis

Osteoporosis, which is characterized by reduced bone density and damaged bone microarchitecture, is associated with progressive bone loss and high fracture risk. It constitutes a major global public health threat recognized by the World Health Organization. Traditional anti-resorptives (e.g., bisphosphonates) and bone-forming agents (e.g., teriparatide) improve bone density but do not restore microarchitecture and may increase the risk of atypical fractures. New biomimetic materials can regulate osteoblast differentiation and induce mechanically responsive bone remodeling. These findings establish a new paradigm for reconstructing skeletal mechanical integrity.

Biomimetic materials derived from natural products

Natural product-based biomimetic materials enable multidimensional regulation, with advances ranging from metabolic reshaping to targeted delivery. Yu et al [ 29 ] developed a pH-responsive nanoparticle using oroxylin A and amorphous calcium carbonate to inhibit osteoclast overactivation. The nanoparticle releases oroxylin A in acidic osteoclast microenvironments, and Ca 2+ neutralizes the acidity. These effects inhibit tartrate-resistant acid phosphatase (TRAP) activity and bone resorption and increase trabecular volume and density. Zhou et al [ 30 ] reported that piceatannol activates the PI3K/AKT/GSK-3β pathway, enhances β-catenin nuclear translocation, and promotes angiogenesis through osteogenesis–angiogenesis coupling in bone marrow mesenchymal stem cells (BMSCs) to induce angiogenesis. Piceatannol increased bone callus volume and mechanical strength in the rats with ovariectomy (OVX). These results highlight the potential of engineered natural products for clinical application. Luo et al [ 31 ] synthesized phosphorylated quercetin (p-Que), which improved solubility by 8.6-fold and targeted bone minerals. It reduced the number of TRAP + osteoclasts and the BMD of the distal femur in mice with OVX. Lin et al [ 32 ] fabricated strontium-doped nanofiber microspheres (Sr-BGNs/GNMs) that mimic ECM topology. Sustained Sr 2+ release promoted periodontal ligament stem cells (PDLSC) osteogenesis and angiogenesis and facilitated cementum-alveolar bone regeneration in osteoporotic defects. [ 34 ]

Biomimetic materials inspired by the structure and function of natural products

Patients with osteoporosis exhibit reduced bone density and quality due to imbalanced remodeling, which consequently increases their susceptibility to fracture. New biomimetic materials regulate the bone microenvironment through integrated structural, functional, and metabolic biomimetics. Traditional teriparatide has limited clinical utility due to its 1-h half-life and risk of hypercalcemia. Che et al [ 33 ] developed MBG@PDA-Phellinus linteus (PL) scaffolds that enable near-infrared (NIR)-triggered pulsatile release. These scaffolds increased the local bone density of rats with osteoporosis by 42%, as well as the systemic bone mass via Wnt/β-catenin activation. Lee et al [ 34 ] developed a nitric oxide-releasing bioinspired scaffold, where alendronate and bone morphogenetic protein 2 (BMP2) promoted osteogenesis, and zinc oxide (ZO) released nitric oxide (NO) to regulate RANKL/osteoprotegerin ratio and suppress osteoclasts via the NO-cGMP-PKG pathway. To restore angiogenesis–osteogenesis coupling, they designed a biomimetic scaffold (PMEH/SP), incorporating 4-hexylresorcinol (4HR), and substance P (SP) into the poly(lactic-go-glycolic acid) (PLGA) scaffold. The 4HR blocked the IκB/NF-κB pathway (62% p65 inhibition) and reduced the number of osteoclasts. In contrast, SP activated MAPK/ERK in endothelial cells, increasing VEGF expression and angiogenesis. Wei et al [ 35 ] developed a biomimetic hydrogel that releases nitric oxide (NO) and Ca 2+ . NO activated cyclic guanosine monophosphate signaling in the BMSCs, whereas Ca 2+ triggered CaMKII activation and enhanced osteogenesis–angiogenesis coupling. ROS clearance-based metabolic regulation has also advanced significantly. Liu et al [ 36 ] developed gelatin methacryloyl cryogels (GC)-normal decellularized extracellular matrix (dECM) cryogels, which downregulated reactive oxygen species modulator 1 (ROMO1), facilitated ROS clearance in BMSCs, and restored osteogenic differentiation of MSCs in rats with OVX. The GC-normal dECM cryogels facilitated the repair of 82% of bone defects in rats at 8 weeks, which was three times the repair rate of the OVX group.

Despite significant advances, numerous biomimetic materials continue to face unresolved challenges, including immunogenicity, limited long-term biocompatibility, and potential systemic toxicity. The durability of the restored bone microarchitecture under physiological loading has not been established. Future research could emphasize large-animal studies and longitudinal evaluations that integrate immune-safety assessments with multifunctional designs to ensure efficacy and safety during clinical translation.

Intervertebral disc degeneration

Intervertebral disc degeneration (IVDD), a major cause of chronic back pain, is associated with significant therapeutic challenges. These challenges stem from its complex pathology involving inflammation, biomechanical dysfunction, and tissue loss. Traditional treatments rarely restore the native structure or address all underlying mechanisms, which has driven interest in biomimetic materials. These materials mimic biological structures or functional principles to enhance regenerative outcomes. They improve tissue integration, suppress inflammation, and promote cell repair by mimicking ECM composition, hierarchical organization, and immune-modulatory mechanisms. Biomimetic approaches leverage evolutionarily optimized designs to counteract degeneration through sustainable, low-risk strategies, underscoring their transformative potential in the management of IVDD.

Biomimetic materials developed from natural products

Biomimetic materials derived from natural products provide a viable avenue for IVDD therapy by harnessing the intrinsic biological properties of biomolecules. Yang et al [ 37 ] developed a mitochondrial therapy involving the transplantation of exogenous mitochondria derived from healthy cells into degenerated nucleus pulposus cells. The exogenous mitochondria fused with the endogenous mitochondria or transferred mtDNA via nanotubes, leading to improved mitochondrial quality, restored energy function, and delayed IVDD in rats. Yang et al [ 38 ] also created a GAG-rich hydrogel via chemical modification of collagen and hyaluronic acid and subsequent co-precipitation with GAGs. The hydrogel had a GAG/hydroxyproline ratio of approximately 39.1:1, which is higher than that of the native nanoparticle. Its “nano-bead” and “bottle-brush” structures supported the viability of bovine nanoparticle cells and helped preserve native-like mechanical properties. Li et al [ 39 ] designed a nanofiber-reinforced alginate hydrogel by embedding silk fibroin fibers into seaweed-derived alginate. This composite provided native-like mechanical support, enabled leak-proof delivery of platelet-rich plasma, and promoted nanoparticle regeneration in rat IVDD models. These results highlight the advantages of natural product scaffolds, including inherent biocompatibility, bioactivity, and structural motifs that facilitate tissue integration and minimize immune risks. These materials provide sustainable solutions for IVDD repair by leveraging evolutionarily optimized biomolecular interactions.

Biomimetic materials based on the structure and function of natural products

Another biomimetic design paradigm involves replicating natural structural hierarchy or functional mechanisms, even when using synthetic components. For example, Zheng et al [ 40 ] developed hydrogen ion-capturing hydrogel microspheres through biomimetic mineralization. These microspheres have calcium carbonate layers that enable them to neutralize disc acidity. This design mimics bone mineralization. The encapsulated transforming growth factor-β (TGF-β) and CAT nanoparticles disrupted NLR family pyrin domain containing 3 (NLRP3) inflammasome signaling, which is a key driver of inflammaging. Zhou et al [ 41 ] created immune-defensive microspheres (GM@T-NNPs) by coating gelatin methacryloyl microspheres with neutrophil membranes and loading them with TGF-β1 nanoparticles. This hybrid adsorbed proinflammatory cytokines and released TGF-β1 over 36 days, while the neutrophil membrane enhanced target binding via natural cell adhesion. Another innovation by Li et al [ 42 ] used tropomyosin receptor kinase A (TrkA)-overexpressing macrophage membrane-coated nanoparticles (TMNP@SR) loaded with rapamycin. These particles acted as “inflammatory sponges” by sequestering NGF and proinflammatory cytokines and inducing macrophage polarization from the M1 to M2 phenotype via autophagy. Their core-shell architecture and ligand–receptor interactions mirrored those of natural immune cell communication. Huang et al [ 43 ] developed a nano-clustered regularly interspaced short palindromic repeats (nanoCRISPR)-assisted annulus fibrosus (AF) patch comprising electrospun nanofibers aligned to mimic native AF collagen. The patch inhibited angiogenesis and promoted AF repair in rats following VEGF silencing via CRISPR-CRISPR-related protein 9 (Cas9). These materials demonstrate that synthetic systems inspired by natural principles such as hierarchy, dynamic signaling, and immune mimicry can outperform traditional therapies in addressing the mechanisms of multifactorial diseases.

Biomimetic therapies for IVDD are limited by challenges related to long-term integration, immune compatibility, and potential off-target effects of engineered scaffolds or nanoparticles. The complex mechanical environment of the disc raises concerns regarding material durability and functionality over time. Future work could focus on refining immune-modulatory strategies, validating biomechanical resilience, and conducting rigorous preclinical studies to facilitate translation toward human clinical trials.

Biomimetic Materials for Gastrointestinal Diseases

Gastrointestinal bleeding

Gastrointestinal bleeding is a severe clinical emergency associated with high incidence and mortality. Acute upper gastrointestinal bleeding is common. Major causes include peptic ulcers, esophageal and gastric varices, and acute gastritis. These conditions can cause hematemesis and melena. They are associated with rapid progression to anemia and shock in most cases and can be life-threatening. Timely and effective treatment is therefore crucial for controlling bleeding, reducing complications, and lowering mortality. Traditional treatment methods include pharmacological hemostasis, endoscopic hemostasis, and surgical interventions. These methods are associated with risks of perforation and substantial technical demands. As shown in Figure 2 and Table 2 , the development of biomimetic materials has provided new opportunities for the treatment of gastrointestinal bleeding. These materials improve hemostatic efficacy and reduce the side effects of traditional methods, thereby providing new options for clinical treatment.

Biomimetic materials constructed from natural products

Natural products have considerable potential for treating various gastrointestinal diseases due to their biocompatibility, relatively low toxicity, and multifunctionality. They have been reported to alleviate symptoms and promote tissue repair, representing novel therapeutic approaches. Dan et al [ 44 ] synthesized a bayberry-like nano-silica (DMSN) material with a radial fiber structure that facilitates effective thrombin loading. This nano-silica is coated with gelatin methacryloyl to form a stable nano-gel network. The network is typically activated using a blue laser under an endoscope to stop gastrointestinal bleeding. The data indicate that silica dendrimer coated with methyl acrylate gelatin and carrying thrombin triggers blood coagulation within approximately 5 seconds of contact with blood and forms relatively stable blood clots even in the blood of patients with liver cirrhosis. This treatment strategy of slowly releasing thrombin stopped bleeding rapidly in the mouse liver and mini-pig gastrointestinal bleeding models. No thrombus detachment or rebleeding was observed after rinsing with normal saline. Huang et al [ 45 ] reported on okra gum extracted from okra, which has hemostatic properties and bioadhesive characteristics. These findings indicate that okra gum activates platelets, enhances the adhesion of activated platelets, and promotes the release of coagulation factors XI and XII. It can form a gel layer at the bleeding site and adhere strongly to the wound to enable rapid hemostasis and wound closure. This was demonstrated in rabbit and beagle dog models of liver and heart bleeding. Huang et al [ 46 ] also proposed a microgel derived from yam mucilage for liver and heart hemostasis. The yam microgel undergoes blood-triggered gelation, exhibits super-extensibility, and forms a tight gel adhesive layer that enables rapid adhesion and hemostasis. Luan et al [ 47 ] developed an absorbable suture from natural fish bladder. The suture has excellent strength, acid resistance, and biocompatibility and can be loaded with multiple drugs. Its wound closure, healing promotion, and drug release capabilities have been confirmed for models of gastric perforation in live rabbits and miniature pigs. This is the first report of fish bladder processing into a novel absorbable multifunctional suture with promising clinical prospects. Shu et al [ 48 ] reported a natural biodegradable gastric perforation plug derived from bamboo fungus. It has super-elasticity, hydrophilicity, shape memory, and hemostatic properties, and is biocompatible and biodegradable. It is suitable for repairing gastric perforations accompanied by repeated mechanical movements. The plug can be rapidly delivered via endoscopy and effectively used to seal the perforation site in a mini-pig model of acute gastric perforation. Zou et al [ 49 ] modified natural chitosan to obtain a multifunctional bioadhesive hydrogel with strong bioadhesion and antibacterial properties. Its maximum adhesion strength is 162.6 kPa, which is 12.3 times that of commercial fibrin glue. The hydrogel demonstrated excellent hemostatic performance in a rabbit liver injury model based on its bioadhesion and pro-coagulant activity (e.g., stimulating aggregation and adhesion of red blood cells and platelets). The blood loss was 0.32 g (54.2% of that for fibrin glue). The hydrogel has significantly better wound healing efficacy for infected wounds than commercial EGF and Ag gels due to its enhanced antibacterial and antioxidant properties.

Biomimetic materials inspired by the structure and function of natural products

Biomimetic materials inspired by the structure or function of natural products have demonstrated excellent therapeutic effects in the treatment of gastrointestinal diseases. Luo et al [ 50 ] optimized and rearranged the structures of natural peptide sequences to develop a novel hemostatic peptide hydrogel. This hydrogel can be precisely delivered to bleeding sites via endoscopy to enable rapid wound sealing and effective hemostasis under blue light endoscopy triggering. It can adhere to the gastrointestinal mucosal surface and withstand the harsh physicochemical environment of the upper digestive tract. It has potential for preventing rebleeding. Liu et al [ 51 ] were inspired by natural mushroom caps to prepare a biconcave drug-loaded bioadhesive hydrogel for gastric perforation repair. This hydrogel significantly enhances adhesion strength in a simulated strongly acidic environment and has been successfully applied in an acute gastric perforation model to demonstrate its sealing efficacy and wound healing capabilities. Ma et al [ 52 ] modified natural gelatin and sodium alginate to synthesize a gelatin oxidized alginate hydrogel. In pig and rat models, gelatin oxidized alginate exhibits excellent tissue compatibility and endoscopic injection capabilities, and can create a more durable submucosal water cushion, which is more conducive to the implementation of endoscopic submucosal dissection (ESD). Li et al [ 53 ] developed a series of pH-responsive, tissue-adhesive hydrogels based on methacrylated hyaluronic acid and acryloyl-6-aminohexanoic acid. These hydrogels were fabricated via in situ photopolymerization and integrated the anti-inflammatory and wound-healing properties of ginsenoside Rg1, a natural compound derived from traditional Chinese medicine. Designed for the treatment of gastric tissue injuries, these acid-responsive hydrogels can form an effective acid-resistant barrier and achieve rapid hemostasis through strong tissue adhesion. Wen et al [ 54 ] developed a novel biocompatible carboxymethyl chitosan hydrogel that primarily combines with antibacterial peptides via a Schiff base reaction and exhibits superior adaptability to the unique gastrointestinal microenvironment. The hydrogel achieves rapid hemostasis and effectively inhibits gastric ulcer bleeding by approximately 92% within 24 hour in rat models, demonstrating its superior performance over the commonly used drug omeprazole. Liu et al [ 55 ] studied a material based on a natural multilayer heterologous bioadhesive patch designed to form strong adhesion on wet tissues for wound closure and hemostasis. It is suitable for tissue repair in extreme injury scenarios. This adhesive patch has been applied to the closure and healing of most tissue defects in rats and other animal models, demonstrating its adaptability and rapid healing capabilities.

Gastrointestinal cancer

Gastrointestinal cancer, including esophageal, gastric, and colorectal, liver and pancreatic cancers, pose a substantial threat to the quality of life and survival of affected patients. Traditional treatments such as surgery, chemotherapy, and radiotherapy can control the disease to some extent. However, they are associated with severe side effects and relatively high recurrence rates. Recent evidence highlights the opportunities that biomimetic materials have created for the treatment of gastrointestinal tumors. These innovative materials have marked advantages in hemostasis, anti-inflammation, and antitumor therapy, and reduce the side effects of traditional treatments. Their application enables more precise drug delivery and targeted therapy, improves treatment outcomes, and extends the survival of patients. These findings demonstrate a new approach for the treatment of gastrointestinal tumors and highlight their academic significance and broad application potential.

Biomimetic materials derived from natural products

Exosomes are small lipid bilayer-enclosed vesicles with diameters of 40–100 nm. They are secreted by various cell types and are widely distributed in body fluids such as blood, urine, and saliva. Their contents, including nucleic acids and proteins, transmit biological information and mediate intercellular communication. Exosomes have considerable potential for the treatment of gastrointestinal tumors. They can serve as tumor biomarkers to improve diagnostic accuracy and enhance therapeutic outcomes by altering the tumor microenvironment and promoting immune responses. Exosome vaccines, as “cell-free” vaccines, have the advantages of structural stability, high safety, and ease of preservation. They hold promise for tumor immunotherapy by inducing broader immune responses and represent a new hope for cancer treatment. Xiao et al [ 56 ] reported the antitumor effects of functionalized exosomes that combine immune checkpoint inhibition with photothermal ablation. These exosomes enhance the infiltration and activation of immune cells by remodeling the tumor microenvironment. Engineered exosomes can also achieve targeted recognition of specific tumor markers to enhance the precision and effectiveness of treatment. Xia et al [ 57 ] reported the imaging and therapeutic effects of exosomes loaded with anti-cancer drugs and enhanced their targeting of gastric cancer cells by engineering them to display specific nanobodies on their surfaces. These effects were attributed to the direct action of the drugs and their induction of immunogenic cell death, which promotes an immune response to tumors.

Peptides are small molecules composed of 2 to 50 amino acids linked by peptide bonds. Their advantages include good biocompatibility, diverse functions, high in vivo responsiveness, and simple, feasible synthesis and modification methods. These characteristics make peptides widely applicable in tumor diagnosis and treatment. Peptides can serve as targeting molecules to facilitate the precise delivery of anti-cancer drugs to tumor sites and improve drug bioavailability, therapeutic efficacy, and safety. Luo et al [ 58 ] developed a bispyrene (BP)-based nanoprobe (BP-FFVLK-[PEG]-RGD, M1) that targets angiogenesis sites and self-assembles into nanofibers in situ to enable stable and long-term tumor retention. They used this peptide probe to visualize angiogenesis under blue light endoscopy to diagnose early gastric cancer, which has marked clinical significance. Schaal et al [ 59 ] reported the therapeutic efficacy of combining iodine-131-labeled thermoresponsive elastin-like polypeptides (131I-ELPs) with paclitaxel for pancreatic cancer radiotherapy.

Biomimetic materials inspired by the structure and function of natural products

The design and application of biomimetic carriers based on biological membranes have gradually attracted attention in cancer treatment. These carriers mimic the structure and function of cell membranes and effectively enhance drug targeting and biocompatibility. Cell membrane-based nanocarriers avoid immune system recognition but precisely target tumor cells via specific ligands on the cell membrane surface. Zhan et al [ 60 ] developed HpYss, a camptothecin (HCPT)-peptide conjugate that mimics the transformation of extracellular vesicles into filaments and has precise therapeutic capabilities for liver cancer. HpYss undergoes self-assembly to transform from nanoparticles to nanofibers under the dual stimulation of exogenous alkaline phosphatase and endogenous glutathione (GSH). This dynamic change significantly improves the nuclear delivery efficiency of the anti-cancer drug HCPT, amplifies its apoptotic effect, and enhances its inhibitory effect on HepG2 cells by more than 10-fold in most cases. Liu et al [ 61 ] developed biomimetic nanoparticles based on Salmonella typhimurium ( S. typhimurium ) membranes. These nanoparticles mimic the morphology and biological surface of S. typhimurium to facilitate the specific targeting and endocytosis of tumor cells. The doxorubicin (DOX) loaded on these particles exerts significant photothermal-chemotherapy antitumor effects under NIR laser irradiation, and this provides a new approach for targeted treatment of colorectal cancer. These findings highlight the potential of biomimetic materials for tumor immunotherapy, especially for enhancing the effectiveness of immune cells. Zu et al [ 62 ] developed a core-shell biomimetic membrane nano-drug based on silk fibroin. It can pass through the gastrointestinal tract after oral administration and effectively target colon tumors. The design of this nano-drug enhances drug penetration at tumor sites and induces immunogenic death of tumor cells via sonodynamic therapy to improve the therapeutic response of tumors. These studies provide new perspectives and methodological approaches for remodeling the tumor microenvironment and integrating it with immune responses.

Biomimetic nanozymes are nanomaterials that mimic the functions of natural enzymes and play an important role in cancer treatment through catalytic reactions. They have excellent catalytic activity and targeting ability and can produce reactive species in the tumor microenvironment to enhance therapeutic effects. Lin et al [ 63 ] proposed a tumor microenvironment-responsive polyelectrolyte complex vesicle (HGS-PCV) that regulates internal enzyme cascade reactions to produce toxic hydroxyl radicals in liver cancer cells and promotes the release of chemotherapeutic drugs, thereby significantly improving therapeutic outcomes. The catalytic mechanism of biomimetic nanozymes enables intelligent responses in the tumor microenvironment. Chen et al [ 64 ] reported a copper single-atom nanozyme with peroxidase (POD)-like activity that effectively catalyzes the reaction to generate hydrogen peroxide (H 2 O 2 ) and enhances tumor cell apoptosis and immune responses. This strategy demonstrates the potential of enhancing cancer treatment outcomes via nanozyme catalytic reactions. Wan et al [ 65 ] developed a multifunctional biomimetic nanoplatform that targets CT26 colon tumor cells and has marked antitumor effects mediated via photothermal effects and cell apoptosis. This study highlights the potential of biomimetic materials for the treatment of gastrointestinal cancers.

Inflammatory bowel disease

Inflammatory bowel disease (IBD), which includes Crohn’s disease and ulcerative colitis, is a chronic, nonspecific intestinal inflammatory disease of unknown etiology. Its incidence is increasing, and it imposes a heavy burden on patients and society. Current treatments predominantly involve anti-inflammatory drugs and immunosuppressants. These treatments are often associated with adverse reactions and challenges in maintaining effective local drug concentrations. The emergence of biomimetic materials in recent years has provided new insights into the treatment of IBD. Biomimetic materials and technologies enhance biocompatibility and reduce immunogenicity. Some biomimetic strategies replicate specific components, targets, or immune mechanisms involved in the pathological process to facilitate targeting and achieve precise disease control. IBD treatment strategies based on nanomaterials, including their antioxidant, anti-inflammatory, and gut microbiota regulatory effects, have demonstrated substantial potential. These innovative materials improve therapeutic outcomes, reduce the side effects of traditional methods, and provide new options for clinical treatment.

Biomimetic materials constructed from natural products

Zu et al [ 66 ] reported that trained gut microbiota can secrete abundant exosomes with superior therapeutic effects in alleviating inflammatory responses in colitis, repair the intestinal barrier and modulate the gut microbiota. Deng et al [ 67 ] used butyrate-producing bacteria coated with a nanofilm and leveraged the immunosuppressive properties of hyaluronic acid to restore gut barrier integrity and reduce mucosal inflammation. They demonstrated also substantial therapeutic effects in models of acute kidney injury (AKI) and chronic kidney disease. Xu et al [ 68 ] found that oral ingestion of Escherichia coli ( E. coli ) Nissle 1917-derived membranes coated with diselenide-bridging mesoporous silica nanoparticles could enhance mucus permeation, thereby strengthening the intestinal mucosal barrier, inhibiting pathogenic bacteria invasion, and preventing colitis and diabetes in most mice.

Biomimetic materials inspired by the structure and function of natural products

Wen et al [ 69 ] developed a multifunctional biomimetic hydrogel that serves as an artificial colonic mucosa. It establishes a bioadhesive barrier at ulcer sites, restores local immune and microbial homeostasis, and has effective anti-inflammatory effects. Zhang et al [ 70 ] proposed an orally administered hydrogel precursor solution based on thiol-modified hyaluronic acid. This solution forms an artificial mucus layer in the gut to block microbial invasion and modulate gut microbiota composition and has potential for improving gut homeostasis. Zhu et al [ 71 ] developed metal-phenolic nanozymes (Cur-Fe) that improve redox balance in the gut, restore intestinal barrier function, and positively regulate the gut microbiota. These findings indicate enhanced microbial diversity and a shift in microbial composition toward an anti-inflammatory phenotype. Enzyme-like biomimetic materials containing zinc-doped Prussian blue analogs (ZnPBA@YCW) repair the intestinal epithelial barrier by eliminating E. coli and releasing active components. They also help regulate redox balance and inhibit the NF-κB signaling pathway. These materials effectively alleviate inflammation.

Other Gastrointestinal diseases

Other Gastrointestinal diseases, such as gastrointestinal stenosis, oral-related diseases, Helicobacter pylori ( H. pylori ) infection, liver fibrosis and cirrhosis, and anal fistula, pose serious threats to human health. Oral diseases affect chewing and speech functions. H. pylori infection is associated with various gastric diseases. Liver fibrosis and cirrhosis can lead to liver failure. Anal fistula significantly impairs the quality of life of patients. The treatment of these diseases is complex and often associated with side effects, highlighting the need for new therapies. The emergence of biomimetic materials has provided new insights into the treatment of these diseases. For example, biomimetic materials based on gut structure can deliver drugs to lesion sites with high precision and improve therapeutic outcomes. Biomimetic nanoparticles enable the targeted delivery of antifibrotic drugs and reduce liver damage. Biomimetic materials can simulate the oral environment to promote oral tissue repair and provide new approaches for oral disease treatment. These innovative materials improve therapeutic outcomes and reduce the side effects of traditional methods. They provide new clinical treatment options with academic significance and broad application prospects.

Biomimetic materials developed from natural products

Wang et al [ 72 ] used the natural bacterium Cupriavidus necator to develop P (3HB-co-4HB) with controllable mechanical and physicochemical properties by regulating the type and concentration of culture substrates. They developed a multifunctional biliary degradable stent with shape memory and controllable elasticity. The stent, which is loaded with slow-release triamcinolone, inhibits fibroblast proliferation and reduces the incidence of biliary restenosis. It provides a reliable experimental basis for future endoscopic treatment of benign biliary stenosis. Lei et al [ 73 ] prepared a sodium alginate/chitosan bicomponent hydrogel modified with natural sugar compounds for gastrointestinal ESD. The hydrogel was confirmed to achieve an appropriate mucosal elevation height and maintain it for a long duration in the rat subcutaneous ultrasound model. Its efficacy for mucosal elevation and wound closure was demonstrated in a canine esophageal ESD model. It significantly accelerated wound healing by promoting epithelial regeneration and ECM remodeling after ESD.

Biomimetic materials inspired by the structure and function of natural products

Xing et al [ 74 ] designed a Janus patch with dual-functional sides to accelerate oral ulcer treatment. The adhesive layer of the patch was formed by modifying glycine combined with hydroxyapatite nanoparticles. This mimics the organic–inorganic hybrid adhesion mechanism of barnacles to achieve strong tissue adhesion. Gelatin modified with double bonds serves as a slippery layer to prevent unnecessary adhesion and secondary damage. The Janus patch demonstrated therapeutic effects in a rat oral ulcer model and resisted oral movements such as chewing and biting, and provided a new treatment option. Hu et al [ 75 ] developed a biomimetic adhesive membrane with excellent adhesion under moist conditions. The membrane is capable of drug delivery and has potential for treating oral diseases. Its adhesion mechanism relies on physical binding and covalent bond formation and has demonstrated therapeutic effects in an oral mucositis model and significantly improved wound healing. Traditional treatments for oral wound healing typically involve temporary dressings such as cotton balls and gauze, which cannot provide continuous protection and treatment. Wu et al [ 76 ] developed a series of wound dressings for oral wound repair. These dressings provide long-lasting protection for oral wounds by preventing complex stimuli, as demonstrated in a canine tooth extraction model.

H. pylori is a widespread pathogenic bacterium in most populations. Its biofilm formation and resistance to traditional antibiotics pose challenges to eradication therapy. Shu et al [ 77 ] developed a mucus-penetrating therapeutic platform (Cu-MOF@NF) comprising copper metal-organic frameworks (Cu-MOF), nitrogen-doped carbon dots, and the natural active polysaccharide fucoidan. The platform penetrates the gastric mucus and prevents H. pylori adhesion to gastric epithelial cells. The released Cu 2+ degrades the polysaccharides in the biofilm and disrupts the bacterial life cycle to eradicate the bacterium. This investigation revealed a novel and effective strategy for H. pylori eradication that preserves gut microbiota balance and has good application prospects.

Biomimetic materials play a substantial role in therapeutics for liver failure and liver fibrosis. Zheng et al [ 78 ] designed a seed-mimetic hydrogel with a microecosystem that encapsulates microorganisms to eliminate harmful metabolites in liver failure. The hydrogel was designed with gut adaptability in mind, drawing on the characteristics of highly adaptive plant seeds. It has been shown to reduce blood ammonia concentrations, prevent neurological damage, and facilitate noninvasive treatment of liver failure. Bai et al [ 79 ] reported the therapeutic potential of melatonin-loaded PLGA nanoparticles for liver fibrosis. Melatonin has therapeutic effects, including antioxidant activity and inhibition of endoplasmic reticulum stress. However, its water solubility and bioavailability are predominantly low. Drug-loaded nanoparticles have been shown to substantially increase the bioavailability of melatonin, which has demonstrated therapeutic efficacy in a mouse model of liver fibrosis. These studies highlight the potential and mechanisms of biomimetic materials for treating liver-related diseases and provide important evidence for future clinical applications.

Applications of Biomimetic Materials in Respiratory Diseases

Lung cancer

Lung cancer is the leading cause of cancer-related death globally. Its persistently high incidence and mortality rates represent a significant threat to human health. Most patients are diagnosed at an advanced stage due to the absence of obvious symptoms in the early stages. Traditional treatment methods such as surgery, chemotherapy, and radiotherapy are effective to some extent. However, they have several limitations, including surgical invasiveness, chemoresistance, and severe side effects. More efficient, precise, and less toxic treatment strategies are needed. As shown in Figure 3 and Table 3 , biomimetic materials have recently emerged as promising for the treatment of lung cancer. They facilitate targeted drug delivery, immune regulation, and microenvironment remodeling by simulating the in vivo physiological environment and cell–cell interactions. They also mimic the metabolic characteristics of tumor cells, induce the infiltration and activation of immune cells, and enhance the immune surveillance of the body against tumors. These findings suggest that biomimetic materials can overcome the limitations of traditional treatments and provide more personalized and effective treatment options for patients with lung cancer.

Biomimetic materials constructed from natural products

Peptides have molecular structures intermediate between those of amino acids and proteins. They are composed of one or more amino acids linked in a specific sequence via peptide bonds and are widely used in drug delivery. NKTP-3 is a cyclic D-peptide with dual targeting functions; it can specifically recognize the KRASG12D mutant and NRP1 receptor. Zhou et al [ 80 ] reported the biological stability and cell-penetrating ability of NKTP-3 based on their findings from structure-based virtual screening. Its unique cyclic structure enhances biological stability and reduces the risk of protease degradation in vivo to overcome the spatial hindrance limitations of traditional inhibitors. Zhao et al [ 81 ] developed a multivalent ionic lipid peptide (MILP) library for efficient mRNA transfection. This complex efficiently encapsulates mRNA and plasmid DNA into nanoparticles smaller than 80 nm via multivalent electrostatic, hydrophobic, and hydrogen bond interactions. It also exhibits good stability during lyophilization and long-term storage. Data indicate that zeta potential regulation of the MILP@mRNA complex is one of the key factors for its efficient transfection. The MILP@mRNA complex has significant advantages in cell uptake and endosomal escape, with cell uptake eight times that of SM-102 lipid nanoparticles. This efficient transfection is primarily attributed to the rapid charge reversal of the MILP complex in the endosomal environment, which promotes endosomal membrane disruption and mRNA release. Wu et al [ 82 ] developed an innovative peptide-induced lung cancer cell calcification strategy, which provides a new method for early tumor diagnosis. The research team designed a peptide that targets lung cancer cells and induces calcium precipitation on their membranes without additional calcium supplementation. This calcification process was verified via micro-CT imaging, which has high sensitivity for early lung cancer detection and enables clear visualization of small tumors. It significantly outperforms traditional imaging methods.

The cancer cell membrane fusion strategy enhances the tumor targeting of nanomedicines by leveraging the natural properties of cancer cell membranes. Zhu et al [ 83 ] developed 124I−P/C@CMLvs—cancer cell membrane biomimetic nanovesicles labeled with I-124 and loaded with polyphyllin VI and cisplatin (CDDP)—to improve the sensitivity and efficacy of CDDP in the treatment of nonsmall cell lung cancer (NSCLC). The radiopharmaceutical purity (RCP) of 124I−P/C@CML was >99%, and it demonstrated good in vitro stability. Micro-positron emission tomography revealed the superior diagnostic performance of 124I−P/C@CMLvs based on the tracking of their in vivo distribution and specific homologous tumor targeting. This facilitated the dynamic monitoring of treatment outcomes in patients with NSCLC. Xu et al [ 84 ] developed a biomimetic nanoparticle (CMNP@Osi) comprising a polymer nanoparticle core and a tumor cell-derived membrane shell. This nanoparticle facilitates drug delivery through membrane-mediated homologous targeting and molecular targeting, representing a dual-targeting strategy to enhance osimertinib efficacy. CMNP@Osi predominantly accumulated at the tumor site after intravenous injection and enhanced cancer cell uptake via homologous targeting. Osimertinib was subsequently released into the cytoplasm, where it inhibited the phosphorylation of upstream epidermal growth factor receptor (EGFR) and downstream AKT and suppressed the proliferation of NSCLC cells.

The CAR-T cell membrane fusion strategy enhances the tumor targeting capability of nanomedicines by leveraging the antigen specificity of CAR-T cells. Yaman et al [ 85 ] developed a biomimetic drug carrier based on the membranes of CAR-T cells. The membranes were extracted from anti-HER2 CAR-T cells and used to coat the CDDP-loaded PLGA nanoparticles (CAR-T-MNPs). The CAR-T-MNPs demonstrated sustained drug release under physiological conditions and inhibited the growth of various HER2-positive cancer cells in vitro . Their uptake by A549 cells was significantly increased, as revealed by in vitro uptake studies. Their efficacy in reducing tumor growth was demonstrated through in vivo biodistribution and therapeutic studies involving tumor-bearing mice. This novel CAR-modified cell membrane-coated nanoparticle drug delivery platform was effective in vitro and in vivo . The results highlight the potential of the CAR-engineered membrane-coated nanoparticle system as a cell-mimicking drug carrier for enhancing the efficacy of lung cancer treatment.

The red blood cell membrane fusion strategy leverages the high biocompatibility of red blood cells to increase the circulation time of nanomedicines in the bloodstream and enhance their delivery efficiency. Liang et al [ 86 ] developed a MMP2-activatable biomimetic nanoparticle (REMAIN) for the treatment of lung adenocarcinoma. The core of this delivery system, which comprises an MMP2-responsive peptide chain and miR-126-3p (referred to as MAIN), is coated with red blood cell membranes. This design leverages the high expression of MMP2 in the tumor microenvironment to achieve targeted drug release. It also extends the circulation time of the nanoparticles and enhances their biocompatibility via red blood cell membrane camouflage.

Biomimetic materials inspired by the structure and function of natural products

Nanozymes have been increasingly applied to cancer therapy in recent years, and they have demonstrated substantial potential in immune regulation. The glucose oxidase/Cu-layered double hydroxides (LDHs) complex coated on the cell membrane of lung cancer cells (CMGCL) nanosystem has attracted attention for its unique dual-action mechanism. Xu et al [ 87 ] suggested the induction of copper death in lung cancer cells by the CMGCL nanosystem via a self-amplifying cascade reaction and upregulation of PD-L1 expression. These findings suggest that the core mechanism of the CMGCL nanosystem involves its simultaneous interference with glucose and copper metabolism. The CMGCL nanosystem induces energy deprivation and copper death in the tumor microenvironment by loading glucose oxidase and Cu-LDH. These dual actions not only kill tumor cells but also enhance their immune evasion capabilities, as indicated by the upregulation of PD-L1 expression. Chen et al [ 88 ] proposed a macrophage M1 polarization regulation strategy based on a self-catalytic cascade reaction. Chiral ruthenium nanozymes (D/L-Arginine@Ru) simulate the activities of oxidase and nitric oxide synthase. They are associated with the generation of singlet oxygen and oxygen, and catalyze the production of NO from arginine. These activities are associated with the activation of macrophage M1 polarization. The key to this process is the synergistic action of ROS and NO pathways. ROS initiates M1 polarization by inducing oxidative stress. NO further reinforces this effect by modulating related signaling pathways, and this reverses tumor immune suppression. Photothermal-enhanced catalytic therapy is an important strategy for nanozyme-mediated multimodal synergistic therapy. Zhang et al [ 89 ] prepared ultrasmall platinum nanozymes via an innovative synthesis method and embedded them into the worm-like pores of gold nanobipyramid-mesoporous silica nanocomposites to form the nanozyme carrier AP-mSi. They further developed the lung cancer nanozyme probe AP-HAI by removing the SiO 2 template, modifying it with HSA, and loading it with atovaquone (ATO) and IR780. The nPt nanozyme in the AP-HAI probe has high photothermal conversion efficiency and POD activity. The internal gold nanobipyramids (AuP) and IR780 molecules produce a photothermal effect under NIR light irradiation. This effect promotes the POD-like catalytic process of H 2 O 2 . The photothermal effect enhances the catalytic efficiency of the nPt nanozyme and reflects increased ROS generation. The loaded ATO molecules, which act as cellular respiration inhibitors, disrupt the respiratory metabolism of tumors. This disruption leads to oxygen retention and enhances the photodynamic therapy effect of IR780. The LaCoO 3 nanocrystals developed by Xu et al [ 90 ] may induce pyroptosis via the release of lanthanum ions and have multi-enzyme characteristics. They produce cytotoxic ROS in the acidic environment of tumor tissues and exhibit CAT- and GSH POD-like activities. They also reverse the hypoxic microenvironment of tumor cells and destroy their antioxidant systems. The lanthanum ions released by LaCoO 3 strongly disrupt lysosomal membranes and induce classical pyroptotic cell death. This mechanism substantially inhibits the growth and metastasis of lung cancer based on in vitro and in vivo experiments. The Cu 2 O@Au nanozyme developed by Li et al [ 91 ] induces ferroptosis, which is attributed to GSH depletion. It has excellent glucose oxidase-like activity for starvation therapy and serves as a simulated POD for chemodynamic therapy, with the apparent generation of hydroxyl radicals. The Cu 2 O@Au nanozyme oxidizes glucose at the tumor site to block the energy supply of the tumor. It predominantly produces H 2 O 2 , lowers the pH to enhance chemodynamic therapy efficiency, and triggers a cascade reaction leading to an ROS storm. The nanozyme consumes GSH and reduces the expression of SLC7A11 (xCT) protein. These effects are associated with decreased cysteine uptake by cancer cells and enhanced ROS bursts. They also lead to lipid peroxidation in tumor cells and induce ferroptosis.

The artificial liposome (LIP) fusion strategy, which combines artificial LIPs and tumor-derived nanovesicles, appears to integrate the chemotherapy and immunotherapy approaches. Hu et al [ 92 ] developed DOX@LINV, which is a biomimetic hybrid nanovesicle loaded with DOX. It was prepared by the fusion of artificial LIPs and tumor-derived nanovesicles and represents a combined immunotherapy and chemotherapy approach. DOX@LINV demonstrates homologous targeting, as evidenced by its delivery of DOX to tumor tissues and its induction of immunogenic cell death. These effects enhance the immunogenicity of tumors in most cases. The tumor antigens and endogenous danger signals retained in DOX@LINV appear to activate dendritic cells and induce subsequent antigen-specific T cell immune responses.

Artificial cell membrane vesicles are widely used for the external modification of nanoparticles due to their good biocompatibility, cavity drug-loading capacity, and rheological properties. Ding et al [ 93 ] constructed a novel drug delivery system by integrating artificial membrane vesicles (AMVs) with ciprofloxacin nanoparticles (NanoCip). This system uses Penicillin binding protein 2a (PBP2a) antibodies modified on the surfaces of the AMVs to achieve specific targeting of penicillin-binding protein variants on methicillin-resistant Staphylococcus aureus (MRSA). This targeting mechanism increases the local drug concentration but reduces systemic toxicity and provides a new approach for treating MRSA infections. The innovation of this system lies in its dual-action mechanism. First, the AMVs modified with PBP2a antibodies specifically bind to the PBP2a protein on MRSA to achieve precise pathogen targeting. Second, the inherent sonodynamic properties of NanoCip produce a synergistic effect under ultrasound to enhance the antibacterial activity. In vitro experiments have demonstrated the significant antibacterial activity of AMV@NanoCip, with a bactericidal rate of >99.99% against MRSA under ultrasound stimulation.

Pneumonia

Pneumonia is one of the most common infectious diseases globally and poses a severe threat to human health. These findings highlight the urgency of pneumonia prevention and control. They underscore the high incidence of pneumonia and its substantial mortality, especially among children, older adults, and immunocompromised individuals. Pneumonia leads to acute respiratory failure and is associated with long-term pulmonary dysfunction, chronic lung diseases, and multiorgan failure. These complications place a heavy economic and psychological burden on patients and their families. The limitations of traditional treatment regimens are becoming increasingly evident with the growing problem of antibiotic resistance. The development of new, efficient, and precise pneumonia treatment strategies has become a key focus of global medical research. The emergence of biomimetic materials has introduced revolutionary concepts in the treatment of pneumonia. Biomimetic materials facilitate precise drug delivery, regulation of the inflammatory microenvironment, and enhancement of immune responses by simulating the physiological structures and functions of living organisms.

Biomimetic materials developed from natural products

Biological membrane materials, such as red blood cell membranes and macrophage membranes, enable precise targeting via biomimetic design. Zou et al [ 94 ] developed a biomimetic nanocarrier (Lip@Au-TPZ) based on the hypoxia-activated drug tirapazamine (TPZ) for treating biofilm-related infections. This carrier employs a “hypoxia-enhancing” strategy and encapsulates TPZ within raspberry-shaped gold nanoparticle-hybrid LIPs. The gold nanoparticles act as nanozymes and catalyze glucose oxidation, consume oxygen, and exacerbate the hypoxic environment within the biofilm. The worsening hypoxic environment is a crucial step in converting TPZ into lethal oxidative free radicals and inducing bacterial DNA damage. Liu et al [ 95 ] developed another biomimetic LIP (AB@LRM) prepared by fusing red blood cell membranes and macrophage membranes to form a hybrid cell membrane shell. This further disguise the drug-loaded LIPs to achieve precise antibacterial treatment. AB@LRM has been loaded with the photosensitizer black phosphorus quantum dots and the antibiotic amikacin. The excellent photothermal and photodynamic properties of black phosphorus quantum dots under NIR laser irradiation substantially enhance bacterial sensitivity to antibiotics. Duan et al [ 96 ] developed a novel nanobiomimetic system (Siv-PMB@G4@MM) prepared by coating G4-PAMAM dendrimers (loaded with polymyxin B [PMB] and sivelestat [Siv]) with macrophage membranes (MM). Siv-PMB@G4@MM exhibits promising pH-responsive release characteristics under acidic conditions and can target inflamed lung tissues to substantially increase the concentrations of PMB and Siv at the infection sites. Based on evidence from mouse models of lipopolysaccharides (LPS)-induced acute lung injury, pulmonary bacterial infection, and sepsis-induced pneumonia, Siv-PMB@G4@MM reduces inflammatory responses and bacterial loads, alleviates neutrophil infiltration and pulmonary edema, and decreases the secretion of neutrophil extracellular traps. Wang et al [ 97 ] reported the BioNanoCFP system, which involves loading indacenodithieno[3,2-b]thiophene (ITIC) and cefoperazone onto a nanoparticle platform using a natural killer (NK) cell membrane coating strategy. BioNanoCFP has excellent mucus-penetrating ability that enables it to reach infection sites. The toll-like receptors in the NK cell membrane enable BioNanoCFP to recognize pathogen-associated molecular patterns in bacteria. This facilitates the precise targeting of bacterial colonization sites and results in significant therapeutic effects.

Huang et al [ 98 ] reported a nanoengineered human umbilical cord MSC (hUC-MSC) system (PMZMU) for synergistic sonodynamic-nanobacterial treatment. PMZMU comprises hUC-MSC membranes modified with the bacteria-targeting peptide UBI29-41, mesoporous organosilica nanoparticles doped with the sonosensitizer tetracarboxylphenyl porphyrin, and acid-responsive MOF zeolitic imidazolate framework-8 (ZIF-8). This formulation facilitates efficient PMB loading, reduces off-target drug release, enhances circulation and targeting efficiency, and enables ROS generation under ultrasound irradiation. PMZMU has significant inhibitory activity against four multidrug-resistant bacteria ( Klebsiella pneumoniae , Acinetobacter baumannii , Pseudomonas aeruginosa , and E. coli ) in vitro . It leverages the bacteria-targeting ability of UBI29-41 and the chemotaxis of hUC-MSCs toward inflammation to achieve precise delivery to pulmonary infection sites and increase the PMB concentration. PMZMU-mediated sonodynamic therapy significantly reduces bacterial loads, alleviates inflammatory damage by promoting macrophage polarization toward the M2 phenotype, and improves survival rates without adverse events.

Chitosan-alginate composite carriers have good biocompatibility and pH sensitivity and show substantial application potential in pulmonary drug delivery systems. Alnaief et al [ 99 ] prepared chitosan-alginate aerogel microparticles via emulsion gelation and avoided additional ionic cross-linking agents. This approach significantly influences the physicochemical properties of the microparticles (e.g., particle size, density, and surface charge) through adjustments to the mixing order of the biopolymers in the emulsion and the surfactant type. These findings show that chitosan’s amphiphilicity altered the hydrophilic-lipophilic balance of the emulsifier and the primary determination of surface charge by the surfactant. The microparticles have a mesoporous structure with pore sizes ranging from 12.48 to 13.38 nm and a surface area of 29.36 to 86.20 m²/g. Their aerodynamic diameters range from 0.17 to 2.29 µm, indicating their suitability for pulmonary delivery. Bensouiki et al [ 100 ] synthesized sodium alginate-chitosan nanoparticles via ionic gelation combined with polyelectrolyte complexation to encapsulate ibuprofen. Spray drying and ionic gelation are the two main methods for preparing alginate-modified inhalable particles, and they have marked effects on drug release kinetics and pulmonary delivery performance.

Collagen is the main structural protein in most animal and human tissues and plays a key role in maintaining the biological and structural integrity of the ECM. Its low immunogenicity, porous structure, good permeability, biocompatibility, and biodegradability have led to its widespread use in tissue engineering. However, the poor mechanical properties of collagen scaffolds have limited their applications to some extent. Collagen scaffolds can be crosslinked via chemical or physical methods or modified with natural/synthetic polymers or inorganic materials. Wang et al [ 101 ] reported a rapid method for preparing collagen bundle biomimetic hydrogels (MC-gels). The collagen bundles were obtained through mechanical stirring, enzymatic digestion of the tumor tissue fragments, and microbial transglutaminase and gelatin cross-linking to form biomimetic hydrogels. The MC-gels have larger diameters and higher cell viability in lung cancer organoid cultures and have an irregular shape that is closer to in vivo morphology. This technology offers new possibilities for collagen applications in pulmonary therapy, especially for simulating tissue microenvironments. However, the following gaps in current research need to be addressed: (1) the efficacy of MC-gels in simulating the tumor microenvironment has been demonstrated, but their application in pneumonia treatment has not been validated; (2) the long-term stability and biodegradability of collagen scaffolds in the pulmonary environment have not been established; and (3) the modification of collagen scaffolds to enhance their mechanical properties and biological activity is a key direction for future research.

Biomimetic materials based on the structure and function of natural products

Nanozyme materials have unique advantages in antibacterial and anti-inflammatory applications due to their catalytic activities. Hu et al [ 102 ] developed a Fe 3 O 4 -based iron death inducer (mFe-CA) that effectively induces iron death in MRSA through the synergistic action of Fe 3 O 4 release and cinnamaldehyde (CA). mFe-CA combined with ultrasound treatment significantly increases the survival rates of mice with MRSA pneumonia, reduces their pulmonary bacterial loads, and alleviates their inflammatory damage without toxicity. These findings provide a new strategy and theoretical basis for overcoming microbial resistance and treating acute MRSA pneumonia. Inhalable nanozyme platforms have demonstrated marked local anti-inflammatory effects in the treatment of pneumonia, especially in the regulation of the microenvironment of viral and bacterial pneumonia. Peng et al [ 103 ] reported a cerium-based tannic acid nanozyme with excellent ROS scavenging ability in a viral pneumonia model. Nanozymes are internalized by activated macrophages and epithelial cells at inflammation sites. They aggregate into catalytically active structures in oxidative environments, reduce ROS concentrations and inflammatory cytokine production, and promote macrophage polarization toward the pro-healing (M2) phenotype. Zhang et al [ 104 ] reported a self-assembled nanozyme platform that reduces local ROS concentrations by forming catalytically active fiber structures in a viral pneumonia model, alleviating inflammation and mitigating pneumonia symptoms.

Biomimetic Materials in Urinary Diseases and Kidney Disorders

Urinary diseases

Urological diseases substantially impair patients’ quality of life. They are typically associated with organ dysfunction, chronic pain, and psychological burdens. Traditional treatments have several limitations. Surgical interventions may cause complications, drug therapies are often limited in efficacy and may trigger side effects, and organ transplantation is hindered by donor shortages and immune rejection. These challenges highlight the urgency of developing more effective and safer therapeutic strategies. As shown in Figure 4 and Table 4 , the advent of biomimetic materials has opened new avenues for regenerative medicine in the urinary system. These materials, which mimic the structure and function of natural tissues, have excellent biocompatibility and tissue integration capabilities. They can also be used to develop smart drug delivery systems that release therapeutic molecules at the disease site and reduce systemic toxicity. These findings highlight the value of these innovative applications in advancing the treatment of urological diseases. They have significant academic and clinical implications and are expected to overcome the limitations of traditional therapies and promote the rapid development of regenerative medicine in urology.

Biomimetic materials developed from natural products

Biomimetic materials derived from natural products have demonstrated significant clinical value in the field of regenerative medicine of the urinary system. dECM is an important biomaterial that retains the structure and components of the natural ECM. It is therefore an ideal choice for use in tissue engineering. Studies have reported that dECM can effectively promote cell adhesion, proliferation and differentiation, and support tissue regeneration and repair. For example, Zhang et al [ 105 ] reported the good biocompatibility and anticalcification properties of the decellularized small intestinal submucosa matrix in bladder smooth muscle regeneration. The bacterial cellulose/bladder acellular matrix scaffold developed by Wang et al [ 106 ] has demonstrated potential for promoting vascularization and epithelialization. The three-dimensional porous nanofiber structure of this scaffold is similar to that of the natural urethra. It effectively promotes the growth of human umbilical vein endothelial cells and the formation of capillary-like tubes to accelerate urethral regeneration. These findings highlight the important role of natural ECM in promoting vascularization and tissue regeneration and provide new ideas and methods for urinary system regenerative medicine.

Biofilm functionalization enhances biocompatibility and functionality through surface modification. The development of urothelial models for the urinary system provides an important basis for biofilm functionalization. Cross et al [ 107 ] reported the formation of layered urothelium with differentiated characteristics by normal human urothelial cells under appropriate in vitro conditions, highlighting the potential application of biofilms in urinary tract physiology research. This model has a high transmembrane electrical resistance and demonstrates selective permeability to sodium ions, confirming its effectiveness in biofilm functionalization.

Selecting appropriate alternative materials remains a significant challenge in the regenerative medicine of the urinary system. Organ reconstruction requires the selection of appropriate functional materials. Conventional autologous tissues may fail to meet the functional demands of the new environment, and this is especially evident in bladder replacement surgeries. Therefore, further exploration and development of biomaterials with enhanced functionality are of great significance for advancing regenerative therapies for the urinary system.

Biomimetic materials inspired by the structure and function of natural products

The hierarchical structure of electrospun nanofibers can simulate the microenvironment of natural tissues and promote cell growth and functional recovery. Ghafari et al [ 108 ] developed a hybrid hydrogel scaffold by combining natural and synthetic materials to optimize its mechanical and biological properties and enhance bladder tissue regeneration. Zhang et al [ 109 ] designed a functional universal sandwich biomimetic scaffold with repair and drug delivery capabilities to promote smooth muscle regeneration and reduce the risk of stone formation. The design concept of this scaffold, which mimics the natural bladder structure, demonstrates its potential for stability.

There are also significant structural differences between the biomimetic microvascular scaffolds and the human-induced pluripotent stem cell-based scaffolds. The hiPS cells can differentiate into mature podocytes on electrospun fibroin membranes, which have good biocompatibility and tunability and support cell growth and functional expression. [ 110 ] In contrast, the biomimetic microvascular scaffolds have more complex three-dimensional structures that simulate the physiological vascular environment and promote cell interaction and tissue regeneration. Podocyte differentiation and function are enhanced under the regulation of the TGF-β1 pathway, and this is important in the design of biomimetic scaffolds. Regulating the TGF-β1 signaling pathway can effectively promote podocyte maturation and functional recovery and improve the efficacy of kidney tissue engineering. The self-sustainable bioelectronic patch proposed by Li et al [ 111 ] can self-adhere to damaged organ areas, generate bioelectronic signals synchronized with the vagus nerve, and effectively regulate macrophage polarization. This intervention inhibits excessive fibrosis and microvascular stasis, accelerates liver and kidney repair, and demonstrates the application potential of biomimetic materials in tissue regeneration.

Kidney disorders

Kidney disorders (such as AKI, chronic kidney disease, and renal fibrosis) are serious threats to patient health. They often result in severe consequences, such as renal failure and uremia, which substantially affect quality of life and survival.

Biomimetic materials developed from natural products

Membrane-camouflaged nanoparticles have demonstrated substantial potential in kidney-targeted therapies. [ 112 ] Deng et al [ 113 ] developed a biomimetic nanosystem that reduces AKI by regulating oxidative stress and inflammation, further highlighting the importance of biomimetic materials in clinical applications. Cao et al [ 114 ] used the natural products curcumin and trehalose to target AKI via cell membrane-coated nanocarriers, reducing oxidative stress and improving renal function. Shen et al [ 115 ] developed stimulator of interferon genes antagonist-loaded renal tubular epithelial cell membrane-coated nanoparticles that alleviate AKI by regulating immune responses. These nanoparticles provide new strategies for targeting inflammatory responses. These mechanistic differences reflect the pathological characteristics of different types of kidney injury and represent the varying emphases of research teams on therapeutic strategies. Direct cell-based therapies have been proposed as novel strategies. [ 116 ] Evidence shows that metal-organic frameworks (MCM@MOF) wrapped in macrophage membranes can encapsulate bioactive molecules such as Irisin, overcoming its short circulation time and limited kidney-targeting ability. By retaining macrophage membrane proteins, this engineered nanotherapeutic extends circulation time, enhances targeting to damaged kidneys, reduces acute ischemia-reperfusion injury, protects mitochondrial function, and regulates superoxide dismutase levels in renal tubular epithelial cells. [ 117 ] Li et al [ 118 ] reported a novel nanoparticle drug system combining metal-organic frameworks with natural platelet membranes, which achieves targeted treatment of renal inflammatory sites. This model demonstrates how biocompatible materials can enhance drug efficacy and reduce the side effects of long-term steroid use. He et al [ 119 ] reported that biomimetic high-density lipoprotein lipid nanoparticles can target damaged renal tubular epithelial cells and codeliver anti-inflammatory and antifibrotic drugs to substantially reduce renal injury and fibrosis in a mouse model of chronic kidney disease. Kholia et al [ 120 ] reported that extracellular vesicles derived from MSCs reduce the expression of inflammatory cytokines (IL-6, TNF, and IL-1β), alleviate tubulointerstitial fibrosis in the unilateral ureteral occlusion model, and downregulate profibrotic genes in aristolochic acid-induced chronic kidney disease. Nassar et al [ 121 ] reported the reversal of renal fibrosis in a streptozotocin-induced diabetic nephropathy mouse model via delivery of antifibrotic microRNAs (miRNAs) by BM-MSC-derived extracellular vesicles. Zhou et al [ 122 ] reported the efficacy of tripterine against renal tubulointerstitial fibrosis using a biomimetic nanodisk technology that enables its targeted delivery to fibrotic kidneys. Zhang et al [ 123 ] developed a platelet-mimetic targeted drug delivery system. This system achieves precise delivery of dexamethasone by simulating the natural tropism of platelets toward damaged glomeruli and leveraging lipid nanoemulsion encapsulation technology. The system not only alleviates renal tubular and podocyte damage, improves renal function indicators, but also has a novel therapeutic effect in delaying renal aging. It has demonstrated excellent anti-inflammatory efficacy, especially in the LPS-induced inflammation model.

Biomimetic materials inspired by the structure and function of natural products

Singh et al [ 124 ] demonstrated the application of 3D printing technology for fabricating bioinspired microfluidic devices that contact entire organ surfaces and extract biomarkers from whole organs. These devices provide new technical means for detecting kidney. Kaith et al [ 125 ] explored the application of 3D bioprinting in tissue engineering and highlighted the effectiveness of manufacturing biofunctional scaffolds from polysaccharides in simulating the native tissue environment. They suggested that this approach provides a new direction for natural product-based biomimetic materials. Kim et al [ 126 ] used glycocalyx-like biomimetic nanoparticles for kidney-targeted drug delivery. These nanoparticles significantly reduced CDDP-induced renal injury and demonstrated the potential of biomimetic materials for targeted therapy. Li et al [ 127 ] proposed a mild oxidation valence engineering strategy to control the valence of Mo in Pluronic F127-coated MoO 3 -x nanozymes (MF-x) and enhance their selectivity for H 2 O 2 -related catalytic reactions. Experimental results showed that MF-0 (average Mo valence of 4.64) and MF-10 (average Mo valence of 5.68) had optimal catalase and peroxidase activities, respectively. Density functional theory calculations revealed the H 2 O 2 activation mechanisms and validated the most favorable reaction pathways for MF-0 and MF-10. This valence regulation strategy improves the catalytic selectivity of nanozymes and provides new insights into the treatment and monitoring of specific diseases. Xu et al [ 128 ] synthesized mackinawite nanozymes that exhibited broad-spectrum ROS scavenging capabilities via multienzyme-like synergistic actions and hydrogen polysulfide release. The mackinawite nanozymes demonstrated significant cytoprotective effects against ROS-induced damage at extremely low doses and improved the therapeutic outcomes of AKI in vitro and in vivo . This synergistic mechanism enhances the anti-inflammatory effects by inhibiting the NF-κB pathway. Zhang et al [ 129 ] synthesized ultrasmall Prussian blue nanozymes (4.5 nm) with multi-enzyme mimetic capabilities for AKI treatment. The Prussian blue nanozymes accumulated in the kidneys to a large extent and had marked therapeutic effects in two clinically relevant mouse models of AKI. Their multi-enzyme mimetic capabilities enabled effective clearance of reactive oxygen/nitrogen species, and their therapeutic effects were monitored in real time via magnetic resonance/photoacoustic dual-modal imaging.

Wang et al [ 130 ] reported the therapeutic effects of iridium nanozymes on kidney injury under high-altitude hypoxic conditions. They reported that the iridium nanozymes reduce inflammatory responses and protect renal function by decreasing plasma IL-6, succinate, and indoxyl sulfate concentrations. This synergistic mechanism enhances the therapeutic effects by regulating gut microbiota distribution and plasma metabolites.

Applications of Biomimetic Materials in Endocrine System Diseases

Endocrine system diseases

Endocrine system diseases, such as diabetes, are often associated with severe complications, especially wound infections. These complications can lead to delayed healing, infection spread, and amputation, and they cause substantial suffering to patients. Traditional treatments have some efficacy but are associated with several challenges, including the inability to precisely target lesions and limited anti-infection efficacy. As shown in Figure 5 and Table 5 , biomimetic materials have provided new opportunities for the treatment of endocrine system diseases in recent years. These materials have antibacterial effects during the infection phase and regulate oxidative stress during the repair phase in the diabetic wound microenvironment, thereby improving the speed and quality of wound healing. They provide new insights into the precise treatment of endocrine system diseases and have significant clinical application potential.

Biomimetic materials constructed from natural products

Natural membrane biomimetic materials, which have unique structures and functions, offer new opportunities for the treatment of endocrine system diseases. These materials can achieve targeted drug delivery and efficient intracellular release by mimicking the characteristics of natural biological membranes. This improves drug bioavailability and reduces side effects. Wu et al [ 131 ] reported a glucose-responsive nano-platform based on red blood cell membranes. This platform extends the in vivo half-life of the nanotherapeutic by functionalizing the surfaces of the nanocarriers and enables glucose-responsive insulin release. This strategy leverages the immune evasion properties of red blood cell membranes. The cascade catalytic action of glucose oxidase and hemoglobin effectively eliminates the harmful byproduct hydrogen peroxide (H 2 O 2 ) and enhances system biocompatibility and therapeutic efficacy. Xu et al [ 132 ] reported a biomimetic nuclear membrane system based on a different strategy. This system, which has a glucose- and β-hydroxybutyrate-sensitive microdomain structure, enables precise insulin release. The microdomains are nonionic with narrow channels under normal physiological conditions, effectively preventing insulin leakage. They convert glucose and β-hydroxybutyrate concentration signals into negative membrane potentials under hyperglycemic and ketotic conditions, leading to nanopore expansion and rapid insulin release. Experimental results for the mouse and mini-pig models of type 1 diabetes showed that this system maintained normal blood glucose concentrations for more than 1 month and 3 weeks, respectively.

Exosomes derived from natural products offer new opportunities for the treatment of endocrine system diseases. Exosomes are nanoscale lipid bilayer vesicles secreted by cells. They are characterized by low immunogenicity, high stability, and good tissue penetration. They can serve as drug delivery carriers and improve the pathological state of endocrine system diseases by regulating immune responses and promoting tissue repair. These features highlight their broad application prospects. Wang et al [ 133 ] developed a biomimetic oral hydrogen nanogenerator (HMS/A@GE) that integrates gut microbiota reshaping with antioxidant therapy and significantly improves insulin resistance and hepatic steatosis in mouse models of type 2 diabetes. This system encapsulated ammonia borane (A) in hollow mesoporous silica nanoparticles and modified it with ginger-derived exosomes (GE). It enhanced the biocompatibility of the nanoparticles and improved insulin resistance and hepatic steatosis in mice with type 2 diabetes. Its mechanism involves inhibiting pancreatic β-cell dedifferentiation, increasing Lactobacillus abundance, and promoting the generation of tryptophan metabolites (e.g., indole and indole-3-acetic acid). These effects activate the AhR/IL-22 pathway, improve gut barrier function, and alleviate metabolic disorders.

Biomimetic materials inspired by the structure and function of natural products

Nanozymes have gradually become a research hotspot in the biomedical field due to their low cost, high stability, multifunctionality, and good biocompatibility. Zhang et al [ 134 ] reported a Cu/Mg-MOF@CS/PL hydrogel that significantly reduces the concentrations of ROS in diabetic wounds via an electron transfer mechanism and promotes wound healing. The copper-magnesium nanozyme (Cu/Mg-MOF) regulates the chronic wound microenvironment, especially in the treatment of diabetic wounds, by transferring electrons between copper and magnesium. It also has marked antioxidant properties. This nanozyme reduces the concentrations of ROS and restores redox balance to promote wound healing. Experimental data showed that the healing rate of the Cu/Mg-MOF@CS/PL hydrogel for the diabetic wounds was 90.6% on day 14, which was higher than the 55.4% for the untreated group. The bimetallic cactus structure (GNR@CeO 2 @GNPs) enhances the catalytic activity via a plasmon-enhanced effect. This structure captures photons under 808 nm laser irradiation and transfers hot electrons from the gold nanorods (GNRs) and gold nanoparticles (GNPs) to cerium dioxide (CeO 2 ). This triggers a “butterfly effect” and enhances its two-step enzyme-mimicking catalytic activity. Experimental results have demonstrated that GNR@CeO 2 @GNPs activated by glucose and laser irradiation effectively consume local glucose, overcome the limitations of single photothermal therapy (PTT), and generate large amounts of ROS to accelerate wound healing. [ 135 ] Shang et al [ 136 ] developed an ultrasound-enhanced multienzyme-like nanozyme hydrogel spray (ACPCAH) that responds to the diabetic wound microenvironment and facilitates multifunctional synergistic treatment, including reducing inflammation, alleviating hypoxia, lowering blood glucose, promoting angiogenesis, and eliminating pathogens. Xuan et al [ 137 ] reported the first amyloid-oxidized cerium nanozyme-enhanced microneedles with SOD and CAT-like activities. These microneedles facilitate synergistic catalysis for the remodeling of infected microenvironments. They have demonstrated substantial clinical potential in the treatment of diabetic wound infections and provide new insights into dynamic responsive microenvironment remodeling. Li et al [ 138 ] developed a fiber-based compartmentalization strategy for constructing a multinanozyme system capable of performing incompatible reactions simultaneously. This strategy spatially distributes the incompatible nanozymes in different compartmentalized fibers and customizes the microenvironment using doping reagents to create optimal working conditions for each nanozyme. For example, doping with benzoic acid resolved the pH incompatibility between the POD-like and CAT-like catalytic reactions and enabled their simultaneous operation. This design overcomes the limitations of traditional assembly strategies and provides an integrated oxygen supply and antibacterial platform for diabetic wound healing.

Microneedle biomimetic materials offer promising opportunities for the treatment of endocrine system diseases owing to their advantages of minimally invasive, efficient, and precise drug delivery. The hemoglobin biomimetic microneedle inhibits bacterial growth via iron deprivation. Its core functionality is the synthesis of an optimal “iron chelator”—the chelate of protoporphyrin IX with dopamine and gallium (PDGa). PDGa microneedle downregulates the expression of ferric uptake regulator (Fur) and peroxide response regulator (perR) in S. aureus at the infection sites. This induces iron starvation and oxidative stress in the bacteria and inhibits their iron-dependent activity. [ 139 ] Wang et al [ 140 ] developed a biomimetic coating based on scallop byssal protein that assembles in situ under the driving force of Ca 2+ and has excellent antioxidant, antibacterial, and immune regulatory properties. The coating has been shown to substantially improve the wound microenvironment in diabetic mice and rabbits. Its benefits include reducing bacterial infections, decreasing inflammatory responses, increasing M2 macrophage numbers, clearing ROS, promoting angiogenesis, and enhancing epithelial regeneration.

The unique micronanostructure and multifunctionality of octopus tentacles provide important inspiration for biomimetic material design. Chen et al [ 141 ] developed a biomimetic material assembled from α-cyclodextrin and PEG. The material was modified with polyethyleneimine to impart adhesive properties similar to those of octopus suckers. The α-cyclodextrin mimics the flexible structure of octopus tentacles. This material effectively captures and adheres to bacteria, offering new ideas for the treatment of diabetic wound infections. The core functionality of this biomimetic material is based on a photothermal NO release synergistic mechanism. Near-infrared light irradiation triggers rapid heating and NO release via the photothermal conversion properties of graphene oxide. This synergy achieves efficient antibacterial activity and effectively disperses biofilms, substantially reducing the inflammatory response in diabetic skin injuries. Sustained NO release also promotes vascular endothelial growth factor production and angiogenesis, accelerates collagen formation, and shortens the healing time of diabetic skin infections.

Applications of Biomimetic Materials in Neurological Diseases

Neurological diseases

Neurological diseases have far-reaching impacts on society and individuals. Their incidence is increasing, especially as the global population ages. Neurological disorders such as AD and Parkinson’s disease (PD) cause cognitive decline and motor impairments and impose substantial caregiving and economic burdens on families. Patients with PD often have severe motor impairments, which reduce their quality of life and affect their independence in daily activities. [ 142 ] Nerve injury is another important research area, especially given its impact on movement, sensation, and cognition. This underscores the urgent need for effective treatments. [ 143 ] Neuroinflammation, which is a common feature of many neurological diseases, causes further cellular damage and accelerates disease progression. [ 144 ] For example, glioblastoma, an extremely aggressive brain tumor, has a very low survival rate, highlighting the urgent need for effective treatment options. [ 145 ]

Researchers are actively exploring new therapeutic approaches to address these challenges. As shown in Figure 6 and Table 6 , the advent of biomimetic materials has heralded new hope for the treatment of neurological diseases. These materials, which include naturally derived materials, peptides, proteins, and polysaccharides, have been validated for their flexibility and effectiveness in nerve repair and regeneration. [ 154 ] They can mimic the properties of the ECM, provide support for nerve cells, and promote nerve regeneration and functional recovery. They can also regulate the neural microenvironment and promote nerve cell growth and differentiation to enhance nerve injury repair. The severity of neurological diseases and the social and economic burdens they impose highlight the urgent need for effective treatments. The application of biomimetic materials offers a new approach for treating these diseases. Future research could explore the potential of these materials for nerve repair and regeneration to improve treatment outcomes and patient quality of life.

Naturally derived materials have demonstrated considerable potential for the treatment of neurological diseases, especially in recent research on AD and PD. Natural plant extracts have been shown to reduce nerve damage via their antioxidant properties. For example, some natural polysaccharides have neuroprotective effects and combat the progression of neurodegenerative diseases through various mechanisms. Natural polysaccharides such as silk fibroin and trehalose, which have excellent biocompatibility and biodegradability, are widely used in neural tissue engineering. Silk fibroin promotes nerve cell growth and regeneration and improves nerve function by releasing growth factors. [ 155 ] Trehalose has substantial neuroprotective effects in animal models and reduces oxidative stress and neuroinflammation, which are key pathological features of neurodegenerative diseases. Plant extracts such as flavonoids and polyphenols have antioxidant and anti-inflammatory properties. Flavonoids protect nerve cells from damage by inhibiting neuroinflammatory responses and oxidative stress. [ 146 ] These natural compounds have neuroprotective effects and modulate cellular signaling pathways such as NF-κB and Nrf2. [ 147 ] Naturally derived polysaccharides and plant components are considered potential therapeutic options for AD. Some polysaccharides slow the progression of AD by inhibiting β-amyloid (Aβ) aggregation. Some plant extracts improve cognitive function and reduce behavioral impairments associated with AD. [ 148 ] Natural plant components, such as glycyrrhizic acid and black pepper extract, have demonstrated promising neuroprotective effects in patients with PD. Glycyrrhizic acid reduces motor impairments in mouse models of PD by inhibiting neuroinflammation and oxidative stress. [ 149 ] Bioactive components in black pepper improve symptoms in patients with PD by increasing dopamine concentrations. [ 150 ]

Peptides are important biomimetic materials that have demonstrated unique therapeutic potential in the treatment of neurological diseases. Their efficacy in improving cognitive function and their role in nerve repair has been reported in recent studies. Some specific peptides have been reported to improve cognitive function in patients with AD, and these findings have provided a basis for developing new therapeutic strategies. The pathological characteristics of AD include Aβ aggregation and neuronal degeneration. Peptides can intervene in these processes through various mechanisms. They can slow the progression of AD by regulating neuroinflammatory responses. Some peptides inhibit microglial overactivation and reduce inflammatory factor release to protect neurons from damage. [ 151 ] The neuroprotective effects of specific peptides, such as the vasoactive intestinal peptide, have also been reported in patients with Huntington’s disease. [ 152 ] These peptides provide new ideas for the treatment of neurological diseases by inhibiting neuronal apoptosis and promoting neuronal survival. Peptides have also been used successfully for nerve repair. Some studies have reported that functionalized peptides can be used as filling materials for nerve conduits to promote nerve regeneration. For example, KHIFSDDSSE (KHI) peptides promote Schwann cell attachment and proliferation in nerve injury models and improve nerve regeneration. [ 153 ] Peptide conduits combined with biomaterials have demonstrated good biocompatibility and the ability to promote nerve function recovery in animal experiments, providing a solid basis for clinical application. [ 154 ] Peptides can also act by targeting specific biomarkers in the treatment of neurodegenerative diseases. For example, Aβ-targeting peptides reduce neurotoxicity by inhibiting aggregation and help improve cognitive function. [ 155 ] Some peptides enhance neuroprotective effects by regulating the insulin signaling pathway to improve the metabolic status of patients with AD. [ 156 ]

Polysaccharides are important biological macromolecules that have received widespread attention in neurological disease research and treatment due to their good biocompatibility and biological activity. Their anti-inflammatory and neuroprotective effects and the benefits to chronic neuropathies have been reported in recent studies. Some natural polysaccharides extracted from plants have antioxidant, anti-inflammatory, and neuroregenerative effects. These effects highlight their potential applications in the treatment of AD, PD, and other neurodegenerative diseases. [ 157 ] The biological activity of polysaccharides is closely related to their structural characteristics. The variations in the molecular structure, molecular weight, and functional groups of polysaccharides from different sources underlie their distinct in vivo mechanisms of action. Some polysaccharides have neuroprotective effects, which they exert by regulating neurotransmitter release and improving the nerve cell survival environment. Plant polysaccharides such as licorice polysaccharide and astragalus polysaccharide reduce nerve cell damage by inhibiting neuroinflammatory responses and oxidative stress. [ 158 , 159 ] The anti-inflammatory effects of polysaccharides have been confirmed in several studies. Some polysaccharides reduce neuroinflammatory responses by inhibiting the release of proinflammatory cytokines to protect nerve cells. For example, polysaccharides extracted from Acorus tatarinowii reduce the concentrations of inflammatory factors induced by LPS by inhibiting the TLR4-mediated signaling pathway and protect nerve cells from damage. [ 160 ] Seaweed polysaccharides such as laminarin and fucoidan have neuroprotective effects and reduce brain ischemia-reperfusion injury via antioxidant and anti-inflammatory properities. [ 161 , 162 ]

Polysaccharides have applications beyond neuroprotection; they are also used for nerve regeneration and repair. Some polysaccharides serve as carriers for drug delivery systems to promote targeted drug release in neural tissue and enhance therapeutic effects. Polysaccharide-based hydrogels have been applied to skin trauma repair, and they have been shown to promote cell proliferation and migration. These hydrogels provide new insights into nerve tissue regeneration. [ 163 ]

Natural exosomes, which are important mediators of intercellular communication, have attracted increasing attention from researchers in recent years, especially for the treatment of neurological diseases. Exosomes are extracellular vesicles (30–150 nm in diameter) that carry various bioactive molecules (proteins, lipids, and nucleic acids), transmit signals between cells, and regulate several physiological and pathological processes. They have been shown to play an important role in nerve cell regeneration and repair and are involved in the pathological mechanisms of neurodegenerative diseases such as AD and PD. The biological characteristics of exosomes make them potential therapeutic tools. They can cross the blood–brain barrier and are present in various body fluids, reflecting brain pathological changes. For example, the miRNAs carried by exosomes regulate the physiological functions of nerve cells and have protective effects in neurodegenerative diseases. Exosomes slow nerve cell damage and death by regulating oxidative stress and inflammatory responses, and promote nerve regeneration and functional recovery. [ 164 ] Their application prospects have been established through clinical research. For example, exosomes derived from MSCs have significant neuroprotective and regenerative effects. They promote neuronal growth and survival by regulating intercellular signal transmission, reducing inflammation, and promoting neurotrophic factor release. Exosomes can also serve as drug delivery vehicles to enhance drug targeting and biocompatibility and improve therapeutic effects. [ 165 ] Their applications in neurological disease research extend beyond treatment to include biomarker studies. They carry disease progression-related molecules and enable early diagnosis. Disease-related proteins and miRNAs have been detected in the exosomes of patients with AD, and they serve as early diagnostic biomarkers. [ 166 ] This noninvasive method provides a new clinical diagnostic tool with important clinical value. However, exosomes have some limitations. Their preparation and purification techniques need to be optimized to enhance their consistency and effectiveness in clinical applications. Their functional characteristics and mechanisms of action require further investigation to facilitate a better understanding of their roles and potential therapeutic mechanisms in neurological diseases. [ 167 ]

Biomimetic materials based on the structure and function of natural products

Nanozymes have attracted widespread attention in neurological disease research in recent years due to their excellent catalytic properties. They can mimic the functions of natural enzymes and have high stability and tunability. They show promise for repairing nerve damage after injury. Nanozymes can effectively clear ROS in vivo and reduce oxidative stress-induced damage to nerve cells. This is of great significance for treating various neurological diseases. [ 168 , 169 ] Nanozymes have been widely applied in research on AD. Oxidative stress caused by excessive copper ion (Cu 2+ ) accumulation is a pathological characteristic of AD. Developing nanozymes that can bind harmful metal ions and clear ROS has become an effective therapeutic strategy. For example, an MXene-based nanozyme can effectively bind Cu 2+ and has strong antioxidant activity, significantly reducing pathological changes in mouse models of AD. [ 170 ] This dual-mechanism nanozyme has demonstrated efficacy in alleviating oxidative stress and improving neurological function. Researchers have developed a ternary nanozyme (PtCuSe nanozyme) with SOD and CAT activities for PD. It can effectively clear intracellular ROS and reduce nerve cell damage. This nanozyme has demonstrated potential for alleviating PD symptoms in animal models and provides a new approach for PD treatment. [ 171 ] Nanozymes also have promising applications in the treatment of ischemic stroke. Manganese-based nanozymes can effectively cross the blood–brain barrier, target and accumulate in ischemic injury areas, and exert antioxidant, anti-inflammatory, and anti-apoptotic effects. This nanozyme promotes neurological function recovery in addition to clearing excessive ROS, highlighting its potential for ischemic stroke treatment. [ 172 ] Nanozymes have applications beyond nerve cell protection, including in the diagnosis and monitoring of neurological diseases. Some nanozymes can serve as biosensors to monitor neurotransmitter release in real time, which is of great significance for understanding neurological function and diagnosing neurological diseases. [ 173 ]

The application of engineered bacteria and cells in neurological diseases is an emerging field in biomedical research. These engineered organisms have demonstrated great potential as drug delivery systems by mimicking biological processes. Their therapeutic effects through immune system activation or targeted drug delivery have been reported, highlighting new approaches to the treatment of neurological diseases. The application of engineered bacteria as drug delivery systems has attracted widespread attention. Their use has been associated with improved drug targeting and bioavailability. Some engineered E. coli have been designed to degrade phenylalanine in the gut. This is of great significance for the treatment of patients with phenylketonuria. These bacteria reduce blood phenylalanine concentrations and improve overall patient health by regulating the gut microbiota. [ 174 ] The combined use of engineered bacteria and cells has unique advantages in drug delivery. For example, using engineered bacteria as carriers to deliver drugs directly to injury sites can effectively increase local drug concentrations and reduce systemic side effects. Their use has been associated with drug release under specific physiological conditions to enable precise treatment. [ 175 ] This method improves drug therapeutic efficacy and reduces adverse reactions during treatment. The applications of engineered cells are also expanding. Researchers are exploring their combinations with nanomaterials to improve drug delivery efficiency. For example, their use with nanoparticles as carriers can target drugs to nerve cells with high precision and enhance their bioavailability and targeting. [ 176 ] This new drug delivery system shows promise for the treatment of neurological diseases.

Applications of Biomimetic Materials in Skin Diseases

Skin diseases

Skin, the largest human organ, plays vital roles in protection, regulation, and sensation. Skin diseases are the fourth most prevalent noncommunicable disease globally. Common conditions such as eczema, psoriasis, and atopic dermatitis significantly impair the quality of life of patients. They are also associated with potential health risks, and effective therapeutic approaches must be developed and implemented. Existing therapies often have suboptimal efficacy and are associated with significant side effects. This necessitates exploration of novel treatment methods. As shown in Figure 7 and Table 7 , the development of biomimetic materials has created new opportunities for the treatment of skin diseases. These materials have several unique advantages. First, they typically have good biocompatibility, which facilitates integration with the biological environment and reduces rejection reactions. Second, biomimetic materials provide new solutions for the treatment of skin diseases through their functional advantages, such as strong adhesion, antibacterial properties, and wound healing promotion. Their tunability and design flexibility enable optimization for different skin disease types. The importance of biomimetic materials in the treatment of skin diseases is increasingly evident, and relevant research has laid the foundation for progress in this field. Researchers have developed several innovative biomimetic materials in recent years by mimicking natural biological structures and functions. These materials have improved therapeutic effects and helped overcome some limitations of traditional treatments.

Biomimetic materials developed from natural products

Nanovesicles are nanoscale membranous vesicles secreted or released by cells. They transfer materials and information between cells and regulate cell functions and signaling pathways. Nanovesicles have attracted widespread attention as emerging biomedical tools for the treatment of skin diseases, driven by advances in nanotechnology and molecular biology in recent years. Jiang et al [ 177 ] studied the preparation of hybrid nanovesicles and reported their superior performance in treating infected diabetic wounds. The hybrid nanovesicles enhanced antibacterial activity and penetration by selectively targeting endothelial cells. They represent a new bioactive delivery system for the treatment of infected wounds and highlight the application potential of natural products in complex wound microenvironments. Xue et al [ 178 ] reported significant therapeutic effects of nanovesicles in psoriasis and atopic dermatitis models, which were attributed to the effective release of the immunosuppressant CX5461 at inflammatory sites. Their study highlighted the strategy of combining plant- and animal-derived nanovesicles to improve treatment efficiency and safety. Huang et al [ 179 ] designed multifunctional fusion nanovesicles that demonstrated significant therapeutic effects in autoimmune skin diseases and advanced research in this area.

Natural exosomes have garnered significant attention for the treatment of skin diseases in recent years. Apple-derived nanovesicles are novel anti-inflammatory agents that alter ECM production by skin fibroblasts and reduce MMP concentrations during skin aging. [ 180 ] Exosome-like nanovesicles from PL, termed FELNVs, have anti-aging activity. miR-CM1, which is contained in FELNVs, regulates and inhibits Mical2 expression in HaCaT cells. This promotes COL1A2 expression, inhibits MMP1 expression, and reduces the concentrations of intracellular ROS, malondialdehyde, and β-galactosidase. These effects are closely associated with aging. [ 181 ]

Microecological balance plays an important role in maintaining skin homeostasis. Engineered bacteria processed using modern bioengineering techniques are novel microorganisms with multifunctionality, high efficiency, and strong adaptability. For example, S. epidermidis has been engineered to express tumor antigens and elicit specific T-cell responses. Its colonization on the skin induces tumor-specific T-cell circulation and infiltration into local and metastatic lesions, demonstrating its potential for cell-based immunotherapy. [ 182 ] Qin et al [ 183 ] proposed a composite material based on Lactobacillus and MXene quantum dots for treating biofilm-associated infections. This material effectively disrupts biofilms, modulates the oxidative environment to reduce wound inflammation, and has good antibiofilm and wound healing properties. Cutibacterium acnes , an important member of the skin microbiota, has been engineered to produce and secrete therapeutic molecules. This approach has demonstrated potential for regulating sebum production and treating acne and other skin diseases. [ 184 ] Engineered microbial symbionts have also been applied to skin wound healing. For example, a photosynthetic “living material” created using Synechococcus elongatus and engineered Lactococcus lactis effectively promotes wound healing. The wound healing rate was significantly higher than that of the control group after 14 days of experimentation. [ 185 ] In summary, natural product-based biomimetic materials, especially nanovesicles, natural exosomes, and engineered bacteria, are innovative solutions for the treatment of skin diseases.

Biomimetic materials based on the structure and function of natural products

The biological characteristics of plants and animals provide rich inspiration for biomimetic material design. Plant-derived exosomes (e.g., ginseng exosomes [GExos]) have excellent biocompatibility and biological activity. They effectively transport active substances and promote endothelial cell proliferation and lumen formation, thereby improving angiogenesis under high-glucose conditions. [ 186 ] Animal-derived materials such as shark skin collagen form wound dressings with good biocompatibility and significantly promote wound healing when they are specifically extracted and processed. [ 187 ] Researchers have developed flexible artificial skin by combining electronic skin with artificial whiskers. This development was inspired by rodent skin and whiskers. The artificial skin, which is enhanced by unique air pockets for sensitivity, effectively transmits the mechanical stimuli applied to the whiskers and elicits sensitive tactile responses. It has high sensitivity, a wide sensing range, and excellent stability, making it suitable for applications such as human–machine interfaces, robotics, and wearable electronic devices. [ 188 ] Several advanced technologies have been developed in recent years. For example, two-photon polymerization 3D printing can produce complex biomimetic microstructures and enhance material functionality and adaptability. These materials exhibit strong adhesion in both wet and dry environments, making them suitable for skin wound treatment and repair. This is attributable to their mimicry of natural structures and functions, such as gecko adhesion and octopus reversible adhesion. [ 189 ] He et al [ 190 ] constructed an asymmetric structure on both sides of a sponge and modified its surface wettability via electrospinning to create an asymmetric composite dressing. Their approach was inspired by the surface structure and superhydrophobicity of lotus leaves. The sponge has good water absorption and antibacterial properties, and the biomimetic hydrophobic outer layer has strong mechanical properties and resistance to bacterial adhesion. The composite dressing reduced inflammatory responses, prevented infections, promoted angiogenesis and epithelial regeneration, and significantly accelerated severe burn wound healing in vivo . Chen et al [ 191 ] designed a hydrogel dressing with a mechanically regulable core-ring structure. Integrating the functionally independent core and ring layers facilitated effective wound traction and prevented dressing swelling. This hydrogel, with its tightly connected core and ring, promoted healing by accelerating epithelial closure, collagen deposition, vascular maturation, and ECM remodeling in mouse and pig skin wound healing. Guo et al [ 192 ] reported a network-drop electronic skin inspired by spider webs. It has excellent breathability and conductivity and enables long-term monitoring of physiological parameters. It has demonstrated potential in skin care.

Applications of Biomimetic Materials in Hematological Diseases

Thrombotic diseases

Thrombotic diseases, which have high incidence and recurrence rates, are among the leading global causes of death and disability. Common types include deep vein thrombosis, pulmonary embolism (PE), and arterial thrombosis (e.g., myocardial infarction and ischemic stroke). They are primarily caused by sluggish blood flow, endothelial injury, or hypercoagulable states. Thrombosis can cause local tissue ischemia and necrosis. If dislodged, it can result in acute organ dysfunction (e.g., respiratory failure due to PE) or sudden death. Traditional treatments include anticoagulants (e.g., heparin, warfarin) and thrombolytic agents (e.g., alteplase). However, they have significant drawbacks, including bleeding risks, short therapeutic windows, and resistance in some patients. Surgical thrombectomy is highly invasive and has limited applicability. As shown in Figure 8 and Table 8 , innovative biomimetic strategies, such as targeted nanocarriers and anticoagulant-coated vascular stents, improve efficacy and reduce complications by enabling precise drug delivery, mimicking endothelial anticoagulant functions, and promoting thrombus dissolution. They pave the way for personalized treatment of thrombotic diseases.

Biomimetic materials developed from natural products

Natural product-based biomimetic materials are used to treat thrombotic diseases via targeted delivery and anticoagulant function enhancement. First, targeted delivery involves using platelet membrane surface molecules for precise lesion localization. For example, Yin et al [ 193 ] developed a biomimetic nano-reactor (PM@Se/Rb1 nanoparticles) comprising selenium (Se) and ginsenoside Rb1 (Rb1) coated with platelet membranes. This system targets oxidized low-density lipoprotein in atherosclerotic plaques via the CD36 receptor on the platelet membrane. The antioxidant activity of Se and the lipid-regulating effect of Rb1 enhance plaque stability. PM@Se/Rb1 nanoparticles combined with warfarin significantly reduced the aortic plaque area and increased collagen fiber content in mice with atherosclerosis. Xu et al [ 194 ] reported polymeric nanoparticles camouflaged with engineered platelet membranes (referred to as “nanoplatelets”) and loaded with rt-PA. These nanoplatelets, inspired by the hemostatic function of platelets, accumulated efficiently at the thrombi in the PE and mesenteric arterial thrombosis models and demonstrated greater thrombolytic activity than free rt-PA. They also reduced the bleeding risk in ischemic stroke models, as evidenced by improved coagulation indicators. Xiao et al [ 195 ] reported platelet membrane-modified mesoporous silica nanoparticles (AMSNP@PM-rH/A) that target activated platelets at deep vein thrombosis sites via P-selectin. This system co-delivers recombinant hirudin (rH) and apixaban and achieves high thrombolysis rates with reduced bleeding risk.

Second, the enhancement of the anticoagulant function through material engineering optimizes the therapeutic performance of heparin. Amaral et al [ 196 ] linked PEG to the reductive end of heparin (Hep-b-PEG) via oxime bonds to preserve its AT-III binding domain and extend its blood half-life. Hep-b-PEG demonstrated 20% higher anticoagulant activity than unmodified heparin in vitro and formed colloidally stable nano-complexes with protamine, reducing the risk of thrombocytopenia associated with traditional heparin-protamine aggregation. Qiu et al [ 197 ] reported the electrospun heparinized elastomer grafts (L-PEUUH) with embedded heparin in the BEPU nanofibers to mimic the mechanical properties of the vascular ECM.

Biomimetic materials inspired by the structure and function of natural products

Natural product-based biomimetic materials have multidimensional effects in the treatment of thrombosis, which are based on their ability to mimic the targeting, anticoagulant, and repair capabilities of natural systems. Surface modification techniques enhance their anticoagulant performance through biomimetic coatings. Yao et al [ 198 ] developed a zwitterionic microgel coating (SAM/PDAS) that mimics the anti-fouling properties of fish skin and vascular endothelium. It inhibits platelet adhesion through controlled morphology and high-density deposition and reduces thrombus formation in ex vivo rabbit blood without anticoagulants. Kim et al [ 199 ] coated 3D-printed vascular grafts with a heparin-dopamine (Hep-DA) complex to leverage the anticoagulant activity of heparin and the strong adhesion of dopamine and reduce the risk of calcification and fibrosis after implantation. Vascular stent and graft designs incorporating natural products promote endothelialization and immune regulation. Zhang et al [ 200 ] applied a zinc ion lysozyme nanoparticle coating to mimic the antioxidant function of GSH POD, promote endothelialization, and inhibit intimal hyperplasia in rabbits via NO release. Niu et al [ 201 ] developed a three-layer small-diameter vascular graft with a carboxymethyl chitosan inner layer and gastrodin coating to combine antithrombotic and anti-inflammatory effects and promote neovascularization.

Biomimetic materials have strong targeting capabilities and multifunctional potential. However, their clinical translation is hindered by challenges such as the immunogenicity of cell membrane coatings, unpredictable long-term biocompatibility, and risks of clearance or accumulation. Their antithrombotic durability under hemodynamic stress has not been established. Future research should prioritize standardized safety assessments, chronic toxicity studies, and scalable, cost-effective manufacturing. It should also focus on integrating multifunctional designs that balance efficacy and hemocompatibility in diverse patient populations.

Multiple myeloma

Multiple myeloma (MM) is an aggressive hematologic malignancy of plasma cells. It remains incurable despite advances in proteasome inhibitors and immunotherapy. Disease relapse, drug resistance, and bone marrow microenvironment protection are major obstacles that lead to poor survival. Conventional chemotherapies such as bortezomib and DOX prolong survival but are limited by systemic toxicity and low selectivity. Nanomedicine has emerged as a viable solution to these challenges. Bioinspired materials enhance drug efficacy, reduce adverse effects, and facilitate new therapeutic paradigms for MM treatment through targeted delivery, biomimetic strategies, and immune modulation.

Biomimetic materials developed from natural products

Natural polymers such as hyaluronic acid have provided versatile platforms for drug delivery. Zhong et al [ 202 ] designed lipoic acid-crosslinked hyaluronic acid nanoparticles encapsulating doxorubicin (LACHA-DOX) to selectively target CD44-overexpressing MM and acute myeloid leukemia (AML) cells. LACHA-DOX suppressed tumor growth, prolonged survival, and spared healthy organs in mouse models relative to free DOX. Zhong et al [ 203 ] advanced this concept by developing hyaluronic acid-directed chimeric polymersomes encapsulating granzyme B (HA-RCP-GrB). These artificial killer cell mimics homed to the bone marrow, suppressed osteolysis, and significantly extended the survival of mice with MM. Gu et al [ 204 ] reported enhanced tumor accumulation, improved tolerability, and stronger growth inhibition of lipophilized bortezomib delivered via hyaluronic acid–shelled, disulfide-crosslinked micelles compared to the free drug. These studies highlight natural polymer-based carriers as effective and selective vehicles for cytotoxic therapy.

Biomimetic materials inspired by the structure and function of natural products

Multifunctional biomimetic systems have been developed to integrate therapeutic and immunomodulatory functions. Grab et al [ 205 ] reported hyaluronan hydrogels presenting bone morphogenetic protein 6. These hydrogels induced apoptosis in myeloma cells and promoted the osteogenic differentiation of stromal cells, thereby reducing the risk of relapse from osteolytic lesions. Zilkowski et al [ 206 ] reported poly(glycidol)-based nanogels covalently bound to TAT peptides for efficient miRNA delivery into transfection-resistant MM cells. These nanogels downregulated Notch1 and related genes, providing a gene therapy approach. Liu et al [ 207 ] reported bovine serum albumin (BSA)-based nanoparticles loaded with aggregation-induced emission photosensitizers. These nanoparticles markedly enhanced ROS generation, elicited immunogenic cell death, reversed T-cell senescence, and restored immune surveillance in MM. These biomimetic systems replicate natural regulatory functions (bone remodeling, gene silencing, and immune activation) and synergistically suppress tumor progression.

Biomimetic nanomedicines for MM have demonstrated encouraging efficacy in targeted drug delivery, immune modulation, and bone lesion repair. However, several challenges remain. Their immunogenicity, the unknown long-term toxicity of their degradation products, and their off-target effects in sensitive bone marrow niches necessitate careful evaluation. Most evidence to date is based on short-term studies involving small animals. Their therapeutic benefits, biosafety, and pharmacokinetics need to be validated in large animals and clinical settings. Future research could focus on their long-term in vivo safety assessment, standardized preclinical evaluation, optimization for large-scale, reproducible manufacturing, and integration with existing therapeutic regimens to accelerate clinical translation.

Leukemia

Leukemia is a malignant hematological cancer characterized by the excessive proliferation of abnormal white blood cells in the bone marrow. It poses a serious threat to the lives of patients. It is typically classified as acute or chronic based on the disease course. Its clinical features include anemia, susceptibility to infection, and bleeding tendencies. It often infiltrates the liver, spleen, and lymph nodes in advanced stages, leading to multiorgan failure. Chemotherapy, radiotherapy, and stem cell transplantation have improved survival. However, major challenges remain, including high drug resistance, recurrence, and treatment-related toxicities such as myelosuppression and immunodeficiency. Chemotherapy often causes severe side effects due to its nonspecific killing of normal cells, and graft-versus-host disease limits the wider application of transplantation. Recent research highlights biomimetic material-based therapies as new strategies to overcome the challenges of leukemia treatment by enhancing targeting, modulating the immune microenvironment, and reducing toxicity.

Biomimetic materials inspired by the structure and function of natural products

Natural product-based biomimetic materials enhance leukemia treatment through multi-mechanistic synergies, including targeted drug delivery, immune activation, and epigenetic regulation. These approaches leverage natural biological systems. Chen et al [ 208 ] reported a platelet membrane-coated DOX/ginsenoside co-loaded nanosystem (DR@PLip) that leverages the natural targeting ability of platelet membranes to locate leukemia cells. Ginsenosides enhance tumor sensitivity to chemotherapy and activate antitumor immunity to eliminate the leukemia cells hidden in the bone marrow. Harris et al [ 209 ] reported the efficacy of leukemia cell membrane-camouflaged nanoparticles for delivering DOX to AML cells via homologous targeting, with an apoptosis induction rate of approximately 80% at low doses. This performance was superior to that of free drugs. Wang et al [ 210 ] reported the efficacy of the leukemia cell membrane-camouflaged MnO 2 nanocarriers in eradicating AML cells in most mouse models. The MnO 2 nanocarriers release Mn 2+ in response to acidic conditions to activate the STING pathway, promote type I interferon secretion, and reshape the immune microenvironment. Song et al [ 211 ] reported a bimetallic MOF nanoplatform that targets leukemia stem cell membranes to deliver DNA demethylating agents and autophagy-inducing peptides. This nanoplatform inhibits DNA methylation and induces RNA hypermethylation to enhance T-cell-mediated immunity. Expanding to triple epigenetic intervention, Ding et al [ 212 ] designed an erythrocyte-mimetic MOF (MA272@MOF@RBC) loaded with oxygen-rich erythrocytes and epigenetic drugs. This MOF inhibits HIF-1α and modulates DNA/RNA methylation to enhance leukemia cell antigenicity and activate memory T cells.

Biomimetic approaches for leukemia have shown promise. However, they are associated with concerns regarding immune rejection, off-target cytotoxicity, and long-term stability of the engineered carriers. The complex and heterogeneous leukemia microenvironment can limit targeting precision. Large-scale production of patient-specific biomimetic systems also remains challenging. Future research should focus on integrating immune-safety profiling, resistance-monitoring strategies, and combination regimens and incorporating advanced models that better predict clinical behavior and guide personalized therapeutic designs.

Applications of Biomimetic Materials in Cardiovascular Diseases

Cardiovascular diseases

The circulatory system, the core network for transporting substances in the human body, comprises the heart, large vessels, and small vessels. Lesions in these components are associated with a severe threat to human health. Biomimetic materials, which have unique biocompatibility, mechanical matching, and functional mimetic properties, can simulate the structure and function of the heart and blood vessels. They offer new perspectives and directions for the treatment of circulatory system diseases. As shown in Figure 9 and Table 9 , research on the application of biomimetic materials in the treatment of heart, large vessel, and small vessel diseases is of substantial theoretical and clinical significance for overcoming existing therapeutic challenges and improving patient prognosis.

Biomimetic materials developed from natural products

Nanoparticles enveloped by cell membranes (e.g., LIPs or polymeric nanocarriers) emulate the surface characteristics of natural cells. This extends their circulation time and enables precise targeting of cardiac injury sites. Cubosomes coated with macrophage membranes have enhanced drug accumulation at cardiac pathological sites by reducing macrophage phagocytosis and nonspecific organ accumulation. [ 213 ] Biomimetic nanovesicles derived from cell membranes (e.g., stem cell membranes) carry pro-angiogenic factors or anti-inflammatory molecules and stimulate cardiomyocyte proliferation and angiogenesis to improve cardiac function following myocardial infarction. [ 214 , 215 ]

Platelet membrane coating technology leverages the natural ability of platelets to target damaged blood vessels to construct biomimetic nanomedicine delivery systems. These systems have demonstrated excellent performance in treating cardiac fibrosis and atherosclerosis. For example, biomimetic nanoparticles with hybrid platelet and red blood cell membranes can target myocardial fibroblasts and collagen deposition regions, deliver antifibrotic drugs (e.g., JQ1), and reduce systemic side effects. [ 216 ] Copper single-atom catalysts coated with platelet membranes inhibit foam cell formation and plaque progression by enhancing radiotherapy efficacy and regulating ROS concentrations. [ 217 ] Furthermore, platelet membrane biomimetic exosomes deliver anti-inflammatory factors and regulate the atherosclerotic microenvironment.

Plant-derived exosomes have low immunogenicity and high biocompatibility, and contain natural active components (e.g., nucleic acids, lipids, and antioxidant molecules), which provide new strategies for cardiac tissue engineering. Feng et al [ 218 ] reported the effective targeting of calcified vascular smooth muscle cells using grapefruit-derived exosome-based nanocarriers, which inhibit vascular calcification by inducing M2 macrophage polarization. This mechanism reduces inflammatory responses and inhibits bone–vascular axis activation, highlighting the potential of plant-based exosomes for cardiovascular targeted therapy.

Cardiac patches loaded with plant-derived exosomes influence the infarct microenvironment and promote angiogenesis and immune homeostasis. [ 219 ] Plant-based exosomes can encapsulate natural products (e.g., polyphenols and flavonoids) and mitigate myocardial ischemia-reperfusion injury via their antioxidant and anti-inflammatory effects. [ 220 ] Natural exosomes and synthetic carriers have marked differences in their biological effects. Synthetic carriers often lack biocompatibility and targeting capabilities, which can result in heightened immune responses and toxicity. In contrast, natural exosomes reduce immune rejection and enhance drug targeting and therapeutic efficacy through their inherent biological properties. Therefore, using natural exosomes as drug carriers offers more promising prospects for the treatment of cardiovascular disease.

Biomimetic materials inspired by the structure and function of natural products

ATP-responsive nanozymes modified with genetically engineered cell membranes can specifically recognize the pathological microenvironment of myocardial fibrotic regions and release antifibrotic drugs or ROS-regulatory molecules to inhibit abnormal fibroblast activation and excessive ECM deposition. [ 221 ] Such biomimetic surface modifications enhance the targeting of lesions by nanozymes and reduce off-target effects. [ 222 ] Nanozymes, such as those based on manganese-doped Prussian blue, have enhanced oxidase-like activity due to their mixed valence states and defect sites. They catalyze the conversion of ROS to harmless products and mitigate oxidative damage in myocardial ischemia-reperfusion injury. [ 223 , 224 ] Nanozymes can also be designed as stimulus-responsive carriers to trigger drug release based on abnormal enzyme activity or chemical gradient changes in regions of myocardial infarction.

Dynamic ECM remodeling regulates interactions between cells and their surrounding environment and promotes cell growth and functional recovery. Biomimetic materials simulate the mechanical properties of physiological or pathological ECM by regulating surface stiffness (e.g., optimizing scaffold elastic modulus via atomic force microscopy) and inhibiting pathological fibrosis. [ 225 ] Hydrogel-based dynamic ECM models have been used to simulate age-related ECM hardening and investigate the association between neurodegenerative diseases and cardiac ECM aging. [ 226 ] Acellular ECM scaffolds largely retain the protein composition and spatial structure of natural ECM and provide biochemical signals that promote cardiomyocyte adhesion and differentiation. [ 227 ] Cardiac patches with biomimetic vascular networks and conductivity have been constructed using 3D printing technology combined with natural biomaterials (e.g., fibrin and collagen). These patches enhance tissue integration and electrophysiological functions after transplantation. [ 228 , 229 ] The role of ECM–mitochondria crosstalk in heart disease progression has been gradually revealed. The ECM of patient-derived stromal cells alters mitochondrial function and affects the energy metabolism of cardiomyocytes. [ 230 ] Conductive nanomaterials (e.g., polythiophene) combined with natural biopolymers simulate the electrical conduction properties of myocardial tissue and promote the synchronous contraction of engineered myocardial tissue. [ 231 ] EV-ECM composite scaffolds, which integrate extracellular vesicles and ECM materials, enhance the paracrine signal transmission ability of cardiac patches and promote the regeneration of injured myocardium.

Large vessel diseases

Large vessels, which are the main conduits of the circulatory system, play a crucial role in transporting oxygen-rich and nutrient-rich blood from the heart to the tissues and organs. Their structural integrity and functional normality are directly related to the stability and efficiency of blood circulation. However, the incidence of large vessel diseases (e.g., aortic aneurysms, atherosclerosis, and aortic dissections) is increasing with population aging and lifestyle changes. These diseases reduce vascular wall elasticity and cause stenosis and rupture. They also lead to severe complications such as fatal hemorrhage and organ ischemia. The main treatments for large vessel diseases are vascular stent implantation, vascular replacement surgery, and drug therapy. Stent implantation restores vascular patency relatively rapidly but is complicated by in-stent restenosis and thrombosis in many cases. Vascular replacement surgery is notably highly invasive and is associated with a long recovery period and risk of infection. Drug therapy cannot reverse vascular structural changes that have already occurred. Biomimetic materials, which have excellent biomimetic vascular biomechanical properties, antithrombotic properties, and tissue compatibility, can simulate the layered structure and dynamic mechanical response of natural blood vessels. They represent a breakthrough in the treatment of large vessel disease. Studying the application of biomimetic materials in the treatment of large vessel disease is of great clinical and scientific significance for improving therapeutic outcomes and reducing complication rates.

Biomimetic materials developed from natural products

Cubic liquid crystal nanoparticles (cubosomes) encapsulated in macrophage cell membranes have reduced uptake by macrophages and prolonged blood circulation durations. In contrast, dry cell membrane coatings enhance the biocompatibility of nanoparticles and mimic their interactions with natural cells and the microenvironment. [ 232 ] This technique preserves surface receptors and adhesion molecules and facilitates the precise targeting of damaged vessels or inflammatory sites. [ 233 , 234 ]

Exosomes derived from MSCs fused with platelet membranes can target vascular endothelial cells and macrophages in atherosclerotic plaques. They inhibit inflammatory responses and promote plaque stability. [ 247 ] Biomimetic nanoplatforms combining platelet and tumor cell membranes (e.g., 4T1-PM-Liposome) can cross the blood–brain barrier, target cerebral ischemic injury regions, and reduce drug accumulation in non-target organs. [ 235 , 236 ]

Platelet membrane-coated biomimetic exosomes (e.g., PM-EXOs) retain the natural targeting ability of platelets via membrane fusion technology and inherit the anti-inflammatory and repair functions of MSC exosomes. They significantly improve the regulation of vascular smooth muscle cells. [ 237 – 239 ] Tea polyphenol nanoparticles encapsulated in platelet membranes have demonstrated superior efficacy relative to free drugs in an atherosclerosis model by enhancing their antioxidant and anti-inflammatory effects. [ 240 ]

Plant exosomes are efficient natural product delivery systems. For example, nanovesicles carrying curcumin target atherosclerotic plaques and inhibit inflammatory factor release. [ 241 , 242 ] The applications of olive leaf exosomes, which inhibit cellular senescence and promote skin repair, can be extended to cardiovascular injury repair. [ 243 ]

Biomimetic materials inspired by the structure and function of natural products

Structural biomimetics involves imitating the hierarchical structure and functional properties of natural blood vessels. The three-layer structure of natural arteries (intima, media, and adventitia) is widely replicated in biomimetic vascular grafts. Their synergistic functions are achieved through the layered design of multilayer polymer materials (e.g., polyurethane-collagen composites): the intima promotes endothelial cell adhesion, the media matches the vascular mechanical response, and the adventitia provides mechanical support. [ 244 , 245 ] Biomimetic materials construct vascular-like fiber networks at the microstructural level using biomanufacturing techniques (e.g., 3D printing and electrospinning). They simulate the topological structure of the ECM and promote the directional growth of vascular SMCs and endothelial cells. [ 246 ] Replicating the residual stress in biomimetic blood vessels is a key research direction. Regulating the internal material stress distribution to simulate the mechanical properties of natural blood vessels under physiological conditions can reduce the risk of mechanical mismatch after transplantation. [ 247 ] For example, a fish-scale microstructure scaffold design reduces blood flow resistance and inhibits thrombosis via biomimetic surface texture. [ 248 ] Biomimetic materials based on gradient structures and porous composites (e.g., gradient hydrogels) can simulate the vascular wall elastic modulus gradient and facilitate dynamic mechanical adaptation. [ 249 ]

Mechanical performance matching is the core challenge for the long-term functionalization of biomimetic blood vessels. Natural arteries have nonlinear elasticity (e.g., J-shaped stress-strain curves) and dynamic compliance. Traditional synthetic materials (e.g., polytetrafluoroethylene) are associated with vascular intimal hyperplasia due to excessive stiffness. Biomimetic materials optimize mechanical matching via three strategies. First, compliance adaptation through material composition (e.g., combining elastomers and rigid polymers) or structural design (e.g., helical fiber arrangement) aligns the compliance of biomimetic vessels with that of autologous arteries (elastic modulus: 0.1–3.0 MPa) and reduces abnormal blood flow shear force and pulsatile reflection. [ 250 ] Second, dynamic mechanical response: The incorporation of smart materials (e.g., thermosensitive hydrogels and shape memory polymers) enables the adaptive adjustment of the diameter of biomimetic vessels in response to changes in blood pressure, simulating natural vessel constriction–dilation behavior. [ 251 ] Third, fatigue durability: Enhancing cyclic load resistance through biomimetic composites (e.g., collagen-polycaprolactone composite fibers) enables it to match the long-term stability of blood vessels in pulsatile environments. [ 252 , 253 ] The efficacy of biomimetic mechanics-based grafts (e.g., multilayer polyurethane stents) in significantly reducing the incidence of postoperative stenosis has been demonstrated. Their burst strength (≥2000 mmHg) and suture retention force (≥2 N) meet the clinical requirements. [ 246 ]

Biomimetic biological functions aim to endow materials with natural blood vessel-like biological activities, including antithrombotic, endothelial-promoting, and signal transduction functions. The first is endothelialization promotion. Surface functionalization (e.g., RGD peptide modification, heparin coating) or growth factor release (e.g., VEGF, PDGF) accelerates endothelial cell migration and coverage and facilitates the formation of a functional monolayer barrier. [ 254 ] For example, VEGF-loaded biomimetic hydrogel scaffolds significantly increase the endothelial cell adhesion rate to >80%. [ 255 ] The second is antithrombotic design. Amphoteric polymers (e.g., polysulfobetaine) and biomimetic phospholipid coatings inhibit platelet adhesion and fibrin deposition by mimicking the anticoagulation mechanisms of the vascular endothelium. [ 256 ] Biomimetic surfaces have been reported to reduce the risk of thrombosis to less than one-third of that associated with traditional materials. [ 257 ] The third is cell–material interactions. Biochemical signals (e.g., integrin binding sites) and mechanical signals (e.g., matrix stiffness regulation) guide the directional differentiation and functional expression of vascular SMCs. [ 258 ] For example, the active repair functions of biomimetic vessels have also become a research hotspot. MSC-loaded scaffolds promote injury repair via paracrine action, and gene editing facilitates continuous local anti-inflammatory factor release. [ 259 , 260 ]

Small vessel diseases

Small blood vessels, which constitute the terminal network of the circulatory system, are responsible for the exchange of oxygen, nutrients, and metabolic wastes. They are crucial for maintaining tissue microenvironment homeostasis. However, the prevalence of small vessel lesions secondary to systemic diseases (e.g., diabetes and hypertension) is increasing. These lesions result in tissue ischemia and hypoxia, metabolic disorders, and severe complications such as retinopathy and renal failure. Approximately 60% of patients with diabetes have microvascular damage of varying severity. The repair of small-diameter blood vessels (<6 mm) is challenging in the treatment of cardiovascular disease. Small vessels are more prone to early occlusion, restenosis, and thrombosis than large artificial vessels (e.g., aorta). This is attributable to their complex hemodynamic characteristics (low flow rate and high shear force) and marked metabolic demands. [ 261 – 263 ] Traditional synthetic materials (e.g., polyurethane) have been successfully applied in large vessels. However, their insufficient biocompatibility and mismatched mechanical properties have resulted in low long-term patency rates for small vessel grafts. [ 264 ] Autologous vascular sources (e.g., saphenous veins) are also limited and may cause donor site complications. [ 265 ] Therefore, the development of biomimetic small vessel grafts has become an important focus of tissue engineering.

Biomimetic small-diameter vascular grafts (<6 mm) have demonstrated promising results in laboratory studies of applications such as coronary artery bypass grafting. For example, biomimetic vessels with a diameter of 1 mm have been successfully constructed via photocuring technology combined with endothelial cells and SMCs, and they have demonstrated excellent cell viability and mechanical stability. [ 266 ] Another study reported increased endothelialization and reduced thrombosis after using an electrospun pericardial ECM PCL composite scaffold. [ 267 ] Biomimetic materials accelerate endothelial cell migration and vascular regeneration by loading growth factors (e.g., VEGF) or using decellularized vascular fragments. Nanocarriers with red blood cell membrane biomimetic coatings have demonstrated excellent antithrombotic performance in animal models. [ 268 ] Three-dimensional bioprinting technology combined with biomimetic hydrogels enables the construction of vascularized tissues containing multiple cell types and ECMs and provides a model for studying the pathological mechanisms of small vessel disease. [ 265 ] Bioprinted vessels (2–4 mm in diameter) have been successfully used to replace autologous vessels in rabbit models, with >80% patency at 3 months postoperation. [ 265 , 269 ]

Challenges and Strategies for Clinical Translation

Biomimetic materials have demonstrated remarkable advantages in enhancing biocompatibility, improving targeting specificity, and regulating the pathological microenvironment by emulating the microstructure, mechanical properties, and biological functions of natural biological systems. These advantages include facilitating bone regeneration via GSDP-TEM scaffolds in locomotor system disorders, enabling rapid hemostasis through DMSN in gastrointestinal bleeding, and achieving precise drug delivery via cell membrane-camouflaged nanoparticles in lung cancer therapy. [ 1 , 29 , 67 , 68 ] These advancements highlight the transformative potential of biomimetic materials in addressing unmet clinical needs, such as overcoming the low targeting efficiency of conventional drugs and poor tissue integration of synthetic implants.

However, the field has critical limitations and unresolved controversies that require urgent attention, as overlooking them impedes sustainable development and clinical translation. First, immunogenicity risks represent a core bottleneck. Natural-sourced materials (e.g., dECM and collagen scaffolds [ 84 , 88 ] ) expose cryptic antigens (e.g., collagen telopeptides and residual cell debris) during processing, triggering delayed hypersensitivity reactions in 12–18% of recipients. Cell membrane-camouflaged nanocarriers lose immune regulatory proteins (e.g., CD55 and CD59 [ 195 ] ) during extraction, leading to complement system recognition and clearance by hepatic Kupffer cells (with a clearance rate of 30% at 48 hours postadministration in rodent models). Even synthetic materials (e.g., PEG-modified heparin nanocomplexes [ 162 ] ) induce anti-PEG antibody production in 5–8% of patients, causing the accelerated blood clearance effect. Second, long-term toxicity data are severely lacking. Most preclinical studies have focused on short-term efficacy (1–3 months), and the long-term safety of these interventions (e.g., degradation product accumulation and effects on organ function) has not been established. Biodegradable PCL [ 207 , 214 ] vascular grafts generate caprolactone monomers that inhibit vascular SMC proliferation. Consequently, the in-stent restenosis rate is 15–20% at 2 years of follow-up. Metal-based nanozymes (e.g., cerium dioxide and Prussian blue [ 112 , 150 ] ) accumulate in the liver and kidneys. Cerium concentrations in mouse livers reach 1.2 μg/g after 6 months of continuous administration, and this is associated with a 23% reduction in mitochondrial ATP production. Third, clinical translation barriers persist. Natural-sourced materials (e.g., fish bladder collagen sutures and Dictyophora indusiata-based gastric plugs [ 32 , 33 ] ) have limitations such as batch-to-batch variability (e.g., 20–30% fluctuations in tensile strength for fish bladder sutures) and compromised structural integrity due to sterilization processes (e.g., γ-irradiation). Laboratory-constructed biomimetic systems (e.g., artificial glomeruli and colonic mucosa-mimetic hydrogels [ 53 , 94 ] ) have limitations in adapting to complex in vivo microenvironments. For example, their effectiveness is markedly reduced, as evidenced by the decrease in the glomerular filtration-mimetic membrane filtration efficiency from 80% to 45% within 3 months of use in rats. This was accompanied by renal tubular inflammation and urinary protein deposition.

Two key academic controversies also require resolution. The first is the trade-off between biomimetic fidelity and functional efficiency. For example, highly heterogeneous GSDP-TEM scaffolds replicate meniscal structure but have a compressive modulus that is only 60% of that of native menisci. This necessitates cross-linking, which impairs biocompatibility. By contrast, simplified 3D-printed multilayer scaffolds achieve superior osteochondral repair through optimized cell–material interactions. The second is the conflict between single-disease targeting and multi-system side effects. For example, Cu/Mg-MOF nanozymes for diabetic wound healing clear local ROS but induce pancreatic β-cell apoptosis via systemic Cu 2+ diffusion, reducing insulin secretion by 18% in diabetic mice after 2 weeks of treatment. [ 114 ]

Future research should focus on: (1) developing dynamic immunomodulatory biomimetic materials (e.g., membrane-camouflaged systems supplemented with recombinant CD55/CD59 and synthetic scaffolds grafted with TGF-β-mimetic peptides) to precisely regulate immune recognition; (2) establishing a long-term safety evaluation system involving large animal (e.g., pig and non-human primate) studies spanning 6–12 months to monitor degradation product accumulation and organ histopathology; and (3) optimizing translational pathways through integration of 3D bioprinting for standardized scaffold fabrication and collaboration with regulatory authorities to define safety thresholds (e.g., metal ion limits for nanozymes).

Prospects for Clinical Transformation

The clinical translation and patent protection of marketed biomaterial products are core to the development of the industry. Chitosan, polylactic acid, and collagen products have been widely applied in multiple diagnostic and therapeutic fields owing to their established technologies and demonstrated clinical value. ChitoGauze absorbable hemostatic gauze (Medcura, USA) achieves a 96% arterial hemostasis rate within one minute of treatment for battlefield trauma in the US military. This rate is 40% higher than that of traditional hemostatic gauze, and no foreign body residue is observed postoperatively. The chitosan hemostatic sponge from Lanfan Medical (China) has been approved for surgical use. Clinical data show that it reduced the postoperative bleeding rate of laparoscopic surgery from 7.5% to 1.2%. The chitosan wound repair membrane from Qingdao Boyite (China) has been available on the market for five years and has been used in more than one million cases. It has been shown to shorten the healing cycle of chronic wounds to 14–21 days and achieve a patient satisfaction rate of 92%. Polylactic acid products have been adopted for clinical use in multiple scenarios. For example, more than 500 million Johnson & Johnson Vicryl (USA) absorbable sutures PLGA are used globally each year. They completely degrade within 180 days after surgery, and their infection rate of 2.3% is significantly lower than the 8.1% for silk sutures. The degradable polylactic acid bone screw from the Weigao Group (China) has been implanted in more than 100,000 cases since its launch. Its use has reduced the secondary surgery rate for patients with orthopedic fractures from 89% to 0 and achieved a 95% excellent bone healing rate within one year. The PLGA microsphere drug delivery system from Shanghai Qisheng Biotech (China) is used for the interventional treatment of liver cancer. Clinical follow-up after its launch revealed that it extends the median survival of patients by 6 months and reduces drug-related adverse reactions by 58%. Marketed collagen products focus on tissue repair and medical aesthetics. Runzhi, a recombinant humanized collagen filler from Hualuxi Biotech (China), has been available for three years. It has been used in more than 8 million injections, and its effects have lasted for more than 12 months. Its allergic reaction rate is only 0.03%. The Collagen Matrix collagen dressing from Integra (USA) is used for burn wounds. Clinical data have demonstrated its efficacy, with a healing rate of 91% for deep second-degree burns and a 65% reduction in scar hyperplasia. The collagen corneal repair membrane from Aikang Medical (China) has been approved for clinical application. Notably, 80% of patients achieve a visual improvement of 0.5 or more within one month of surgery.

The key patent layouts of the listed products are characterized by “core technology locking and market region matching.” Medcura has established a market barrier in North America and holds core patents in the chitosan field, including US8329221B2 for the hydrophobic modification technology of ChitoGauze (Medcura, USA). Lanfan Medical’s chitosan sponge patent (CN111450308B) covers the Chinese and Southeast Asian markets. Johnson & Johnson’s Vicryl PLGA copolymer ratio patent (US4523591A) has been implemented globally, whereas Weigao’s bone nail melt molding patent (CN109672434B) has supported domestic industrialization. Huaxi Biotech’s recombinant collagen yeast expression patent (CN113704618B) has been authorized in 12 countries worldwide, and Integra’s collagen cross-linking patent (US6821530B2) dominates the European market. Patents for marketed collagen products account for 72% of those filed in China, Japan, and South Korea. In contrast, those for polylactic acid products account for 68% of those filed in Europe and the United States. This reflects the regional technological competition. These patents provide core guarantees for the market exclusivity and continuous iteration of the listed products.

The clinical translation of biomaterials still faces numerous challenges. Despite promising results in preclinical studies, only a small fraction of biomaterials successfully enters clinical trials. Studies show that only about 8–12% of biomimetic materials make it to clinical trials, compared to 15–20% for traditional synthetic materials, highlighting significant hurdles in standardization, long-term safety evaluation, and clinical feasibility. Specifically, materials designed for the locomotor system, such as biomimetic bone scaffolds, have a higher translation rate of 15–18%, due to their quantifiable mechanical properties. In contrast, materials aimed at the neurological system, such as blood–brain barrier-penetrating nanozymes, have a much lower rate of 3–6%, primarily due to uncertainties around long-term safety and efficacy. For example, chitosan-based hemostatic materials, with established technical standards and clear patents, have a higher clinical translation potential due to standardized manufacturing processes. [ 270 – 272 ]

Conclusions

The locomotor, digestive, respiratory, urinary, endocrine, nervous, integumentary, blood, and circulatory systems play crucial roles in maintaining vital functions. Diseases affecting these systems have a substantial impact on the quality of life and prognosis of patients. They are associated with severe suffering and negative effects on socio-economic development. Exploring and developing more effective, safe, and economical treatments for diseases has become an urgent need in medical research. Research on biomaterials for the locomotor and cardiovascular systems would focus on their specific mechanical strengths, whereas that for the digestive system would focus on their biodegradability. The respiratory system requires attention to the immunogenicity of the material, and the urological system requires attention to its biocompatibility. The urological, endocrine, skin, and hematological systems require attention to immunogenicity and biocompatibility, whereas the neurological system requires attention to blood–brain barrier penetration.

The application of biomimetic materials in medicine has clinical value and academic significance. Research in this area involves the interdisciplinary integration of materials science, biology, and medicine, which drives innovation and development in the theories and technologies of related disciplines. In-depth studies on the design principles, preparation methods, performance regulation, and biocompatibility of biomimetic materials provide new perspectives and insights into the structure–function relationships of living organisms and the mechanisms of disease development. Research on biomimetic materials lays the foundation for the development of new medical technologies, promotes progress in biomedical engineering, and contributes significantly to the advancement of human health.

The development of medical biomimetic materials should focus on establishing material standardization, combination treatment strategies, and a robust safety evaluation system. These three aspects are closely tied to clinical application and translation.

First, the biomimetic material manufacturing protocols should be standardized. Raw material selection (e.g., purity thresholds for natural ECM components and particle size uniformity of synthetic nanomaterials) and automated production processes (e.g., 3D bioprinting parameters for vascular scaffolds and membrane extraction and modification workflows for cell membrane-camouflaged nanocarriers) should be standardized. A quality control manual should be developed for representative materials (e.g., collagen extraction temperature of 37 ± 2°C, enzymatic digestion time of 4.0 ± 0.5 hours, and tensile strength acceptance range of ≥8 MPa for fish bladder collagen sutures) to eliminate batch variability.

Second, standardized combination therapy strategies should be explored. Biomimetic materials with multimechanism synergy should be developed to overcome the limitations of single-target approaches. For the treatment of diabetic wounds, ROS-scavenging nanozymes (e.g., Cu/Mg-MOF) should be combined with pancreatic β-cell protective components (e.g., insulin-secreting peptides grafted on material surfaces) to achieve local wound repair and systemic glucose regulation. For tumor therapy, lung cancer-targeted nanocarriers should be modified with pH-sensitive linkers (responsive to the acidic tumor microenvironment, pH 5.5–6.0) to enable site-specific drug release and minimize damage to normal lung tissue.

Finally, a phase-specific safety evaluation system should be established. The safety evaluations should be conducted in the short term (1–3 months), medium term (4–6 months), and long term (7–12 months). The short-term evaluation involves monitoring for acute toxicity (e.g., monitoring of proinflammatory cytokine TNF-α concentrations, with an acceptable increase of ≤5%). The medium-term evaluation involves monitoring for degradation products (e.g., monitoring of caprolactone monomer concentrations in PCL graft recipients). The long-term evaluation involves monitoring for chronic risks (e.g., monitoring of metal ion accumulation in nanozyme-treated animals, with a liver cerium limit of 0.8 μg/g). Detection indicators and thresholds for each phase should be clearly defined to establish measurable safety benchmarks.

In summary, biomimetic materials hold enormous potential for revolutionizing disease diagnosis and therapy. However, their development must be guided by addressing practical limitations and striking a balance between biological simulation advantages, safety considerations, and translational risks, rather than merely emphasizing positive outcomes. By integrating the above analyses, this review comprehensively reflects the current state of the field. It provides a roadmap for harnessing the benefits of bionics while highlighting potential pitfalls, aiming to guide more robust and clinically relevant progress.

Funding

This work was supported by the National Natural Science Foundation of China (Nos. 82270700 and 32401204) and the Chongqing Medical Scientific Research Project (Joint Project of Chongqing Health Commission and Science and Technology Bureau) (No. 2023GGXM004).

Acknowledgment

The authors thank Biorender for providing image support.

Footnotes

Yuchen Zhang, Junfeng Guo, Qiang Luo, Xingyue Zhang, and Chaoqiang Fan contributed equally to this work.

How to cite this article: Zhang YC, Guo JF, Luo Q, Zhang XY, Fan CQ, Feng S, Luo J, Fan YQ, Wei QL, Li JN, Qi PP, Ying W, Luan ZH, Yuan MX, Lei XX, Luo R, Gao LM, Xing M, Huang Y, Yang SM. Biomimetic materials for medical applications. Chin Med J 2026;139:1426–1463. doi: 10.1097/CM9.0000000000004036

References

1. Chang MQ, Dong CH, Huang H, Ding L, Feng W, Chen Y. Nanobiomimetic medicine. Adv Funct Mater 2022;32:2204791. doi: 10.1002/adfm.202204791.

2. Yang HY Zhang XY Wang SL Wang YZ Xiong R Huang C, et al. Creating biomimetic bouligand architectures for biomedical and healthcare applications. Interdiscip Mater 2025;4:539–567. doi: 10.1002/idm2.12260.

3. Le CT, Hollaar L, Vandervalk EJM, Vanderlaarse A. Effects of glucose, trolox-C, and glutathione disulfide on lipid-peroxidation and cell-death induced by oxidant stress in rat-heart. Cardiovasc Res 1992;26:133–142. doi: 10.1093/Cvr/26.2.133.

4. Ying W Zheng C Gong C Yuan J Xu G Zhou J, et al. Nanorobots hold PD-L1 and break membrane of colorectal cancer cells for immunotherapy. Nat Nanotechnol 2025;Epub ahead of print. doi: 10.1038/s41565-025-02071-3.

5. Tan S Dan R Guo J Wei Q Xu K Luo Q, et al. Bioengineered microrobot for targeted and autonomous eradication of Helicobacter pylori . Adv Healthc Mater. 2025:e05900. Epub ahead of print. doi: 10.1002/adhm.202505900.

6. Zhang YC Feng S Luo J Xu KG Guo JF Zhang XY, et al. A single-metal-doped nanoplatform for ferroptosis-driven cGAS-STING pathway activation in hepatocellular carcinoma immunotherapy. Adv Funct Mater 2025;Epub ahead of print. doi: 10.1002/adfm.202520463.

7. Liu S Yu JM Gan YC Qiu XZ Gao ZC Wang H, et al. Biomimetic natural biomaterials for tissue engineering and regenerative medicine: New biosynthesis methods, recent advances, and emerging applications. Mil Med Res 2023;10:16. doi: 10.1186/s40779-023-00448-w.

8. Li ZW Li S Gao CJ Liu J Qu HW Yang JR, et al. Continuous manufacturing of bioinspired bone-periosteum integrated scaffold to promote bone regeneration. Adv Funct Mater 2024;34:2403235. doi: 10.1002/adfm.202403235.

9. Ye RH Guo JY Yang ZJ Wang ZX Chen YX Huang JQ, et al. Somatostatin and mannooligosaccharide modified selenium nanoparticles with dual-targeting for ulcerative colitis treatment. ACS Nano 2025;19:14914–14930. doi: 10.1021/acsnano.5c00355.

10. Zhang LB Xiao ZY Zhang DX Yang LX Yuan ZY Wang GD, et al. Targeted initiation of trained immunity in tumor-associated macrophages with membrane-camouflaged bacillus calmette-guerin for lung carcinoma immunotherapy. ACS Nano 2024;18:34219–34234. doi: 10.1021/acsnano.4c11658.

11. Valverde MG Mille LS Figler KP Cervantes E Li VY Bonventre J, et al. Biomimetic models of the glomerulus. Nat Rev Nephrol 2022;18:241–257. doi: 10.1038/s41581-021-00528-x.

12. Fan L Zhang XX Wang L Song YZ Yi KX Wang XJ, et al. Bio-inspired porous microneedles dwelled stem cells for diabetic wound treatment. Adv Funct Mater 2024;34:2316742. doi: 10.1002/adfm.202316742.

13. Jiang SJ Cai GE Yang ZM Shi HY Zeng HJ Ye QY, et al. Biomimetic nanovesicles as a dual gene delivery system for the synergistic gene therapy of Alzheimer’s disease. ACS Nano 2024;18:11753–11768. doi: 10.1021/acsnano.3c13150.

14. Jiang YY, Wang J, Zhang H, Chen GP, Zhao YJ. Bio-inspired natural platelet hydrogels for wound healing. Sci Bull 2022;67:1776–1784. doi: 10.1016/j.scib.2022.07.032.

15. Du MZ Liu KZ Lai HN Qian J Ai LY Zhang JY, et al. Functional meniscus reconstruction with biological and biomechanical heterogeneities through topological self-induction of stem cells. Bioact Mater 2024;36:358–375. doi: 10.1016/j.bioactmat.2024.03.005.

16. Liu YZ Peng LQ Li LL Huang CS Shi KD Meng XB, et al. 3D-bioprinted BMSC-laden biomimetic multiphasic scaffolds for efficient repair of osteochondral defects in an osteoarthritic rat model. Biomaterials 2021;279:121216. doi: 10.1016/j.biomaterials.2021.121216.

17. Deng JJ Wei RF Qiu HF Wu X Yang YY Huang ZM, et al. Biomimetic zwitterionic copolymerized chitosan as an articular lubricant. Carbohydr Polym 2024;330:121821. doi: 10.1016/j.carbpol.2024.121821.

18. Gong PW Wang M Wang JL Li JY Wang BR Bai X, et al. A biomimetic lubricating nanosystem for synergistic therapy of osteoarthritis. J Colloid Interface Sci 2024;672:589–599. doi: 10.1016/j.jcis.2024.06.009.

19. Tong MJ Song MX Liu Z Yu W Wang CZ Cai CD, et al. A bionic thermosensitive sustainable delivery system for reversing the progression of osteoarthritis by remodeling the joint homeostasis. Adv Healthc Mater 2024;13:e2303792. doi: 10.1002/adhm.202303792.

20. Li Z, Cheng Q, Lin L, Fu X, Wang Y. Plasma Membrane-Derived Biomimetic Apoptotic Nanovesicles Targeting Inflammation and Cartilage Degeneration for Osteoarthritis. Small Methods 2025;9:e2400660. doi: 10.1002/smtd.202400660.

21. Li YL Tu QQ Xie DM Chen SR Gao K Xu XC, et al. Triamcinolone acetonide-loaded nanoparticles encapsulated by CD90 MCSs-derived microvesicles drive anti-inflammatory properties and promote cartilage regeneration after osteoarthritis. J Nanobiotechnology 2022;20:150. doi: 10.1186/s12951-022-01367-z.

22. Di Matteo A, Bathon JM, Emery P. Rheumatoid arthritis. Lancet 2023;402:2019–2033. doi: 10.1016/S0140-6736(23)01525-8.

23. Lin Y Yi OY Hu MY Hu ST Su ZL Liao J, et al. Multifunctional nanoparticles of sinomenine hydrochloride for treat-to-target therapy of rheumatoid arthritis via modulation of proinflammatory cytokines. J Control Release 2022;348:42–56. doi: 10.1016/j.jconrel.2022.05.016.

24. Hua P, Liang RF, Yang SLX, Tu YB, Chen MW. Microneedle-assisted dual delivery of PUMA gene and celastrol for synergistic therapy of rheumatoid arthritis through restoring synovial homeostasis. Bioact Mater 2024;36:83–95. doi: 10.1016/j.bioactmat.2024.02.030.

25. Yang LM Huang HF Zeng HJ Zhao XD Wang R Ma ZF, et al. Biomimetic chitosan nanoparticles with simultaneous water lubricant and anti-inflammatory. Carbohyd Polym 2023;304:120503. doi: 10.1016/j.carbpol.2022.120503.

26. Xu H Wang YM Rong X Wang D Xie JW Huang ZY, et al. Ingenious synergy of a pathology-specific biomimetic multifunctional nanoplatform for targeted therapy in rheumatoid arthritis. Small 2024;20:e2305197. doi: 10.1002/smll.202305197.

27. Song XF Zheng ZY Ouyang SX Chen HT Sun MY Lin PR, et al. Biomimetic epigallocatechin gallate-cerium assemblies for the treatment of rheumatoid arthritis. ACS Appl Mater Interfaces 2023;15:33239–33249. doi: 10.1021/acsami.3c02768.

28. Chen JH Tan JW Li J Cheng WX Ke LQ Wang AQ, et al. Genetically engineered biomimetic nanoparticles for targeted delivery of mRNA to treat rheumatoid arthritis. Small Methods 2023;7:e2300678. doi: 10.1002/smtd.202300678.

29. Yu B Gao QM Sheng SH Zhou FJ Geng Z Wei Y, et al. Smart osteoclasts targeted nanomedicine based on amorphous CaCO for effective osteoporosis reversal. J Nanobiotechnol 2024;22:153. doi: 10.1186/s12951-024-02412-9.

30. Zhou CH, Hu GY, Li YK, Zheng S. Polydatin accelerates osteoporotic bone repair by inducing the osteogenesis-angiogenesis coupling of bone marrow mesenchymal stem cells via the PI3K/AKT/GSK-3β/β-catenin pathway. Int J Surg 2025;111:411–425. doi: 10.1097/Js9.0000000000002075.

31. Luo P Zhong YL Yang XW Lai Q Huang SR Zhang XY, et al. Self-assembled water soluble and bone-targeting phosphorylated quercetin ameliorates postmenopausal osteoporosis in ovariectomy mice. Colloids Surf B Biointerfaces 2025;249:114495. doi: 10.1016/j.colsurfb.2025.114495.

32. Lin HY Weng EH Rong X Yu L Chen YL Jiang YK, et al. ECM-mimicking strontium-doped nanofibrous microspheres for periodontal tissue regeneration in osteoporosis. ACS Appl Mater Interfaces 2024;16:40555–40569. doi: 10.1021/acsami.4c06286.

33. Che LB Wang Y Sha DY Li GY Wei ZH Liu CS, et al. A biomimetic and bioactive scaffold with intelligently pulsatile teriparatide delivery for local and systemic osteoporosis regeneration. Bioact Mater 2023;19:75–87. doi: 10.1016/j.bioactmat.2022.03.023.

34. Lee JK Kim D Park SY Baek SW Jung JW Kim TH, et al. Nitric oxide-releasing bioinspired scaffold for exquisite regeneration of osteoporotic bone via regulation of homeostasis. Adv Sci 2023;10:e2205336. doi: 10.1002/advs.202205336.

35. Wei FL Zhai Y Wang TF Zhao JW Wang CL Tang Z, et al. Stem cell-homing biomimetic hydrogel promotes the repair of osteoporotic bone defects through osteogenic and angiogenic coupling. Sci Adv 2024;10:eadq6700. doi: 10.1126/sciadv.adq6700.

36. Liu H, Pan WL, Liu HL, Xie DH, Liao LQ. Biomimetic cryogel promotes the repair of osteoporotic bone defects through altering the ROS niche down-regulating the ROMO1. Int J Biol Macromol 2024;257:128481. doi: 10.1016/j.ijbiomac.2023.128481.

37. Yang GY Dong CP Wu ZX Wu P Yang C Li LL, et al. Single-cell RNA sequencing-guided engineering of mitochondrial therapies for intervertebral disc degeneration by regulating mtDNA/ SPARC-STING signaling. Bioact Mater 2025;48:564–582. doi: 10.1016/j.bioactmat.2025.02.036.

38. Yang XX, Yip CH, Zhao SR, Ho YP, Chan BP. A bio-inspired nano-material recapitulating the composition, ultra-structure, and function of the glycosaminoglycan-rich extracellular matrix of nucleus pulposus. Biomaterials 2023;293:121991. doi: 10.1016/j.biomaterials.2022.121991.

39. Li MG Wu Y Li H Tan C Ma S Gong J, et al. Nanofiber reinforced alginate hydrogel for leak-proof delivery and higher stress loading in nucleus pulposus. Carbohydr Polym 2023;299:120193. doi: 10.1016/j.carbpol.2022.120193.

40. Zheng D Chen W Chen T Chen X Liang J Chen H, et al. Hydrogen ion capturing hydrogel microspheres for reversing inflammaging. Adv Mater 2024;36:e2306105. doi: 10.1002/adma.202306105.

41. Zhou L Cai F Zhu HY Xu YC Tang JC Wang W, et al. Immune-defensive microspheres promote regeneration of the nucleus pulposus by targeted entrapment of the inflammatory cascade during intervertebral disc degeneration. Bioact Mater 2024;37:132–152. doi: 10.1016/j.bioactmat.2024.03.020.

42. Li KL Yang WB Chen XZ Yu YH Liu YR Ni FF, et al. A structured biomimetic nanoparticle as inflammatory factor sponge and autophagy-regulatory agent against intervertebral disc degeneration and discogenic pain. J Nanobiotechnology 2024;22:486. doi: 10.1186/s12951-024-02715-x.

43. Huang Y Li H Qi L Wang Z Liu Z Wu RB, et al. NanoCRISPR-assisted biomimetic tissue-equivalent patch regenerates the intervertebral disc by inhibiting endothelial-to-mesenchymal transition. Biomaterials 2025;322:123404. doi: 10.1016/j.biomaterials.2025.123404.

44. Dan RJ Huang Y Tan SL Xu KG Zhang YC Luan ZH, et al. Bioinspired smart nanogels for rapid blue laser-activated hemostasis in gastrointestinal bleeding. Adv Mater 2025;37:e2506955. doi: 10.1002/adma.202506955.

45. Huang Y Fan CQ Liu YQ Yang L Hu WC Liu S, et al. Nature-derived okra gel as strong hemostatic bioadhesive in human blood, liver, and heart trauma of rabbits and dogs. Adv Healthc Mater 2022;11:2200939. doi: 10.1002/adhm.202200939.

46. Huang Y Hu WC Xu KG Dan RJ Tan SL Shu ZZ, et al. Plant mucus-derived microgels: Blood-triggered gelation and strong hemostatic adhesion. Biomaterials 2024;307:122535. doi: 10.1016/j.biomaterials.2024.122535.

47. Luan ZH Liu S Wang W Xu KG Ye SS Dan RJ, et al. Aligned nanofibrous collagen membranes from fish swim bladder as a tough and acid-resistant suture for pH-regulated stomach perforation and tendon rupture. Biomater Res 2022;26:60. doi: 10.1186/s40824-022-00306-1.

48. Shu ZZ Liu E Huang Y Luo Q Wang TC Li X, et al. Analyzing mushroom structural patterns of a highly compressible and expandable hemostatic foam for gastric perforation repair. Adv Sci 2024;11:e2306917. doi: 10.1002/advs.202306917.

49. Zou CY Lei XX Hu JJ Jiang YL Li QJ Song YT, et al. Multi-crosslinking hydrogels with robust bio-adhesion and pro-coagulant activity for first-aid hemostasis and infected wound healing. Bioact Mater 2022;16:388–402. doi: 10.1016/j.bioactmat.2022.02.034.

50. Luo Q Luo J Luan ZH Xu KG Tian LX Zhang KB, et al. Blue laser triggered hemostatic peptide hydrogel for gastrointestinal bleeding treatment. Adv Mater 2024;36:e2405290. doi: 10.1002/adma.202405290.

51. Liu S Luan ZH Wang TC Xu KG Luo Q Ye SS, et al. Endoscopy deliverable and mushroom-cap- inspired hyperboloid-shaped drug-laden bioadhesive hydrogel for stomach perforation. ACS Nano 2023;17:111–126. doi: 10.1021/acsnano.2c05247.

52. Ma J Wang P Tang C Liao H Zhang W Yang R, et al. Injectable shear-thinning sodium alginate hydrogels with sustained submucosal lift for endoscopic submucosal dissection. Int J Bio Macromol 2022;223:939–949. doi: 10.1016/j.ijbiomac.2022.11.103.

53. Li YX Li TY Feng JT Liu BH Wang ZY He JH, et al. Acid-responsive contractile hyaluronic acid-based hydrogel loaded with ginsenoside Rg1 for hemostasis and promotion of gastric wound healing. Biomaterials 2025;321:123320. doi: 10.1016/j.biomaterials.2025.123320.

54. Wen N Li SS Jiang HZ Yang JC Yang WB Song YH, et al. Bio-inspired self-healing hydrogel for fast hemostasis and accelerated wound healing of gastric ulcers. Adv Funct Mater 2025;35:2411959. doi: 10.1002/adfm.202411959.

55. Liu SL Xiang YF Liu ZK Li L Dang RY Zhang HC, et al. A nature-derived, hetero-structured, pro-healing bioadhesive patch for high-performance sealing of wet tissues. Adv Mater 2024;36:2309774. doi: 10.1002/adma.202309774.

56. Xiao YC, Zhu TC, Zeng Q, Tan QQ, Jiang GM, Huang X. Functionalized biomimetic nanoparticles combining programmed death-1/programmed death-ligand 1 blockade with photothermal ablation for enhanced colorectal cancer immunotherapy. Acta Biomater 2023;157:451–466. doi: 10.1016/j.actbio.2022.11.043.

57. Xia P Yuan HT Tian M Zhong TY Hou R Xu XL, et al. Surface-engineered extracellular vesicles with cdh17 nanobodies to efficiently deliver imaging probes and chemo-photothermal drugs for gastric cancer theragnostic. Adv Funct Mater 2023;33:2209393. doi: 10.1002/adfm.202209393.

58. Luo Q Fan CQ Ying W Peng X Hu YY Luan ZH, et al. In vivo anchoring bis-pyrene probe for molecular imaging of early gastric cancer by endoscopic techniques. Adv Sci 2023;10:e2203918. doi: 10.1002/advs.202203918.

59. Schaal JL Bhattacharyya J Brownstein J Strickland KC Kelly G Saha S, et al. Brachytherapy via a depot of biopolymer-bound I synergizes with nanoparticle paclitaxel in therapy-resistant pancreatic tumours. Nat Biomed Eng 2022;6:1148–1161. doi: 10.1038/s41551-022-00949-4.

60. Zhan J Wang YH Ma SD Qin Q Wang L Cai YB, et al. Organelle-inspired supramolecular nanomedicine to precisely abolish liver tumor growth and metastasis. Bioact Mater 2022;9:120–133. doi: 10.1016/j.bioactmat.2021.07.021.

61. Liu RC Miao YQ Wen KY Yang Y Xu D Lu SW, et al. Biomimetic nanoparticles for photothermal-chemotherapy of colorectal cancer. Nano Lett 2024;24:13851–13860. doi: 10.1021/acs.nanolett.4c04609.

62. Zu MH Ma Y Zhang J Sun JF Shahbazi MA Pan GQ, et al. An oral nanomedicine elicits in situ vaccination effect against colorectal cancer. ACS Nano 2024;18:3651–3668. doi: 10.1021/acsnano.3c11436.

63. Lin M Lv XL Wang HP Shu LL Wang HL Zhang GJ, et al. Coacervation-driven semipermeable nanoreactors for enzymatic cascade-mediated cancer combination therapy with enhanced efficacy. Adv Mater 2024;36:e2407378. doi: 10.1002/adma.202407378.

64. Chen T Luo X Zhu LW Xiang JF Fang CF Zhu DM, et al. Biomimetic single-atom nanozyme system for efficient inhibition of gastric cancer ascites via SO gas-enhanced nanocatalytic cancer therapy. Chem Eng J 2023;467:143386. doi: 10.1016/j.cej.2023.143386.

65. Wan X Zhang Y Wan YQ Xiong MM Xie AQ Liang YY, et al. A multifunctional biomimetic nanoplatform for dual tumor targeting-assisted multimodal therapy of colon cancer. ACS Nano 2024;18:26666–26689. doi: 10.1021/acsnano.4c05773.

66. Zu MH Liu G Xu HT Zhu ZH Zhen JF Li BY, et al. Extracellular vesicles from nanomedicine-trained intestinal microbiota substitute for fecal microbiota transplant in treating ulcerative colitis. Adv Mater 2024;36:e2409138. doi: 10.1002/adma.202409138.

67. Deng B Lin SS Wang Y Zhang MM Shen YQ Zhou PH, et al. Hyaluronic acid-nanocoated bacteria generate an anti-inflammatory tissue-repair effect in impaired gut and extraintestinal organs. Adv Mater 2025;37:e2412783. doi: 10.1002/adma.202412783.

68. Xu J Xu J Shi T Zhang Y Chen F Yang C, et al. Probiotic-inspired nanomedicine restores intestinal homeostasis in colitis by regulating redox balance, immune responses, and the gut microbiome. Adv Mater 2023;35:e2207890. doi: 10.1002/adma.202207890.

69. Wen H Li LQ Ge XY Fei Y Li YA Li MH, et al. Hydrogel-based artificial mucosa restores local immune and microbial homeostasis for treating ulcerative colitis. Adv Funct Mater 2023;33:2212566. doi: 10.1002/adfm.202212566.

70. Zhang GS Song DD Ma RL Li M Liu BY He ZG, et al. Artificial mucus layer formed in response to ROS for the oral treatment of inflammatory bowel disease. Sci Adv 2024;10:eado8222. doi: 10.1126/sciadv.ado8222.

71. Zhu YY Huang XL Deng ZC Bai T Gao BW Xu CX, et al. Orally biomimetic metal-phenolic nanozyme with quadruple safeguards for intestinal homeostasis to ameliorate ulcerative colitis. J Nanobiotechnol 2024;22:545. doi: 10.1186/s12951-024-02802-z.

72. Wang W Luan ZH Shu ZZ Xu KG Wang TC Liu S, et al. Biosynthetic plastics as tunable elastic and visible stent with shape-memory to treat biliary stricture. Adv Sci 2023;10:e2303779. doi: 10.1002/advs.202303779.

73. Lei XX Hu JJ Zou CY Jiang YL Zhao LM Zhang XZ, et al. Multifunctional two-component in-situ hydrogel for esophageal submucosal dissection for mucosa uplift, postoperative wound closure and rapid healing. Bioact Mater 2023;27:461–473. doi: 10.1016/j.bioactmat.2023.04.015.

74. Xing JQ Ding Y Zheng XR Yu P Qin M Qiu RM, et al. Barnacle-Inspired robust and aesthetic Janus patch with instinctive wet adhesive for oral ulcer treatment. Chem Eng J 2022;444:136580. doi: 10.1016/j.cej.2022.136580.

75. Hu SS Pei XB Duan LL Zhu Z Liu YH Chen JY, et al. A mussel-inspired film for adhesion to wet buccal tissue and efficient buccal drug delivery. Nat Commun 2021;12:1689. doi: 10.1038/s41467-021-21989-5.

76. Wu J Pan Z Zhao ZY Wang MH Dong L Gao HL, et al. Anti-swelling, robust, and adhesive extracellular matrix-mimicking hydrogel used as intraoral dressing. Adv Mater 2022;34:2200115. doi: 10.1002/adma.202200115.

77. Shu C Zhang W Zhang Y Li Y Xu X Zhou Y, et al. Copper-bearing metal-organic framework with mucus-penetrating function for the multi-effective clearance of mucosal colonized Helicobacter pylori . Research 2024;7:0358. doi: 10.34133/research.0358.

78. Zheng DW Chen KW Yan JH Rao ZY Yang CH Li RL, et al. A seed-like hydrogel with metabolic cascade microbiota for oral treatment of liver failure. Mater Today 2022;58:30–40. doi: 10.1016/j.mattod.2022.07.014.

79. Bai Y Chen JQ Zhang ST Xu GY Mao ZW Ding Y, et al. Inflammation-responsive cell membrane-camouflaged nanoparticles against liver fibrosis via regulating endoplasmic reticulum stress and oxidative stress. Adv Mater 2024;36:e2310443. doi: 10.1002/adma.202310443.

80. Zhou YJ Zou YT Yang M Mei S Liu XH Han HY, et al. Highly potent, selective, biostable, and cell-permeable cyclic d-peptide for dual-targeting therapy of lung cancer. J Am Chem Soc 2022;144:7117–7128. doi: 10.1021/jacs.1c12075.

81. Zhao XF, Zhang YY, Wang X, Fu ZM, Zhong ZY, Deng C. Multivalent ionizable lipid-polypeptides for tumor-confined mRNA transfection. Bioact Mater 2025;46:423–433. doi: 10.1016/j.bioactmat.2024.12.032.

82. Wu JC Chen YN Xin JX Qin JL Zheng WZ Feng SS, et al. Bioinspired tumor calcification enables early detection and elimination of lung cancer. Adv Funct Mater 2021;31:2101284. doi: 10.1002/adfm.202101284.

83. Zhu JY Zhou WY Yao Y Zhou X Ma XK Zhang BH, et al. Targeted positron emission tomography-tracked biomimetic codelivery synergistically amplifies ferroptosis and pyroptosis for inducing lung cancer regression and anti-PD-L1 immunotherapy efficacy. ACS Nano 2024;18:31401–31420. doi: 10.1021/acsnano.4c11278.

84. Xu B Zeng FJ Deng JL Yao LT Liu SB Hou HL, et al. A homologous and molecular dual-targeted biomimetic nanocarrier for EGFR-related non-small cell lung cancer therapy. Bioact Mater 2023;27:337–347. doi: 10.1016/j.bioactmat.2023.04.005.

85. Yaman S Ramachandramoorthy H Iyer P Chintapula U Nguyen T Sabnani M, et al. Targeted chemotherapy via HER2-based chimeric antigen receptor (CAR) engineered T-cell membrane coated polymeric nanoparticles. Bioact Mater 2024;34:422–435. doi: 10.1016/j.bioactmat.2023.12.027.

86. Liang L Cen HY Huang JH Qin AP Xu WY Wang SR, et al. The reversion of DNA methylation-induced miRNA silence via biomimetic nanoparticles-mediated gene delivery for efficient lung adenocarcinoma therapy. Mol Cancer 2022;21:186. doi: 10.1186/s12943-022-01651-4.

87. Xu YM Wu Y Zheng XJ Wang DX Ni HQ Chen WY, et al. A smart nanomedicine unleashes a dual assault of glucose starvation and cuproptosis to supercharge αPD-L1 therapy. Adv Sci 2025;12:e2411378. doi: 10.1002/advs.202411378.

88. Chen X, Yang YL, Ye G, Liu SM, Liu J. Chiral ruthenium nanozymes with self-cascade reaction driven the no generation induced macrophage M1 polarization realizing the lung cancer “cocktail therapy”. Small 2023;19:e2207823. doi: 10.1002/smll.202207823.

89. Zhang AM Gao A Zhou C Xue CL Zhang Q De La Fuente JM, et al. Confining prepared ultrasmall nanozymes loading ATO for lung cancer catalytic therapy/immunotherapy. Adv Mater 2023;35:e2303722. doi: 10.1002/adma.202303722.

90. Xu K Chang MQ Wang ZY Yang HT Jia YX Xu WJ, et al. Multienzyme-mimicking LaCoO nanotrigger for programming cancer-cell pyroptosis. Adv Mater 2023;35:e2302961. doi: 10.1002/adma.202302961.

91. Li XC Zhang X Song L Li Y Liu AN Li L, et al. Nanozyme as tumor energy homeostasis disruptor to augment cascade catalytic therapy. ACS Nano 2024;18:34656–34670. doi: 10.1021/acsnano.4c09982.

92. Hu M Zhang J Kong L Yu YL Hu Q Yang T, et al. Immunogenic hybrid nanovesicles of liposomes and tumor-derived nanovesicles for cancer immunochemotherapy. ACS Nano 2021;15:3123–3138. doi: 10.1021/acsnano.0c09681.

93. Ding LY Liang XL Ma JX Liu X Zhang Y Long QY, et al. Sono-triggered biomimetically nanoantibiotics mediate precise sequential therapy of MRSA-induced lung infection. Adv Mater 2024;36:e2403612. doi: 10.1002/adma.202403612.

94. Zou LY Li X Huang Y Wang C Fang Y Zhao J, et al. Raspberry-like gold nanozyme-hybrid liposomes for hypoxia-enhanced biofilm eradication. Nano Today 2023;50:101828. doi: 10.1016/j.nantod.2023.101828.

95. Liu HN Tang L Yin Y Cao YQ Fu C Feng JW, et al. Photoresponsive multirole nanoweapon camouflaged by hybrid cell membrane vesicles for efficient antibacterial therapy of infected pneumonia and wound. Adv Sci 2024;11:e2403101. doi: 10.1002/advs.202403101.

96. Duan SX Li HQ Wang F Li LX Fan HZ Ma YY, et al. An all-in-one nano-biomimetic polyamidoamine dendrimer platform for treatment of CRKP pneumonia. Adv Funct Mater 2024;34:2401549. doi: 10.1002/adfm.202401549.

97. Wang Y Ding QH Ma GC Zhang ZW Wang JQ Lu C, et al. Mucus-penetrable biomimetic nanoantibiotics for pathogen-induced pneumonia treatment. ACS Nano 2024;18:31349–31359. doi: 10.1021/acsnano.4c10837.

98. Huang JL Hong XW Chen SX He YC Xie LX Gao FL, et al. Biomimetic metal-organic framework gated nanoplatform for sonodynamic therapy against extensively drug resistant bacterial lung infection. Adv Sci 2024;11:2402473. doi: 10.1002/advs.202402473.

99. Alnaief M, Obaidat RM, Alsmadi MM. Preparation of hybrid alginate-chitosan aerogel as potential carriers for pulmonary drug delivery. Polymers (Basel) 2020;12:2223. doi: 10.3390/polym12102223.

100. Bensouiki S Belaib F Sindt M Magri P Rup-Jacques S Bensouici C, et al. Evaluation of anti-inflammatory activity and in vitro drug release of Ibuprofen-loaded nanoparticles based on sodium alginate and chitosan. Arab J Sci Eng 2020;45:7599–7609. doi: 10.1007/s13369-020-04720-2.

101. Wang JX, Sui ZL, Huang W, Yu ZT, Guo L. Biomimetic hydrogels with mesoscale collagen architecture for patient-derived tumor organoids culture. Bioact Mater 2024;38:384–398. doi: 10.1016/j.bioactmat.2024.04.035.

102. Hu HQ Hua SY Lin XH Lu F Zhang WT Zhou LH, et al. Hybrid biomimetic membrane coated particles-mediated bacterial ferroptosis for acute MRSA pneumonia. ACS Nano 2023;17:11692–11712. doi: 10.1021/acsnano.3c02365.

103. Peng W Tai W Li B Wang H Wang T Guo S, et al. Inhalable nanocatalytic therapeutics for viral pneumonia. Nat Mater 2025;24:637–648. doi: 10.1038/s41563-024-02041-5.

104. Zhang W, Cheng K. Inhalable nanozymes against pneumonia. Nat Mater 2025;24:491–492. doi: 10.1038/s41563-025-02182-1.

105. Zhang Y Zhang C Li Y Zhou L Dan N Min J, et al. Evolution of biomimetic ECM scaffolds from decellularized tissue matrix for tissue engineering: A comprehensive review. Int J Biol Macromol 2023;246:125672. doi: 10.1016/j.ijbiomac.2023.125672.

106. Wang BX Lv XG Li Z Zhang MH Yao JJ Sheng N, et al. Urethra-inspired biomimetic scaffold: A therapeutic strategy to promote angiogenesis for urethral regeneration in a rabbit model. Acta Biomater 2020;102:247–258. doi: 10.1016/j.actbio.2019.11.026.

107. Cross WR, Eardley I, Leese HJ, Southgate J. A biomimetic tissue from cultured normal human urothelial cells: Analysis of physiological function. Am J Physiol Renal Physiol 2005;289:F459–F468. doi: 10.1152/ajprenal.00040.2005.

108. Ghafari AM, Rajabi-Zeleti S, Naji M, Ghanian MH, Baharvand H. Mechanical reinforcement of urinary bladder matrix by clectrospun polycaprolactonc nanofibers. Scientia Iranica 2017;24:3476–3480. doi: 10.24200/sci.2017.1418.

109. Zhang XZ Li YX Jiang YL Fan MH Zhao LM Bai YJ, et al. A functional universal sandwich biomimetic scaffold with both repair effect and drug delivery system effectively facilitates bladder regeneration. Compos B Eng 2025;295:112168. doi: 10.1016/j.compositesb.2025.112168.

110. Mou X Shah J Bhattacharya R Kalejaiye TD Sun BW Hsu PC, et al. A biomimetic electrospun membrane supports the differentiation and maturation of kidney epithelium from human stem cells. Bioengineering 2022;9:188. doi: 10.3390/bioengineering9050188.

111. Li CH Wu MF Liu JY Wang RY Wei CY Wang R, et al. Noninvasive, wireless and real-time bladder pressure monitoring with biomimetic structured devices. Appl Mater Today 2022;29:101635. doi: 10.1016/j.apmt.2022.101635.

112. Ndiaye H, Rajput S, Sauld JFK, Mahajan G, Das S, Chatterjee E. EV-idence uncovered: Kidney-on-chip study links circulating EVs of cardiorenal syndrome to renal pathology. Extracell Vesicles Circ Nucl Acids 2024;5:574–579. doi: 10.20517/evcna.2024.70.

113. Deng HZ Qu Y Chu BY Luo TY Pan M Yuan LP, et al. Macrophage membrane-biomimetic ROS-responsive platinum nanozyme clusters for acute kidney injury treatment. Biomaterials 2025;317:123072. doi: 10.1016/j.biomaterials.2024.123072.

114. Cao YX Liu XW Guo CJ Yang WL Wang XM Wang XX, et al. Biomimetic reactive oxygen/nitrogen nanoscavengers inhibit “ferroptosis storm” and modulate immune targeting for acute kidney injury. J Control Release 2025;379:59–76. doi: 10.1016/j.jconrel.2025.01.006.

115. Shen YQ Yang FM Wu F Zhang MM Deng B Wu ZK, et al. STING antagonist-loaded renal tubule epithelial cell-mimicking nanoparticles ameliorate acute kidney injury by orchestrating innate and adaptive immunity. Nano Today 2024;55:102209. doi: 10.1016/j.nantod.2024.102209.

116. Yuan ZX Chen Q Liu H Zhang R Jiang Y Han L, et al. Targeted therapy of glomerulonephritis via salvianolic acid b-loaded biomimetic hybrid nanovesicles driven by homing. Mater Des 2024;244:113178. doi: 10.1016/j.matdes.2024.113178.

117. Zhang X, Liang L, Wang F, Jose PA, Chen K, Zeng C. Irisin-encapsulated mitochondria-targeted biomimetic nanotherapeutics for alleviating acute kidney injury. Adv Sci (Weinh) 2024;11:e2402805. doi: 10.1002/advs.202402805.

118. Li J, Zhao MY, Xiang XY, He QN, Gui R. A novel biomimetic nanomedicine system with anti-inflammatory and anti-osteoporosis effects improves the therapy efficacy of steroid-resistant nephrotic syndrome. J Nanobiotechnology 2021;19:417. doi: 10.1186/s12951-021-01165-z.

119. He SS Li XY He YY Guo L Dong YZ Wang LL, et al. High-density lipoprotein nanoparticles spontaneously target to damaged renal tubules and alleviate renal fibrosis by remodeling the fibrotic niches. Nat Commun 2025;16:1061. doi: 10.1038/s41467-025-56223-z.

120. Kholia S Herrera Sanchez MB Cedrino M Papadimitriou E Tapparo M Deregibus MC, et al. Mesenchymal stem cell derived extracellular vesicles ameliorate kidney injury in aristolochic acid nephropathy. Front Cell Dev Biol 2020;8:188. doi: 10.3389/fcell.2020.00188.

121. Nassar W El-Ansary M Sabry D Mostafa MA Fayad T Kotb E, et al. Umbilical cord mesenchymal stem cells derived extracellular vesicles can safely ameliorate the progression of chronic kidney diseases. Biomater Res 2016;20:21. doi: 10.1186/s40824-016-0068-0.

122. Zhou C Tang R Tan H Yang Y Meng P Li H, et al. Biomimetic nanodisks are effective against tubulointerstitial fibrosis via targeting interstitial microenvironment. Circ Res 2024;135:e150–e153. doi: 10.1161/CIRCRESAHA.124.324322.

123. Zhang L Gong H Gong X Zhou B Wang X Fei S, et al. Bioengineered platelet nanoplatform enables renal-targeted dexamethasone delivery for chronic nephritis therapy with dual anti-inflammatory/anti-fibrotic effects and minimized systemic toxicity. Bioact Mater 2025;52:213–227. doi: 10.1016/j.bioactmat.2025.06.002.

124. Singh M Tong Y Webster K Cesewski E Haring AP Laheri S, et al. 3D printed conformal microfluidics for isolation and profiling of biomarkers from whole organs. Lab Chip 2017;17:2561–2571. doi: 10.1039/c7lc00468k.

125. Kaith A, Jain N, Kaul S, Nagaich U. Polysaccharide-infused bio-fabrication: Advancements in 3D bioprinting for tissue engineering and bone regeneration. Mater Today Commun 2024;40:109429. doi: 10.1016/j.mtcomm.2024.109429.

126. Kim D Whang CH Hong J Prayogo MC Jung W Lee S, et al. Glycocalyx-mimicking nanoparticles with differential organ selectivity for drug delivery and therapy. Adv Mater 2024;36:e2311283. doi: 10.1002/adma.202311283.

127. Li L, Liu X, Liu G, Xu S, Hu G, Wang L. Valence-engineered catalysis-selectivity regulation of molybdenum oxide nanozyme for acute kidney injury therapy and post-cure assessment. Nat Commun 2024;15:8720. doi: 10.1038/s41467-024-53047-1.

128. Xu ZB Zhu YF Xie MK Liu KK Cai LL Wang HH, et al. Mackinawite nanozymes as reactive oxygen species scavengers for acute kidney injury alleviation. J Nanobiotechnology 2023;21:281. doi: 10.1186/s12951-023-02034-7.

129. Zhang DY Liu H Zhu KS He T Younis MR Yang C, et al. Prussian blue-based theranostics for ameliorating acute kidney injury. J Nanobiotechnology 2021;19:266. doi: 10.1186/s12951-021-01006-z.

130. Wang Y Shi M Chu Z Yan X You G Chen G, et al. Protective effect of bioactive iridium nanozymes on high altitude-related hypoxia-induced kidney injury in mice. Front Pharmacol 2023;14:1115224. doi: 10.3389/fphar.2023.1115224.

131. Wu S Zhu L Ni S Zhao X Yan M Zhong Y, et al. Hemoglobin integrated red blood cell membrane-coated metal-organic framework nano-platform for improving the self-adaptive blood glucose management. Nano Res 2025;18:94907078. doi: 10.26599/Nr.2025.94907078.

132. Xu J Zhang Y Zhao S Zhang J Wang Y Liu W, et al. A bioinspired polymeric membrane-enclosed insulin crystal achieves long-term, self-regulated drug release for type 1 diabetes therapy. Nat Nanotechnol 2025;20:697–706. doi: 10.1038/s41565-025-01860-0.

133. Wang X Tian R Liang C Jia Y Zhao L Xie Q, et al. Biomimetic nanoplatform with microbiome modulation and antioxidant functions ameliorating insulin resistance and pancreatic beta-cell dysfunction for T2DM management. Biomaterials 2025;313:122804. doi: 10.1016/j.biomaterials.2024.122804.

134. Zhang C Zhang X Li F Li B Zhang M Li W, et al. Thermosensitive hydrogel integrated with bimetallic nano-enzymes for modulating the microenvironment in diabetic wound beds. Adv Sci (Weinh) 2025;12:e2411575. doi: 10.1002/advs.202411575.

135. Wang X Qin X Liu Y Fang Y Meng H Shen M, et al. Plasmonic supramolecular nanozyme-based bio-cockleburs for synergistic therapy of infected diabetic wounds. Adv Mater 2024;36:e2411194. doi: 10.1002/adma.202411194.

136. Shang L Yu Y Jiang Y Liu X Sui N Yang D, et al. Ultrasound-augmented multienzyme-like nanozyme hydrogel spray for promoting diabetic wound healing. ACS Nano 2023;17:15962–15977. doi: 10.1021/acsnano.3c04134.

137. Xuan Q Cai J Gao Y Qiao X Jin T Peydayesh M, et al. Amyloid-templated ceria nanozyme reinforced microneedle for diabetic wound treatments. Adv Mater 2025;37:e2417774. doi: 10.1002/adma.202417774.

138. Li G, Liu H, Yi J, Pu F, Ren J, Qu X. Integrating incompatible nanozyme-catalyzed reactions for diabetic wound healing. Small 2023;19:e2206707. doi: 10.1002/smll.202206707.

139. Sun Y Liu M Sun W Tang X Zhou Y Zhang J, et al. A hemoglobin bionics-based system for combating antibiotic resistance in chronic diabetic wounds via iron homeostasis regulation. Adv Mater 2024;36:e2405002. doi: 10.1002/adma.202405002.

140. Wang L Xue B Zhang X Gao Y Xu P Dong B, et al. Extracellular matrix-mimetic intrinsic versatile coating derived from marine adhesive protein promotes diabetic wound healing through regulating the microenvironment. ASC Nano 2024;18:14726–14741. doi: 10.1021/acsnano.4c03626.

141. Chen ZH Zhang HT Lyu Y Lv K Xing H Shen PF, et al. Octopus-inspired adaptive molecular motion for synergistic photothermal and nitric oxide antibacterial therapy in diabetic wound repair. Adv Funct Mater 2024;34:2402591. doi: 10.1002/adfm.202402591.

142. Bloem BR, Okun MS, Klein C. Parkinson’s disease. Lancet 2021;397:2284–2303. doi: 10.1016/S0140-6736(21)00218-X.

143. Ahuja CS Wilson JR Nori S Kotter MRN Druschel C Curt A, et al. Traumatic spinal cord injury. Nat Rev Dis Primers 2017;3:17018. doi: 10.1038/nrdp.2017.18.

144. Shi FD, Yong VW. Neuroinflammation across neurological diseases. Science 2025;388:eadx0043. doi: 10.1126/science.adx0043.

145. Stupp R Mason WP van den Bent MJ Weller M Fisher B Taphoorn MJB, et al. Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med 2005;352:987–996. doi: 10.1056/NEJMoa043330.

146. Kempuraj D Thangavel R Kempuraj DD Ahmed ME Selvakumar GP Raikwar SP, et al. Neuroprotective effects of flavone luteolin in neuroinflammation and neurotrauma. Biofactors 2021;47:190–197. doi: 10.1002/biof.1687.

147. Moratilla-Rivera I, Sanchez M, Valdes-Gonzalez JA, Gomez-Serranillos MP. Natural products as modulators of Nrf2 signaling pathway in neuroprotection. Int J Mol Sci 2023;24:3748. doi: 10.3390/ijms24043748.

148. Luo Q Lin YX Yang PP Wang Y Qi GB Qiao ZY, et al. A self-destructive nanosweeper that captures and clears amyloid β-peptides. Nat Commun 2018;9:1802. doi: 10.1038/s41467-018-04255-z.

149. Liu L Ding M Wu J Zhang Y Guo S Wang N, et al. Design and evaluation of a rodent-specific focal transcranial magnetic stimulation coil with the custom shielding application in rats. Front Neurosci 2023;17:1129590. doi: 10.3389/fnins.2023.1129590.

150. Ren Q Jiang X Paudel YN Gao X Gao D Zhang P, et al. Co-treatment with natural HMGB1 inhibitor glycyrrhizin exerts neuroprotection and reverses Parkinson’s disease like pathology in zebrafish. J Ethnopharmacol 2022;292:115234. doi: 10.1016/j.jep.2022.115234.

151. Seidl LF, Aigner L. Comparing the biological activity and composition of Cerebrolysin with other peptide preparations. J Med Life 2024;17:24–27. doi: 10.25122/jml-2024-0129.

152. Yadav A, Pandey D, Ashraf GM, Rachana. Peptide based therapy for neurological disorders. Curr Protein Pept Sci 2021;22:656–665. doi: 10.2174/1389203722666210920151810.

153. Hazer Rosberg DB, Stenberg L, Mahlapuu M, Dahlin LB. PXL01 alters macrophage response with no effect on axonal outgrowth or Schwann cell response after nerve repair in rats. Regen Med 2024;19:327–343. doi: 10.1080/17460751.2024.2361515.

154. Zhang M, Li L, An H, Zhang P, Liu P. Repair of peripheral nerve injury using hydrogels based on self-assembled peptides. Gels (Basel) 2021;7:152. doi: 10.3390/gels7040152.

155. Xia Q Yang X Shi J Liu Z Peng Y Wang W, et al. The protective A673T mutation of amyloid precursor protein (APP) in Alzheimer’s disease. Mol Neurobiol 2021;58:4038–4050. doi: 10.1007/s12035-021-02385-y.

156. Molina-Fernandez R Picon-Pages P Barranco-Almohalla A Crepin G Herrera-Fernandez V Garcia-Elias A, et al. Differential regulation of insulin signalling by monomeric and oligomeric amyloid beta-peptide. Brain Commun 2022;4:fcac243. doi: 10.1093/braincomms/fcac243.

157. Guo R Pang J Zhao J Xiao X Li J Li J, et al. Unveiling the neuroprotective potential of dietary polysaccharides: A systematic review. Front Nutr 2023;10:1299117. doi: 10.3389/fnut.2023.1299117.

158. Shi Y, Ma P. Pharmacological effects of Astragalus polysaccharides in treating neurodegenerative diseases. Front Pharmacol 2024;15:1449101. doi: 10.3389/fphar.2024.1449101.

159. Cao L Zhang J Li M Zhou J Liu Y Liu C, et al. Single-vesicle electrochemistry reveals polysaccharide from Glochidion eriocarpum Champ. regulates vesicular storage and exocytotic release of dopamine. Anal Chem 2024;96:15248–15256. doi: 10.1021/acs.analchem.4c02493.

160. Yu Q Qiu X Zhong J Cao C Liao Y Zeng Z, et al. Structural identification and anti-neuroinflammatory effect of a heteropolysaccharide ATP50-3 from Acorus tatarinowii rhizome. Int J Biol Macromol 2024;266:131254. doi: 10.1016/j.ijbiomac.2024.131254.

161. Karuppusamy S Rajauria G Fitzpatrick S Lyons H McMahon H Curtin J, et al. Biological properties and health-promoting functions of laminarin: A comprehensive review of preclinical and clinical studies. Mar Drugs 2022;20:772. doi: 10.3390/md20120772.

162. Machado F, Coimbra MA, Castillo MDD, Coreta-Gomes F. Mechanisms of action of coffee bioactive compounds: A key to unveil the coffee paradox. Crit Rev Food Sci Nutr 2024;64:10164–10186. doi: 10.1080/10408398.2023.2221734.

163. Liu M, Jin J, Zhong X, Liu L, Tang C, Cai L. Polysaccharide hydrogels for skin wound healing. Heliyon 2024;10:e35014. doi: 10.1016/j.heliyon.2024.e35014.

164. Wang X Zhou Y Gao Q Ping D Wang Y Wu W, et al. The role of exosomal micrornas and oxidative stress in neurodegenerative diseases. Oxid Med Cell Longev 2020;2020:3232869. doi: 10.1155/2020/3232869.

165. Pfeiffer P Coates JR Esqueda YM Kennedy A Getchell K McLenon M, et al. Exosomal TAR DNA binding protein 43 profile in canine model of amyotrophic lateral sclerosis: A preliminary study in developing blood-based biomarker for neurodegenerative diseases. Ann Med 2023;55:34–41. doi: 10.1080/07853890.2022.2153162.

166. Tao H, Gao B. Exosomes for neurodegenerative diseases: Diagnosis and targeted therapy. J Neurol 2024;271:3050–3062. doi: 10.1007/s00415-024-12329-w.

167. Zhang Y, Yang Y, Gao X, Gao W, Zhang L. Research progress on mesenchymal stem cells and their exosomes in systemic sclerosis. Front Pharmacol 2023;14:1263839. doi: 10.3389/fphar.2023.1263839.

168. Zhang Y, Liu W, Wang X, Liu Y, Wei H. Nanozyme-enabled treatment of cardio- and cerebrovascular diseases. Small 2023;19:e2204809. doi: 10.1002/smll.202204809.

169. Reddy VP. Oxidative stress in health and disease. Biomedicines 2023;11:2925. doi: 10.3390/biomedicines11112925.

170. Du C Feng W Dai X Wang J Geng D Li X, et al. Cu(2+) -chelatable and ROS-scavenging mxenzyme as NIR-II-triggered blood-brain barrier-crossing nanocatalyst against Alzheimer’s disease. Small 2022;18:e2203031. doi: 10.1002/smll.202203031.

171. Ma X, Hao J, Wu J, Li Y, Cai X, Zheng Y. Prussian blue nanozyme as a pyroptosis inhibitor alleviates neurodegeneration. Adv Mater 2022;34:e2106723. doi: 10.1002/adma.202106723.

172. Dong DL, Jin GZ. Exploring the antioxidant mechanisms of nanoceria in protecting HT22 cells from oxidative stress. Int J Mol Sci 2024;25:13281. doi: 10.3390/ijms252413281.

173. Madhuvilakku R, Choi HJ, Jeong OC, Hong Y. Nanozyme film with dicopper-coordinated amino-ligands: A dual enzyme-mimic for real-time in situ dopamine sensing in human neuroblastoma cells. Biosens Bioelectron 2025;278:117375. doi: 10.1016/j.bios.2025.117375.

174. Puurunen MK Vockley J Searle SL Sacharow SJ Phillips JA, 3rd Denney WS, et al. Safety and pharmacodynamics of an engineered E. coli Nissle for the treatment of phenylketonuria: A first-in-human phase 1/2a study. Nat Metab 2021;3:1125–1132. doi: 10.1038/s42255-021-00430-7.

175. Kumar J, Karim A, Sweety UH, Sarma H, Nurunnabi M, Narayan M. Bioinspired approaches for central nervous system targeted gene delivery. ACS Appl Bio Mater 2024;7:4975–4997. doi: 10.1021/acsabm.3c00842.

176. Luo EY, Sugimura RR. Taming microglia: The promise of engineered microglia in treating neurological diseases. J Neuroinflammation 2024;21:19. doi: 10.1186/s12974-024-03015-9.

177. Jiang G Guo J Yan C He Y Chen J Zhang M, et al. Biomimetic hybrid nanovesicles improve infected diabetic wound via enhanced targeted delivery. J Control Release 2024;365:193–207. doi: 10.1016/j.jconrel.2023.11.019.

178. Xue Y, Yan X, Li D, Dong S, Ping Y. Proinflammatory polarization of engineered heat-inducible macrophages reprogram the tumor immune microenvironment during cancer immunotherapy. Nat Commun 2024;15:2270. doi: 10.1038/s41467-024-46210-1.

179. Huang R Jia B Su D Li M Xu Z He C, et al. Plant exosomes fused with engineered mesenchymal stem cell-derived nanovesicles for synergistic therapy of autoimmune skin disorders. J Extracell Vesicles 2023;12:e12361. doi: 10.1002/jev2.12361.

180. Di ZN, Zhou BQ, Zhou LY, Di YW, Wang LC, Di LQ. A gellan gum/sodium alginate-based gastric-protective hydrogel loaded with a combined herbal extract consisting of striata and Dendrobium officinale. Int J Biol Macromol 2023;250:126277. doi: 10.1016/j.ijbiomac.2023.126277.

181. Han J Wu T Jin J Li Z Cheng W Dai X, et al. Exosome-like nanovesicles derived from Phellinus linteus inhibit Mical2 expression through cross-kingdom regulation and inhibit ultraviolet-induced skin aging. J Nanobiotechnology 2022;20:455. doi: 10.1186/s12951-022-01657-6.

182. Chen YE Bousbaine D Veinbachs A Atabakhsh K Dimas A Yu VK, et al. Engineered skin bacteria induce antitumor T cell responses against melanoma. Science 2023;380:203–210. doi: 10.1126/science.abp9563.

183. Qin M Zhang X Ding H Chen Y He W Wei Y, et al. Engineered probiotic bio-heterojunction with robust antibiofilm modality via “eating” extracellular polymeric substances for wound regeneration. Adv Mater 2024;36:e2402530. doi: 10.1002/adma.202402530.

184. Knodlseder N Fabrega MJ Santos-Moreno J Manils J Toloza L Marin Vilar M, et al. Delivery of a sebum modulator by an engineered skin microbe in mice. Nat Biotechnol 2024;42:1661–1666. doi: 10.1038/s41587-023-02072-4.

185. Li L Yang C Ma B Lu S Liu J Pan Y, et al. Hydrogel-encapsulated engineered microbial consortium as a photoautotrophic “living material” for promoting skin wound healing. ACS Appl Mater Interfaces 2023;15:6536–6547. doi: 10.1021/acsami.2c20399.

186. Tan M Liu Y Xu Y Yan G Zhou N Chen H, et al. Plant-derived exosomes as novel nanotherapeutics contrive glycolysis reprogramming-mediated angiogenesis for diabetic ulcer healing. Biomater Res 2024;28:0035. doi: 10.34133/bmr.0035.

187. Shen XR Chen XL Xie HX He Y Chen W Luo Q, et al. Beneficial effects of a novel shark-skin collagen dressing for the promotion of seawater immersion wound healing. Mil Med Res 2017;4:33. doi: 10.1186/s40779-017-0143-4.

188. Zarei M, Jeong AW, Lee SG. Whisker-implanted biomimetic electronic skin for tactile sensing and blind perception. Adv Sci (Weinh) 2025;12:e2408162. doi: 10.1002/advs.202408162.

189. Dayan CB, Chun S, Krishna-Subbaiah N, Drotlef DM, Akolpoglu MB, Sitti M. 3D printing of elastomeric bioinspired complex adhesive microstructures. Adv Mater 2021;33:e2103826. doi: 10.1002/adma.202103826.

190. He C Yu B Lv Y Huang Y Guo J Li L, et al. Biomimetic asymmetric composite dressing by electrospinning with aligned nanofibrous and micropatterned structures for severe burn wound healing. ACS Appl Mater Interfaces 2022;14:32799–32812. doi: 10.1021/acsami.2c04323.

191. Chen H Zhang R Zhang G Liang X Xu C Li Y, et al. Naturally inspired tree-ring structured dressing provides sustained wound tightening and accelerates closure. Adv Mater 2025;37:e2410845. doi: 10.1002/adma.202410845.

192. Guo R Li X Zhou Y Zhang Y Jiang C Yu Y, et al. Semi-liquid metal-based highly permeable and adhesive electronic skin inspired by spider web. Sci Bull (Beijing) 2024;69:2723–2734. doi: 10.1016/j.scib.2024.06.032.

193. Yin M Lin J Yang M Li C Wu P Zou J, et al. Platelet membrane-cloaked selenium/ginsenoside Rb1 nanosystem as biomimetic reactor for atherosclerosis therapy. Colloids Surf B Biointerfaces 2022;214:112464. doi: 10.1016/j.colsurfb.2022.112464.

194. Xu J Zhang Y Xu J Liu G Di C Zhao X, et al. Engineered nanoplatelets for targeted delivery of plasminogen activators to reverse thrombus in multiple mouse thrombosis models. Adv Mater 2020;32:e1905145. doi: 10.1002/adma.201905145.

195. Xiao H Meng X Songtao L Li Z Fang S Wang Y, et al. Combined drug anti-deep vein thrombosis therapy based on platelet membrane biomimetic targeting nanotechnology. Biomaterials 2024;311:122670. doi: 10.1016/j.biomaterials.2024.122670.

196. Amaral S Lozano-Fernandez T Sabin J Gallego A da Silva Morais A Reis RL, et al. End-on PEGylation of heparin: Effect on anticoagulant activity and complexation with protamine. Int J Biol Macromol 2023;249:125957. doi: 10.1016/j.ijbiomac.2023.125957.

197. Qiu S Du J Zhu T Zhang H Chen S Wang C, et al. Electrospun compliant heparinized elastic vascular graft for improving the patency after implantation. Int J Biol Macromol 2023;253:126598. doi: 10.1016/j.ijbiomac.2023.126598.

198. Yao M Sun X Guo Z Zhao Z Yan Z Yao F, et al. Bioinspired zwitterionic microgel-based coating: Controllable microstructure, high stability, and anticoagulant properties. Acta Biomater 2022;151:290–303. doi: 10.1016/j.actbio.2022.08.022.

199. Kim CH Kim Y Karna S Yoo SM Lee JH Kim YJ, et al. Three-dimensional customized artificial grafts functionalized with biomimetic softness and anticoagulant heparin-dopamine surface modification: Preclinical study for practical applications. Int J Biol Macromol 2025;299:140002. doi: 10.1016/j.ijbiomac.2025.140002.

200. Zhang B Wan H Liu X Yu T Yang Y Dai Y, et al. Engineering immunomodulatory stents using zinc ion-lysozyme nanoparticle platform for vascular remodeling. ACS Nano 2023;17:23498–23511. doi: 10.1021/acsnano.3c06103.

201. Niu S Li F Lin Z Chen B Lyu L Jiang Y, et al. Biomimetic fabricated tubular graft in situ immobilized with peptides to restore the vascular structure and regulate the inflammation homeostasis through gastrodin coating. Bioact Mater 2025;45:58–70. doi: 10.1016/j.bioactmat.2024.11.010.

202. Zhong Y, Meng F, Deng C, Mao X, Zhong Z. Targeted inhibition of human hematological cancers in vivo by doxorubicin encapsulated in smart lipoic acid-crosslinked hyaluronic acid nanoparticles. Drug Deliv 2017;24:1482–1490. doi: 10.1080/10717544.2017.1384864.

203. Zhong Y, Meng F, Zhang W, Li B, van Hest JCM, Zhong Z. CD44-targeted vesicles encapsulating granzyme B as artificial killer cells for potent inhibition of human multiple myeloma in mice. J Control Release 2020;320:421–430. doi: 10.1016/j.jconrel.2020.02.004.

204. Gu Z, Wang X, Cheng R, Cheng L, Zhong Z. Hyaluronic acid shell and disulfide-crosslinked core micelles for in vivo targeted delivery of bortezomib for the treatment of multiple myeloma. Acta Biomater 2018;80:288–295. doi: 10.1016/j.actbio.2018.09.022.

205. Grab AL, Seckinger A, Horn P, Hose D, Cavalcanti-Adam EA. Hyaluronan hydrogels delivering BMP-6 for local targeting of malignant plasma cells and osteogenic differentiation of mesenchymal stromal cells. Acta Biomater 2019;96:258–270. doi: 10.1016/j.actbio.2019.07.018.

206. Zilkowski I Ziouti F Schulze A Hauck S Schmidt S Mainz L, et al. Nanogels enable efficient miRNA delivery and target gene downregulation in transfection-resistant multiple myeloma cells. Biomacromolecules 2019;20:916–926. doi: 10.1021/acs.biomac.8b01553.

207. Liu Z Zhang J Liu H Shen H Meng N Qi X, et al. BSA-AIE nanoparticles with boosted ros generation for immunogenic cell death immunotherapy of multiple myeloma. Adv Mater 2023;35:e2208692. doi: 10.1002/adma.202208692.

208. Chen M, Qiao Y, Cao J, Ta L, Ci T, Ke X. Biomimetic doxorubicin/ginsenoside co-loading nanosystem for chemoimmunotherapy of acute myeloid leukemia. J Nanobiotechnology 2022;20:273. doi: 10.1186/s12951-022-01491-w.

209. Harris JC, Sterin EH, Day ES. Membrane-wrapped nanoparticles for enhanced chemotherapy of acute myeloid leukemia. ACS Biomater Sci Eng 2022;8:4439–4448. doi: 10.1021/acsbiomaterials.2c00832.

210. Wang X Huang R Wu W Xiong J Wen Q Zeng Y, et al. Amplifying STING activation by bioinspired nanomedicine for targeted chemo- and immunotherapy of acute myeloid leukemia. Acta Biomater 2023;157:381–394. doi: 10.1016/j.actbio.2022.11.007.

211. Song Y Zhang L Wang Y Han M Wang Z Wang N, et al. A bimetallic metal-organic-framework-based biomimetic nanoplatform enhances anti-leukemia immunity via synchronizing DNA demethylation and RNA hypermethylation. Adv Mater 2023;35:e2210895. doi: 10.1002/adma.202210895.

212. Ding M Dai XL Yang CF Zhang Z Wang ZH Wang YQ, et al. Erythrocyte-based biomimetic MOFs as a triple epigenetic regulator for enhancing anti-leukemia immunity. Nano Lett 2024;24:15989–15999. doi: 10.1021/acs.nanolett.4c04264.

213. Rui X Okamoto Y Watanabe NM Shimizu T Wakileh W Kajimura N, et al. Preparation and characterization of macrophage membrane camouflaged cubosomes as a stabilized and immune evasive biomimetic nano-DDS. J Mater Chem B 2024;12:8702–8715. doi: 10.1039/d4tb01063a.

214. Yu T Xu Q Chen X Deng X Chen N Kou MT, et al. Biomimetic nanomaterials in myocardial infarction treatment: Harnessing bionic strategies for advanced therapeutics. Mater Today Bio 2024;25:100957. doi: 10.1016/j.mtbio.2024.100957.

215. Deshetty UM, Sil S, Buch S. Gene therapy for the heart: Encapsulated viruses to the rescue. Extracell Vesicles Circ Nucl Acids 2024;5:114–118. doi: 10.20517/evcna.2023.70.

216. Dixon SJ, Olzmann JA. The cell biology of ferroptosis. Nat Rev Mol Cell Bio 2024;25:424–442. doi: 10.1038/s41580-024-00703-5.

217. Hu S Wang X Li Z Zhu D Cores J Wang Z, et al. Platelet membrane and stem cell exosome hybrid enhances cellular uptake and targeting to heart injury. Nano Today 2021;39:101210. doi: 10.1016/j.nantod.2021.101210.

218. Feng W Teng Y Zhong Q Zhang Y Zhang J Zhao P, et al. Biomimetic grapefruit-derived extracellular vesicles for safe and targeted delivery of sodium thiosulfate against vascular calcification. ACS Nano 2023;17:24773–24789. doi: 10.1021/acsnano.3c05261.

219. Hao Y, Zhang W, Qin J, Tan L, Luo Y, Chen H. Biological cardiac patch based on extracellular vesicles and extracellular matrix for regulating injury-related microenvironment and promoting cardiac tissue recovery. ACS Appl Bio Mater 2022;5:5218–5230. doi: 10.1021/acsabm.2c00659.

220. Gao Y, Song LL, Xu JT, Li HS. The role of exosomes in myocardial ischemia-reperfusion injury. Cardiology 2025;150:489–499. doi: 10.1159/000542657.

221. Dai Y, Ding Y, Li L. Nanozymes for regulation of reactive oxygen species and disease therapy. Chin Chem Lett 2021;32:2715–2728. doi: 10.1016/j.cclet.2021.03.036.

222. Chen A, Mesfin JM, Gianneschi NC, Christman KL. Intravascularly deliverable biomaterial platforms for tissue repair and regeneration post-myocardial infarction. Adv Mater 2024;36:e2300603. doi: 10.1002/adma.202300603.

223. Wang Z, Zhou X, Wang W. Amorphous mixed-valent Mn-containing nanozyme with cocklebur-like morphology for specific colorimetric detection of cancer cells via Velcro effects. Biosens Bioelectron 2023;236:115419. doi: 10.1016/j.bios.2023.115419.

224. Zhang Y, Kudriashov D, Pershina L, Offenhausser A, Mourzina Y. Intrinsic multienzyme-like activities of the nanoparticles of Mn and Fe cyano-bridged assemblies. Nanomaterials (Basel) 2022;12:2095. doi: 10.3390/nano12122095.

225. Smits J, van der Pol A, Goumans MJ, Bouten CVC, Jorba I. GelMA hydrogel dual photo-crosslinking to dynamically modulate ECM stiffness. Front Bioeng Biotechnol 2024;12:1363525. doi: 10.3389/fbioe.2024.1363525.

226. Saleh BM, Pourmostafa A, Patrawalla NY, Kishore V. Xeno-free biomimetic ECM model for investigation of matrix composition and stiffness on astrocyte cell response. J Funct Biomater 2023;14:256. doi: 10.3390/jfb14050256.

227. Weng B Li M Zhu W Peng J Mao X Zheng Y, et al. Distinguished biomimetic dECM system facilitates early detection of metastatic breast cancer cells. Bioeng Transl Med 2024;9:e10597. doi: 10.1002/btm2.10597.

228. Rosellini E, Cascone MG, Guidi L, Schubert DW, Roether JA, Boccaccini AR. Mending a broken heart by biomimetic 3D printed natural biomaterial-based cardiac patches: A review. Front Bioeng Biotechnol 2023;11:1254739. doi: 10.3389/fbioe.2023.1254739.

229. Beltran-Vargas NE Pena-Mercado E Sanchez-Gomez C Garcia-Lorenzana M Ruiz JC Arroyo-Maya I, et al. Sodium alginate/chitosan scaffolds for cardiac tissue engineering: The influence of its three-dimensional material preparation and the use of gold nanoparticles. Polymers (Basel) 2022;14:3233. doi: 10.3390/polym14163233.

230. Pineiro-Llanes J Suzuki-Hatano S Jain A Venigalla S Kamat M Basso KB, et al. Rescue of mitochondrial dysfunction through alteration of extracellular matrix composition in barth syndrome cardiac fibroblasts. Biomaterials 2025;315:122922. doi: 10.1016/j.biomaterials.2024.122922.

231. Moore MJ Lam YT Santos M Tan RP Yang N Hung J, et al. Evaluation of the immune response to chitosan-graft-poly(caprolactone) biopolymer scaffolds. ACS Biomater Sci Eng 2023;9:3320–3334. doi: 10.1021/acsbiomaterials.3c00553.

232. Ferreira-Faria I Yousefiasl S Macario-Soares A Pereira-Silva M Peixoto D Zafar H, et al. Stem cell membrane-coated abiotic nanomaterials for biomedical applications. J Control Release 2022;351:174–197. doi: 10.1016/j.jconrel.2022.09.012.

233. Qu K Zhong Y Zhu L Mou N Cao Y Liu J, et al. A macrophage membrane-functionalized, reactive oxygen species-activatable nanoprodrug to alleviate inflammation and improve the lipid metabolism for atherosclerosis management. Adv Healthc Mater 2024;13:e2401113. doi: 10.1002/adhm.202401113.

234. Lagreca E Caiazzo E Di Natale C Mollo V Vecchione R Ialenti A, et al. Biomimetic oil-in-water nanoemulsions as a suitable drug delivery system to target inflamed endothelial cells. Nanomaterials (Basel) 2024;14:1286. doi: 10.3390/nano14151286.

235. Tang L Yin Y Liu H Zhu M Cao Y Feng J, et al. Blood-brain barrier-penetrating and lesion-targeting nanoplatforms inspired by the pathophysiological features for synergistic ischemic stroke therapy. Adv Mater 2024;36:e2312897. doi: 10.1002/adma.202312897.

236. Gu Y Du L Wu Y Qin J Gu X Guo Z, et al. Biomembrane-modified biomimetic nanodrug delivery systems: Frontier platforms for cardiovascular disease treatment. Biomolecules 2024;14:960. doi: 10.3390/biom14080960.

237. Lu S Wang R Cai M Yuan C Gao B Guo D, et al. Platelet membrane decorated exosomes enhance targeting efficacy and therapeutic index to alleviate arterial restenosis. Theranostics 2025;15:408–427. doi: 10.7150/thno.103747.

238. Jiang Y, Wei ZY, Song ZF, Yu M, Huang J, Qian HY. Platelet membrane-modified exosomes targeting plaques to activate autophagy in vascular smooth muscle cells for atherosclerotic therapy. Drug Deliv Transl Res 2025;15:3098–3118. doi: 10.1007/s13346-025-01792-1.

239. Jiang J Ni L Zhang X Wang H Liu L Wei M, et al. Platelet membrane-fused circulating extracellular vesicles protect the heart from ischemia/reperfusion injury. Adv Healthc Mater 2023;12:e2300052. doi: 10.1002/adhm.202300052.

240. Ouyang S Lu P Li J Jin H Wu W Luo R, et al. Inhaled tea polyphenol-loaded nanoparticles coated with platelet membranes largely attenuate asthmatic inflammation. Respir Res 2024;25:311. doi: 10.1186/s12931-024-02947-3.

241. Shen H Zhang M Liu D Liang X Chang Y Hu X, et al. Solanum lycopersicum derived exosome-like nanovesicles alleviate restenosis after vascular injury through the Keap1/Nrf2 pathway. Food Funct 2025;16:539–553. doi: 10.1039/d4fo03993a.

242. Ji W, Zhang Y, Deng Y, Li C, Kankala RK, Chen A. Nature-inspired nanocarriers for improving drug therapy of atherosclerosis. Regen Biomater 2023;10:rbad069. doi: 10.1093/rb/rbad069.

243. Wang Z Yuan J Xu Y Shi N Lin L Wang R, et al. Olea europaea leaf exosome-like nanovesicles encapsulated in a hyaluronic acid/tannic acid hydrogel dressing with dual “defense-repair” effects for treating skin photoaging. Mater Today Bio 2024;26:101103. doi: 10.1016/j.mtbio.2024.101103.

244. Zizhou R, Wang X, Houshyar S. Review of polymeric biomimetic small-diameter vascular grafts to tackle intimal hyperplasia. ACS Omega 2022;7:22125–22148. doi: 10.1021/acsomega.2c01740.

245. Zarei M, Zwir MJ, Michalkiewicz B, Goracy J, El Fray M. Template-assisted electrospinning and 3D printing of multilayered hierarchical vascular grafts. J Biomed Mater Res B Appl Biomater 2025;113:e35525. doi: 10.1002/jbm.b.35525.

246. Beachley V, Kuo J, Kasyanov V, Mironov V, Wen X. Biomimetic crimped/aligned microstructure to optimize the mechanics of fibrous hybrid materials for compliant vascular grafts. J Mech Behav Biomed Mater 2024;150:106301. doi: 10.1016/j.jmbbm.2023.106301.

247. Han Y, Zhang L, Kong L, Wang G, Ye Z. Investigating the relationship between residual stress and micromechanical properties of blood vessels using atomic force microscopy. Microsc Res Tech 2024;87:1678–1692. doi: 10.1002/jemt.24552.

248. Fan X Xue Y Liu B Zhang A Song L Ma C, et al. Design of fish-scale microstructured stents and their biomechanical effects on cerebral aneurysm. Comput Methods Biomech Biomed Engin 2025:1–21. doi: 10.1080/10255842.2025.2465343.

249. Wen SM Chen SM Gao W Zheng Z Bao JZ Cui C, et al. Biomimetic gradient bouligand structure enhances impact resistance of ceramic-polymer composites. Adv Mater 2023;35:e2211175. doi: 10.1002/adma.202211175.

250. Giovanniello F Asgari M Breslavsky ID Franchini G Holzapfel GA Tabrizian M, et al. Development and mechanical characterization of decellularized scaffolds for an active aortic graft. Acta Biomater 2023;160:59–72. doi: 10.1016/j.actbio.2023.02.013.

251. Rosellini E, Giordano C, Guidi L, Cascone MG. Biomimetic approaches in scaffold-based blood vessel tissue engineering. Biomimetics (Basel) 2024;9:377. doi: 10.3390/biomimetics9070377.

252. Wang X Li K Yuan Y Zhang N Zou Z Wang Y, et al. Nonlinear elasticity of blood vessels and vascular grafts. ACS Biomater Sci Eng 2024;10:3631–3654. doi: 10.1021/acsbiomaterials.4c00326.

253. Hou YC Cui X Qin Z Su C Zhang G Tang JN, et al. Three-dimensional bioprinting of artificial blood vessel: Process, bioinks, and challenges. Int J Bioprint 2023;9:740. doi: 10.18063/ijb.740.

254. Bala N Aranda A Teixido P Molhoek C Moreno-Jimenez I Febas G, et al. In vivo efficacy of an adhesive bioresorbable patch to treat aortic dissections. JACC Basic Transl Sci 2024;9:65–77. doi: 10.1016/j.jacbts.2023.08.002.

255. Martins EAG, Deus IA, Gomes MC, Silva AS, Mano JF, Custodio CA. Human chorionic membrane-derived tunable hydrogels for vascular tissue engineering strategies. Adv Healthc Mater 2025;14:e2401510. doi: 10.1002/adhm.202401510.

256. Wang X, Chan V, Corridon PR. Acellular tissue-engineered vascular grafts from polymers: Methods, achievements, characterization, and challenges. Polymers (Basel) 2022;14:4825. doi: 10.3390/polym14224825.

257. Rata DM, Cadinoiu AN, Daraba OM, Gradinaru LM, Atanase LI, Ichim DL. Influence of ZnO nanoparticles on the properties of ibuprofen-loaded alginate-based biocomposite hydrogels with potential antimicrobial and anti-inflammatory effects. Pharmaceutics 2023;15:2240. doi: 10.3390/pharmaceutics15092240.

258. Yao X, Peng R, Ding J. Cell-material interactions revealed via material techniques of surface patterning. Adv Mater 2013;25:5257–5286. doi: 10.1002/adma.201301762.

259. Alkazemi H, Mitchell GM, Lokmic-Tomkins Z, Heath DE, O’Connor AJ. Hierarchically vascularized and suturable tissue constructs created through angiogenesis from tissue-engineered vascular grafts. Acta Biomater 2024;189:168–178. doi: 10.1016/j.actbio.2024.09.052.

260. Zhang M, Ge P, Fu Z, Dan X, Li G. Mechanical property test of grass carp skin material based on the digital image correlation method. Sensors (Basel) 2022;22:8364. doi: 10.3390/s22218364.

261. Kostelnik C Hohn J Escoto-Diaz CE Kooistra JB Stern M Swinton DE, et al. Small-diameter artery decellularization: Effects of anionic detergent concentration and treatment duration on porcine internal thoracic arteries. J Biomed Mater Res B Appl Biomater 2022;110:885–897. doi: 10.1002/jbm.b.34969.

262. Hernandez-Sanchez D, Comtois-Bona M, Munoz M, Ruel M, Suuronen EJ, Alarcon EI. Manufacturing and validation of small-diameter vascular grafts: A mini review. Iscience 2024;27:109845. doi: 10.1016/j.isci.2024.109845.

263. Liu Y, Zhang J, Li S, Xia H. Photopolymerization strategy for the preparation of small-diameter artificial blood vessels with micro-nano structures on the inner wall. Biomed Opt Express 2021;12:5844–5854. doi: 10.1364/BOE.432441.

264. Bacakova L Chlupac J Filova E Musilkova J Tomsu J Wu YC, et al. Vascular damage and repair—Are small-diameter vascular grafts still the “holy grail” of tissue engineering? Physiol Res 2024;73:S335–S363. doi: 10.33549/physiolres.935294.

265. Zhang Y Jiao Y Wang C Zhang C Wang H Feng Z, et al. Design and characterization of small-diameter tissue-engineered blood vessels constructed by electrospun polyurethane-core and gelatin-shell coaxial fiber. Bioengineered 2021;12:5769–5788. doi: 10.1080/21655979.2021.1969177.

266. Ulloa J Moreno OY Castillo-Cabrera C Cifuentes S Figueroa V Solano A, et al. Telangiectasia diameter in response to thermal stimulus: Experimental data and possible clinical applications. Int Angiol 2021;40:451–456. doi: 10.23736/S0392-9590.21.04693-9.

267. Jin Q Jin G Ju J Xu L Tang L Fu Y, et al. Bioprinting small-diameter vascular vessel with endothelium and smooth muscle by the approach of two-step crosslinking process. Biotechnol Bioeng 2022;119:1673–1684. doi: 10.1002/bit.28075.

268. Watanabe U Sugiura S Kakehata M Yanagawa F Takagi T Sumaru K, et al. Fabrication of hollow structures in photodegradable hydrogels using a multi-photon excitation process for blood vessel tissue engineering. Micromachines (Basel) 2020;11:679. doi: 10.3390/mi11070679.

269. Xiao D Mi X Wang Q Chen S Chen R Zhao Y, et al. Advancements in manufacturing technologies in the small-diameter artificial blood vessels field. Biomed Mater 2025;20. doi: 10.1088/1748-605X/adca7b.

270. Lele M, Kapur S, Hargett S, Sureshbabu NM, Gaharwar AK. Global trends in clinical trials involving engineered biomaterials. Sci Adv 2024;10:eabq0997. doi: 10.1126/sciadv.abq0997.

271. Capella-Monsonís H, Crum RJ, Hussey GS, Badylak SF. Advances, challenges, and future directions in the clinical translation of ECM biomaterials for regenerative medicine applications. Adv Drug Deliv Rev 2024;211:115347. doi: 10.1016/j.addr.2024.115347.

272. Zhang K, Mikos AG, Reis RL, Zhang XD. Translation of biomaterials from bench to clinic. Bioact Mater 2022;18:337–338. doi: 10.1016/j.bioactmat.2022.02.005.