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Biosynthesis and biotechnological engineering of aminoglycosides: Pathways, enzymes, and industrial prospects.

Aminoglycosides (AGs) are a broad class of antibiotics widely used in medicine since the 1950s. Challenges remain in creating highly stereoselective modifications with traditional chemical methods. Biosynthesis, which involves enzymatic formation of AGs via genetically encoded pathways in microbes, offers a more efficient, selective, and eco-friendly alternative. The biosynthetic routes of key AGs such as neomycin (NEO), kanamycin (KAN), gentamicin (GEN), tobramycin (TOB), apramycin (APR), and sisomicin (SIS) have been mapped out, involving enzymatic steps like aminocyclitol core formation, gl

Granaticin biosynthesis and engineering: mechanistic understanding, production bottlenecks, and computational opportunities.

Granaticin, as a member of the benzoisochromanequinone (BIQ) family, exhibits a range of biological activities, including antibacterial, ant … sses-granaticin research is shifting from empirical optimization toward system-level and predictive engineering.This review systematically summarizes recent progress in granaticin research, with particular emphasis on biosynthetic mechanisms, pathway regulation, metabolic engineering strategies, tailoring enzyme functions, heterologous expression systems, and …

Modular PEG coatings for engineering a biomimetic glycocalyx on lipid membranes.

Engineering synthetic cells with biomimetic surface architectures requires precise control over the spatial organization and mechanical properties of the membrane surface. Inspired by the protective and regulatory functions of the natural glycocalyx, we present a modular platform for constructing hierarchical, crosslinked PEG networks on fluid lipid membranes. Through spatially controlled, sequential strain-promoted azide-alkyne cycloaddition (SPAAC), we assemble a tunable, multilayered PEG mesh that mimics the dynamic, dense, and mechanically resilient architecture of the glycocalyx. By incor…

EZPro-Multi: Contrastive Learning-Enhanced Multi-property Prediction for Enzyme Engineering.

Accurately predicting the functional attributes of enzyme mutants is crucial for accelerating enzyme engineering and optimizing biocatalytic systems. Most existing methods focus on enzyme information or a limited set of properties while overlooking key interactions between enzyme mutants and their substrates. To address this limitation, we propose EZPro-Multi, a unified deep learning framework for predicting multiple biochemical properties, including catalytic efficiency (kcat), stability (ΔΔG), and solubility (ΔSol). EZPro-Multi integrates ProtT5-based protein representations with Molformer-b…

Engineering Kidney-Targeted Drug Delivery Systems: Principles, Materials, and Emerging Strategies.

Kidney-targeted drug delivery is pivotal for treating renal diseases while minimizing systemic toxicity. To navigate the organ's complex physiological barriers, advanced nanomedicines employ integrated strategies. Our comprehensive narrative review provides a structured analysis of these strategies through a dual lens: first, by examining the fundamental mechanisms of renal targeting-including passive filtration, active receptor-mediated uptake, and their synergistic combination; and second, by deconstructing delivery systems into several fundamental pillars, the carrier platforms, the functio

Engineering chitosan-functionalized liposomes for targeted drug delivery and biomedical applications.

Chitosan (CS) is a naturally derived cationic polysaccharide that has attracted sustained interest in drug delivery due to its favorable biocompatibility, biodegradability, and chemical versatility. Liposomes are well-established lipid-based nanocarriers capable of encapsulating both hydrophilic and hydrophobic therapeutics; however, their clinical performance is often compromised by limited physicochemical stability, premature drug leakage, rapid clearance, and insufficient interaction with biological barriers. Surface functionalization of liposomes with CS has emerged as an effective hybridi

Engineering High-Performance Inhalable Monoclonal Antibody Powders via Spray Freeze Drying.

Spray freeze-drying (SFD) is a cutting-edge technique for producing dry powders, ideal for pulmonary drug delivery, owing to its ability to generate porous microparticles with low density and excellent aerodynamic properties. The SFD process, involving atomisation, freezing, and drying, is particularly suited for formulating biologics, e.g., monoclonal antibodies (mAbs), due to its low-temperature conditions. However, the method poses challenges, including the potential denaturation of mAbs due to shear, freezing, and dehydration stresses during processing. Here, we investigated how formulatio

Engineering Antivenom: Research Progress and Future Directions in Snakebite Envenoming Therapy.

Snakebite envenoming remains a major neglected tropical disease, causing substantial mortality and morbidity worldwide. While plasma-derived antivenoms have been the mainstay of treatment for over a century, they present important limitations related to safety, efficacy, specificity, scalability, and accessibility. Recent advances in biotechnology, venom and toxin characterization, and antibody engineering have enabled the development of new types of envenoming therapeutics, including recombinant antivenoms based on monoclonal antibodies and nanobody-based formats, as well as small-molecule in…

Biodegradable Natural Polymer-Based Drug Delivery Systems for Bone Tissue Engineering.

The increasing incidence of bone diseases and injuries, especially among aging populations, has underscored the shortcomings of traditional … affolds, focusing on their structural characteristics and drug delivery capabilities in bone tissue engineering. Four principal scaffold architectures-sponges, nanofibers, hydrogels, and microspheres-are examined with respect to their regenerative functionality, associated limitations, and recent engineering advancements. In particular, we discuss the use of …

Advances and Clinical Translation Potentials of Functional Nanomaterials in Tissue Engineering.

Functional nanomaterials, such as functionalized nanoparticles, nanofibers, nanocrystals, MXene and liposomes, have emerged as game-changers in tissue engineering, enabling precise modulation of cellular behaviors and dynamic biomimetic microenvironments. This review comprehensively summarizes and discusses the cutting-edge applications of nanomaterials in tissue regeneration (including bone, skin, neural and cardiac tissue regeneration), with a focus on their unique physicochemical properties (e.g., stimuli-responsiveness, nano-topography) and hybrid system design. Recent breakthroughs includ…

Computational Advances in Biomaterial Engineering: Mapping Research Trajectories Through Bibliometric Analysis.

Alternatives to animal models, including computational-based approaches, are now prioritized by regulatory and funding agencies in biomedical research. Despite this shift in policy, computer models in tissue engineering and regenerative medicine remain underutilized and have not been fully integrated into research and development pipelines. This study aims to identify current and emerging computational techniques in regenerative biomaterials through comprehensive bibliometric analysis and to examine future directions in the evolving field of tissue engineering. Using the Web of Science databas…

Enzyme-Resistant Glycocalyx Bionic Coating for Corneal Bandage Lens Surface Engineering.

Advanced implantable medical devices often need to integrate multiple functions onto one surface to meet the complex needs in vivo. The construction of glycocalyx bionic coatings that mimic the natural multifunctional glycocalyx barrier of blood vessels, intestines, and ocular surfaces is an emerging strategy for function integration. However, in practical application scenarios such as corneal bandage lens (CBL) for corneal injury treatment, bio-enzymes from immune cells and bacteria can degrade the natural polymers constructing the glycocalyx bionic coating, such as hyaluronic acid, resulting

Corneal Tissue Engineering Using Organoid Models for Vision Restoration: Translational Outlooks.

Corneal blindness has been a significant, in most cases, reversible cause of visual impairment worldwide due to donor deficiency and donor graft failure, which has encouraged the consideration of donor-independent techniques for regeneration. This review aims to discuss the advances in corneal organoid-based tissue engineering and its potential application in the translation to vision restoration. This review was conducted through an analysis of publications related to corneal organoids, biomaterials, bioprinting, preclinical models, and early human studies, published between 2005-2025 in Scop…

Engineering TCR-directed T-cells for the treatment of multiple myeloma.

Multiple myeloma (MM) is a virtually incurable plasma cell malignancy characterized by malignant cells that expand within the tumor-permissive bone marrow (BM) microenvironment. Novel strategies are urgently needed to improve the outcomes of patients with difficult-to-treat and therapy-refractory disease. The ability to genetically manipulate T-cells and the introduction of adoptive cellular therapies (ACTs) has improved the treatment of relapsed and/or refractory (RR)MM. Emerging evidence supports the efficacy of ACTs as early lines of cancer treatment, potentially even as an alternative to a

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… Engineered T-cells expanded, persisted, trafficked to BM and exhibited a cytotoxic phenotype. Persistence of engineered T-cells in blood was inversely associated with NY-ESO-1 levels in BM. … Engineering anti-myeloma responses using affinity-enhanced TCR-engineered T cells . Cancer Cell . ( 2015 ) 28 : 281 – 283 . doi: 10.1016/j.ccell.2015.08.009 , PMID: 26373276 125 Subklewe M . BiTEs better than CAR T cells . …

Piezoelectric amino acids and peptides: Mechanisms, molecular engineering, and biomedical applications.

Piezoelectric amino acids and peptides have attracted growing attention in biomedical research because of their intrinsic piezoelectricity, superior biocompatibility, and biodegradability. The electrical signals generated by these materials resemble endogenous bioelectric signals in tissues, making them promising for biosensing, tissue regeneration, antimicrobial therapy, and cancer treatment. This review summarizes the piezoelectric mechanisms, classifications, molecular modification approaches, external-field-assisted fabrication methods, and reported biomedical applications of amino acid- a

Optimizing Primary Human Salivary Stem/Progenitor Cells for Tissue Engineering Applications.

This work aimed to establish a translationally viable, xeno-free, serum-free platform and protocol for the isolation and expansion of human salivary stem/progenitor cells (hS/PCs) suitable for regulatory qualification and future FDA-approved first-in-human autologous regenerative therapy trials for the treatment of hyposalivation disorders. Parotid gland specimens from non-cancerous regions/tissues were collected from consented surgical patients. Primary hS/PCs were isolated from tissue specimens, cultured in animal-component-free conditions, expanded to produce millions of cells, then enriche

Platelet Lysate-Based Biomaterials for Regenerative Tissue Engineering: A Comprehensive Review.

Platelet lysate (PL), enriched with growth factors, cytokines, and proteins, exhibits strong regenerative potential, positioning it as a promising bioactive agent in tissue engineering (TE). This review systematically summarizes the research progress, applications, and mechanisms of PL-loaded biomaterials in TE. PL-integrated carriers, including hydrogels, scaffolds, and nanoparticles, transform labile liquid PL into stable, tunable platforms that retain its capacities to promote cell proliferation, angiogenesis, immunomodulation, and tissue repair, while enabling spatiotemporal control of eff…

Effector-cell-engaging bispecific antibodies for cancer therapeutics: Engineering precision immunity.

The bispecific antibody (bsAb) is a novel immune therapeutic platform that consists of a single molecule that simultaneously binds two distinct antigens, tumor-associated antigens and immune effector cells, to enhance the targeted killing of tumor cells. bsAbs can target T cells and natural killer (NK) cells or macrophages through receptors such as CD3, CD16 or CD47 and generate strong, MHC-independent antitumor activity. This review outlines the evolution of effector-cell-engaging bsAb formats, such as BiTEs, DARTs, TandAbs and IgG-like constructs, along with engineering strategies to enhance…

Towards a bioengineered airway: advances in tracheal tissue engineering and biofabrication.

Tracheal damage arising from inflammation, trauma, congenital anomalies, or tumors can lead to life-threatening complications, yet current treatments, including surgical reconstruction, stenting, laser therapies, autografts, and allografts, remain inadequate, especially for long-segment defects. As a result, tracheal tissue engineering has emerged as a promising alternative, aiming to create functional biomimetic constructs that reduce dependence on complex surgeries, long-term stenting, and immunosuppression. Advances in additive manufacturing and 3D bioprinting have accelerated progress towa…

Engineering the Human Endometrial-Embryo Interface: Breakthroughs in 3D Uterine Models.

Three-dimensional (3D) organoid and co-culture models have emerged as transformative tools for studying human endometrial function, implantation, and placental development, overcoming key limitations of animal and two-dimensional in vitro systems. This review synthesises available information of recent advances in endometrial epithelial organoids (EEOs), trophoblast organoids (TBOs), and increasingly complex co-culture platforms incorporating stromal, vascular, and trophoblast compartments to model epithelial-stromal crosstalk, decidualisation, angiogenesis, and embryo implantation. Emerging d