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Pathology-driven catalytic nanozyme-integrated adhesive hydrogel disrupts the hyperglycemia-ROS-hypoxia loop to accelerate vascularized fracture healing in diabetes.

Diabetes mellitus severely impair fracture healing due to a pathological microenvironment characterized by persistent hyperglycemia, excessi … ic rat femoral fracture model, local implantation of Gel-FQG significantly accelerates vascularized bone regeneration and fracture healing. These findings demonstrate that Gel-FQG actively remodels the diabetic fracture microenvironment and offers a promising strategy for diabetic bone repair.

TH17-Associated Polyamine Metabolism-Guided Nanozyme Promotes Alveolar Bone Repair in Periodontitis.

Periodontitis is a chronic inflammatory disease characterized by persistent inflammation and limited repair at sites of alveolar bone loss. Although excessive reactive oxygen species (ROS) are recognized drivers of periodontal tissue damage, oxidative stress alone does not fully explain the persistence of inflammation and the failure of regeneration. The immune and metabolic processes that cooperate with oxidative stress in sustaining this disease-supporting microenvironment remain incompletely defined. In this study, a pronounced TH17-skewed CD4+ T cell response is identified in experimental

Heterotopic Ossification: Molecular Drivers, Subtype-Specific Mechanisms, and Translational Therapeutic Advances.

Heterotopic ossification (HO), the pathological formation of mature bone in non-skeletal soft tissues (e.g., muscles, tendons), severely impairs patient mobility and quality of life. Despite decades of research, systematic analysis of signaling networks across HO subtypes (acquired traumatic HO, hereditary Fibrodysplasia Ossificans Progressiva (FOP), Progressive Osseous Heteroplasia (POH)) remains insufficient, and clinical therapies suffer from high recurrence and severe side effects. This review synthesizes recent advances in HO pathogenesis: FOP involves gain-of-function activin A receptor

Advanced biomaterial-based approaches for medication-related osteonecrosis of the jaw.

Medication-related osteonecrosis of the jaw (MRONJ) is a debilitating adverse effect linked to anti-resorptive and anti-angiogenic therapies, with an incidence of 4.34 % (6.22 % in oncology patients and 0.59 % in osteoporosis patients) based on a pooled analysis of 92 observational studies (2015-2020), characterized by persistent bone exposure and poor healing. Conventional treatment modalities often yield suboptimal outcomes, with recurrence and procedural morbidity. In recent years, biomaterial-based strategies have emerged as promising alternatives by targeting MRONJ's complex pathophysiolo

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… The ideal porosity for bone regeneration scaffolds is suggested to be greater than 60 %, with pore sizes exceeding 100 μm [ 147 ]. … These ions modulate inflammation, enhance cytokine expression, and upregulate CGRP signaling to support vascularized bone regeneration [ 150 ], 161 ]. …

Temporally programmed dual-function scaffold with simultaneous cellulose and calcium lactate regeneration for enhanced osteogenesis via lactate-induced OR5AN1 activation.

Electrospun scaffolds that couple structural guidance with cell-instructive cues remain a key objective in bone regeneration. Here, we developed a multifunctional PCL/cellulose scaffold that exploits lactic acid (LA) as a triple-role reagent-an electrospinning plasticizer, a precursor for in situ calcium lactate (CaL) formation, and a handle for chemokine conjugation. LA incorporation enables the formation of ultrafine nanofibers with a surface-enriched outer region; subsequent Ca(OH)₂ treatment simultaneously deacetylates cellulose acetate (CA) to cellulose and converts LA into a conformal Ca…

Strontium-incorporated thermoresponsive hydrogel platform co-delivering graphene oxide-mannose nanocomplexes: An osteoimmunomodulatory strategy for periodontitis therapy.

Periodontitis is an immune-mediated disease that destroys tooth-supporting tissues, yet existing treatments cannot synchronize inflammation resolution with bone regeneration. To address this unmet need, we report an injectable, strontium-incorporated an injectable thermoresponsive hydrogel (composed of chitosan, 0.6% gelatin, and β-glycerophosphate) platform engineered for the delivery of graphene oxide-mannose nanocomplexes (designated GM-Sr@Hydrogel). Upon injection, this platform undergoes rapid thermoresponsive stiffening, enabling the localized and controlled release of Sr2+ and GO-DM nan…

3D printing in musculoskeletal interface engineering: Current progress and future directions.

The musculoskeletal system relies on critical tissue interfaces for its function; however, these interfaces are often compromised by injuries and diseases. Restoration of these interfaces is complex by nature which renders traditional treatments inadequate. An emerging solution is three-dimensional printing, which allows for precise fabrication of biomimetic scaffolds to enhance tissue regeneration. This review summarizes the use of 3D printing in creating scaffolds for musculoskeletal interfaces, mainly focusing on advanced techniques such as multi-material printing, bioprinting, and 4D print

Efficacy of hydroxyapatite and fibrin sealant as carriers for bone morphogenetic protein-2 in maxillary sinus floor augmentation: a retrospective study.

The aim of this retrospective study was to assess the efficacy of recombinant human bone morphogenetic protein-2 (rhBMP-2) with hydroxyapati … itional use of FS as a carrier for rhBMP-2/HA in MSFA was found to improve surgical convenience and bone regeneration ability.

New Biocompatible Ti-MOF@hydroxyapatite Composite Boosted with Gentamicin for Postoperative Infection Control.

The standard clinical management of osteomyelitis involves prolonged antibiotic therapy, which frequently necessitates the excision of infected tissues. However, the efficacy of such treatments is increasingly compromised by the rise of antibiotic-resistant pathogens, underscoring an urgent need for innovative approaches. This study introduces a novel composite material designed to offer dual functionality: robust antimicrobial activity and promotion of bone regeneration. The composite integrates biocompatible hydroxyapatite nanoparticles (HA) with a titanium(IV)-metal-organic framework, MIL-1…

Sequential soft- and hard-tissue augmentation after clear aligner-mediated adjustment of traumatic occlusion: A case report.

BACKGROUND: Oral health and esthetic concerns have increasingly motivated adults with periodontitis to seek orthodontic care. Patients with … onnective tissue graft was used to alter the thin periodontal phenotype. Three months later, guided bone regeneration with corticotomy was performed to increase bone mass, and orthodontic traction was used at 2 weeks after surgery. Orthodontic treatment was continued until all the spaces had been closed. Clinical and radiographic evaluations conducted at the 6-mont …

Phosphatase and tensin homologue determine inflammatory status by differentially regulating the expression of Akt1 and Akt2 in macrophage alternative polarization of periodontitis.

AIM: Macrophages are closely involved in periodontitis. However, the molecular mechanism by which macrophages influence periodontitis is not well understood. We investigated the effects of phosphatase and tensin homologue (PTEN) on macrophage polarization, the underlying mechanism and the regulatory roles in periodontium regeneration. MATERIALS AND METHODS: PTEN expression in periodontitis macrophages was detected ex vivo. The effects of PTEN on macrophage polarization and the underlying mechanisms were investigated in vitro. We also analysed the ability of PTEN inhibitors to repair periodont

In Vitro and Ectopic In Vivo Studies toward the Utilization of Rapidly Isolated Human Nasal Chondrocytes for Single-Stage Arthroscopic Cartilage Regeneration Therapy.

Nasal chondrocytes (NCs) have a higher and more reproducible chondrogenic capacity than articular chondrocytes, and the engineered cartilage tissue they generate in vitro has been demonstrated to be safe in clinical applications. Here, we aimed at determining the feasibility for a single-stage application of NCs for cartilage regeneration under minimally invasive settings. In particular, we assessed whether NCs isolated using a short collagenase digestion protocol retain their potential to proliferate and chondro-differentiate within an injectable, swiftly cross-linked and matrix-metalloprotei

Evaluation of a hyaluronic acid hydrogel (Restylane Lyft) as a scaffold for dental pulp regeneration in a regenerative endodontic organotype model.

Scaffolds are crucial elements for dental pulp regeneration. Most of the currently used scaffolds in regenerative endodontic procedures (REPs) are unsuitable for chairside clinical use. This study aimed to evaluate the effect of an injectable synthetic scaffold (Restylane Lyft) on human bone marrow mesenchymal stem cell (hBMSC) viability, proliferation, and osteo/dentinogenic differentiation in a regenerative endodontic organotype model (REM). hBMSC were loaded in an REM either alone (hBMSC group) or mixed with the Restylane Lyft scaffold (Restylane/hBMSC group) and cultured in basal culture m

Protective Effects of a Hyaluronan-Binding Peptide (P15-1) on Mesenchymal Stem Cells in an Inflammatory Environment.

Mesenchymal stem cells (MSCs) obtained from various sources, including bone marrow, have been proposed as a therapeutic strategy for the improvement of tissue repair/regeneration, including the repair of cartilage defects or lesions. Often the highly inflammatory environment after injury or during diseases, however, greatly diminishes the therapeutic and reparative effectiveness of MSCs. Therefore, the identification of novel factors that can protect MSCs against an inflammatory environment may enhance the effectiveness of these cells in repairing tissues, such as articular cartilage. In this

Collagen Structure-Function Mapping Informs Applications for Regenerative Medicine.

Type I collagen, the predominant protein of vertebrates, assembles into fibrils that orchestrate the form and function of bone, tendon, skin, and other tissues. Collagen plays roles in hemostasis, wound healing, angiogenesis, and biomineralization, and its dysfunction contributes to fibrosis, atherosclerosis, cancer metastasis, and brittle bone disease. To elucidate the type I collagen structure-function relationship, we constructed a type I collagen fibril interactome, including its functional sites and disease-associated mutations. When projected onto an X-ray diffraction model of the native

Mesenchymal stem cells: amazing remedies for bone and cartilage defects.

Skeletal disorders are among the leading debilitating factors affecting millions of people worldwide. The use of stem cells for tissue repair has raised many promises in various medical fields, including skeletal disorders. Mesenchymal stem cells (MSCs) are multipotent stromal cells with mesodermal and neural crest origin. These cells are one of the most attractive candidates in regenerative medicine, and their use could be helpful in repairing and regeneration of skeletal disorders through several mechanisms including homing, angiogenesis, differentiation, and response to inflammatory conditi

Bioprinting a Synthetic Smectic Clay for Orthopedic Applications.

Bioprinting technology has emerged as an important approach to bone and cartilage tissue engineering applications, because it allows the printing of scaffolds loaded with various components, such as cells, growth factors, or drugs. In this context, the bone has a very complex architecture containing highly vascularized and calcified tissues, while cartilage is avascular and has low cellularity and few nutrients. Owing to this complexity, the repair and regeneration of these tissues are highly challenging. Identification of the appropriate biomaterial and fabrication technologies can provide su

Inhibiting PPARγ by erythropoietin while upregulating TAZ by IGF1 synergistically promote osteogenic differentiation of mesenchymal stem cells.

Erythropoietin (EPO) is reported to promote osteogenesis and inhibit adipogenesis of mesenchymal stem cells (MSC) through inhibiting PPARγ, while insulin-like growth factor 1 (IGF1) is able to enhance osteogenesis via upregulating transcriptional coactivator with PDZ-binding motif (TAZ). The different targets of EPO and IGF1 suggested their potential synergism to enhance osteogenesis. In this study, we aimed to determine the potential synergism of EPO and IGF1 and its efficacy on MSC differentiation. Rat adipose-derived mesenchymal stem cells (ADSCs) were separately treated with EPO, IGF1 and

Trojan-Like Internalization of Anatase Titanium Dioxide Nanoparticles by Human Osteoblast Cells.

Dentistry and orthopedics are undergoing a revolution in order to provide more reliable, comfortable and long-lasting implants to patients. Titanium (Ti) and titanium alloys have been used in dental implants and total hip arthroplasty due to their excellent biocompatibility. However, Ti-based implants in human body suffer surface degradation (corrosion and wear) resulting in the release of metallic ions and solid wear debris (mainly titanium dioxide) leading to peri-implant inflammatory reactions. Unfortunately, our current understanding of the biological interactions with titanium dioxide nan

Abdominal wall regenerative medicine for a large defect using tissue engineering: an experimental study.

PURPOSE: Treatment for a large abdominal wall defect remains challenging. The aim of this study was to optimize tissue engineering therapy of muscle constructs using a rat model. METHODS: Experimental abdominal wall defects were created in Wister rats. The animal model was divided into three groups: collagen sponge (CS), hybrid scaffold (HS) and hybrid scaffold containing bone marrow liquid (HSBM). Hybrid scaffolds comprised collagen sponge and poly L-lactide (PLLA) sheets. Abdominal wall defects were covered by three kinds of sheets. Thereafter, the bone marrow liquid was spread onto the she