Search Results (2,523)

Vascularization is one of the key components of tissue engineering and must accompany the ingrowth of new tissues to establish an environment conducive to repair and regeneration of damaged tissue. The overarching objective of this study was to investigate whether the hyper-crosslinked carbohydrate polymer (HCCP) could promote the establishment of new vasculature compared to hydroxyapatite/beta-tricalcium phosphate (HA/β-TCP), which is widely used in orthopedic procedures. Sprague Dawley rats (n = 12) were implanted subcutaneously with HCCP or HA/β-TCP and evaluated histologically for the ingrowth of new vasculature at 3, 14, and 28 days post-implantation. HCCP showed significantly greater levels of vascularization when compared to HA/β-TCP at all time points evaluated (p < 0.05). HA/β-TCP showed transient inflammation at 14 days post-implantation, whereas minimal immune activities were noted in HCCP. These findings suggest that HCCP promotes the establishment of new vasculature without a significant immune response. Full article

Mechanical loading generated during physical activity and exercise is a fundamental determinant of musculoskeletal development, adaptation, and regeneration. Exercise-based mechanotherapy, encompassing structured movement, resistance training, stretching, and device-assisted loading, has evolved from empirical rehabilitation toward mechanism-driven and precision-oriented therapeutic strategies. At the macroscopic level, biomechanical principles governing load distribution, stress–strain relationships, and tissue-specific adaptation provide the physiological basis for exercise-induced tissue remodeling. At the molecular level, mechanical cues are transduced into biochemical signals through conserved mechanotransduction pathways, including integrin–FAK–RhoA/ROCK signaling, mechanosensitive ion channels such as Piezo, YAP/TAZ-mediated transcriptional regulation, and cytoskeleton–nucleoskeleton coupling. These mechanisms orchestrate extracellular matrix (ECM) remodeling, cellular metabolism, and regenerative responses across bone, cartilage, muscle, and tendon. Recent advances in mechanotherapy leverage these biological insights to promote musculoskeletal tissue repair and regeneration, while emerging engineering innovations, including mechanoresponsive biomaterials, 4D-printed dynamic scaffolds, and artificial intelligence-enabled wearable systems, enable mechanical loading to be quantified, programmable, and increasingly standardized for individualized application. Together, these developments position exercise-informed precision mechanotherapy as a central strategy for prescription-based regenerative rehabilitation and long-term musculoskeletal health. Full article

Background: Guided Bone Regeneration (GBR) relies on barrier membranes, for which polylactic acid (PLA) and its copolymer poly(lactic-co-glycolic acid) (PLGA) are promising biodegradable polymers. However, their inherent hydrophobicity limits biological performance, and the evidence regarding how specific modifications affect key human cell types, particularly osteoblasts and fibroblasts, remains scattered. Methods: A systematic review was conducted to synthesize the in vitro evidence on the response of primary human osteoblasts and fibroblasts to polylactic acid-based materials. Following a pre-registered protocol (10.17605/OSF.IO/CE8KB), a comprehensive search was performed across four major databases, and the risk of bias in the included studies was assessed using an adapted OHAT tool. Results: Twenty-six studies were included, which showed that polylactic acid-based materials have limited bioactivity, and their modification significantly improves cellular responses. The incorporation of bioceramics and growth factors, or alterations in surface topography, notably enhanced osteogenic differentiation and mineralization in osteoblasts. For gingival fibroblasts, topographical modifications like micro-grooves guided cell alignment and modulated proliferation. Conclusions: Native polylactic acid-based materials display limited bioactivity. However, functionalization through bioceramics incorporation, growth factor delivery, and surface topographical modification is crucial for transforming them into bioactive scaffolds capable of achieving the dual biofunctionality required for successful GBR. Full article

The human body’s ability to recover from bone injuries is remarkable; however, in specific conditions, interventions are required to restore function and prevent complications. To accelerate osteogenesis, several strategies have been explored, including grafts, biomaterials, and adjuvant therapies. The aim of this narrative review was to analyze the preclinical evidence regarding the combination of particulate biomaterials and fibrin derivatives for bone regeneration. Publications using hydroxyapatite, bovine bone, β-tricalcium phosphate, and bioglass in association with fibrin glue, heterologous fibrin sealants, or platelet-rich fibrin were examined to identify recurrent experimental patterns and biological outcomes. According to the studies, hydroxyapatite and bovine bone were the most frequently investigated scaffolds, whereas fibrin glue and heterologous fibrin sealants showed consistent adhesion and favorable host response profiles in animal models. β-tricalcium phosphate demonstrated faster remodeling but lower volumetric stability, and bioglass showed high bioactivity in isolated reports. Despite heterogeneity in particle size, fibrin formulations, defect models, and follow-up periods, most studies reported enhanced bone deposition, vascularization, and integration when particulate biomaterials were combined with fibrin-based matrices. Overall, the evidence suggests that these combinations promote more organized and biologically favorable bone healing under experimental conditions. Future translational and clinical research is required to standardize protocols and determine the therapeutic applicability of these strategies in human bone repair. Full article

Diabetic wounds remain chronically non-healing due to impaired angiogenesis, persistent inflammation, and defective extracellular matrix remodelling. In recent years, stem cell-derived exosomes have emerged as a potent cell-free regenerative strategy capable of recapitulating the therapeutic benefits of mesenchymal stem cells while avoiding risks associated with direct cell transplantation. This review critically evaluates the preclinical evidence supporting the use of exosomes derived from adipose tissue, bone marrow, umbilical cord, and induced pluripotent stem cells for diabetic wound repair. These exosomes deliver bioactive cargos such as microRNAs, proteins, lipids, and cytokines that modulate key signalling pathways, including Phosphatidylinositol 3-kinase/Protein kinase (PI3K/Akt), Nuclear factor kappa B (NF-κB), Mitogen-activated protein kinase (MAPK), Transforming growth factor-beta (TGF-β/Smad), and Hypoxia inducible factor-1α/Vascular endothelial growth factor (HIF-1α/VEGF), thereby promoting angiogenesis, accelerating fibroblast and keratinocyte proliferation, facilitating re-epithelialization, and restoring immune balance through M2 macrophage polarization. A central focus of this review is the recent advances in exosome-based delivery systems, including hydrogels, microneedles, 3D scaffolds, and decellularized extracellular matrix composites, which significantly enhance exosome stability, retention, and targeted release at wound sites. Comparative insights between stem cell therapy and exosome therapy highlight the superior safety, scalability, and regulatory advantages of exosome-based approaches. We also summarize progress in exosome engineering, manufacturing, quality control, and ongoing clinical investigations, along with challenges related to standardization, dosage, and translational readiness. Collectively, this review provides a comprehensive mechanistic and translational framework that positions stem cell-derived exosomes as a next-generation, cell-free regenerative strategy with the potential to overcome current therapeutic limitations and redefine clinical management of diabetic wound healing. Full article

Corilagin is a hydrolyzable ellagitannin and naturally occurring polyphenolic compound widely distributed in medicinal plants. It is also present in longan (Dimocarpus longan), known as lumyai in Thailand, a subtropical fruit extensively cultivated across China and Southeast Asia. Corilagin has been reported to exhibit strong antioxidant, anti-inflammatory, hepatoprotective, and anticancer activities through modulation of multiple cellular signaling pathways. However, despite these well-established pharmacological properties, its potential role in regulating bone marrow mesenchymal stem cell (BM-MSC) differentiation has not been fully explored in biomedical applications. In this study, we investigated the effects of corilagin on BM-MSC viability, protein-binding interactions, and lineage-specific differentiation toward osteogenic and chondrogenic pathways. Cytotoxicity assessment using human synovial SW-982 cells demonstrated that corilagin maintained cell viability at concentrations ranging from 1.56 to 50 µg/mL within 48 h, whereas prolonged exposure resulted in a time-dependent reduction in viability. In BM-MSCs, corilagin significantly enhanced osteogenic and chondrogenic differentiation in a dose-dependent manner, as evidenced by increased mineral deposition and cartilage matrix formation, as revealed by Alizarin Red S, Toluidine Blue, and Alcian Blue staining. Quantitative analyses further showed the upregulation of key lineage-specific genes, including Runx2 and osteopontin (OPN) for osteogenesis and Sox9 and aggrecan for chondrogenesis. Protein-binding assays confirmed the molecular interaction capacity of corilagin, supporting its biological activity. Overall, these findings demonstrate that corilagin promotes MSC-mediated osteogenic and chondrogenic differentiation while maintaining acceptable cytocompatibility, highlighting its potential as a natural small-molecule candidate for bone and cartilage tissue engineering and other biomedical fields with regenerative medicine applications. Full article

The design of biomaterial scaffolds for bone tissue engineering requires a balance between bioactivity, porosity, mechanical stability, and osteoinductivity. Kappa- (KC) and iota-carrageenan (IC) have been explored for scaffold fabrication due to their biocompatibility and structural similarity to glycosaminoglycans. However, there are limited reports on how their distinct sulfation degree affects the osteogenic differentiation of cells cultured on them. While laponite has been reported as an osteoinductive nanoclay, its combined effect with different carrageenan types and its concentration-dependent effect on scaffold functionality remain unexplored. Therefore, we developed composite scaffolds comprising poly(vinyl alcohol) (PVA) and gelatin (GEL), reinforced with kappa- or iota-carrageenan (KC, IC) and functionalized with two different concentrations of laponite (LAP), 0.5 and 1% w/v, to monitor composition-structure-function relationships. The scaffolds were fabricated via lyophilization and dual crosslinking, and characterized for their physicochemical, structural, mechanical, and biological properties. The incorporation of both carrageenans into scaffolds, maintained high swelling ratios of 600% after 24 h, and increased porosity without altering their apparent density (0.09–0.11 g/cm³), whereas LAP preserved interconnectivity, densified pore walls, raised their compressive modulus at >220 kPa, and improved stability (>60% mass retained after 40 days). In vitro validation using MC3T3-E1 pre-osteoblastic cells demonstrated robust cytocompatibility, with the LAP-containing scaffolds significantly promoting cell adhesion, proliferation, and osteogenic differentiation, evidenced by elevated alkaline phosphatase activity, calcium production and collagen secretion. Direct comparison between KC and IC scaffolds confirmed that differences in sulfate substitution modulated scaffold stiffness, swelling, and degradation, while variation in LAP concentration affected the biological response, with the 0.5 wt% concentration favoring early cell proliferation, whereas the 1 wt% significantly promoted the osteogenic differentiation. This compositional strategy demonstrates how tuning the interplay between carrageenan and laponite can balance scaffold hydration, mechanical and biological properties, thereby guiding the design of scaffolds for bone repair. Full article

Biocompatible poly(lactic acid) (PLA) was plasticized with poly(ethylene glycol) (PEG) added at concentrations of 10, 15, and 20 wt.% relative to PLA, and then processed into gyroid triply periodic minimal surface (TPMS) scaffolds using fused filament fabrication (FFF) 3D printing. The influence of PEG concentration and gyroid structure (50% infill density) on thermal transitions, crystallinity, and low–temperature shape-memory performance was systematically investigated. The shape-memory effect (SME) of the PLA–based scaffolds was tailored through compositional control and structural design. Shape recovery under thermal activation at 40 °C and 50 °C was examined to reveal the correlation between composition and structure in governing low–temperature shape-memory behavior. The optimal composition (PLA/10 PEG, 50% gyroid infill) achieved shape recovery with a recovery ratio (R_r) of 97 ± 1% at 40 °C within 6 ± 1 min, demonstrating optimal shape-memory activation close to physiological temperature. Structural and morphological changes were characterized using ATR–FTIR, Raman spectroscopy, DSC, XRD, and SEM, providing comprehensive insight into the plasticization of the PLA matrix and its impact on structure–property relationships relevant to bone tissue engineering. Full article

Medication-related osteonecrosis of the jaw (MRONJ) is a devastating complication arising primarily after invasive dentoalveolar procedures in patients treated with antiresorptive, antiangiogenic, or targeted therapies. Although recognized risk factors are established, the distinctive vulnerability of jawbones compared to long bones is not fully understood. This review comprehensively synthesizes recent advances regarding the embryological, anatomical, and physiological disparities that contribute to region-specific susceptibility to MRONJ. Recent evidence suggests that jawbones diverge significantly from long bones in embryonic origin, ossification pathways, vascular architecture, innervation patterns, and regenerative capacities. These differences affect bone metabolism, healing dynamics, response to pharmacologic agents, and local cellular activities, such as enhanced bisphosphonate uptake and specialized microcirculation. Experimental and clinical evidence reveals that mandibular periosteal cells exhibit superior osteogenic and angiogenic potentials, and the jaws respond differently to metabolic challenges, trauma, and medication-induced insults. Furthermore, site-specific pharmacologic and inflammatory interactions, including altered periosteal microcirculation and leukocyte–endothelial interactions, may explain the development of MRONJ, although rare cases of medication-related osteonecrosis have also been reported in long bones. Emerging research demonstrates that immune dysregulation, particularly M1 macrophage polarization with overexpression of matrix metalloproteinase-13 (MMP-13), plays a crucial role in early MRONJ development. Understanding these mechanisms highlights the critical need for region-specific preventive measures and therapeutic strategies targeting the unique biology of jawbones. This comparative perspective offers new translational insights for designing targeted interventions, developing tissue engineering solutions, and improving patient outcomes. Future research should focus on gene expression profiling and cellular responses across skeletal regions to further delineate MRONJ pathogenesis and advance personalized therapies for affected patients. Full article

The development of effective bone substitutes remains a central goal in regenerative medicine. In this study, lithium-modified bioglass-ceramics based on the 47.5S5 silicate oxide system were synthesized using the sol–gel method, followed by calcination and axial pressing to form cylindrical samples. These materials were sintered at 700 and 800 °C and subsequently examined to evaluate their structural, mechanical, and biological performance. Structural and microstructural analyses confirmed the presence of crystalline phases such as combeite (Na₆Ca₃Si₆O₁₈), NaLiSiO₄, Li₂SiO₃, and calcium silicates, indicating the successful incorporation of lithium within the glass-ceramic network. The bioceramics exhibited improved densification, deformability, and compressive strength with increasing sintering temperature. In vitro degradation in simulated body fluid revealed a consistent increase in mass loss with higher lithium content, suggesting enhanced resorbability linked to lithium oxide. Antibacterial testing indicated moderate antimicrobial activity, with slightly better results observed at higher sintering temperatures. Cell viability assays further supported the materials cytocompatibility. Taken together, these findings suggest that lithium substitution contributes positively to both mechanical robustness and biological behaviour, positioning these ceramics as promising bioresorbable bone substitutes with controlled degradation, suitable for bone tissue engineering where durability, bioactivity, and antimicrobial function are required. Full article

Traditional hydroxyapatite materials are inherently stiff and brittle, limiting their applications. Flexible ultralong hydroxyapatite nanowires, characterized by nano-scale diameters and micrometer-scale lengths, offer a promising alternative as one-dimensional flexible building blocks for constructing high-performance biomimetic materials. Nature has evolved a variety of high-performance materials with hierarchically ordered structures assembled from nano-scale building blocks, which provide valuable insights into the design and ordered assembly of flexible nanofibers for building high-performance biomimetic materials. Currently, how to distill the structural design principles of natural materials to engineer flexible nanofibers into advanced high-performance biomimetic materials with excellent properties and multifunctions remains a frontier scientific challenge. In 2014, the authors’ research group reported for the first time the calcium oleate precursor solvothermal method for the synthesis of flexible ultralong hydroxyapatite nanowires and their applications. Since then, many soft functional materials and high-performance biomimetic materials have been designed and prepared using flexible ultralong hydroxyapatite nanowires, and their applications in various fields have been explored. These studies demonstrate the successful assembly of flexible ultralong hydroxyapatite nanowires into hierarchical biomimetic structures inspired by natural materials such as enamel, nacre, and bone, which exhibit enhanced mechanical properties, including improved strength, toughness, and flexibility, alongside multifunctional capabilities like thermal insulation and biomedical compatibility. These findings suggest that flexible ultralong hydroxyapatite nanowires provide a versatile platform for designing and constructing advanced biomimetic materials with promising applications in various fields. This review article aims to briefly review recent advances in this exciting and rapidly evolving research field. The synthetic methods, assembly strategies, properties, and applications of flexible ultralong hydroxyapatite nanowires and their derivative biomimetic materials are discussed, enlightening their structural design principles and potential applications. Finally, we propose future research directions and future perspectives in this exciting frontier research field. Full article

This study aimed to develop a sustainable route for processing biogenic calcium carbonate from Perna perna mussel shell waste and converting it into hydroxyapatite (HA), as well as to evaluate its potential for bone and dental tissue engineering applications. Mussel shells were decarbonized (400 °C), milled, and converted to HA via wet chemical precipitation using a nominal Ca/P molar ratio of 1.67 during synthesis followed by thermal treatment (900 °C). Comprehensive characterization included SEM, FTIR, XRD, Raman spectroscopy, XRF, TGA, and BET analysis. Biological evaluation involved cytotoxicity assays (MTT), antimicrobial testing, and odontogenic differentiation studies (Alizarin Red) using SHEDs. Statistical analysis by one-way ANOVA and Tukey post hoc tests (α = 0.05). SEM revealed a microstructured morphology composed of agglomerates, favorable for biomedical applications. FTIR and XRD confirmed the conversion of CaCO₃ to hydroxyapatite, while thermal analysis demonstrated the material’s stability. The HA exhibited secondary minor phase (13%) β-TCP form of calcium phosphate (Ca_2.997H_0.006(PO₄)₂), high crystallinity (about 80%), and nanoscale crystallite size (85 nm, 2.5–5.0 m²/g), despite forming larger agglomerates in suspension. The material showed favorable physicochemical properties (neutral pH, −18.5 mV zeta potential), but no inhibition was detected in antimicrobial testing. In vitro assays showed excellent cytocompatibility (viability > 70% at 12.5 µg/mL) and significant osteogenic potential (high mineralization vs. controls, p < 0.05). Mussel shell-derived HA presents a sustainable, clinically relevant biomaterial with ideal properties for bone regeneration. The study establishes a complete waste-to-biomaterial pipeline while addressing key requirements for dental and orthopedic applications. Full article

Repairing bone defects with implants is an important topic in the field of regenerative medicine, but bacterial infection presents a significant barrier in clinical practice. Therefore, bone implants with antibacterial functionality are currently in high demand. Fresh seaweed-derived exosomes (EXOs) exhibited promising antibacterial activity against bacteria, indicating their potential as natural antimicrobial agents. Moreover, equipping the exosomal lipid bilayer with bacteria-targeting aptamers (Apt), termed EXOs-Apt, enabled precise bacterial killing, thereby promoting more effective antibacterial functions. In our design, porous polyetheretherketone (PEEK) scaffolds were 3D-printed using the melt deposition manufacturing process. Subsequently, the scaffold surfaces were modified via dopamine self-polymerization, resulting in the formation of a polydopamine (PDA) coating. Then, EXOs-Apt was applied to functionalize PEEK scaffolds with antibacterial activity. Given that EXOs display bactericidal effects while Apt facilitates bacterial capture, we engineered a surface coating platform that incorporates both components to produce a multifunctional scaffold with synergistic antibacterial activity. The results showed that modifying EXOs-Apt on PEEK scaffolds significantly improved their antibacterial performance against Escherichia coli and Staphylococcus aureus. To our knowledge, this is the first study to use EXOs-Apt as antibacterial coatings modified on PEEK scaffolds. This study provides new strategies and ideas for the development of antibacterial PEEK orthopedic implants with promising clinical value for infection-resistant repair of bone defects. Full article

Background/Objectives: Mesenchymal stem cells (MSCs) are recognized for their therapeutic potential due to their ability to secrete bioactive molecules. Among these secreted factors, bone morphogenetic protein-2 (BMP-2) is known as a secreted factor that plays a crucial role in bone healing and regeneration. However, MSCs naturally secrete only small amounts of BMP-2. To improve the bone healing capacity of MSCs, it is essential to enhance the secretion of BMP-2 in MSCs. One approach that can be used to achieve this goal is by genetically engineering MSCs. Incorporating signal peptides (SPs) into the inserted gene sequence can significantly improve protein secretion efficiency. In this proof-of-concept study, we explored the role of SPs in optimizing BMP-2 secretion in umbilical cord-derived MSCs; Methods: Three human-derived SPs, namely glial-derived neurotrophic factor (GDNF), chemotactic antibacterial glycoprotein 7 (CAP7), and platelet-derived growth factor subunit B (PDGFB), were selected. Transfection of MSCs was performed using polyethylenimine, Lipofectamine 2000^®, and Lipofectamine 3000^®. Transfection efficiency confirmed based on Green Fluorescence Protein expression. BMP-2 secretion levels were quantified using an ELISA assay; Results: Lipofectamine 3000^® achieved the highest transfection efficiency, reaching approximately 10%. BMP-2 secretion levels varied significantly depending on the SPs used, with PDGFB yielding the highest BMP-2 concentration (279.21 ± 6.91 pg/mL), followed by GDNF (265.65 ± 11.49 pg/mL) and CAP7 (233.72 ± 32.33 pg/mL); Conclusions: These findings demonstrate that SP selection critically influences BMP-2 secretion efficiency in genetically engineered MSCs and underscore its potential to enhance the therapeutic applicability of MSC-based strategies for bone healing. Full article

Background and Objectives: Reduced bone quality due to osteoporosis significantly complicates oral rehabilitation and bone regeneration therapies. While Vitamin D (Vit. D3) is crucial for osteogenesis, systemic administration often lacks local efficacy. This study aimed to evaluate the osteoregenerative potential of a novel Chitosan-based nanostructured scaffold (NS) loaded with Vit. D3, underlining its efficacy in vitro and in an ovariectomized (OVX) rat model of osteoporosis. Materials and Methods: Chitosan NSs were fabricated with varying Vit. D3 concentrations. In vitro assessments included cytotoxicity (MTT assay), cell viability (Alamar Blue), and mineralization (Alizarin Red) using human dental follicle stem cells. In vivo, 30 Wistar rats were ovariectomized to induce osteoporosis (confirmed by biomarkers Osteocalcin and β-CTX) and were divided into three groups (n = 10). Bilateral maxillary bone defects were treated with (1) a Control (clot only), (2) a Hemostatic Sponge with Vit. D3 (HS/Vit. D3), or (3) an NS loaded with Vit. D3 (NS/Vit. D3-6.25 ng/mL). Histological and morphometric analyses were performed at 4 and 8 weeks. Results: In vitro, the NS loaded with 6.25 ng/mL Vit. D3 demonstrated superior cytocompatibility, achieving a cell viability of 117.77% at 72 h and significantly enhanced calcium nodule deposition compared to controls. In vivo, a total of 44 defect sites were analyzed following the exclusion of compromised samples (Control: 16 sites; HS/Vit. D3: 16 sites; NS/Vit. D3: 12 sites). The NS/Vit. D3-6.25 ng/mL group exhibited the highest degree of mature bone formation and vascularization (p < 0.05) compared to the Control and HS/Vit. D3 groups. While cellular activity (osteoblasts/osteocytes) was initially higher in the HS/Vit. D3 group, the NS/Vit. D3-6.25 ng/mL group achieved superior structural integration and scaffold replacement by mature bone tissue over time. Conclusions: The novel Vit. D3-loaded Chitosan NS effectively promotes bone regeneration in osteoporotic conditions. It supports osteogenic differentiation in vitro and enhances bone matrix maturation in vivo, suggesting its potential as a bioactive scaffold for regenerative dentistry. Full article