Search Results (2,371)

Critical-sized bone defects lack spontaneous healing capacity. While mesenchymal stem cell-derived exosomes (sEVs) are promising osteoinductive agents, their rapid in vivo clearance limits their free-form efficacy. Here, we fabricated a nano-hydroxyapatite/chitosan (nHA/CTS) composite scaffold as a protective, sustained-delivery platform for human umbilical cord blood-derived mesenchymal stem cell exosomes (HUCB-MSCs-exos) to accelerate bone repair. The 3D porous CTS/10% nHA scaffold exhibited excellent cytocompatibility and a degradation rate commensurate with new bone ingrowth. Critically, it enabled a biphasic exosome release profile—an initial burst followed by a 14-day sustained release (89.73% cumulative release). In vitro, HUCB-MSCs-exos significantly promoted the proliferation, migration, and osteogenic differentiation of bone marrow-derived MSCs, as demonstrated by enhanced alkaline phosphatase activity and matrix mineralization. In a rabbit condylar defect model (5 mm diameter), the CTS/10% nHA-exo scaffold achieved a 57.44 ± 8.42% healing rate at two months, nearly two-fold greater than the scaffold-only group (29.33 ± 6.94%). Histological and immunohistochemical analyses at two months confirmed the formation of mature, well-vascularized trabecular bone, accompanied by robust expression of late-stage osteogenic markers (OCN and OPN). These findings demonstrate that the CTS/10% nHA scaffold synergistically integrates osteoconductive structural guidance with exosome-mediated osteoinductive paracrine signaling, providing a compelling and translatable strategy for critical-sized bone-defect management. Full article

Bone defects from trauma, tumour resection, infection, and degenerative disease remain a major clinical burden, and autografts face limitations of supply and donor-site morbidity. Three-dimensional (3D) printing offers a route to patient-specific, architecturally defined bone scaffolds, while biopolymers from natural sources provide biodegradability, biocompatibility, and extracellular matrix-mimicking cues consistent with sustainable, green biomaterials science. This review synthesises recent progress in 3D printing of biopolymer-based scaffolds for bone tissue engineering. We first examine the principal feedstocks—alginate, gelatin and gelatin methacryloyl, collagen, chitosan, silk fibroin, cellulose, and microbial polyesters—and their preparation, crosslinking chemistry, and printability. We then compare extrusion, light-based, and indirect printing technologies and the process–property relationships governing resolution, mechanical competence, and cell viability. Composite and functionalisation strategies, including biopolymer–bioceramic hybrids and controlled delivery of growth factors and antimicrobial agents, are analysed as routes to osteoinduction, vascularisation, and infection control. Finally, we evaluate translational performance in preclinical models and outline central challenges of vascularisation, mechanical–degradation matching, scalability, and regulatory standardisation. Biopolymer 3D printing is positioned as a ve rsatile, sustainable platform whose clinical maturation depends on integrated material, structural, and biological design. Full article

This study evaluates the intrinsic osteogenic potential of β-tricalcium phosphate (β-TCP)-containing composite scaffolds (PLCL–TCP, PLGA–TCP, and ZnO–TCP) on chorion-derived mesenchymal stem cells (CMSCs) under non-osteogenic in vitro conditions. CMSCs were cultured on the three biomaterials for 35 days without osteogenic supplements to isolate the material-driven cellular response. Cell viability was assessed via MTT assay, while osteogenesis-associated markers (alkaline phosphatase, type I collagen, and osteocalcin) were quantified using ELISA. Scaffold surface morphology and elemental composition were characterized before and after cultivation utilizing SEM and EDX. All investigated scaffolds supported long-term CMSC viability and induced measurable osteogenic responses. PLCL–TCP demonstrated a consistently strong biological response, characterized by sustained metabolic activity, elevated ALP and COL I production, and increased osteocalcin levels at later stages of cultivation. ZnO–TCP also exhibited favorable osteogenesis-associated responses, particularly with respect to late-stage osteocalcin production, while maintaining high structural stability. In conclusion, β-TCP composites can intrinsically modulate CMSC behavior without biochemical supplements. Osteogenic outcomes depend on a complex interplay of surface chemistry, scaffold architecture, and degradation profiles, with PLCL–TCP demonstrating favorable overall performance among the investigated biomaterials. Full article

Musculoskeletal disorders involving bone, cartilage, tendon, and joint tissues represent a leading cause of disability worldwide, and conventional surgical and graft-based interventions are limited by donor site morbidity, incomplete integration, and finite durability. Despite substantial preclinical progress, translation into reliable clinical benefit has remained inconsistent. This narrative review synthesizes recent advances in bioengineered approaches to bone and joint repair, emphasizing how materials design and regenerative strategy selection influence translational feasibility. Advances in scaffold-based systems highlight the role of material composition, architectural organization, and structure–function matching in supporting musculoskeletal regeneration. Regenerative platforms including stem cell therapies, extracellular matrix-derived constructs, and smart materials are evaluated for biological performance, manufacturability, and regulatory feasibility. Early translational and clinical studies demonstrate encouraging outcomes across selected musculoskeletal indications; however, variability in efficacy and adoption highlights persistent barriers to broader implementation. Key challenges include scalable manufacturing, cost and reimbursement uncertainty, and heterogeneity in clinical infrastructure, factors that may also influence access to advanced regenerative therapies. Future innovations should emphasize manufacturability and real-world evidence generation that align with practical clinical pathways. Full article

Polyhydroxyalkanoates (PHAs) are bio-based, biodegradable polyesters increasingly explored as sustainable biomaterials for regenerative medicine. This review summarizes recent advances in PHA-based bone substitute materials, highlighting their properties, fabrication methods, and biological performance. PHAs combine biocompatibility, tunable mechanical behavior, and degradation into non-toxic metabolites, while copolymerization and monomer selection modulate the stiffness, crystallinity, and resorption rate. Processing techniques such as solvent casting, electrospinning, and additive manufacturing allow the production of porous architectures that mimic bone extracellular matrix. Electrospinning is particularly suitable for nanoscale fibrous matrices, whereas 3D printing enables patient-specific scaffolds with controlled geometry and interconnected porosity. Scaffold performance can be further improved through the incorporation of osteoconductive fillers, including hydroxyapatite, β-tricalcium phosphate, bioactive glasses, graphene oxide, and carbon nanotubes, as well as through drug-delivery and pro-angiogenic functionalization. In vitro and in vivo studies consistently report favorable cytocompatibility, enhanced osteogenic differentiation, vascularization, and effective repair of bone defects in animal models. However, clinical translation remains limited by production costs, variability in polymer quality, thermal processing constraints, and regulatory challenges. Future progress will rely on more efficient biosynthesis, medical-grade purification, multifunctional scaffold design, and stronger collaboration between academia, industry, and clinicians to unlock the full potential of PHAs in regenerative bone therapies. Full article

Recent advances in three-dimensional (3D)-bioprinted hydrogels show promise for overcoming the limitations of conventional techniques for dental tissue regeneration. This scoping review systematically analyses the physical, mechanical, and rheological properties of these hydrogels in dental applications, aiming to identify knowledge gaps, limitations, and current and future directions for advancing and translating hydrogel-based 3D bioprinting in dentistry. In accordance with PRISMA-ScR guidelines, a comprehensive literature search was conducted across Ovid, PubMed, EBSCOhost, and Web of Science up to January 2026. Included studies focused on (i) 3D-bioprinted hydrogels, (ii) quantitative characterisation, and (iii) dental tissue engineering. A total of twenty-one studies met the inclusion criteria. The findings revealed substantial variability in formulations and properties. Gelatine-based hydrogels reinforced with β-tricalcium phosphate demonstrated the highest compressive strength within the range of cancellous bone, whereas GelMA/PEGDA composites exhibited tunable stiffness suitable for soft tissue applications. Extrusion-based bioprinting emerged as the predominant method, with photocrosslinking and ionic crosslinking as the primary gelation techniques. Biodegradation rates varied notably with composition and regenerative objectives. This review uniquely consolidates the physical, mechanical, and rheological evaluations of 3D-bioprinted hydrogels for dental applications. The review highlights critical gaps in methodological standardisation and validation, emphasising the importance of biomaterial selection to optimise scaffolds and regenerative outcomes in periodontal, bone, and pulp tissue engineering. Full article

Tissue engineering and regenerative medicine (TERM) rely on advanced biomaterials and scaffolds that require strict sterilization without sacrificing their structural and functional properties. Conventional sterilization methods, including steam, ethylene oxide, and gamma irradiation, often compromise scaffold integrity, alter surface chemistry and/or leave toxic residues. Ozone (O₃) has emerged as a promising alternative sterilant because of its strong oxidizing potential, broad-spectrum antimicrobial activity, and residue-free decomposition. Importantly, ozone sterilization can preserve—and in some cases enhance—scaffold bioactivity by maintaining cytocompatibility and favorable surface chemistries that support cell adhesion and differentiation. This review critically evaluates the role of ozone sterilization in the context of TERM applications, focusing on its physicochemical properties, disinfection kinetics, material compatibility and regulatory perspectives. Evidence from studies on polymethyl methacrylate (PMMA) scaffolds, bone implants, and hydrogel-based systems suggests that, under optimized conditions, ozone can achieve high sterilization efficacy without significant degradation of mechanical or chemical properties. However, challenges related to process validation, health and safety considerations, and scalability remain. The review highlights opportunities for integrating ozone into automated biomanufacturing workflows and identifies key research gaps to support the broader adoption of ozone sterilization in TERM applications. Full article

Bone loss in the maxillofacial region arises from multiple causes, including periodontal disease, trauma, surgical procedures, infection, congenital anomalies, and cancer. Traditional treatment relies on bone grafting, either alone or in combination with biomaterials. Advances in tissue engineering have introduced synthetic or natural scaffolds to mimic the mineralized bone matrix. Natural scaffolds offer excellent biocompatibility and similarity to native tissue but often lack sufficient mechanical strength and exhibit poor degradation rates. Synthetic scaffolds provide tunable porosity and mechanical stability; however, their biological inertness makes them poor sources of osteogenic signaling. A key factor in the success of any scaffold is its interaction with the host immune system. Upon implantation, the innate immune response is initiated, with neutrophils and macrophages being the first cells to contact the scaffold. Macrophage polarization toward proinflammatory (M1) or anti-inflammatory (M2) phenotypes determines whether the microenvironment favors inflammation or remodeling. The adaptive immune response also plays a critical role: T and B lymphocytes may promote tolerance and integration through Th2/Treg pathways and antibody-mediated regulation, or they may trigger chronic inflammation and rejection through Th1/Th17 activation. This review examines the natural and synthetic materials used for bone remodeling and their biological properties. It then outlines the sequence of immune events occurring from the moment a scaffold is implanted to its potential integration or failure. Finally, this study highlights the relevance of cellular models and in vitro assays for the early evaluation of immunogenicity and biocompatibility, which are essential for optimizing scaffold design and improving outcomes in maxillofacial bone regeneration. Full article

Three-dimensional scaffolds based on triply periodic minimal surfaces (TPMSs) have attracted growing interest in bone tissue engineering because of their high interconnectivity and ability to combine high porosity with mechanical integrity. However, in fused deposition modeling (FDM), printed architecture may systematically deviate from the nominal design, thereby affecting structural fidelity and mechanical performance. This study investigated the influence of FDM processing parameters and nozzle diameter on the effective microarchitecture and compressive elastic modulus of polycaprolactone (PCL) gyroid scaffolds. First, a Taguchi L18 design was used to evaluate the effects of extrusion temperature, printing speed, and flow rate on pore size for two nozzle diameters (0.4 and 0.3 mm). In a second experimental stage, prismatic specimens fabricated at three nominal porosity levels were compression-tested to determine the elastic modulus (E), and measured porosity (ϕ) was quantified by densimetric measurements. A systematic mismatch was observed between the nominal design and the printed scaffold architecture, with both pore size and measured porosity consistently lower than their intended values. The dominant process parameter associated with pore-size variability was nozzle-specific: extrusion temperature contributed most for the 0.4 mm nozzle, whereas printing speed contributed most for the 0.3 mm nozzle. In compression, E decreased with increasing measured porosity, and statistical analysis showed that the E–ϕ relationship was nozzle-dependent. Overall, these findings support a process–structure–property interpretation based on the effective printed microarchitecture rather than on nominal design parameters alone. The experimental stiffness ranges obtained here also provide an exploratory mechanical contextualization relative to reported trabecular bone domains, without implying site-specific scaffold selection. Full article

Background/Objectives: Stroke remains the second leading cause of death worldwide, and cell therapy is among the most actively investigated strategies for its treatment. Recent transcriptomic evidence has revealed that 293T cells—the most widely used transient transfection model—possess a neural crest/neuronal lineage, making them a candidate for acute neural tissue engineering. Methods: We implanted iron oxide nanoparticle-labeled 293T cells (293T-ION) into an ischemic rat brain and monitored them longitudinally by 7T MRI, using ION-labeled bone marrow-derived mesenchymal stem cells (rMSC-ION) as a direct comparison. Functional recovery was assessed via mNSS and corner test scores, and infarct size was quantified by MRI. Results: 293T-ION cells showed no migration throughout the 40-day observation period, and functional recovery plateaued early compared with the progressive improvement seen with rMSC-ION. 293T cell implantation provoked pronounced, localized CD68-positive microglial hyperactivation at both implantation and ischemic sites, without migration toward the choroid plexus (CP). In contrast, rMSC-ION actively migrated to the CP and drove superior neuroplasticity marker expression (Ki67, Nestin, NeuN). Conclusions: 293T cells produce transient localized microglial activation and limited brain plasticity, whereas rMSCs drive sustained neurorestoration. Synergistic co-administration of these cell types may represent a future therapeutic strategy bridging hyper-acute and chronic recovery phases. Full article

Vascular–osteogenic coupling plays a central regulatory role in bone regeneration, but it is frequently impaired under pathological conditions, including aging, ischemia, and chronic inflammation, which compromises efficient bone repair. Gelatin methacryloyl (GelMA) hydrogels, which combine extracellular matrix-like bioactivity, adjustable mechanical properties, and compatibility with three-dimensional biomanufacturing, have become a widely used material platform for vascularized bone regeneration. From the perspective of vascular–osteogenic coupling, this review reframes and synthesizes GelMA-based approaches for vascularized bone regeneration, grouping existing strategies into three categories: (i) intrinsic material design, in which pore architecture, microchannels, dynamic networks, and interfacial functionalization are used to guide vascular ingrowth; (ii) exogenous bioactive delivery, involving growth factors, extracellular vesicles, cells, and inorganic ions to enhance vascularization; and (iii) smart responsive strategies, including ROS/pH-responsive systems, sequential release, and external stimulation, which aim to recapitulate the evolving microenvironment during bone repair. This review further compares these strategies in terms of evidence level, reproducibility, and translational potential. Exogenous delivery systems currently have the strongest preclinical support, but issues related to dose standardization, burst release, and long-term safety remain unresolved. Intrinsic material programming is less extensively studied, yet may be more compatible with manufacturing consistency, sterilization, and engineering translation. Most stimuli-responsive systems, by contrast, remain largely at the small-animal or proof-of-concept stage. Future GelMA-based systems should therefore shift from increasing functional complexity toward improving predictability, reproducibility, and clinical feasibility. Compositionally defined and structurally controllable GelMA composites that integrate vascular regulation with mechanical support may provide a more realistic path for vascularized bone regeneration. Full article

The long-term stability of dental implants is limited by multiple factors, including peri-implant infection, impaired osseointegration, and poor soft tissue sealing. Compared with conventional passive surface modification strategies, piezoelectric materials can convert mechanical energy into local electrical signals under occlusal loading, cell traction, or ultrasonic stimulation. With the aid of defect engineering, heterostructure construction, and co-catalytic design, these materials can also induce the generation of reactive oxygen species and reactive nitrogen species, thereby enabling on-demand antibacterial activity. This review systematically summarizes the bioelectric basis of bone tissue and clarifies how piezoelectricity and piezocatalysis may be used in dental implant surface engineering. Their applications are discussed in terms of antibiofilm and antibacterial activity, osteogenesis and osseointegration, osteoimmunomodulation, soft tissue healing, and temporally programmed therapy. In addition, this review also discusses issues that remain unresolved, such as polymer-based composite systems, realistic activation windows, evaluation standards, device–material integration, and multi-omics validation. Overall, piezoelectric surface engineering is evolving from a single osteogenesis-oriented strategy into an integrated platform that coordinates infection control, immune remodeling, and osseointegration. However, the actual effectiveness of its clinical application still needs to be determined through more rigorous mechanism analysis, long-term stability assessment, biosafety assessment, and standardized preclinical research. Full article

One-dimensional fibrous scaffolds with tunable bioactivity offer promise for bone tissue regeneration, yet optimal calcium phosphate phases for enhancing osteogenic performance remain underexplored. This study aimed to evaluate the impact of monetite-, brushite-, and cerium-doped phosphate deposition on electrospun nylon nanofibres functionalised via matrix-assisted pulsed laser evaporation (MAPLE). Five nylon fibre compositions were synthesised, coated with three calcium phosphate phases, and calcined at varying temperatures (500–800 °C) before laser deposition. Physicochemical properties were assessed using energy-dispersive X-ray spectroscopy (EDS), scanning electron microscopy (SEM), and fibre diameter measurements, averaging $62.1\pm 23.8$ nm. Biocompatibility assays following MC3T3 preosteoblast seeding and incubation evaluated biological performance. EDX confirmed homogeneous phase deposition; SEM showed phase- and temperature-dependent morphology, with monetite yielding uniform granular structures and cerium-doped phosphate at 800 °C forming dense aggregates. Brushite-coated fibres exhibited superior preosteoblast metabolic activity, reaching $178\pm 2\%$ after 48 h (p < 0.001), indicating phase-specific stimulation of bone cell growth. These phosphate-functionalised nylon fibres retain structural integrity, hierarchical porosity, and enhanced bioactivity, providing a versatile electrospinning-MAPLE platform for customisable bone grafts with clinical potential. Full article

Sports injuries, especially musculoskeletal and neurological types from strenuous exercise, are a global public health challenge. Characterized by a high incidence and slow recovery, these injuries differ from typical trauma, often resulting in severe mechanical transmission loss and an imbalanced immune microenvironment. Consequently, standard interventions struggle to achieve true tissue regeneration. Gelatin, a collagen-derived biomaterial, offers RGD-mediated cell adhesion, MMP-responsive degradation, and high modifiability. These qualities make it an excellent foundation for biomimetic repair scaffolds. This paper reviews the design principles and recent advances in gelatin-based multifunctional hydrogels in sports medicine. First, we analyse their structure and engineering advantages. Next, we summarise strategies and mechanisms for modules like conductivity, antibacterial activity, self-healing, stimulus responsiveness, and tissue adhesion. The review links these modules to types of injuries: bone or cartilage, tendon or ligament, skeletal muscle, spinal cord, and peripheral nerve. It clarifies their clinical and translational value in remodelling immune microenvironments, regulating electrophysiology, promoting interfacial regeneration, and restoring motor function. This review provides focused insights from materials science and sports rehabilitation to advance precision treatments for sports injuries. Full article

Segmental bone defects and age-related osteoarthritis (OA) are clinically challenging in terms of treatment. Although preclinical studies have demonstrated efficacy for bone defect healing and OA using ex vivo gene therapy or biomaterial sustained-release delivery, few such treatments have translated into clinical therapies due to safety concerns. Bone morphogenetic proteins belong to the transforming growth factor β (TGFβ) superfamily and are effective in bone and cartilage regeneration/repair. Among BMPs, BMP4 is not only effective in promoting bone and cartilage repair but also promotes stem cell renewal potential and exhibits anti-aging effects. Therefore, the aim of this study is to investigate whether human BMP4 mRNA encapsulated in lipid nanoparticles (hBMP4 mRNA/LNP) can promote bone and cartilage repair. In vitro data demonstrated that hBMP4 mRNA/LNP-treated human MSCs secreted BMP4 protein, as detected by ELISA, and enhanced osteogenic differentiation. In vivo results demonstrated that hBMP4 mRNA/LNP at a 50 µg dose promoted limited new bone formation only at 2 weeks after creation of defect in critical-sized calvarial bone defects in aged mice when delivered using fibrin sealant hydrogel, as revealed by micro-CT and histology. However, intra-articular injection (IA) of lower doses (2.5 and 5 µg) in aged mice knee joints prevented cartilage loss, as demonstrated by micro-CT; decreased OARSI histology scores; and improved cartilage-specific matrix COL2. hBMP4 mRNA/LNP at a 5 μg dose significantly increased SOX9⁺ cells per normalized cartilage area as well as the percentage of SOX9⁺ cells in the cartilage area. hBMP4 mRNA/LNP treatment showed a trend of pain alleviation and did not change serum hyaluronic acid levels. In conclusion, human BMP4 mRNA encapsulated in lipid nanoparticles improved cartilage repair and delayed cartilage degeneration in aged mice, while having a limited effect on bone healing, even at a higher dosage. These results suggest that hBMP4 mRNA encapsulated with lipid nanoparticles represents a promising treatment for age-related OA. Full article