Search Results (476)

Piezoelectric biomaterials have attracted considerable interest in osteochondral tissue engineering owing to their inherent ability to produce electrical signals in response to mechanical stimuli without external power, thereby closely mimicking the physiological electrical microenvironment required for tissue regeneration. This review comprehensively summarizes recent insights into biological piezoelectricity from the molecular to the macroscopic level, highlighting its interplay with streaming potentials and its regulatory roles in bone and cartilage regeneration. We critically analyze recent advances in major piezoelectric material systems, including ceramics, polymers, and composite scaffolds, with emphasis on their structural characteristics, bioactive performance, and suitability for tissue-specific repair. Among them, polymer-based composite and hybrid piezoelectric scaffolds appear particularly promising for the development of flexible, high-performance osteochondral repair platforms, as they offer a more favorable balance between mechanical compliance, electromechanical output, and biological adaptability. Despite encouraging preclinical findings, significant challenges remain, including biocompatibility, controlled degradation kinetics, and the precise modulation of electrical cues for specific biological contexts. To address these barriers, future research should focus on optimizing scaffold design, integrating responsive and multimodal stimulation strategies, and establishing standardized protocols for preclinical evaluation and clinical translation. Overall, piezoelectric biomaterials hold substantial potential for the development of innovative regenerative therapies for complex osteochondral defects. Full article

Temporomandibular joint osteoarthritis (TMJOA) is a degenerative disease characterized by progressive cartilage degeneration and subchondral bone remodeling, resulting in chronic pain and functional impairment. Although conservative treatments such as physical therapy and non-steroidal anti-inflammatory drugs (NSAIDs) are commonly used, their effectiveness is limited due to the poorly understood pathophysiology of TMJOA. Identifying reliable molecular biomarkers is essential to improving early diagnosis and guiding therapeutic development. This proof-of-concept study aims to identify candidate salivary biomarkers for TMJOA using an integrative approach combining clinical validation with in silico analysis. RNA sequencing was performed on saliva samples from TMJOA patients and healthy controls. In parallel, publicly available transcriptomic dataset GSE205389 was analyzed to identify differentially expressed genes (DEGs). DEGs were validated using qRT-PCR. Gene set enrichment analysis (GSEA) and Metascape were used to explore biological pathways associated with TMJOA. Integration of clinical and in silico RNA sequencing datasets identified 2758 and 3548 DEGs, respectively, with 743 overlapping genes. Pathway enrichment analyses highlighted immune-related, metabolic and osteoclast-related pathways. Four genes, CRIP1, PPA1 and TARS1 (statistically significant) and GCLC (non-significant trend), were validated by qRT-PCR in the clinical saliva samples, confirming elevated expression in TMJOA patients. Validation of the in silico dataset showed an upregulation of PTK2B, ABL1, TNF and IL-1B, supporting their relevance as salivary biomarkers in TMJOA. This exploratory study identifies four candidate salivary genes, CRIP1, PPA1, TARS1 and GCLC, as candidate salivary biomarkers for TMJOA, offering insights into disease mechanisms. Larger studies are needed to validate these findings and assess their clinical utility. Full article

Osteoarthritis (OA) is increasingly conceptualized as a whole-joint disorder, in which pathological processes across articular cartilage, subchondral bone, synovium, and periarticular tissues are tightly interconnected. Within this context, miRNAs have emerged as central post-transcriptional regulators capable of integrating mechanical, inflammatory, and metabolic cues at the network level. In human OA, extensive evidence links miRNA dysregulation to cartilage catabolism, impaired stress adaptation, inter-tissue communication, and the emergence of extracellular and circulating miRNA (cmiRNA) signatures with diagnostic and translational relevance. In contrast, miRNA research in canine OA remains limited, despite dogs developing a naturally occurring form of the disease that closely mirrors human OA in clinical presentation, joint pathology, and biomechanical drivers. To date, only a single pilot study has systematically investigated miRNA expression in spontaneous canine OA, underscoring both the feasibility of miRNA profiling and the substantial gaps that persist in tissue validation and functional characterization. This review critically synthesizes miRNA-mediated regulatory mechanisms in human OA and leverages this evidence to define research priorities in canine OA, where experimental validation remains limited. By focusing on shared molecular contexts rather than assumed equivalence, the review defines a comparative framework highlighting cmiRNAs as promising non-invasive translational targets. Full article

In regenerative medicine, three-dimensional (3D) printing provides precise spatial control over the fabrication of complex, biomimetic tissue constructs, enabling the production of architecturally defined and functionally tailored scaffolds. By enabling precise layer-by-layer deposition of cells, biomaterials, and bioactive compounds, 3D printing overcomes many limitations associated with conventional scaffold fabrication methods. This approach facilitates the development of tailored structures that mimic the mechanical, biological, and structural characteristics of native tissues, thereby enhancing cellular organization, proliferation, and differentiation. Extensive research in tissue engineering has led to the development of 3D-printed scaffolds for the regeneration of vascular, skin, bone, cartilage, and soft tissues. Advances in bioink formulations—including growth factor-loaded systems, decellularized extracellular matrix components, and natural and synthetic polymers—have further improved tissue-specific functionality. Moreover, multimaterial and multiscale printing strategies enable the fabrication of heterogeneous constructs with controlled porosity, mechanical gradients, and spatially regulated biological cues. Although vascularized tissue constructs remain a major challenge for clinical translation, recent bioprinting advancements have significantly accelerated progress in this area. Integration of computer-aided design with patient-specific imaging data has further strengthened the potential of 3D printing for personalized regenerative therapies. Despite these advances, challenges related to scalability, regulatory approval, and long-term functionality persist. Nevertheless, continued progress in printing technologies, biomaterials, and regulatory and standards frameworks is expected to drive the clinical adoption of 3D printing. Ultimately, 3D printing represents a transformative approach in tissue engineering, redefining strategies for functional tissue regeneration and translational regenerative medicine. Full article

Marine algae, microalgae, and Cyanophyceae emerge as sustainable and versatile sources of biomacromolecules for the fabrication of hydrogels with broad biomedical potential. Their phycocolloids, such as alginate, agar, carrageenan, ulvan, and extracellular polysaccharides (EPS), exhibit intrinsic biocompatibility, tunable gelation behavior, and bioactive sulfated structures that support cell viability, tissue regeneration, and therapeutic delivery. This review provides a comprehensive overview of hydrogel fabrication strategies, including physical, chemical, and hybrid crosslinking approaches, and highlights recent advances in composite systems incorporating proteins, glycosaminoglycans, and functional nanomaterials. Applications in skin repair, cartilage and bone regeneration, neural and cardiovascular engineering, and controlled drug delivery are examined, alongside the expanding role of marine-derived hydrogels as bioinks for 3D and 4D bioprinting. Despite their promise, challenges remain related to extract variability, purification complexity, mechanical limitations, and the need for standardized characterization. Future perspectives emphasize genetic engineering of algae and cyanobacteria, development of multifunctional hybrid hydrogels, sustainable large-scale production, and pathways toward clinical translation. Together, these insights position marine-derived hydrogels as next-generation biomaterials with significant potential for regenerative medicine and therapeutic innovation. Full article

Knee osteoarthritis (KOA) is a degenerative joint disorder characterized by chronic inflammation and progressive cartilage degradation. Mesenchymal stem cell (MSC)-based therapies have demonstrated therapeutic potential; however, increasing evidence suggests that their efficacy primarily arises from paracrine factors, highlighting the potential of cell free approaches. In this study, we developed an injectable, thermosensitive composite hydrogel incorporating adipose-derived MSC (AD-MSC) supernatant within a Pluronic F-127 (PF-127)/sodium hyaluronate (HA) matrix. The hydrogel exhibited a solution state at a low temperature and rapidly transitioned into a stable gel at a physiological temperature without chemical crosslinkers. Microstructural analysis revealed a porous, interconnected three-dimensional network favorable for the sustained release of bioactive factors. In a rat model of KOA, intra-articular administration of the AD-MSC supernatant-loaded hydrogel significantly improved joint architecture and locomotor performance, alleviated synovial inflammation, and preserved cartilage integrity. Radiographic and histological assessments demonstrated reduced cartilage degeneration and subchondral bone alterations. Moreover, the treatment markedly decreased intra-articular levels of proinflammatory cytokines (IL-1β and TNF-α) and the cartilage degradation marker CTX-II in a time-dependent manner. These findings indicated that the sustained local delivery of AD-MSC-derived supernatant effectively modulated joint inflammation and attenuated cartilage degeneration, with the hydrogel serving primarily as a delivery vehicle for these bioactive factors. This cell-free injectable biomaterial platform could offer a promising therapeutic strategy for the treatment of knee osteoarthritis. Full article

Three-dimensional (3D) bioprinting has rapidly emerged as a transformative technology at the interface of biomedical engineering and regenerative medicine. By enabling the spatially controlled deposition of living cells, biomaterials, and bioactive molecules, it offers an unprecedented potential to fabricate functional tissues and potentially whole organs in the future. This review explores recent advances in bioprinting materials, processes, and applications, emphasizing the integration of bioinks, printing methods, and mechanical design principles that underpin tissue functionality. Natural and synthetic biomaterials such as hydrogels (e.g., collagen, alginate), polyethylene glycol (PEG), and polyesters like PLGA are evaluated in terms of biocompatibility, printability, and degradation behavior. Key bioprinting modalities, including extrusion, inkjet, and laser-assisted bioprinting, are compared based on printing resolution, cell viability, and scalability. Structural considerations such as scaffold architecture, mechanical stability, and biomimetic design are discussed in relation to native tissue mechanics and requirements. The review also surveys emerging applications in tissue engineering (e.g., bone, cartilage, skin replacements), organ-on-a-chip systems for drug testing, and patient-specific implants, while addressing persistent challenges such as standardization of biofabrication, regulatory and ethical considerations, and manufacturing scale-up. Finally, future trends, including the integration of artificial intelligence (AI) and robotic automation, multi-material and four-dimensional (4D) bioprinting, and the maturation of personalized bioprinting strategies, are highlighted as pathways toward more autonomous and clinically relevant bioprinting systems. Collectively, these developments signify a paradigm shift in how biological constructs are designed and manufactured, bridging the gap between laboratory research and clinical translation. Full article

Decellularization removes immunogenic intracellular components of fish tissues while keeping the extracellular matrix (dECM) structure, mechanical integrity, and bioactivity. Fish-derived dECM retains native bioactive components, exhibiting high biocompatibility, low immunogenicity, and biodegradability, while supporting cell adhesion, proliferation, and tissue regeneration. Due to its abundance, minimal ethical concerns, and low zoonotic risks, fish wastes are emerging as sustainable sources of dECM, offering an eco-friendly alternative to mammalian biomaterials. This review highlights advances in decellularizing fish wastes such as skin, scales, bones, viscera, and swim bladders from species including tilapia, tuna, milkfish, carp, goldfish, and sturgeon. Physical, chemical, biological, and hybrid decellularization methods are assessed for cell removal, ECM preservation, and mechanical performance. Recent advances in polymer-dECM composites, crosslinking, and 3D bioprinting have significantly improved scaffold performance, making fish-derived dECM applicable for healing of wounds, regeneration of bone and cartilage, and repair of soft tissues. Despite its potential, challenges remain in optimizing perfusion rates, temperature variations, and tissue-specific protocols, as well as developing eco-friendly decellularization techniques using biodegradable reagents. Future perspectives include expanding decellularized fish tissue sources, innovating bio-inks for 3D bioprinting, and refining tissue-specific processing methods to maximize the potential of fish-derived dECM in regenerative medicine and tissue engineering. Full article

Bone resorption and formation are known to change in response to mechanical stress. The mechano-transduction mechanism by which bone tissue senses the stress, altering cellular activity in response via intracellular signaling pathways, ultimately leading to physiological and pathological changes, is beginning to be elucidated. Furthermore, excessive mechanical stress on bone and joints due to aging, obesity, overload, and overuse is thought to cause decreased chondrocyte activity, degeneration and destruction of the cartilage collagen matrix, degeneration of the subchondral bone, and joint dysfunction, contributing to the progression of osteoarthritis (OA). However, much remains unknown about how osteoblasts, responsible for bone formation, and chondrocytes, responsible for cartilage homeostasis, sense and respond to mechanical stress. Furthermore, whether there are mechanisms to protect against pathological and excessive mechanical stress in bone and cartilage tissue, their associated molecular mechanisms, and the relationship between mechanical stress responses and osteochondral degeneration, remain unknown. Understanding these mechanisms is considered essential for the development of new therapeutic strategies for osteochondral diseases. Our research aims to deepen our understanding of the etiology and pathophysiology of bone and cartilage diseases (osteoporosis, fragility fracture, and OA) and to develop new treatments from the perspective of mechanical stress response. In this paper we review the latest findings regarding the roles of cellular energy regulators (glucose transporters and energy sensors) and mechanical stress response factors, and the relationship between these factor-mediated changes in energy metabolism and osteochondral degeneration. This minireview discusses how energy metabolism regulators control the activity of both osteoblasts and chondrocytes in osteochondral tissue in response to mechanical stress. Full article

A biomimetic cartilage scaffold featuring a continuous hydroxyapatite (HA) concentration gradient and a spatially curved architecture was developed using a dual-channel mixing extrusion-based 3D printing approach. By dynamically regulating the feeding rates of two bioinks during printing, a continuous HA gradient decreasing from the bottom to the top of the scaffold was precisely achieved, mimicking the compositional transition from the calcified to the non-calcified cartilage region in native articular cartilage. The integration of gradient material deposition with synchronized multi-axis motion enabled accurate fabrication of curved geometries with high structural fidelity. The printed scaffolds exhibited stable swelling and degradation behavior and showed improved compressive performance compared with step-gradient counterparts. Rheological analysis confirmed that the bioinks possessed suitable shear-thinning and recovery properties, ensuring printability and shape stability during extrusion. In vitro evaluations demonstrated good cytocompatibility, supporting bone marrow mesenchymal stem cell (BMSC) adhesion and proliferation. Chondrogenic assessment based on scaffold extracts indicated that the incorporation of HA and its gradient distribution did not inhibit cartilage-related extracellular matrix synthesis, confirming the biosafety of the composite hydrogel system. Overall, this study presents a controllable and versatile fabrication strategy for constructing curved, compositionally graded cartilage scaffolds, providing a promising platform for the development of biomimetic cartilage tissue engineering constructs. Full article

Long bone formation in vertebrates proceeds via endochondral ossification, a sequential process that begins with mesenchymal condensation, advances through cartilage anlage formation, and culminates in its replacement by mineralized bone. Recent advances in inducible lineage tracing and single-cell genomics have revealed that, rather than being a uniform event, mesenchymal condensation rapidly segregates into progenitor pools with distinct fates. Centrally located Sox9⁺/Fgfr3⁺ chondroprogenitors expand into the growth plate and metaphyseal stroma, peripheral Hes1⁺ boundary cells refine condensation via asymmetric division, and outer-layer Dlx5⁺ perichondrial cells generate the bone collar and cortical bone. Concurrently, dorsoventral polarity established by Wnt7a–Lmx1b and En1 ensures that dorsal progenitors retain positional identity throughout development. These lineage divergences integrate with signaling networks, including the Ihh–PTHrP, FGF, BMPs, and WNT/β-catenin networks, which impose temporal control over chondrocyte proliferation, hypertrophy, and vascular invasion. Perturbations in these programs, exemplified by mutations in Fgfr3, Sox9, and Dlx5, underlie region-specific skeletal dysplasias, such as achondroplasia, campomelic dysplasia, and split-hand/foot malformation, demonstrating the lasting impacts of embryonic patterning errors. Based on these insights, regenerative strategies are increasingly drawing upon developmental principles, with organoid cultures recapitulating ossification centers, biomimetic hydrogels engineered for spatiotemporal morphogen delivery, and stem cell- or exosome-based therapies harnessing developmental microRNA networks. By bridging developmental biology with biomaterials science, these approaches provide both a roadmap to unravel skeletal disorders and a blueprint for next-generation therapies to reconstruct functional bones with the precision of the embryonic blueprint. Full article

Bone tissue engineering, as an important branch of regenerative medicine, integrates multidisciplinary knowledge from cell biology, materials science, and biomechanics, aiming to develop novel biomaterials and technologies for functional repair and regeneration of bone tissue. Hydrogels are among the most commonly used scaffold materials; however, conventional hydrogels exhibit significant limitations in physical properties such as strength, tensile strength, toughness, and fatigue resistance, which severely restrict their application in load-bearing bone defect repair. As a result, the development of high-strength hydrogels has become a research hotspot in the field of bone tissue engineering. This paper systematically reviews the latest research progress in this area: First, it delves into the physicochemical characteristics of high-strength hydrogels at the molecular level, focusing on core features such as their crosslinking network structure, dynamic bonding mechanisms, and energy dissipation principles. Next, it categorically summarizes novel high-strength hydrogel systems and different types of biomimetic hydrogels developed based on various reinforcement strategies. Furthermore, it provides a detailed evaluation of the application effects of these advanced materials in specific anatomical sites, including cranial reconstruction, femoral repair, alveolar bone regeneration, and articular cartilage repair. This review aims to provide systematic theoretical guidance and technical references for the basic research and clinical translation of high-strength hydrogels in bone tissue engineering, promoting the effective translation of this field from laboratory research to clinical application. Full article

Osteoarthritis (OA) is the most common form of arthritis and represents a major clinical and socioeconomic burden. Epidemiological data consistently show that OA affects women more frequently and, in several joints, more severely than men. Nevertheless, current in vitro models rarely consider sex-specific variables, limiting their ability to capture the biological mechanisms that shape the pathogenesis and progression of OA. Increasing evidence indicates that age-related hormonal fluctuations and subchondral bone remodeling strongly influence OA evolution, and that these processes differ between the sexes. For instance, the decline in estrogen levels during menopause has been associated with accelerated cartilage degeneration, increased osteoclastic activity, and a higher susceptibility to subchondral bone alterations, which may contribute to more aggressive clinical manifestations in women. These mechanisms are only partially reproduced in widely used experimental systems, including traditional biomaterial scaffolds and simplified osteochondral constructs, leaving important sex-dependent pathways unresolved. While advanced biomaterials enable precise control of stiffness, porosity, and biochemical cues, most current in vitro OA models still rely on sex-neutral design assumptions, limiting their ability to reproduce the divergent disease trajectories observed in men and women. By integrating material properties with dynamic loading and tunable hormonal conditions, next-generation in vitro systems could improve mechanistic understanding, increase the reliability of drug screening, and better support the development of sex-specific therapies through the combined efforts of bioengineering, materials science, cell biology, and translational medicine. 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

Osteoarthritis (OA) is a prevalent chronic pain syndrome and a leading cause of disability worldwide, characterized by progressive deterioration of articular cartilage. This degradation leads to pain, swelling, inflammation, and eventual stiffness as the cartilage wears down, causing bone-on-bone friction. Current medical treatments primarily aim at pain relief; however, many interventions, especially invasive or surgical ones, carry risks of adverse outcomes. Consequently, intra-articular (IA) therapy, particularly hyaluronic acid (HA) injections, is widely adopted as a conservative treatment option. HA plays a crucial role in maintaining joint homeostasis by supporting proteoglycan synthesis and scaffolding, restoring optimal HA concentrations in synovial fluid, and providing chondroprotective and anti-inflammatory effects. In recent years, hydrogels composed of natural and synthetic materials have emerged as promising candidates for OA treatment. Our research focuses on the biosynthesis and characterization of novel hydrogel composites combining short peptide hydrogelators with aminated graphene oxide (a-GO) nanosheets functionalized with HA (a-GO-HA@Hgel). These a-GO-HA@Hgel nanocomposites are designed to facilitate the controlled release of HA into the extracellular matrix, aiming to promote cartilage regeneration and mitigate inflammation. The strategy is to exploit the oxygen-containing functional groups of GO nanosheets to enable covalent coupling or physical adsorption of HA molecules through various chemical approaches. The resulting a-GO-HA are incorporated within hydrogel matrices to achieve sustained and controlled HA release. We study the influence of a-GO-HA on the native hydrogel structure and its viscoelastic properties, which are critical for mimicking the mechanical environment of native cartilage tissue. Through this multidisciplinary approach combining advanced materials science and cellular biology, this work aims to develop innovative nanocomposite hydrogels capable of delivering HA in a controlled manner, enhancing cartilage repair and providing a potential therapeutic strategy for OA management. Full article