Multifunctional integrated hydrogels have emerged as advanced biomaterials that integrate diverse functional properties, including bioactivity, mechanical adaptability, controlled drug release, and electrical/magnetic responsiveness, exhibiting substantial potential in tissue regeneration and repair. These hydrogels provide a versatile platform to mimic the complex microenvironment of native tissues, thereby facilitating cell proliferation, differentiation, and tissue remodeling. Despite rapid progress in their design and development, optimizing performance for specific tissues (e.g., bone, cartilage, skin, nerve, myocardium) remains challenging. Current research focuses on innovative design strategies and the incorporation of key functional modules to tailor hydrogels for targeted regenerative applications. Moreover, translating these materials from bench to bedside requires overcoming barriers related to biocompatibility, scalability, regulatory approval, and long-term functional stability. This review comprehensively summarizes recent advances in multifunctional integrated hydrogels, highlights their applications across different tissue regeneration scenarios, and critically evaluates translational challenges. By synthesizing cutting-edge findings, this work aims to guide the development of next-generation smart tissue engineering scaffolds and accelerate their clinical adoption, ultimately advancing regenerative medicine.
Bone regeneration remains a significant clinical challenge in conditions such as trauma, osteoporosis, and aging-related bone loss. Recent advances have highlighted the crucial role of extracellular vesicles, especially exosomes, in intercellular signaling pathways that support bone homeostasis and repair. Among their bioactive cargoes, exosomal RNAs—particularly messenger RNAs and microRNAs—have emerged as central regulators of osteogenesis by modulating gene expression, cellular differentiation, and communication within the bone microenvironment. In this review, we provide a comprehensive summary of exosome biology, including their biogenesis, secretion, uptake mechanisms, and RNA cargo characteristics. We critically examine current evidence on how exosomal RNAs influence the molecular mechanisms of bone formation, remodeling, and regeneration under both physiological and pathological conditions such as fractures, diabetes, osteoporosis, and osteoarthritis. Furthermore, we discuss the emerging therapeutic potential of engineered exosomes as RNA delivery systems in bone tissue engineering and regenerative medicine. A better understanding of the functional roles and clinical relevance of exosomal RNAs may pave the way for next-generation, RNA-based therapies in skeletal repair and treatment of bone-related diseases. This review highlights the crucial role of exosomal mRNAs and microRNAs in regulating osteogenesis and bone regeneration. By elucidating the molecular mechanisms and signaling pathways involved, it provides new insights into the potential of exosome-based therapies in bone tissue engineering. This work may accelerate the development of innovative RNA-based regenerative strategies, ultimately improving treatment outcomes for bone diseases and injuries.
Low back pain, linked to nucleus pulposus degeneration and annulus fibrosus (AF) defects, is a significant cause of global disability. The AF’s multilayered structure supports the spine, but its limited self-repair capacity makes treating AF injuries and herniation difficult. Traditional surgical interventions like discectomy often fail to restore AF integrity, resulting in high reherniation rates. In response, biomaterial-based strategies have emerged as promising alternatives, aiming to replicate AF structure, deliver bioactive factors, and promote tissue regeneration. This review evaluates the composition, biomechanics, and pathophysiology of the AF, emphasizing the fundamental properties of available biomaterials, integration with host tissues, mechanical properties, and biomimetic microenvironments in AF tissue remodeling and repair. We examine recent advances in AF repair biomaterials, including natural and synthetic hydrogels, decellularized extracellular matrix, electrospun scaffolds, and emerging technologies like three-dimensional bioprinting. These materials provide mechanical reinforcement, enhance cell adhesion, and modulate the degenerative microenvironment through controlled drug or growth factor release, offering a comprehensive approach to address the challenges of AF repair.
Diabetes mellitus is a global public health problem, and impaired wound healing is a complication that significantly reduces patients' quality of life. Dysregulation of mitochondrial homeostasis is a key pathological feature contributing to impaired wound healing in diabetes. This dysregulation increases oxidative stress, resulting in impaired energy metabolism, endothelial dysfunction, and prolonged inflammatory responses. Photobiomodulation (PBM) is a noninvasive therapy that has been successfully used to promote diabetic wound healing by modulating mitochondrial homeostasis via multiple mechanisms. In this review, we have systematically summarized the following roles of PBM in restoring mitochondrial homeostasis to accelerate diabetic wound healing: improving mitochondrial dysfunction and oxidative stress through cytochrome C oxidase in the electron transport chain, thereby enhancing oxidative phosphorylation and adenosine triphosphate production; modifying mitochondrial dynamics by inhibiting the expression of dynamin-related protein 1 and promoting mitofusin-2 expression to restore mitochondrial morphology and function; reducing inflammation and promoting macrophage polarization from the M1 to M2 phenotype; activating signaling pathways (e.g., VEGF, PI3K/AKT/mTOR/GSK3-β, AMPK, RAS/MAPK, JAK/STAT, NF-κB, TGF-β/Smad) to enhance cell proliferation and angiogenesis and resolve inflammation. Beyond monotherapy, this review synthesizes the burgeoning field of PBM in combination with advanced therapeutic strategies, such as hydrogels, nanomaterials, small-molecule drugs, adipose-derived stem cells, and extracellular vesicles, highlighting their synergistic potential for enhanced efficacy. Finally, this review critically addresses the prevailing challenges in clinical translation, particularly the lack of standardized treatment parameters, and proposes future research directions. This comprehensive overview aims to solidify the scientific foundation of PBM and inspire the design of integrated, precision therapeutic strategies for diabetic wound management.
Osteonecrosis of the femoral head (ONFH) is a progressive, multifactorial bone disease characterized by ischemia-induced osteocyte death, microenvironmental imbalance, and failed tissue regeneration. According to recent advances in pathophysiological understanding, vascular injury, oxidative stress, and inflammatory storms form a pathogenic cascade leading to osteogenic dysfunction, adipogenic lineage drift of mesenchymal stem cells (MSCs), and epigenetic alterations that exacerbate bone degeneration. Despite improvements in early detection, traditional interventions-including bisphosphonates, hyperbaric oxygen therapy, and surgical decompression-have limited efficacy, particularly in the mid-to-late stages. This review systematically synthesizes emerging regenerative approaches across three domains: (1) Cellular and molecular therapies: Autologous MSC transplantation, exosomes, and apoptotic extracellular vesicles restore osteogenesis, modulate immunity, and promote angiogenesis, while gene-editing technologies such as CRISPR/Cas9 enhance MSC functionality. (2) Nanobiomaterial synergy: Enzyme-mimetic nanozymes and multifunctional polymeric scaffolds improve lesion targeting, reactive oxygen species clearance, and microenvironmental regulation. (3) Advanced bioengineering: Organoid models and 3D-bioprinted living joint prostheses enable the integration of vascularization, mechanical support, and precise drug delivery, representing transformative strategies in personalized repair. Together, these innovations highlight a future paradigm shift from passive support to active, mechanism-targeted regeneration, offering new hope for structural and functional reconstruction in ONFH. Multidisciplinary integration-bridging materials science, stem cell biology, and digital medicine-will be essential for successfully developing functional cures.
Three-dimensional (3D) printing technology, or additive manufacturing, has fundamentally transformed medical paradigms by shifting dentistry from traditional subtractive manufacturing to an era of personalized, biological regeneration. This review provides a comprehensive overview of the primary 3D printing classifications currently utilized, including stereolithography, fused deposition modeling, selective laser sintering, and material jetting, analyzing their specific technical principles and material capabilities. We systematically categorize their applications across diverse dental disciplines, ranging from endodontics, periodontal disease management, and prosthodontics to orthodontics, maxillofacial reconstruction, and temporomandibular joint regeneration. Beyond the fabrication of anatomical models and surgical guides, this article critically evaluates the efficacy of these technologies in constructing bioactive scaffolds and cell-laden hydrogels designed to induce osteogenesis and angiogenesis. Special emphasis is placed on the paradigm shift from passive mechanical restoration to active biological regeneration, highlighting the potential of bioprinting in restoring physiological vitality to native tissues. Despite current barriers regarding the trade-off between mechanical durability and biological activity, as well as vascularization challenges, the convergence of artificial intelligence and 4D printing promises to establish 3D printing as a foundational standard for the next generation of regenerative dental therapeutics.
Anaplastic thyroid carcinoma (ATC) is a highly aggressive and treatment-resistant form of thyroid cancer, characterized by poor prognosis, rapid metastasis, and resistance to conventional therapies. Current treatment options, including surgery, chemotherapy, and radiation, are often ineffective in controlling the disease, underscoring the urgent need for novel therapeutic approaches. Nanotechnology has emerged as a promising strategy to overcome these challenges, offering innovative solutions for targeted drug delivery and noninvasive therapeutic modalities. This review explores the latest advancements in nanotechnology-driven strategies for treating ATC, with a particular focus on noninvasive therapies such as sonodynamic therapy and nano-pulse stimulation, as well as the development of nanomaterial-based drug delivery systems. These systems, including RNA-based nanocarriers, radionuclide-labeled nanoparticles, and nanoclay-based delivery systems, provide enhanced specificity and efficacy, overcoming the limitations of traditional treatments. Additionally, dual-modality theranostic systems, which combine diagnostic imaging and therapeutic payloads, hold great promise in improving early detection and real-time treatment monitoring. Despite the promising preclinical results, challenges such as tumor heterogeneity, drug resistance, and biocompatibility of nanomaterials remain in the clinical use. This review provides a comprehensive overview of the potential of nanotechnology to revolutionize the treatment of ATC, offering new hope for patients with this highly aggressive malignancy.
This systematic review and meta-analysis evaluated the efficacy of platelet-rich plasma (PRP)-loaded scaffolds for endometrial regeneration in preclinical in vivo models. Endometrial damage, manifesting as endometrial thinning or adhesion formation within the uterine cavity, is a major cause of infertility. While PRP is a promising regenerative therapy, its short half-life limits its effectiveness. The hypothesis was that combining PRP with a hydrogel-based scaffold would provide sustained growth factor release and improve regenerative outcomes compared with monotherapies. The review was conducted per PRISMA guidelines and registered in PROSPERO (CRD420251004274). A comprehensive search of PubMed, Scopus, Web of Science, and Cochrane databases was carried out through April 2025. Seven studies in rodent models met the inclusion criteria. The meta-analysis demonstrated that PRP/scaffold combinations significantly enhanced key outcomes over untreated controls, including endometrial thickness (standardized mean difference [SMD] = 2.85, p < 0.001), gland density (SMD = 4.11, p < 0.001), angiogenesis (SMD = 6.13, p < 0.001), fibrosis reduction (SMD = -5.21, p < 0.001), and embryo implantation rates (SMD = 4.04, p < 0.001). Injectable hydrogels were particularly effective. Compared with PRP alone, the PRP/hydrogels demonstrated improved performance across the majority of structural and functional parameters, though statistical significance varied, partly attributable to variability in scaffold materials and PRP preparation methods. These results suggest that PRP-loaded scaffolds represent a promising approach for improving both structural and functional endometrial regeneration. The therapeutic success is closely tied to the scaffold's degradation kinetics and its ability to preserve PRP bioactivity. This evidence supports the further development of standardized, degradable PRP-scaffold systems for clinical translation in treating endometrial infertility.
Sensorineural hearing loss is a major public health concern, yet its treatment remains limited by the anatomical complexity and biological barriers protecting the cochlea. Among these, the round window membrane (RWM) constitutes a key interface for local drug delivery to the inner ear. However, passive diffusion via intratympanic injection is often insufficient, particularly for hydrophilic, large, or negatively charged molecules such as gene therapy vectors. This systematic review aimed to evaluate biomechanical and biochemical strategies to enhance RWM permeability for more efficient and targeted drug delivery to the inner ear, including direct permeability modulation of the RWM properties or indirect enhancement mechanisms increasing drug delivery without altering intrinsic membrane permeability. Following Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines, a comprehensive literature search was conducted using the Scopus, MEDLINE/PubMed, Cochrane, and CINAHL electronic databases. In vivo studies and clinical trials involving biochemical or biomechanical strategies to enhance RWM permeability were included. Risk of bias was assessed using the SYRCLE (Systematic Review Center for Laboratory Animal Experimentation) tool. Out of 1776 screened articles, 89 met the inclusion criteria. Four biochemical approaches and three biomechanical strategies were identified, respectively: (1) hydrogels, thermogels, and emulsions, (2) nanosystems, (3) microsystems, and (4) permeabilizers, and (1') sonoporation, (2') acoustic stimulation, and (3') magnetic systems. Most studies reported improved drug delivery to the inner ear or therapeutic efficacy. While earlier research focused on hydrogels, thermogels, emulsions, permeabilizers, and acoustic stimulation for small molecules such as corticoids and antioxidants, recent studies increasingly explore nanosystems, microsystems, sonoporation, and magnetic methods to facilitate the delivery of larger agents, including gene therapy. This review also highlights that while many strategies are already available and effective in animal models, further research is essential to facilitate the clinical translation of both existing and emerging delivery methods.
Hydrogels have emerged as promising delivery vehicles for periodontal ligament stem cells (PDLSCs) due to their biocompatibility and resemblance to the native extracellular matrix. The objective of this systematic review was to evaluate the efficacy of hydrogels as delivery vehicles for PDLSCs in animal models of bone regeneration. This systematic review is reported according to the (Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and included only in vivo studies evaluating PDLSCs encapsulated in hydrogels for the regeneration of periodontal, alveolar, mandibular, calvarial, or orthodontic defects. Searches were conducted in PubMed, Scopus, Embase, and Web of Science until March 2025. The risk of bias was assessed using the Systematic Review Centre for Laboratory Animal Experimentation tool. Eleven studies were included. Hydrogels included gelatin methacrylate, alginate, chitosan-based matrices, collagen, and thermosensitive poly (lactic-co-glycolic acid)-polyethylene glycol-poly (lactic-co-glycolic acid), functionalized or not with growth factors, bioactive peptides, or nanoparticles. Quantitative microcomputed tomography (micro-CT) analyses assessed bone volume/total volume, bone mineral density, and trabecular thickness. Osteogenic induction typically involved the use of dexamethasone, β-glycerophosphate, and ascorbic acid. Histology confirmed new bone formation and, occasionally, vascularization. In periodontal defects, five studies showed enhanced bone fill and periodontal ligament-like tissue formation. Alveolar bone models reported improved mineralization and neovascularization in two studies. Mandibular defects, evaluated in large animals, exhibited trabecular bone formation. One calvarial and one orthodontic bone loss model reported increased bone density and accelerated deposition, respectively. Due to substantial methodological heterogeneity, a qualitative synthesis was performed. The risk of bias was generally high or unclear in the blinding and allocation domains. The main limitations of this review included heterogeneity across animal models, hydrogel formulations, and outcome measures. Hydrogel-encapsulated PDLSCs promote bone regeneration across diverse defect types, particularly when delivered via injectable and functionalized scaffolds in animal models.
Degeneration of the lumbar intervertebral discs is a leading cause of low back pain, a condition that affects a substantial proportion of the global population. The earliest degenerative changes typically manifest in the central nucleus pulposus (NP) region of the disc and are characterized by elevated local inflammation and a cell-mediated reduction in proteoglycan content and transition to a fibrotic extracellular matrix. The application of adult mesenchymal stem cells (MSCs) to arrest and reverse degenerative changes in the NP has received significant interest due to the availability and superior safety profile of these cells compared with other therapeutic cell types. Preclinically and clinically, however, the efficacy of MSC-based disc treatments is mixed, due in part to the limited ability of these cells to survive and function within the degenerate NP microenvironment. A potential strategy to improve the in vivo survival and anabolic performance of MSCs in the degenerate NP is preconditioning prior to implantation using a variety of biochemical and biophysical stimuli. In this review, we present an overview of existing techniques used for preconditioning MSCs to enhance their therapeutic performance in the degenerate NP. We outline respective advantages and challenges associated with each of these techniques and provide recommendations for their further refinement.
Multimodal bioelectronic materials have emerged as a promising platform for synergistic neuromodulation, addressing the increasing clinical demand for precise and safe neural interventions. This review highlights recent advances in three pivotal classes of functional materials-liquid metals, magnetoelectric coupling materials, and high-entropy oxides-that offer unique physicochemical properties and versatile fabrication techniques tailored for neural interfaces. We first discuss the clinical significance and advantages of multimodal materials in neuromodulation, followed by an in-depth analysis of the structural characteristics, synthesis methods, and neurointerface applications of these materials. Integrating the latest theoretical models and experimental findings, we elucidate how these materials enable the synergistic application of electrical, magnetic, and mechanical stimuli to enhance neuromodulation efficacy. Despite their promising potential, challenges remain in optimizing biocompatibility, long-term stability, and functional integration. Finally, we provide a forward-looking perspective on the future directions and hurdles for the deployment of multimodal bioelectronic materials in neural disease therapies and intelligent neural interfaces. This review aims to foster a deeper understanding and inspire further innovation in the interdisciplinary field of neuromodulation.
This study analyzed 10,461 iPSC-related publications retrieved from the Web of Science Core Collection-Science Citation Index Expanded, focusing on annual publication, journal, author, institution, country/region, reference, and author keyword, with networkvisualization performed using VOSviewer. The annual publication has shown remarkable growth, first exceeding 500 in 2013 and reaching 1,107 in 2021. Stem Cell Research published the most publications (n = 1,472) and received the highest citations (n = 6,561), followed by PLoS One and Scientific Reports. The United States was the most productive country with 3,525 publications and 208,413 citations. Among the institutions, Kyoto University ranked first in productivity with 480 publications and 33,455 citations. Wu Joseph C. was the most prolific author, having 119 publications and 8,855 citations. Five main clusters were identified through the co-occurrence analysis of the top 177 author keywords: iPSCs differentiation & tissue engineering, neurodegenerative diseases & neurobiology, regenerative medicine in Parkinson's disease, cardiac disease models & gene editing, and ESCs & reprogramming mechanisms. This study presented the first comprehensive bibliometric analysis of global iPSC research, aiming to map the domain's intellectual structure and collaborative networks. It revealed the global landscape, drivers of the growth trajectory, knowledge base, research hotspots, and future perspectives in the domain, thereby offering a strategic roadmap to accelerate progress and innovation.
Nerve injuries pose a significant clinical challenge in both the central and peripheral nervous systems, which often lead to permanent functional deficits. Nerve tissue engineering offers a promising path forward, and gelatin methacryloyl (GelMA) hydrogels have emerged as a powerful and versatile platform in this endeavor. Derived from natural collagen, GelMA possesses inherent biocompatibility and cell-adhesive properties, while its photocrosslinkable nature allows for the precise tuning of its mechanical stiffness, degradation rate, and porous architecture to recapitulate the native neural microenvironment. This review comprehensively elucidates the evolution of GelMA from a passive physical support to an active and instructive biomaterial. We explore a wide array of functionalization strategies, including the incorporation of therapeutic cells, the sustained delivery of neurotrophic factors, and the integration of conductive materials to guide regeneration. Furthermore, we discuss the development of advanced stimuli-responsive systems and the application of 3D bioprinting to fabricate anatomically complex nerve guidance conduits. Ultimately, this work establishes GelMA as a pivotal technology for developing the next generation of intelligent and clinically translatable strategies for nerve repair.Impact StatementThis review highlights the transformative potential of gelatin methacryloyl (GelMA) hydrogels in nerve tissue engineering. By comprehensively analyzing advanced functionalization strategies and "smart" stimuli-responsive systems that adapt to pathological microenvironments, this work underscores the capacity of GelMA to overcome critical barriers in neural repair. We detail how these versatile scaffolds can be engineered for precise drug delivery, electrical conductivity, and gene editing. These insights provide a roadmap for developing next-generation, autonomous biomaterials, paving the way for personalized clinical solutions that significantly enhance functional recovery in patients with severe neuronal injuries.
Alternatives to animal models, including computational-based approaches, are now prioritized by regulatory and funding agencies in biomedical research. Despite this shift in policy, computer models in tissue engineering and regenerative medicine remain underutilized and have not been fully integrated into research and development pipelines. This study aims to identify current and emerging computational techniques in regenerative biomaterials through comprehensive bibliometric analysis and to examine future directions in the evolving field of tissue engineering. Using the Web of Science database, a total of 678 studies with a primarily computational component between January 1, 2014, and March 31, 2025, were included in the analysis. Studies were grouped by computational method (e.g., computational fluid dynamics [CFD], molecular dynamics [MD], agent-based modeling) and by tissue type (e.g., bone, cartilage). Our analysis found that CFD/finite element modeling (FEM) was the most common computational method used for biomaterial research. Based on co-citation and co-keyword network analyses, CFD/FEM was primarily applied to study and optimize material properties like viscoelasticity, porosity, and microstructure. Parameter estimation and sensitivity analysis were a key application across all computational methods. Timeline and thematic analyses identified that modeling of stem cell biomaterials is an emerging topic, including research to emulate cell behavior, scaffold mechanics, and their complex interactions. Hybrid models, especially combining CFD/FEM with MD, are likely to become more prevalent to integrate multimodel data. Since 2023, data-driven models including machine learning and artificial intelligence have emerged as surrogate models for complex mechanistic simulations. However, concerns about data scarcity and the interpretability of these models must still be addressed to meet regulatory standards. Integrating data-driven and mechanistic models creates a synergistic solution that overcomes the limitations of either method alone. Informed by insights from this bibliometric review, researchers can confidently apply computational techniques for innovative biomaterial solutions in tissue engineering and regenerative medicine.Impact StatementComputational modeling is at the forefront of design and development in tissue engineering and regenerative medicine. This review uses bibliometric analysis to synthesize the research landscape of computational modeling for regenerative biomaterials over the last decade. We identified established and emerging computational techniques, such as computational fluid dynamics and mathematical models, for the optimization of scaffolds, cell dynamics, and manufacturing methods. Owing to the growing complexity of biomaterial engineering, partly driven by high-throughput data, future computational pipelines will likely rely on hybrid models that integrate mechanistic modeling with machine learning and artificial intelligence.
Calcium hydroxylapatite (CaHA) has evolved from hard tissue applications to become a prospective bioactive filler for facial rejuvenation, offering both immediate volumization and long-term regenerative benefits. This review synthesizes literature up to 2025 to summarize the material properties, mechanisms of action, and clinical applications of CaHA-based fillers, evaluating their safety and efficacy. CaHA-based fillers provide structural support and stimulate collagen synthesis by activating fibroblasts, leading to sustained improvements in skin quality, volume restoration, and contour enhancement. Clinical evidence confirms the effectiveness of both pure CaHA and composite formulations combining CaHA with hyaluronic acid, which integrate rapid correction with prolonged regeneration. However, risks such as nodule formation, technical challenges, and the absence of reversal agents require consideration. CaHA-based fillers represent a significant advancement in minimally invasive facial rejuvenation by merging mechanical support with biological regeneration. Future research should focus on optimizing particle design, standardizing injection protocols, and developing multifunctional carriers to enhance safety and predictability.Impact StatementAs a traditional material for bone and dental repair, calcium hydroxylapatite (CaHA) has surprisingly emerged as a bioactive soft-tissue filler for facial rejuvenation. This review clarifies why this inorganic material can stimulate collagen, restore volume, and improve skin quality, bridging its regenerative mechanisms with clinical practice. By summarizing current applications, efficacy evidence, and safety considerations, we aim to enhance professional understanding, promote wider adoption, and inspire further translational research in minimally invasive aesthetic medicine.
Injuries to the avascular region of the knee meniscus-the inner "white-white" zone-pose a significant therapeutic challenge due to its lack of vascular supply and limited intrinsic healing capacity. While conventional meniscal repair techniques often fail in this region, recent advances in regenerative medicine have turned to explant culture systems as a bridge between simple cell cultures and complex in vivo models. This review synthesizes the current literature on the role of explant cultures in understanding and advancing avascular meniscus repair. Explant cultures maintain native extracellular matrix structure and provide a controlled three-dimensional environment to study cellular responses to injury. Within these systems, a distinct subpopulation of cells termed migratory meniscus cells emerge from the tissue edge, exhibiting progenitor-like features, including clonogenicity, multipotency, and responsiveness to transforming growth factor-β signaling. These cells have demonstrated the capacity to infiltrate defect zones, remodel extracellular matrix, and synthesize reparative fibrocartilaginous tissue. Experimental manipulations within explant models, including fibrin scaffolds, enzymatic border conditioning, sequential growth factor delivery, mechanical loading, and electrical stimulation, have shown promise in enhancing integration strength and tissue quality. These studies underscore the importance of biochemical and biophysical cues in orchestrating effective repair in avascular regions. Current explant systems, however, are constrained by limited culture durations, the absence of vascular and immune components, and species-specific differences in matrix biology, thereby limiting their ultimate utility in translational research. Despite these limitations, explant models remain essential for dissecting the mechanistic basis of meniscal repair and for evaluating candidate therapies in a reproducible, hypothesis-driven manner. Looking ahead, next-generation platforms incorporating perfusion bioreactors, immune cocultures, and validated integration assays will be critical to better replicate in vivo physiology. Personalized strategies targeting patient-specific tear characteristics and cellular profiles, including autologous progenitor cell delivery and biomaterial-based signaling systems, hold potential for transforming the clinical management of avascular meniscus injuries. This review highlights the central role of explant cultures in shaping such innovations and guiding their translation into meaningful orthopedic therapies.Impact StatementThis review summarizes the current state of meniscal explant culture models for avascular-zone repair and explains how they can serve as a practical, translational bridge between cell studies and in vivo models. This will help guide development of true meniscus-preserving therapies that will eventually lead to deliverable solutions that will revolutionize meniscus injury care.
Dental follicle stem cells (DFSCs) originate from the dental follicle during tooth development and possess multilineage differentiation potential, contributing to periodontal tissue regeneration, bone repair, and immunomodulation. This review highlights the recent advances in the application of DFSCs and biological scaffolds for regenerative medicine, with a focus on oral and craniofacial tissue. DFSCs exhibit key advantages for regenerative therapies, including high accessibility, robust self-renewal capacity, and multipotent differentiation potential, enabling their differentiation into odontogenic (dentin- and enamel-forming), osteogenic, and fibroblastic lineages. We discuss the embryonic origin of DFSCS and their unique ability to maintain stable cellular properties in long-term in vitro culture. Importantly, DFSCs play a pivotal role in tooth morphogenesis, periodontal tissue formation, and craniofacial bone regeneration, making them promising for functional oral tissue restoration. A critical aspect of DFSC-based regeneration is the integration with bioactive scaffolds, which provide structural support, promote cell adhesion, proliferation, and differentiation, and facilitate vascularization. We analyze how scaffold properties, such as biodegradability, porosity, and permeability, influence DFSC behavior and therapeutic outcomes. Finally, we explore future challenges and opportunities in optimizing DFSC-scaffold interaction, emphasizing advancements in biomaterial design and emerging bioengineering technologies. Preliminary evidence suggests that integrating DFSCs with engineered scaffold systems may offer potential benefits for personalized regenerative therapies, though further validation is required before clinical translation. Such approaches could contribute to advancing tooth and craniofacial reconstruction strategies. This review consolidates existing insights and explores potential avenues for future research to support advancements in DFSC-based regenerative medicine.
The thyroid gland is an endocrine organ responsible for production of triiodothyronine and thyroxine, essential hormones that regulate human metabolism. A wide range of conditions can impair its function, leading to potential life-threatening consequences such as myxedema coma. The standard treatment for hypothyroidism is lifelong levothyroxine supplementation, which, despite being a significant therapeutic breakthrough, has notable limitations and does not fully restore quality of life for many patients. Biomimetic thyroid gland has emerged as a promising alternative treatment strategy for patients with hypothyroidism. Most research to date has focused on generating thyroid organoids from primary thyroid cells or stem cells. However, there is growing interest in other approaches, including the use of biomaterials, bioreactors, and 3D bioprinting as potential alternatives or supplementary technologies to the organoids. While in vitro and preclinical studies have shown encouraging results, clinical application of biomimetic thyroid gland requires further studies in several key areas, including long-term functional validation, studies on large animal models, immunological compatibility and scaffold biodegradation, and absence of standardized good manufacturing practice (GMP)-compliant production protocols.
