Tissue Engineering. Part B, Reviews最新文献

Dentin matrix is a natural scaffold derived from complete or partial demineralization of human or animal dentin, capable of releasing growth factors and proteins essential for tissue regeneration and repair. Recent studies have identified the dentin matrix as an exceptional scaffold for the regeneration of dental and osseous tissues, attributed to its excellent biocompatibility, advantageous mechanical properties, and capacity for chemotactic induction. A substantial body of evidence supports its efficacy in promoting the formation of dentin bridges, facilitating the regeneration of the pulp-dentin complex, enhancing de novo bone formation, and mitigating alveolar bone resorption, thereby presenting innovative therapeutic approaches for the reconstruction of oral tissues. This review categorizes dentin matrices based on the degree of demineralization into partially demineralized dentin matrix and completely demineralized dentin matrix. Furthermore, the review consolidates current advancements and outlines future directions for the application of dentin matrix in pulp-dentin complex and alveolar bone regeneration. Despite the ongoing challenges related to the establishment of standardized preparation protocols, the continuous advancements in tissue engineering and regenerative medicine exhibit an advantageous potential for clinical application.

The dynamics of cell biology have always been an active area of research. To visualize and quantify this complex cellular process in vivo, we need optics with a high spatiotemporal resolution. The advancement in optics and image acquisition techniques has revolutionized the field of microscopy. Light-sheet fluorescence microscopy is one of the most advanced imaging tools, which offers a good spatiotemporal resolution, fast imaging, and less phototoxicity to a sample when compared with conventional microscopy techniques. Cell culture techniques have evolved from traditional two-dimensional planar cultures to three-dimensional cultures in the form of spheroids. Spheroid culture truly mimics physiological conditions due to better cell-to-cell and cell-to-matrix interactions within the spheroids. Spheroids have been extensively studied as a model for drug screening, cancer biology, and regenerative medicine. However, the opacity of the core within spheroids restricts its imaging through conventional microscopy. Light-sheet fluorescence microscopy proves to be an effective tool to overcome this problem, as it provides a suitable combination of deep penetration with an ultralow intensity of excitation light, thereby reducing the photobleaching of spheroids. Over the period of years, the light-sheet microscopy technique underwent many modifications, such as adaptive optics and the integration of artificial intelligence and machine learning modules based on its design and applications. Therefore, the present review will focus on the development of the light-sheet microscopy technique, its advancements, application for spheroid imaging, and will also explore the futuristic development trajectory for this technique.

Tissue-engineered organoids hold great promise for regenerative medicine, but insufficient vascularization remains a major barrier to their functionalization and clinical translation. Effective vascular networks are essential for organoid scalability, long-term survival, and functionality. Recent research has focused on strategies such as microfluidics, 3D bioprinting, self-assembly, and smart biomaterials to reconstruct functional vasculature. However, challenges persist, including poor structural stability, functional decline, and limited clinical applicability. The concept of "vascularized homeostasis"-a dynamic balance of vascular formation and remodeling-is seen as key to sustaining long-term organoid function. This review summarizes current advances and limitations in organoid vascularization and highlights the role of homeostatic regulation in enhancing repair potential and clinical translation.

Periodontal tissue regeneration remains a major challenge in oral regenerative medicine, aiming to restore functional structures such as cementum, periodontal ligament, and alveolar bone. Animal models are essential for evaluating the biocompatibility and regenerative efficacy of biomaterials, elucidating repair mechanisms, and supporting clinical translation. This review systematically summarizes chronic and acute periodontal defect models, their establishment protocols, and applications, covering oral gavage, periodontal inoculation, ligature, fenestration, dehiscence, intrabony, and furcation defects. The advantages and limitations of each model are analyzed in relation to simulating pathological microenvironments, testing regenerative scaffolds, and assessing drug delivery systems, with attention to combined modeling strategies. Evaluation methods from histology and immunohistochemistry to molecular assays and omics technologies are outlined, forming a multilevel assessment framework. Integrative multiomics approaches reveal key signaling pathways and metabolic networks in regeneration, guiding biomaterial design and targeted therapy development. This review offers a comprehensive methodological reference to bridge basic research with clinical application and to optimize experimental systems.

Despite antiretroviral therapy's success in human immunodeficiency virus (HIV) management, no cure or preventive vaccine exists; three-dimensional (3D) human tissue models-emerging from biomedical research, tissue engineering, and microfluidics-offer new potential, yet a scientometric analysis of their progress remains lacking. We reviewed the current status of three in vitro 3D models for HIV research: organoids, organ-on-a-chip, and 3D bioprinting. We conducted a bibliometric comparative analysis of 3D human tissue models in HIV research. A total of 852 documents published between 2014 and 2024 were retrieved and analyzed. We found that brain organoids, intestinal organoids, tonsil organoids, kidney organoids, and thymus and spleen organoids effectively support HIV infection and are widely used in in vitro HIV research. Organ-on-a-chip has been primarily used for rapid HIV detection, while 3D bioprinting models have been used in areas such as in vitro HIV detection and diagnosis. Our results showed that the yearly output of articles in 3D human tissue models for HIV has remained relatively stable over the past decade. European institutions impacted greatly on the scientific society of HIV research in 3D human tissue models. The hotspots of 3D human tissue models for HIV research expanded from antiretroviral therapy and molecular docking to 3D printing and organoids. This comparative study presented a unique perspective to understand the evolutive history and future trends of 3D human tissue models for HIV and emerging human-relevant in vitro organotypic models.

The repair and reconstruction of oral mucosal defects are critical for restoring both function and aesthetics of the oral cavity. Tissue engineering, which integrates principles from engineering and life sciences, has enabled the development of biological substitutes that closely mimic the native structure and function of oral mucosa, significantly reducing the risks and complications associated with autologous transplantation. With the rapid advancement of tissue-engineered oral mucosa (TEOM) technology, its applications in regenerative medicine and oral disease modeling have become increasingly prominent. In recent years, innovative strategies such as the development of organoids, prevascularization, immunomodulation, and dermal-epidermal junction biomimicry have emerged, providing effective solutions to challenges related to inadequate vascularization, immune dysregulation, and mechanical performance in TEOM constructs. In addition, the application of cutting-edge manufacturing technologies such as 3D bioprinting has accelerated the translation of TEOM toward clinical use. This review outlines the fundamental principles, design strategies, and potential applications of TEOM, and discusses novel approaches and challenges that must be addressed to facilitate its clinical implementation. Impact Statement This review provides a critical synthesis of recent advances in tissue-engineered oral mucosa, emphasizing cutting-edge methodologies in biomaterial development, cell engineering, and microenvironment modulation. By identifying unresolved challenges such as vascularization and immunomodulation, and proposing innovative strategies, including organoids and smart biomaterials, this article provides a valuable framework for researchers and clinicians striving to translate laboratory breakthroughs into effective regenerative therapies. This integrative perspective is poised to accelerate progress in oral mucosal repair across a variety of clinical applications.

Synthetic bone transplantation has emerged in recent years as a highly promising strategy to address the major clinical challenge of bone tissue defects. In this field, bioactive glasses (BGs) have been widely recognized as a viable alternative to traditional bone substitutes due to their unique advantages, including favorable biocompatibility, pronounced bioactivity, excellent biodegradability, and superior osseointegration properties. This article begins with a comprehensive overview of the development and success of BGs in bone tissue engineering, and then focuses on their composite reinforcement systems with biodegradable metals, calcium-phosphorus (Ca-P)-based bioceramics, and biodegradable medical polymers, respectively. Moreover, the article outlines some frequently used manufacturing methods for three-dimensional BG-based bone bioscaffolds and highlights the remarkable achievements of these scaffolds in the field of bone defect repair in recent years. Lastly, based on the many potential challenges encountered in the preparation and application of BGs, a brief outlook on their future directions is presented. This review may help to provide new ideas for researchers to develop ideal BG-based bone substitutes for bone reconstruction and functional recovery.

Osteoarthritis (OA) is a common degenerative joint disease characterized by progressive cartilage degradation, subchondral bone remodeling, and synovial inflammation. Current treatments cannot halt or reverse OA progression, necessitating the development of novel noninvasive therapies. Therapeutic ultrasound (US), particularly low-intensity pulsed US, has demonstrated efficacy in slowing OA progression. Therapeutic US generates significant thermal and nonthermal effects through noninvasive mechanical forces, exerting biological effects and regulating cell behavior. Therapeutic US has been explored for bone and cartilage repair and shows broad potential in tissue repair when combined with biomaterials. This review summarizes the enhanced or synergistic effects of US and biomaterials in OA. This study elucidated the molecular mechanisms underlying the effects of US on synovium, cartilage, subchondral bone, and mesenchymal stem cells. Notably, the combination of US with various biomaterials can modulate cellular behavior in OA through synergistic effects, including tissue regeneration, enhanced mechanical stimulation, drug delivery, and microenvironment regulation. For each cell type, we summarize the biological mechanisms underlying the therapeutic effects of US and biomaterials, demonstrating their potential to mitigate OA progression. Furthermore, this article explores the limitations and future research prospects of combining US and biomaterials as a therapeutic strategy. Overall, the integration of US and biomaterials holds significant promise as a novel treatment for OA, with potential applications in broader musculoskeletal tissue repair and regenerative medicine. Impact Statement Osteoarthritis (OA) is a complex degenerative disorder that remains challenging to manage. This review highlights the innovative therapeutic potential of combining ultrasound (US), particularly low-intensity pulsed US, with biomaterials for OA treatment. By leveraging synergistic effects such as enhanced tissue repair, targeted drug delivery, and microenvironment regulation, this approach offers a noninvasive and effective strategy to mitigate OA progression and paves the way for advancements in musculoskeletal regenerative medicine.

Multiple studies have been conducted recently to fabricate lyophilized platelet-rich fibrin (LyPRF) as a biological agent. These analyses have also encompassed the integration of LyPRF into various biomaterials for the objective of bone tissue engineering (BTE). However, a definitive manufacturing procedure has not yet been established, and precise data regarding the characterization of LyPRF are still lacking. This systematic literature review aimed to compile existing evidence on the physicochemical and biological properties of this biomaterial as a scaffold for BTE. A comprehensive literature search was performed in SCOPUS, ScienceDirect, PubMed, and Web of Science to identify eligible articles published related to the various in vitro analyses conducted on the biomaterial for its characterization. The inclusion criteria allowed us to concentrate on papers published in English between 2019 and 2025. The study excluded review papers, meta-analyses, editorials, conference pieces, theses, methodological articles, and research that conducted clinical trials or exclusively in vivo analyses. This classification also includes literature with no open access. The preliminary database search produced 3,047 publications, of which only 15 were selected following the application of inclusion and exclusion criteria. LyPRF is beneficial to lengthen the shelf life of the product and can be incorporated into other biomaterials to improve compatibility and reduce degradation time. Therefore, based on the compiled analysis of the included studies, it is found that the surface morphology of LyPRF is irregular, porous, densely populated with fibrin network, and exhibits a uniform aggregation of cells. Furthermore, it is shown that LyPRF demonstrates elements that are analogous to craniofacial bone properties, thereby enhancing its utility in BTE. Additionally, the lyophilization process preserves growth factors present in LyPRF, leading to its consistent and gradual release, increasing the cell proliferation potential of this biomaterial. Existing evidence indicates that LyPRF is a promising candidate for BTE. Future research should prioritize comparative evaluations of fabrication protocols and rigorous biocompatibility testing to establish its suitability as a biomaterial for bioscaffold production in BTE.

Osteoporosis, affecting the entire skeletal system, can cause bone mass to diminish, thereby reducing bone strength and elevating fracture risk. Fracture nonunion and bone defects are common in patients with fractures, and pain and loss of function may cause serious distress. The search for a new therapeutic strategy is essential because of the limited therapeutic options available. Bone marrow mesenchymal stem cells (BMSCs) are crucial for bone metabolism and development due to their high self-renewal capabilities. Wnt signaling is a key pathway that plays a significant role in bone formation by regulating the differentiation of BMSCs. Therefore, the osteogenic differentiation of BMSCs can be regulated by activating Wnt signaling as an idea for bone tissue repair. In this review, we systematically compile and analyze the roles of various drugs, biomolecules, exosomes, and biomaterials in influencing the Wnt/β-catenin signaling pathway during the osteogenic differentiation of BMSCs. It is also discussed how these factors impact on BMSCs and the Wnt/β-catenin pathway. Finally, we also present recent advances in combining bone regeneration materials through these factors, which will help subsequent clinical treatment and translation.