{"title":"Clinical Bioprinting Is Coming of Age: <i>Ex Vivo</i> Versus <i>In Vivo</i>: Response to the Letter to the Editor.","authors":"Vladimir A Mironov, Alexey V Kovalev","doi":"10.1177/19373368261450071","DOIUrl":"https://doi.org/10.1177/19373368261450071","url":null,"abstract":"","PeriodicalId":23134,"journal":{"name":"Tissue Engineering. Part B, Reviews","volume":" ","pages":"19373368261450071"},"PeriodicalIF":4.6,"publicationDate":"2026-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148006856","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Shuaiwu Chen, Yuqi Cao, Yuanbo Wang, Chenggang Liu
{"title":"Gelatin Methacryloyl Hydrogels as a Multifaceted Platform for Promoting Nerve Regeneration.","authors":"Shuaiwu Chen, Yuqi Cao, Yuanbo Wang, Chenggang Liu","doi":"10.1177/19373368261450049","DOIUrl":"https://doi.org/10.1177/19373368261450049","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":23134,"journal":{"name":"Tissue Engineering. Part B, Reviews","volume":" ","pages":"19373368261450049"},"PeriodicalIF":4.6,"publicationDate":"2026-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148006835","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Meniscus Explants as a Platform for Evaluating Cell-Based Strategies for Avascular Meniscus Repair: A Literature Review.","authors":"Oladapo Ekundayo, Adetola B Adesida","doi":"10.1177/19373368261450073","DOIUrl":"https://doi.org/10.1177/19373368261450073","url":null,"abstract":"<p><p>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 <i>in vivo</i> 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 <i>in vivo</i> 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 <i>in vivo</i> models. This will help guide development of true meniscus-preserving therapies that will eventually lead to deliverable solutions that will revolutionize meniscus injury care","PeriodicalId":23134,"journal":{"name":"Tissue Engineering. Part B, Reviews","volume":" ","pages":"19373368261450073"},"PeriodicalIF":4.6,"publicationDate":"2026-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148006843","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Meghana Munipalle, Annie Dang, Adam Celiz, Jianyu Li, Nicole Y K Li-Jessen
{"title":"Computational Advances in Biomaterial Engineering: Mapping Research Trajectories Through Bibliometric Analysis.","authors":"Meghana Munipalle, Annie Dang, Adam Celiz, Jianyu Li, Nicole Y K Li-Jessen","doi":"10.1177/19373368261449957","DOIUrl":"https://doi.org/10.1177/19373368261449957","url":null,"abstract":"<p><p>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 artif","PeriodicalId":23134,"journal":{"name":"Tissue Engineering. Part B, Reviews","volume":" ","pages":"19373368261449957"},"PeriodicalIF":4.6,"publicationDate":"2026-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148006860","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Xiaoying Jin, Fanyu Meng, Qirui Hu, Yizhou Wang, Zhongqing Wang, Bo Liu
{"title":"Global Research Trends of Induced Pluripotent Stem Cells: A Data-Driven Bibliometric Analysis.","authors":"Xiaoying Jin, Fanyu Meng, Qirui Hu, Yizhou Wang, Zhongqing Wang, Bo Liu","doi":"10.1177/19373368261450045","DOIUrl":"https://doi.org/10.1177/19373368261450045","url":null,"abstract":"<p><p>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 (<i>n</i> = 1,472) and received the highest citations (<i>n</i> = 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.</p>","PeriodicalId":23134,"journal":{"name":"Tissue Engineering. Part B, Reviews","volume":" ","pages":"19373368261450045"},"PeriodicalIF":4.6,"publicationDate":"2026-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148006846","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Natalia A Alexandrushkina, Valentina S Glazieva, Maria A Vodopetova, Roman Yu Eremichev, Yu-Chen Hu, Pavel I Makarevich
{"title":"Reconceptualizing Mesenchymal Stromal Cell Sheets: From Delivery Tool to Models of Morphogenesis.","authors":"Natalia A Alexandrushkina, Valentina S Glazieva, Maria A Vodopetova, Roman Yu Eremichev, Yu-Chen Hu, Pavel I Makarevich","doi":"10.1177/19373368261448752","DOIUrl":"https://doi.org/10.1177/19373368261448752","url":null,"abstract":"<p><p>Over the past three decades, cell sheet technology has evolved from its original scaffold-free approach developed for epithelial cells into a versatile platform applicable to mesenchymal stromal cells (MSC). Despite numerous experimental achievements and convincing preclinical outcomes, MSC-based cell sheets have yet to reach the stage of a clinically reproducible product. This gap reflects not so much the technological limitations of the method as an incomplete understanding of its biological nature. MSC-based cell sheets represent more than a vehicle for cell delivery; they are self-organizing systems governed by intrinsic biophysical and morphogenetic principles. Their structural maturation involves (1) cellular condensation, (2) extracellular matrix deposition, and (3) contractile remodeling-processes that mirror the early phases of granulation tissue formation. Viewing the cell sheet as an <i>in vitro</i> model of connective tissue regeneration opens new research avenues extending beyond its therapeutic applications. This review summarizes the key milestones in the development of MSC-derived cell sheet technology, identifies major challenges and conceptual inconsistencies, and discusses the potential of studying these constructs as autonomous biological systems. The integration of mechanobiology, spatial omics technologies, and tissue engineering approaches may help reconceptualize MSC-based cell sheets both as tools for translational therapy and as a fundamental model for studying self-organizing regenerative processes.</p>","PeriodicalId":23134,"journal":{"name":"Tissue Engineering. Part B, Reviews","volume":" ","pages":"19373368261448752"},"PeriodicalIF":4.6,"publicationDate":"2026-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147857249","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Dental Follicle Stem Cells and Biological Scaffolds in Dental Regenerative Medicine.","authors":"Lu Xuan, Xiaomei Liu, Jiahao Chen, Zhuomin Sha, Jiarui Yang, Yuanna Zheng, Hua Li, Xuepeng Chen","doi":"10.1177/19373368261419610","DOIUrl":"https://doi.org/10.1177/19373368261419610","url":null,"abstract":"<p><p>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 <i>in vitro culture</i>. 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.</p>","PeriodicalId":23134,"journal":{"name":"Tissue Engineering. Part B, Reviews","volume":" ","pages":"19373368261419610"},"PeriodicalIF":4.6,"publicationDate":"2026-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147609828","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Sabrina N VandenHeuvel, Lucia L Nash, Shreya A Raghavan
{"title":"Dormancy in Metastatic Colorectal Cancer: Tissue Engineering Opportunities for <i>In Vitro</i> Modeling.","authors":"Sabrina N VandenHeuvel, Lucia L Nash, Shreya A Raghavan","doi":"10.1089/ten.teb.2025.0009","DOIUrl":"10.1089/ten.teb.2025.0009","url":null,"abstract":"<p><p>Colorectal cancer (CRC) recurs at a striking rate, specifically in patients with liver metastasis. Dormant CRC cells disseminated following initial primary tumor resection or treatment often resurface years later to form aggressive, therapy-resistant tumors that result in high patient mortality. Routine imaging-based screenings often fail to detect dormant cancer cell clusters, and there are no overt symptomatic presentations, making dormant CRC a major clinical challenge to diagnose and treat. Tissue engineering approaches are ideally suited to model dormant cancer cells and enable the discovery of therapeutic vulnerabilities or unique mechanistic dependencies of dormant CRC. Emerging evidence suggests that tissue-engineered approaches have been successfully used to model dormant breast and lung cancer. With CRC responsible for the second most cancer-related deaths worldwide and CRC patients commonly experiencing recurrence, it is essential to expand dormancy models to understand this phenomenon in the context of CRC. Most published <i>in vitro</i> models of CRC dormancy simplify the complex tumor microenvironment with two-dimensional culture systems to elucidate dormancy-driving mechanisms. Building on this foundation, future research should apply tissue engineering methods to this growing field to generate competent three-dimensional models and increase mechanistic knowledge. This review summarizes the current state of <i>in vitro</i> CRC dormancy models, highlighting the techniques utilized to give rise to dormant CRC cells: nutrient depletion, anticancer drugs, physical extracellular matrix interactions, and genetic manipulation. The metrics used to validate dormancy within each model are also consolidated to demonstrate the lack of established standards and the ambiguity around comparing studies that have been validated differently. The methods of these studies are organized in this review to increase comprehensibility and identify needs and opportunities for future bioengineered <i>in vitro</i> models to address dormancy-driven mortality in patients with CRC liver metastasis.</p>","PeriodicalId":23134,"journal":{"name":"Tissue Engineering. Part B, Reviews","volume":" ","pages":"126-142"},"PeriodicalIF":4.3,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13557508/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143804243","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Exploring Biomaterial Scaffolds for Eyelid Reconstruction: A Synthesis of Experimental Findings.","authors":"Jincheng Liu, Mange Zhang, Mengling Zhou, Qingyi Wang, Xin Jiang, Qin Huang","doi":"10.1089/ten.teb.2024.0364","DOIUrl":"10.1089/ten.teb.2024.0364","url":null,"abstract":"<p><p>This review synthesizes experimental findings on various biomaterial scaffolds used in eyelid reconstruction. It examines the structural properties, cellular responses, and functional outcomes of scaffolds such as chitosan, poly(propylene glycol fumarate)-2-hydroxyethyl methacrylate, poly(propylene glycol fumarate) - type I collagen (PPF-Col), decellularized matrix-polycaprolactone, branched polyethylene, collagen, poly(3-hydroxybutyrate-co-3-hydroxyhexanoate, and poly(lactic-co-glycolic acid. These scaffolds exhibit diverse mechanical and biological properties, with some demonstrating good biocompatibility, tunable properties, and potential for tissue repair. However, there are limitations, including concerns about long-term functionality and a lack of comprehensive evaluations. This review highlights the need for multifunctional scaffolds that combine lid replacement and ocular surface function restoration, as well as the establishment of standardized research methods. The goal is to guide future innovation in the field and improve the quality of life for patients with eyelid defects.</p>","PeriodicalId":23134,"journal":{"name":"Tissue Engineering. Part B, Reviews","volume":" ","pages":"143-156"},"PeriodicalIF":4.6,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144011407","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"The Regulation of Pericellular Matrix Synthesis During Articular Cartilage Tissue Engineering.","authors":"Marloes van Mourik, Florencia Abinzano, Keita Ito","doi":"10.1089/ten.teb.2024.0316","DOIUrl":"10.1089/ten.teb.2024.0316","url":null,"abstract":"<p><p>Articular cartilage, vital to the health and functioning of joints, remains challenging to regenerate. The pericellular matrix (PCM) is critical for transducing biophysical stimuli to the articular chondrocytes (ACs) that it envelops. Given the mechanobiological sensitivity of ACs, it is pivotal in maintaining the chondrogenic phenotype and the production of extracellular matrix (ECM) during articular cartilage tissue engineering. While the maintenance of the native PCM significantly improves the quality of neocartilage, current isolation methods are limited. A solution to this challenge is facilitating ACs to regenerate their PCM. However, the regulation of PCM synthesis remains poorly understood, hindering the development of effective tissue engineering strategies. This narrative review aims to provide a comprehensive analysis of the complex interplay between extracellular cues and intracellular pathways regulating PCM synthesis during articular cartilage tissue engineering. Our analysis reveals that mechanical cues, such as material stiffness and mechanical stimulation, are the primary regulators of PCM synthesis. Additionally, the use of scaffold-free techniques potentially affects the structuring of newly created PCM. Tuning these stimuli can significantly impact the quality of the formed PCM, ultimately influencing neocartilage quality. Furthermore, we highlight intracellular mechanisms involved in the transduction of these extracellular cues, including actin polymerization, yes-associated protein and transcriptional coactivator with PDZ-binding motif localization, and transforming growth factor beta-induced Smad signaling. Although the current literature suggests the involvement of these signaling pathways in regulating the synthesis of PCM components, we found that studies investigating these processes in ACs are lacking. Elucidating the relationships between extracellular stimuli, intracellular signaling, and the expression of PCM components could provide a framework for designing new cartilage tissue engineering approaches that facilitate proper PCM synthesis. Ultimately, this can improve ECM quality and advance articular cartilage regeneration.</p>","PeriodicalId":23134,"journal":{"name":"Tissue Engineering. Part B, Reviews","volume":" ","pages":"157-170"},"PeriodicalIF":4.6,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144127727","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}