软骨再生工程类器官的研究及应用前景

Research and Application Prospects of Organoids for Cartilage Regeneration Engineering

摘要: 骨关节炎已成为威胁人类健康的重要疾病。开发更有效的软骨再生治疗手段，是当前临床实践面临的重要挑战。二维细胞培养、动物实验等传统研究方法存在局限性，近年来发展起来的类器官技术因此受到广泛关注。作为干细胞来源的自组织三维细胞聚集体，类器官能够在体外更逼真地模拟软骨组织的复杂结构与生物学功能。近年来，依托组织工程技术、间充质干细胞诱导分化技术及多能干细胞分化技术构建的软骨类器官体系逐步建立，为软骨缺损修复带来了新的希望。本文综述了软骨类器官模型的构建策略与最新研究进展，阐述其在软骨再生医学领域的应用价值，并探讨软骨类器官培养存在的局限性，同时展望未来发展方向，以期通过工程化策略为多阶段干细胞介导的软骨再生研究提供指导。单纯的体外细胞培养、动物模型与人体真实生理状态之间的差异是客观存在的。最新发展的类器官技术能够模拟人体软骨的微观生理特征，在一定程度上为软骨疾病研究提供了理想模型，也为基础研究向软骨再生临床转化搭建了桥梁。本文归纳总结了软骨类器官在关节软骨修复领域的应用场景，最后评述了当前软骨类器官研究存在的局限性，并展望了工程化软骨类器官的未来发展方向，包括将类器官技术与基因编辑技术、3D打印技术、微流控芯片技术进行深度融合，以期推动软骨类器官的进一步发展与应用。

Abstract: Osteoarthritis has emerged as a major public health concern affecting human well-being. Developing more effective therapeutic approaches for cartilage regeneration remains a key challenge in clinical practice. Due to the limitations of conventional research models such as 2D cell cultures and animal experiments, organoid technology, which has advanced rapidly in recent years, has attracted significant attention. As self-organizing 3D cell clusters derived from stem cells, organoids can more accurately simulate the complex structure and biological functions of cartilage tissue in vitro. In recent years, cartilage organoids established through tissue engineering, induced mesenchymal stem cell differentiation, and pluripotent stem cell differentiation technologies have gradually been developed, offering new hope for the repair of cartilage defects. This review summarizes the construction strategies and latest progress of cartilage organoid models, their applications in the field of cartilage regenerative medicine, discusses the limitations in cartilage organoid culture, and outlines future development directions for guiding stem cell-based multi-stage development using engineering strategies. Objective differences exist between simple in vitro cell culture, animal models, and the real physiological state of the human body. The newly developed organoid technology can simulate the microphysiological characteristics of human cartilage, providing an ideal model for the study of cartilage diseases to a certain extent, and also building a bridge for the clinical translation of basic research into cartilage regeneration. This paper summarizes the application scenarios of cartilage organoids in the field of articular cartilage repair, reviews the current limitations in cartilage organoid research, and prospects the future development directions of engineered cartilage organoids, including the in-depth integration of organoid technology with gene editing, 3D printing, and microfluidic chip technologies, so as to promote the further development and application of cartilage organoids.