Lyu Xukun, Wang Jian, Su Jiacan
Department of Orthopedics, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Trauma Orthopedics Center, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Cell Prolif. 2025 Apr 26:e70043. doi: 10.1111/cpr.70043.
Osteoarthritis (OA) is the most prevalent degenerative joint disease worldwide, imposing a substantial global disease burden. However, its pathogenesis remains incompletely understood, and effective treatment strategies are still lacking. Organoid technology, in which stem cells or progenitor cells self-organise into miniature tissue structures under three-dimensional (3D) culture conditions, provides a promising in vitro platform for simulating the pathological microenvironment of OA. This approach can be employed to investigate disease mechanisms, carry out high-throughput drug screening and facilitate personalised therapies. This review summarises joint structure, OA pathogenesis and pathological manifestations, thereby establishing the disease context for the application of organoid technology. It then examines the components of the arthrosis organoid system, specifically addressing cartilage, subchondral bone, synovium, skeletal muscle and ligament organoids. Furthermore, it details various strategies for constructing OA organoids, including considerations of cell selection, pathological classification and fabrication techniques. Notably, this review introduces the concept of intelligent manufacturing of OA organoids by incorporating emerging engineering technologies such as artificial intelligence (AI) into the organoid fabrication process, thereby forming an innovative software and hardware cluster. Lastly, this review discusses the challenges currently facing intelligent OA organoid manufacturing and highlights future directions for this rapidly evolving field. By offering a comprehensive overview of state-of-the-art methodologies and challenges, this review anticipates that intelligent, automated fabrication of OA organoids will expedite fundamental research, drug discovery and personalised translational applications in the orthopaedic field.
骨关节炎(OA)是全球最普遍的退行性关节疾病,带来了巨大的全球疾病负担。然而,其发病机制仍未完全明确,且仍缺乏有效的治疗策略。类器官技术是指干细胞或祖细胞在三维(3D)培养条件下自组织形成微型组织结构,为模拟OA的病理微环境提供了一个有前景的体外平台。这种方法可用于研究疾病机制、进行高通量药物筛选并促进个性化治疗。本综述总结了关节结构、OA发病机制及病理表现,从而为类器官技术的应用建立疾病背景。接着,本文考察了关节类器官系统的组成部分,特别阐述了软骨、软骨下骨、滑膜、骨骼肌和韧带类器官。此外,本文详细介绍了构建OA类器官的各种策略,包括细胞选择、病理分类和制造技术等方面的考虑因素。值得注意的是,本综述引入了通过将人工智能(AI)等新兴工程技术融入类器官制造过程来实现OA类器官智能制造的概念,从而形成一个创新的软硬件集群。最后,本综述讨论了当前智能OA类器官制造面临的挑战,并突出了这个快速发展领域的未来方向。通过全面概述最先进的方法和挑战,本综述预计OA类器官的智能、自动化制造将加快骨科领域的基础研究、药物发现和个性化转化应用。