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REVIEW ARTICLE

Modular construction of osteochondral organoids: Recapitulating gradients and microenvironment

Zihan Xu1 ,  Yixing Ren2* ,  Xiaoming Li1*
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1 Key Laboratory for Biomechanics and Mechanobiology of Ministry of Education, Key Laboratory of Innovation and Transformation of Advanced Medical Devices of Ministry of Industry and Information Technology, National Medical Innovation Platform for Industry-Education Integration in Advanced Medical Devices (Interdiscipline of Medicine and Engineering), Beijing Advanced Innovation Center for Biomedical Engineering, School of Biological Science and Medical Engineering, Beihang University, Beijing , China
2 Department of Joint Surgery, The Fourth Central Hospital of Baoding City, Baoding , China
OR, 026360031 https://doi.org/10.36922/OR026360031
Received: 31 August 2026 | Revised: 28 September 2026 | Accepted: 1 October 2026 | Published online: 15 October 2026
© 2026 by the Author(s). This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution 4.0 International License ( https://creativecommons.org/licenses/by/4.0/ )
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Abstract

In recent years, bone and cartilage organoid technology has attracted increasing attention and undergone rapid development, offering emerging approaches and broad prospects for osteoarthritis (OA) treatment, tissue engineering, regenerative medicine, and related fields. Despite the documented progress of bone and cartilage organoid models in structural biomimetic design, their limitation in the holistic reproduction of osteochondral unit, including interface gradient and physiological functions, remains a challenge for clinical application. Based on cutting-edge research, this review summarizes modular construction strategies of bone and cartilage organoids, targeting three types of signals in the osteochondral unit microenvironment: mechanical, metabolic, and immune. First, this review analyzes the microenvironment characteristics of the osteochondral unit, including the interface gradient and major signal pathways, then discusses the essential requirements for construction of osteochondral organoid. Then, based on different emphases, various osteochondral or cartilage organoid examples are classified and reviewed. Furthermore, this paper analyzes their advantages, bottlenecks, and feasibility, thereby outlining a design framework for modular organoids. Next, the technical pathways for functional coupling between modules are discussed, mainly including 3D bioprinting, organoid assembly, and microfluidic chips, in an attempt to provide solutions to the integrated challenge of osteochondral organoids. Then, the monitoring of multidimensional signals in organoids culture system is discussed. Finally, feasibility of artificial intelligence (AI) and machine learning in this field is discussed, with the aim to establish a closed-loop system for intelligent organoid culture.

Keywords
Organoid
Osteochondral
Osteoarthritis
Microenvironment
Artificial intelligence
3D bioprinting
Funding
This work was supported by the National Natural Science Foundation of China (Nos. 32571560 and 32171345), the Hebei Natural Science Foundation (No. H2024104023), the Beijing Nova Programme Interdisciplinary Cooperation Project (No. 20230484464), the Fok Ying Tung Education Foundation (No. 141039), the 111 Project (No. B13003), and the International Joint Research Center of Aerospace Biotechnology and Medical Engineering, Ministry of Science and Technology of China.
Conflict of interest
The authors declare they have no conflict of interest.
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Organoid Research, Electronic ISSN: 3082-8503 Published by AccScience Publishing
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