Issue

Vol. 18 (2026)

Next-Generation Joint-on-a-Chip: Toward Precision Mechanical Control in Multi-Tissue Systems

https://doi.org/10.1007/s40820-025-02031-5
Zhenjun Lv
Department of Biomedical Engineering, Research Center for Nano‑Biomaterials and Regenerative Medicine, Shanxi Key Laboratory of Functional Proteins, College of Artificial Intelligence, Taiyuan University of Technology, Taiyuan 030024, People’s Republic of China
Yuwei Chai
Department of Biomedical Engineering, Research Center for Nano‑Biomaterials and Regenerative Medicine, Shanxi Key Laboratory of Functional Proteins, College of Artificial Intelligence, Taiyuan University of Technology, Taiyuan 030024, People’s Republic of China
Xiumei Zhang
Department of Biomedical Engineering, Research Center for Nano‑Biomaterials and Regenerative Medicine, Shanxi Key Laboratory of Functional Proteins, College of Artificial Intelligence, Taiyuan University of Technology, Taiyuan 030024, People’s Republic of China
Weiwei Lan
Department of Biomedical Engineering, Research Center for Nano‑Biomaterials and Regenerative Medicine, Shanxi Key Laboratory of Functional Proteins, College of Artificial Intelligence, Taiyuan University of Technology, Taiyuan 030024, People’s Republic of China
Junchao Wei
Shanxi Key Laboratory of Bone and Soft Tissue Injury Repair, Second Hospital of Shanxi Medical University, Taiyuan 030024, People’s Republic of China
Lu Li
Shanxi Key Laboratory of Bone and Soft Tissue Injury Repair, Second Hospital of Shanxi Medical University, Taiyuan 030024, People’s Republic of China
Weiyi Chen
Department of Biomedical Engineering, Research Center for Nano‑Biomaterials and Regenerative Medicine, Shanxi Key Laboratory of Functional Proteins, College of Artificial Intelligence, Taiyuan University of Technology, Taiyuan 030024, People’s Republic of China
Yiting Lei
Department of Biomedical Engineering, Faculty of Engineering, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong SAR, People’s Republic of China
Jun Liu
Department of Biomedical Engineering, Faculty of Engineering, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong SAR, People’s Republic of China
Zhong Alan Li
Department of Biomedical Engineering, Faculty of Engineering, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong SAR, People’s Republic of China
Di Huang
Department of Biomedical Engineering, Research Center for Nano‑Biomaterials and Regenerative Medicine, Shanxi Key Laboratory of Functional Proteins, College of Artificial Intelligence, Taiyuan University of Technology, Taiyuan 030024, People’s Republic of China

Corresponding Author: Di Huang

huangjw2067@163.com

Nano-Micro Letters, Vol. 18 (2026), Article Number: 187

Abstract

Osteoarthritis is among the leading causes of disability worldwide, and no pharmacological therapies currently exist to reverse its progression. This lack of therapies is primarily attributed to the inadequacies of conventional in vitro models of joint physiology and pathology, which significantly hinder advancements in disease mechanism research and drug development. As an emerging in vitro joint model, joint-on-a-chip (JoC) technology allows low-cost, efficient simulation of physiological and pathological joint activities, making it a focal point of current research. Cartilage, subchondral bone, and synovium are among the key tissues required for constructing in vitro joint models, with cartilage playing a central load-bearing role in joint movement. This article provides a detailed overview of the structure and function of these tissues, with an emphasis on the load-bearing mechanisms of cartilage, and identifies the microenvironmental characteristics that JoC should aim to replicate. Subsequently, we review the current types of JoC and highlight their core challenge: the seamless integration of multi-tissue co-culture with specific mechanical stimulation. To address this issue, we propose potential solutions and present a conceptual design for a JoC prototype. Finally, we discuss the challenges and issues related to the outlook for JoC. Our ultimate goal is to develop a JoC capable of replicating the key microenvironments of joints, serving as a high-performance in vitro joint model to advance the study of disease mechanisms and facilitate drug development.


Highlights:
1 Outlines key structural and microenvironmental features of joints.
2 Discusses strategies to integrate mechanical stimulation with multi-tissue co-culture.
3 Proposes innovative design concepts toward next-generation joint-on-a-chip platforms.

Keywords

Joint-on-a-chip Osteoarthritis Tissue microenvironment Mechanical stimulation Multi-tissue co-culture
Lv, Zhenjun, Yuwei Chai, Xiumei Zhang, Weiwei Lan, Junchao Wei, Lu Li, Weiyi Chen, Yiting Lei, Jun Liu, Zhong Alan Li, and Di Huang. 2026. “Next-Generation Joint-on-a-Chip: Toward Precision Mechanical Control in Multi-Tissue Systems”. Nano-Micro Letters 18 (January):187. https://doi.org/10.1007/s40820-025-02031-5.
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