Creation of a Knee Joint-on-a-Chip for Modeling Joint Diseases and Testing Drugs

Meagan J. Makarcyzk, Zhong Alan Li, Ilhan Yu, Haruyo Yagi, Xiurui Zhang, Lauren Yocum, Eileen Li, Madalyn R. Fritch, Qi Gao, Bruce A. Bunnell, Stuart B. Goodman, Rocky S. Tuan, Peter G. Alexander, Hang Lin

Research output: Contribution to journalArticlepeer-review


The high prevalence of debilitating joint diseases like osteoarthritis (OA) poses a high socioeconomic burden. Currently, the available drugs that target joint disorders are mostly palliative. The unmet need for effective disease-modifying OA drugs (DMOADs) has been primarily caused by the absence of appropriate models for studying the disease mechanisms and testing potential DMOADs. Herein, we describe the establishment of a miniature synovial joint-mimicking microphysiological system (miniJoint) comprising adipose, fibrous, and osteochondral tissue components derived from human mesenchymal stem cells (MSCs). To obtain the three-dimensional (3D) microtissues, MSCs were encapsulated in photocrosslinkable methacrylated gelatin before or following differentiation. The cell-laden tissue constructs were then integrated into a 3D-printed bioreactor, forming the miniJoint. Separate flows of osteogenic, fibrogenic, and adipogenic media were introduced to maintain the respective tissue phenotypes. A commonly shared stream was perfused through the cartilage, synovial, and adipose tissues to enable tissue crosstalk. This flow pattern allows the induction of perturbations in one or more of the tissue components for mechanistic studies. Furthermore, potential DMOADs can be tested via either "systemic administration" through all the medium streams or "intraarticular administration" by adding the drugs to only the shared "synovial fluid"-simulating flow. Thus, the miniJoint can serve as a versatile in vitro platform for efficiently studying disease mechanisms and testing drugs in personalized medicine.

Original languageEnglish
JournalJournal of Visualized Experiments
Issue number191
StatePublished - 27 Jan 2023


Dive into the research topics of 'Creation of a Knee Joint-on-a-Chip for Modeling Joint Diseases and Testing Drugs'. Together they form a unique fingerprint.

Cite this