University of Pittsburgh Swanson School of Engineering 1 article published in JoVE Bioengineering Creation of a Knee Joint-on-a-Chip for Modeling Joint Diseases and Testing Drugs Meagan J. Makarcyzk1,2, Zhong Alan Li1,3, Ilhan Yu1, Haruyo Yagi1, Xiurui Zhang1, Lauren Yocum1, Eileen Li1, Madalyn R. Fritch1, Qi Gao4, Bruce A. Bunnell5, Stuart B. Goodman4,6, Rocky S. Tuan1,8, Peter G. Alexander1,7, Hang Lin1,2,7 1Department of Orthopaedic Surgery, University of Pittsburgh School of Medicine, 2Department of Bioengineering, University of Pittsburgh Swanson School of Engineering, 3Department of Neurobiology, University of Pittsburgh School of Medicine, 4Department of Orthopaedic Surgery, Stanford University, 5Department of Microbiology, Immunology, and Genetics, University of North Texas Health Science Center, 6Department of Bioengineering, Stanford University, 7McGowan Institute for Regenerative Medicine, University of Pittsburgh School of Medicine, 8The Chinese University of Hong Kong We provide detailed methods for generating four types of tissues from human mesenchymal stem cells, which are used to recapitulate the cartilage, bone, fat pad, and synovium in the human knee joint. These four tissues are integrated into a customized bioreactor and connected through microfluidics, thus generating a knee joint-on-a-chip.