Abstract

Human Cartilage-Bone-Synovium Chip to Study Post-Traumatic Osteoarthritis Pathogenesis and Treatment on Earth and in Space

Alan Grodzinsky, Professor of Biological, Electrical and Mechanical Engineering, Director of the MIT Center for Biomedical Engineering, Massachusetts Institute of Technology (MIT)

Acute joint injuries from sports, exercise or accident-related trauma often progress to post-traumatic Osteoarthritis (PTOA), comprising ~12% of all OA cases. Such joint injuries can cause mechanical damage to cartilage combined with an inflammatory response associated with the synovial lining of the joint capsule. Together, these events lead to cartilage and subchondral bone pathologies including cell death, tissue degradation, neo-angiogenesis, osteophyte and cyst formation and synovial fibrosis. Astronauts are known to sustain a higher rate of exercise-related joint injuries, during their mission period. Since PTOA commonly affects young and otherwise healthy individuals, knee replacement is not a desirable option. Acknowledging the urgent need to identify disease-modifying therapeutics to ameliorate degenerative evolution of OA/PTOA, we carried out this study to (1) simulate aspects of acute joint injury biology on earth and in space using a human Cartilage-Bone-Synovium coculture model (CBS-MPS), (2) to investigate the potential of selected therapeutics to reduce cell death and tissue degradation, and (3) to utilize the Techshot Multi-Use Variable-g Platform (MVP) to study PTOA-related pathogenesis and management on the ISS.