Abstract

Tissue Chips in Space: Human Cartilage-Bone-Synovium Microphysiological System for Post-Traumatic Osteoarthritis

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

Post-traumatic osteoarthritis (PTOA) is caused by a traumatic impact joint injury associated with an augmented inflammatory environment (such as an ACL rupture). This results in loss of cartilage and impaired joint function, severely impacting the quality of life of otherwise healthy individuals, compounded by the fact that there are no disease-modifying drugs available for OA/PTOA, only short acting pain killers that do not halt disease progression. Astronauts may be at heightened risk of altered musculoskeletal physiology, thus impacting their Space mission. With an aim of PTOA disease management on Earth and supporting astronaut health during long space missions, our overall objective has been to develop a microphysiological system (MPS) to simulate aspects of PTOA pathogenesis and progression in vitro, and to use this MPS to develop therapeutic regimens incorporating appropriate drugs and dynamic exercise loading to prevent disease progression and stimulate pro-anabolic responses. Analyses to date from ISS experiments show changes in human knee tissues indicative of the earliest events in the initiation and progression of PTOA. The effects of human variability are also under study. Use of such an MPS on earth and in LEO-based platforms could enable accelerated disease modeling, providing unique insights into disease progression and development of therapeutic interventions. Effects of altered loading of joint cartilage in space may affect the rate of cartilage breakdown leading to OA. Microgravity may uniquely enable the study of joint-disuse versus exercise in management of OA and PTOA.