(69f) Articular Joint on a Chip: An in-Vitro Co-Culture System of Cartilage and Joint Capsule Synovium to Simulate Post-Traumatic Osteoarthritis
Post-traumatic Osteoarthritis (PTOA) is a degenerative joint disease triggered by a traumatic joint injury such as an anterior cruciate ligament (ACL) tear. PTOA accounts for ~12% of over 90 million adults in the United States who have OA. While degradation of cartilage is the hallmark of OA/PTOA, it is a disease of the entire joint, including tissues such as subchondral bone and the joint capsule synovium. There are currently no effective disease modifying OA drugs (DMOADs) to slow or halt progression of the disease. While there are promising new therapeutic drug candidates along with nanocarriers to deliver drugs in a targeted manner which are tested in vitro and in animal models of PTOA to prove efficacy, there have been no successful clinical trials in humans. To ensure that efficacy in preclinical trials translates to success in clinical trials, it is important that the in vitro and in vivo models closely simulate the human disease. Currently, most in vitro models to test potential DMOADs and their delivery carriers for OA/PTOA have focused on cell and explant cultures involving cartilage alone using mechanically induced injury or inflammatory cytokines to induce proteolytic cartilage matrix degradation. However, there is increasing evidence that cartilage, bone and joint capsule synovium all contribute to disease progression, both individually and through cross talk with each other. To capture these interactions, we have developed an in vitro model involving the co-culture of cartilage and synovium. Individual cultures of cartilage alone and synovium alone were included as controls. These experiments were carried out with tissues harvested from young bovine calves and from normal human donors (without osteoarthritis). Increased expression of pro-inflammatory cytokines was found in mono-cultures and co-cultures involving synovium (both human and bovine). Importantly, the levels of these cytokines are similar to those found in the human joint immediately after an ACL tear. Additionally, the presence of synovium in the co-culture led to an increase in cartilage extracellular matrix degradation and a decrease in cartilage cell viability compared to cartilage mono-culture. Therefore, the co-culture system is able to simulate aspects of PTOA and joint tissue interactions that are not necessarily captured by a mono-culture system. We are now using this physiologically relevant co-culture system to test potential PTOA therapeutics and drug delivery nanocarriers.