Discovering drugs to treat osteoarthritis with a knee joint-on-a-chip model

Osteoarthritis (OA) is the most prevalent degenerative joint disease, which is mainly characterized by pain and physical disability. Currently, no FDA-approved disease-modifying OA drugs (DMOADs) are currently available to stop, slow, or reverse the progression of OA. Numerous DMOADs have been investigated, but the results were disappointing and subsequently terminated. The reasons for the failures included unexpected toxicity and poor treatment outcomes that were not identified during preclinical studies, suggesting deficiencies of currently available models for the development of DMOADs. Recently, with grant support from the NCATS/NIAMS (UG3/UH3TR002136), our team has successfully developed an in vitromulti-component microphysiological joint chip (microJoint), integrating engineered osteochondral complexes, synovium, adipose tissue, and immune cells (macrophages). In this teaming grant, we will build a multidisciplinary team from schools of Medicine, Engineering, and Pharmacy that is needed for a successful application of the next large-scale external funding. The new team will develop a collaboration plan and work together on a project to generate preliminary data for the next grant application. In particular, we will add the additional features, including mechanical stimuli emulations into the current microJoint system and work with drug discovery scientists to test the drugs. Our multidisciplinary team under this teaming grant proposal will also start to work together with the OA physician. The team will have a bi-weekly meeting to discuss the progress toward the milestones and development of the next large-scale grant application. The PIs also communicate on an almost daily basis, either by e-mail or phone, to discuss related matters. In addition, we will hold a quarterly journal club for the entire team and discuss the publications that are relevant to tissue chip. With the success of teaming grant, we will organize the work into a manuscript and submit it. This publication is critical component to show the collaboration history of the team and feasibility in the new proposal.