PI: Sabrina Jedlicka
Co-PI: Susan Perry
University: Lehigh University
Industry partner: Sachdev Orthopedics
Knee Osteoarthritis (OA) is a progressive, debilitating condition affecting millions of adults over the age of 50. In the United States alone, the economic burden of OA exceeds $27 billion annually in healthcare expenditures. Current standard-of-care treatments primarily focus on palliative symptom management rather than halting the underlying disease progression. Consequently, many patients eventually face "bone-on-bone" contact, necessitating total knee arthroplasty. There is an urgent clinical need for disease-modifying therapies that preserve joint cartilage and delay surgical intervention. Autologous biologics—including bone marrow extract and platelet-rich plasma—have emerged as promising alternatives. However, recent research indicates significant variability in the protein composition of these therapies, creating uncertainty regarding their long-term safety and efficacy. Specifically, the role of alpha-2-macroglobulin (A2M), a known chondroprotective molecule, remains under-characterized. While commercial devices now exist to concentrate A2M from human blood, the impact of its various native isoforms remains unknown. This project investigates the molecular profile and therapeutic utility of A2M extracts in the knee joint, examining the activity level of A2M in protease inhibition, but also examining how the ratio of proteins in A2M extracts (such as albumin and IgG1) impacts this activity. By elucidating the biochemical behavior of these specific molecular targets, this research aims to optimize autologous biological treatments. The goal is to provide a precision-medicine approach to knee OA that reduces patient pain, improves joint longevity, and significantly extends the time before a total joint replacement is required.