It is estimated that only about 15% of young patients suffering from!activity limiting hip osteoarthritis (OA) choose to undergo traditional hip replacement surgery. This low percentage is attributed to the shortened projected lifetime of hip implants for active patients and the subsequent need for revision surgeries that are plagued with higher complication rates and overall decreased effectiveness. To address the needs of this young arthritic patient population with debilitating disease, we have developed a functional bi-layered implant that is comprised of a three-dimensionally (3D) woven scaffold on its surface that is microscopically bonded to a rigid printed substrate. The top layer of the implant is engineered from a high-performance 3D woven bioresorbable (poly(e-caprolactone) or PCL) textile to mimic many of the constitutive properties of native articular cartilage, and the bioprinted base layer is engineered (also from PCL) to facilitate integration with host bony tissues. In total, the implant is designed to resurface pathologic areas of the articular surfaces afflicted with arthritic disease and, consequently, provides a ?biosynthetic? solution to this young patient in a manner less invasive than is required for a traditional joint prosthesis. The implant can be easily manufactured in a variety of anatomical shapes or even custom shaped to fit the exact contour of the patient?s anatomy. In the present study, our goal is to perform in vivo studies in a canine OA model that we have recently developed to examine the potential of repairing the load bearing cartilage of the hip femoral head, a site often implicated in the initiation of OA in the young patient. The following three groups will be tested: 1) a 10 mm diameter x 2 mm deep empty defect on the cranio-dorsal aspect of the femoral head (OA control group), 2) the same 10 mm x 2 mm defect filled with our biomimetic implant (acellular experimental treatment group), and 3) the same defect seeded with MSCs, and pre-cultured ex vivo to create an anatomically shaped layer of living cartilage (tissue- engineered treatment group). All groups will be tested in vivo for 12 months ? this duration is consistent with FDA recommendations for cartilage repair models and will therefore facilitate engagement with FDA to define preclinical testing strategies and plans for our implant. Outcome measures (limb girth, radiography, kinetic gait analysis, and spontaneous activity measurement) will be obtained at baseline and every month for 12 months following surgery. Sequential radiographs of the hip (baseline and every month) will also be taken to monitor any joint morphological changes. At sacrifice, the histological and biomechanical properties of the joint tissues will be compared to radiograph-based measurements. Serum, synovial fluid, synovium, and lymph nodes will be analyzed for biomarkers of osteoarthritis, as well as for adverse inflammatory reactions. We expect that positive outcomes from this study will enable us to move this technology closer to clinical practice, with the ultimate goal of developing tissue-engineered strategies to treat OA and other cartilage-related disease. We further expect to use these data to attract investors as we seek capital to advance this technology to market. !
The purpose of this project is to further the development of a treatment for osteoarthritis in the young patient population that currently has no good treatment options. Our approach comprises a unique bilayered scaffold that is engineered to withstand joint loading while supporting the regeneration of diseased joint tissues, thereby offering distinct advantages over invasive prosthetic devices. A successful outcome will help move this technology closer to the clinic, potentially becoming a viable treatment for osteoarthritis and other joint diseases.
