The overall goal of this study is to develop a tissue-engineered total joint replacement from an engineered biomaterial scaffold combined with adult bone marrow-derived mesenchymal stem cells (MSCs) for regeneration of the entire femoral surface of the hip joint. We have developed a novel three-dimensionally (3D) woven scaffold that mimics the biomechanical properties of native articular cartilage at the initial time of cell seeding. This anatomically formed scaffold is seeded with MSCs and pre-cultured ex vivo to create a hemispherical layer of living cartilage that can be used to completely replace a damaged joint surface. In the present study, we propose to perform in vivo studies in our canine osteoarthritis model to examine the potential of completely replacing the cartilage surface of the femoral head of the hip. The following two groups will be tested: 1) cartilage denuded from femoral head with implantation of fixation devices (i.e., anchors and suture) only (positive osteoarthritis control group), and 2) preformed 3D woven scaffold precultured with autologous MSCs (2 week ex vivo culture). All groups will be tested in vivo for 6 months. Primary outcomes will be based on joint function and comfort as measured by static and dynamic kinetic analysis, and validated semi-quantitative pain scales. 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 and to test for wear debris in the joint. Acetabular wear and labral damage will also be assessed histologically.
The goal of this study is to develop a technology for total bioartificial joint resurfacing as a treatment for hip osteoarthritis. The technologic basis involvs a combination of adult stem cells, retrieved from bone marrow, and a novel three-dimensionally woven scaffold that is designed to withstand joint loading and induce differentiation of the stem cells. The ultimate goal of this study is to develop tissue-engineering technologies that can eventually be used to treat osteoarthritis and other joint diseases.
|Little, Dianne; Johnson, Stephen; Hash, Jonathan et al. (2016) Functional outcome measures in a surgical model of hip osteoarthritis in dogs. J Exp Orthop 3:17|
|Moutos, Franklin T; Glass, Katherine A; Compton, Sarah A et al. (2016) Anatomically shaped tissue-engineered cartilage with tunable and inducible anticytokine delivery for biological joint resurfacing. Proc Natl Acad Sci U S A 113:E4513-22|
|Chainani, Abby; Little, Dianne (2016) Current Status of Tissue-Engineered Scaffolds for Rotator Cuff Repair. Tech Orthop 31:91-97|
|Liao, I-Chien; Moutos, Franklin T; Estes, Bradley T et al. (2013) Composite three-dimensional woven scaffolds with interpenetrating network hydrogels to create functional synthetic articular cartilage. Adv Funct Mater 23:5833-5839|