Osteonecrosis of the femoral head (ONFH) is a potentially debilitating disease that is increasing in incidence worldwide. In the United States alone, approximately 20,000 cases of ONFH are diagnosed each year. Up to 18% of total hip replacements (THR) performed in the USA are a result of ONFH. In the early stages of ONFH, various hip joint preserving medical and surgical treatments have been tried with limited success. This is due to the fact that maintenance of the patient's own femoral head requires both mechanical and biological strategies to withstand intermittent loading and, at the same time, reconstitute the necrotic femoral head segment. Our long-term goal is to improve the treatment of ONFH using a tissue engineering approach. Our overall hypothesis is that the combination of a biomimetic functionally-graded scaffold (FGS), and preconditioned or genetically modified (GM) mesenchymal stem cells (MSCs) with anti-inflammatory, osteogenic and vascular promoting signals will provide enhanced mechanical and biological cues to reconstitute the osteonecrotic segment in ONFH. To test these hypotheses, our established team with expertise in orthopaedic surgery, biomaterials, and tissue engineering proposes the following Specific Aims:
Aim 1 is to establish the efficacy of FGS for reconstitution of the femoral head in steroid-induced ONFH.
Aim 2 is to establish superior efficacy of enhanced, preconditioned or GM MSCs, compared to unmodified MSCs for reconstitution of bone in the femoral head in steroid-induced ONFH.
Aim 3 is to confirm that the combination of the FGS and enhanced MSCs optimizes the mechanical and biological properties in ONFH to a greater degree than either treatment or core decompression alone. This directly translational project will revolutionize and significantly improve the treatment of ONFH by introducing two novel adjunctive therapies consisting of a biomimetic resorbable load- bearing implant together with preconditioned or GM MSCs for femoral head reconstitution and preservation. 1
Osteonecrosis (death of cells) of the femoral head (ONFH) usually affects individuals between 30 and 50 years of age, and generates about 20,000 new cases each year in USA. This eventually leads to collapse of bone and cartilage, and severe, painful, debilitating degenerative arthritis. To prevent the progression of the disease, we propose to develop a biodegradable composite scaffold with functionally-graded structural and mechanical properties, in combination with preconditioned or genetically-modified mesenchymal stem cells, to revitalize the osteonecrotic area of the femoral head. 1' '
|Maruyama, Masahiro; Nabeshima, Akira; Pan, Chi-Chun et al. (2018) The effects of a functionally-graded scaffold and bone marrow-derived mononuclear cells on steroid-induced femoral head osteonecrosis. Biomaterials 187:39-46|
|Lin, Tzuhua; Kohno, Yusuke; Huang, Jhih-Fong et al. (2018) NF?B sensing IL-4 secreting mesenchymal stem cells mitigate the proinflammatory response of macrophages exposed to polyethylene wear particles. J Biomed Mater Res A 106:2744-2752|