Tissue Engineering Approaches for Improved Treatment of Early Stage Osteonecrosis of the Hip

项目摘要 股骨头坏死(ONFH)是一种发病率呈上升趋势的潜在致衰性疾病。 全世界。仅在美国，每年就有大约2万例ONFH被诊断出来。至.为止 在美国进行的全髋关节置换术(THR)中，有18%是由ONFH引起的。在ONFH早期阶段， 各种保留髋关节的内科和外科治疗已经尝试过，但收效甚微。这是由于 事实上，维护患者自己的股骨头需要机械和生物策略 以承受间歇性负荷，同时重建坏死的股骨头节段。我们的 长期目标是使用组织工程学方法改善ONFH的治疗。我们的整体 假说是仿生功能分级支架(FGS)和预条件或 具有抗炎、成骨和血管功能的转基因间充质干细胞 促进信号将提供增强的机械和生物线索，以重建骨坏死 ONFH中的段。为了验证这些假设，我们拥有矫形外科专业知识的成熟团队， 生物材料和组织工程提出了以下具体目标：目标1是建立 FGS在激素性股骨头坏死股骨头重建中的应用目标2是建立更好的疗效 与未修饰的MSCs相比，增强的、预适应的或GM MSCs在骨重建中的作用 激素性股骨头坏死。目标3是确认FGS和Enhanced的组合 MSCs在更大程度上优化了ONFH的机械和生物学特性，而不是治疗或 仅核心解压。这个直接翻译项目将带来革命性的变化并显著改善 通过引入两种新的辅助疗法治疗ONFH，该辅助疗法包括仿生可吸收负荷- 轴承植入联合预处理或GM-MSCs重建和保存股骨头。 1“ “

Project Abstract 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" "