Biodegradable Matrices for Bone Healing

项目摘要/摘要：用于骨修复的可生物降解基质 在美国，每年有超过650万例骨科手术需要使用移植物来修复骨缺损 只有我们两个。大段骨缺损的修复是重建外科领域的难题。几次植骨 包括自体移植物、同种异体移植物和可生物降解的多孔支架在内的选择已经在临床上被常规使用。 只取得了有限的成功。例如，在骨组织工程支架中，组织向内生长仅限于表面 (BTE)，因为很难获得细胞和支架内的营养物质。支撑所需的孔隙度 BTE支架中的组织植入导致骨科用这些材料的次优力学性能 申请。因此，有必要开发满足两种孔隙率要求的BTE支架 是组织生长和血管形成所必需的，也是承载所必需的最佳机械性能。 此外，骨传导、骨诱导和骨整合特性将提高骨的成功率。 嫁接材料。我们正在进行的研究和出版物已经证明了开发的可行性 机械强度高的无孔复合支架，由具有不同降解特性的材料制成 导致在复合材料内逐渐形成相互连接的孔，从而允许组织向内生长 在一段时间内(1，2)。同样，使用螺旋结构的脚手架，我们已经展示了几何体可以 旨在促进细胞的增殖、渗透和均匀的矿化基质沉积 脚手架建筑(3-6个)。这些机械稳定的最初无孔支架能够支撑骨。 大鼠颅骨缺损区和兔颅骨节段中基质降解导致的多孔结构演化导致的向内生长 无生长因子和细胞包涵体的骨缺损。基于这些发现，我们假设通过改变 脚手架的组成和几何形状我们将能够创建BTE脚手架与可编程的机械 强度和多孔结构，以更好地满足承重部位的骨愈合要求。这项研究 项目将分为以下四个阶段：目标1：优化材料成分和几何结构以实现 承载骨愈合应用所需的机械稳定性和渐进性降解。目标2： 了解支架降解对人骨髓间充质干细胞的影响 黏附、渗透、增殖、分化和矿化基质的产生。目标3：在体内评估 支架内的生物相容性和动态孔隙形成。目的4：评价人工骨的骨愈合能力。 不同几何形状和机械强度的支架在兔尺骨的临界大小节段性缺损处。

Project Summary/Abstract: Biodegradable Matrices for Bone Healing More than 6.5 million orthopaedic procedures require the use of grafts to repair bone defects every year in the US alone. Repair of large bone defects is a challenging problem in reconstructive surgery. Several bone graft options including autografts, allografts, and biodegradable porous scaffolds have been routinely used in the clinics with limited success. For example, tissue ingrowth is limited to the surface in bone tissue engineering scaffolds (BTE) because of poor access to cells and nutrients within scaffolds. The porosity that is necessary to support tissue ingrowth in BTE scaffolds results in sub-optimal mechanical properties of these materials for orthopedic applications. Therefore, there is a need to develop BTE scaffolds which will fulfill the requirements of both porosity necessary for tissue ingrowth and vascularization, and optimal mechanical properties necessary for load bearing. In addition, osteoconductive, osteoinductive, and osteointegrative properties will improve the success of bone graft materials. Our ongoing studies and publications have demonstrated the feasibility of developing mechanically strong non-porous composite scaffolds from materials with differential degradation profiles that result in the progressive formation of interconnected pores within the composite material allowing tissue ingrowth over a period of time (1, 2). Likewise, using spirally structured scaffolds we have shown that geometry can be designed to promote cell proliferation, infiltration, and homogenous mineralized matrix deposition throughout the scaffold architecture (3-6). These mechanically stable initially non-porous scaffolds were able to support bone ingrowth due to evolving porous architecture via matrix degradation in rat calvarial defects and rabbit segmental bone defects without inclusion of growth factors and cells. Based on these findings we hypothesize that by altering scaffold composition and geometry we will be able to create BTE scaffolds with programmable mechanical strength and porous structure to better serve the bone healing requirements at load bearing sites. The research project will have the four following phases: Aim 1: To optimize material composition and geometry to achieve necessary mechanical stability and progressive degradation for load-bearing bone-healing applications. Aim 2: To understand the effect of scaffold degradation on human bone marrow derived mesenchymal stem cell (MSCs) adhesion, infiltration, proliferation, differentiation, and mineralized matrix production. Aim 3: To assess in vivo biocompatibility and dynamic pore formation within the scaffolds. Aim 4: To evaluate the bone healing ability of scaffolds with different geometry and mechanical strength in a critical size segmental defect in the rabbit ulna.