Vascularized Bone Grafts for Tissue Engineering

候选人Edward Botchwey博士在骨科生物材料和组织工程方面经验丰富。 他的长期职业目标是建立一个独立的研究实验室， 发展实验和计算方法来研究血管生成的作用， 骨组织工程中的微血管重建。他的中期目标是共同努力 与导师托马斯Skalak博士，弗吉尼亚大学生物医学工程主席，利用 在弗吉尼亚大学提供的巨大资源，以实现这一目标。该提案概述了职业发展 计划设计和建立新的使能技术，能够共同培养成骨细胞和血管， 组织工程支架内的内皮细胞，并改变细胞的几何排列， 可以探索骨重建和新血管形成两者的优化。体内实验 将开发评估和新的计算建模方法，以确定 组合的细胞分布，最有利于骨愈合和血管重塑。具体 该提案的目标是：1）量化灌注流速和内部孔隙网络的影响 基于三维微球内rMSC增殖、基因表达和矿化沉积的几何学 定制灌注的支架。2)建立新的大鼠微血管共培养的实验方法 Aim1中形成的矿化rMSC构建体内的内皮细胞（rVEC）。具体而言，rVEC将是 根据两个预定的几何构型培养，（a）均匀分散的网络， 所述支架，和（B）围绕所述支架的外部层压层。3)将联合收割机的实验和 计算方法来确定血管内皮细胞的几何分布是否 Aim 2开发的矿化骨组织工程支架增强微血管网络 重建和异位骨形成在定制的大鼠窗室模型在体内。

The candidate, Dr. Edward Botchwey, is experienced in orthopaedic biomaterials and tissue engineering. His long term career goal is to establish an independent research laboratory to pursue his interests in the development of experimental and computational methods to study the role of angiogenesis and microvascular remodeling in bone tissue engineering. His intermediate term objective is to work together with mentor Dr. Thomas Skalak, chair of biomedical engineering at the University of Virginia, to leverage the tremendous resources available at UVA to achieve this goal. This proposal outlines a career development plan to design and build new enabling technologies capable of co-cultivating osteoblastic cells and vascular endothelial cells within tissue engineered scaffolds, and varying the geometric arrangement of cells so that optimization of both bone remodeling and neo-vascularization can be explored. In vivo experimental assessment and novel computational modeling approaches will be developed to identify the geometries of combined cell distribution that are most conducive to bone healing and vascular remodeling. The specific objectives of the proposal are 1) to quantify the effects of perfusion flow velocity and internal pore network geometry on rMSC proliferation, gene expression, and mineralized deposition within 3-D microsphere based scaffolds in a customized perfusion. 2) to develop new experimental methods to co-culture rat microvascular endothelial cells (rVECs) within mineralized rMSC constructs formed in Aim1. Specifically, rVECs will be cultivated according to two predetermined geometric configurations, (a) uniformly dispersed network within the scaffolds, and (b) externally laminated layer around the scaffolds. 3) to combine experimental and computational methods to determine whether the geometric distribution of vascular endothelial cells within mineralized bone tissue engineered scaffolds developed in Aim 2 enhance microvascular network remodeling and ectopic bone formation in a customized rat window chamber model in vivo.