Vascularized Bone Grafts for Tissue Engineering

用于组织工程的血管化骨移植物

• 批准号: 7034319
• 负责人: Edward A. Botchwey
• 金额: $ 12.55万
• 依托单位: UNIVERSITY OF VIRGINIA
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-03-05 至 2010-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7034319
• 关键词: angiogenesis; bioengineering /biomedical engineering; biotechnology; bone regeneration; cell proliferation; computational biology; computed axial tomography; flow cytometry; gene expression; hematopoietic stem cells; hemodynamics; histology; intercellular connection; laboratory rat; mathematical model; microcapsule; microcirculation; microsurgery; mixed tissue /cell culture; molecular dynamics; normal ossification; osteoblasts; technology /technique development; tissue engineering; tissue support frame; vascular endothelium

DESCRIPTION (provided by applicant): 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 viv.

应聘者描述(申请人提供)：应聘者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，以追求他对开发实验和计算方法的兴趣，以研究血管生成和微血管重塑在骨组织工程中的作用。 他的中期目标是与导师、弗吉尼亚大学生物医学工程主席Thomas Skalak博士合作，利用UVA现有的巨大资源来实现这一目标。这份提案概述了一项职业发展计划，旨在设计和建立新的使能技术，能够在组织工程支架内共同培养成骨细胞和血管内皮细胞，并改变细胞的几何排列，以便探索骨重建和新生血管的优化。体内实验评估和新的计算建模方法将被开发出来，以确定最有利于骨愈合和血管重建的组合细胞分布的几何形状。 该建议的具体目标是1)量化灌流速度和内部孔网络几何形状对RMSC增殖、基因表达和定制灌流中三维微球支架内矿化沉积的影响。2)建立新的实验方法，将大鼠微血管内皮细胞(RVECs)与Aim1形成的矿化RMSC共培养。具体来说，rVEC将根据两种预定的几何构型进行培养，(A)均匀分散在支架内的网络，和(B)支架周围的外部叠层。3)采用实验和计算相结合的方法，确定Aim 2开发的矿化骨组织工程支架中血管内皮细胞的几何分布是否促进了定制的大鼠VIV窗口室模型的微血管网络重构和异位骨形成。