Composite Scaffolds for Vascular Tissue Engineering

描述（由申请人提供）： 如果要生产血管替代品并在临床修复过程中使用，毫无疑问需要改进支架。全生物聚合物支架的优点是细胞能够识别并结合它们，并最终用新的基质重塑和/或替换它们。该项目采用的创新方法是将胶原蛋白和纤维蛋白结合起来开发一类新型复合支架，直接解决当前生物聚合物基质的主要缺点之一：缺乏足够的机械强度。我们的假设是，与单独的任何一种材料相比，层压结构中的胶原蛋白和纤维蛋白的组合和/或作为互穿双聚合物网络将提供优异的机械性能。此外，我们假设纤维蛋白对这些胶原纤维蛋白构建体中的血管平滑肌细胞（SMC）的生化作用将诱导细胞增殖和基质沉积，从而进一步改善构建体的特性。这些假设将通过完成以下具体目标进行检验：1) 构建胶原蛋白和纤维蛋白的层状复合材料和混合复合材料结构并对其进行机械表征，2) 确定胶原蛋白-纤维蛋白复合材料对 SMC 增殖、基质合成和表型特异性蛋白表达的影响。胶原蛋白和纤维蛋白的浓度、比例和分层结构将用于优化机械性能。此外，更好地了解细胞-基质相互作用及其对 SMC 功能的影响将允许定制支架组合物，以促进强健组织的发育。因此，我们将表征所产生的基质的物理和生化功能，目的是结合这些信息来产生一种新型的全生物复合材料，该材料可以承受血管系统的力，同时支持适当的细胞功能和组织重塑。

DESCRIPTION (provided by applicant): There is an unquestionable need for improved scaffolds if vascular substitutes are to be produced and used clinically in reparative procedures. Fully biological polymer scaffolds have the advantage that cells are able to recognize and bind to them, and ultimately to remodel and/or replace them with new matrix. The innovative approach used in this project is to combine collagen and fibrin to develop a new class of composite scaffolds that directly address one of the main shortcomings of current biopolymer matrices: the lack of adequate mechanical strength. Our hypothesis is that the combination of collagen and fibrin in a laminate architecture and/or as an interpenetrating double polymer network will provide superior mechanical properties, compared to either material alone. In addition, we hypothesize that the biochemical effects of fibrin on vascular smooth muscle cells (SMC) in these collagen-fibrin constructs will induce cell proliferation and matrix deposition that will further improve construct properties. These hypotheses will be tested by completing the following Specific Aims: 1) Construct and mechanically characterize layered composite and mixed composite structures of collagen and fibrin, and 2) Determine the effect of collagen-fibrin composites on SMC proliferation, matrix synthesis and phenotype-specific protein expression. The concentration, ratio and layering configuration of collagen and fibrin will be used to optimize mechanical properties. In addition, a better understanding of cell-matrix interactions and their effects on SMC function will allow the scaffold composition to be tailored to encourage the development of robust tissues. We will thus characterize the physical and biochemical functionality of the matrices produced, with the objective of combining this information to yield a novel type of fully biological composite material that can withstand the forces of the vascular system, while supporting appropriate cell function and tissue remodeling.