Composite Scaffolds for Vascular Tissue Engineering

血管组织工程复合支架

• 批准号: 6915572
• 负责人: JAN P. STEGEMANN
• 金额: $ 17.33万
• 依托单位: RENSSELAER POLYTECHNIC INSTITUTE
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-08-01 至 2007-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6915572
• 关键词: bioengineering /biomedical engineering; biomaterial compatibility; biomaterial development /preparation; biomaterial evaluation; biomaterial interface interaction; biomechanics; cell proliferation; collagen; extracellular matrix; fibrin; polymers; tissue engineering; tissue support frame; vascular smooth muscle

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.

描述（由申请人提供）： 如果要在修复程序中生产并使用血管替代品，则毫无疑问需要改善脚手架。完全的生物聚合物支架具有一个优势，即细胞能够识别并结合它们，并最终用新矩阵重塑和/或替换它们。该项目中使用的创新方法是将胶原蛋白和纤维蛋白结合起来，以开发一类新的复合支架，直接解决当前生物聚合物矩阵的主要缺点之一：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，胶原蛋白和纤维蛋白在层压板结构中和/或作为互穿的双聚合物网络的组合将提供出色的机械性能。此外，我们假设纤维蛋白对这些胶原蛋白 - 纤维蛋白构建体血管平滑肌细胞（SMC）的生化作用将诱导细胞增殖和基质沉积，从而进一步改善构造特性。这些假设将通过完成以下特定目的来测试：1）构造和机械表征胶原蛋白和纤维蛋白的分层复合材料和混合复合结构，以及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质表达的影响。胶原蛋白和纤维蛋白的浓度，比率和分层构型将用于优化机械性能。此外，更好地了解细胞矩阵相互作用及其对SMC功能的影响将使脚手架成分可以量身定制，以鼓励稳健组织的发展。因此，我们将表征产生的矩阵的物理和生化功能，目的是结合此信息，以产生一种新型的完全生物复合材料，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。