TISSUE ENGINEERED VASCULAR GRAFTS

描述(逐字摘自提案)：这是一个长期目标 建议开发适合于小鼠的组织工程化血管移植物 采用新型水凝胶支架材料的直径应用和遗传 改良的血管细胞。我们将使用的脚手架材料是 含有细胞等生物活性基团的光聚合水凝胶材料 粘附肽和固定化生长因子。机械性能， 例如，水凝胶支架材料的弹性模量可以广泛应用 通过改变聚合物的相对分子质量和交联度而变化。我们会 利用由内皮层和/或光滑层组成的管状结构 水凝胶支架中的肌肉细胞。种植到支架中的细胞可以 在体外进行转基因以改善组织性能，例如更好 转染型一氧化氮合酶或更好的抗凝血剂 用赖氨酸等交联酶转染法获得的力学性能 氧化物酶。细胞在组织生长过程中所经历的机械条件将 对组织工程的最终性能有很大的贡献 建造。探讨机械环境对组织的影响 形成工程化的血管移植物，我们将设计一种脉动流 生物反应器可以模拟活体所经历的机械条件。 组织工程构建物将暴露于不同水平的 同时控制壁面剪应力和循环的生理性流动 紧张。我们将研究动态机械环境对 工程化组织的特性包括细胞取向、形态和 增殖；细胞外基质合成、交联和组织； 血管活性基因的表达。

DESCRIPTION (verbatim from the proposal): The long-term objective of this proposal is to develop tissue engineered vascular grafts suitable for small diameter applications using novel hydrogel scaffold materials and genetically modified vascular cells. The scaffold materials that we will use are photopolymerized hydrogel materials containing bioactive moieties such as cell adhesion peptides and immobilized growth factors. The mechanical properties, such as the elastic modulus, of the hydrogel scaffold materials can be widely varied by changing the polymer molecular weight and crosslink density. We will utilize tubular constructs consisting of layers of endothelial and/or smooth muscle cells in the hydrogel scaffolds. The cells seeded into the scaffolds can be genetically modified ex vivo to improve tissue performance, e.g. better thromboresistance by transfection with nitric oxide synthase or better mechanical properties by transfection with crosslinking enzymes such as lysyl oxidase. Mechanical conditions experienced by cells during tissue growth will contribute significantly to the final properties of the tissue engineered construct. To investigate the influence of the mechanical environment on tissue formation of engineered vascular grafts, we will design a pulsatile flow bioreactor than can simulate the mechanical conditions experience in vivo. Tissue engineered constructs will be exposed to different levels of physiological flow with control over both the wall shear stress and cyclic strain. We will investigate the effects of a dynamic mechanical environment on properties of engineered tissues including cell orientation, morphology, and proliferation; extracellular matrix synthesis, crosslinking, and organization; and expression of vasoactive genes.