TISSUE ENGINEERED VASCULAR GRAFTS

组织工程血管移植物

• 批准号: 6491785
• 负责人: Kytai Truong Nguyen
• 金额: $ 3.48万
• 依托单位: UT SOUTHWESTERN MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-08-01 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6491785
• 关键词: biodegradable product; biomaterial development /preparation; bioreactors; cardiovascular transplantation; cell components; cell proliferation; crosslink; extracellular matrix; gene expression; hemodynamics; polymers; tissue /cell culture; tissue engineering; vascular endothelium

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.

描述（来自提案的逐字逐句）：该提案的长期目标 一项建议是开发适合小血管的组织工程血管移植物， 直径的应用，使用新的水凝胶支架材料和遗传 修饰的血管细胞我们将使用的支架材料是 含有生物活性部分的光聚合水凝胶材料 粘附肽和固定化生长因子。机械性能， 例如弹性模量，可以广泛地 通过改变聚合物分子量和交联密度而改变。我们将 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。接种到支架中的细胞可以 离体遗传修饰以改善组织性能，例如更好地 通过用一氧化氮合酶或更好的转染的抗血栓性 通过用交联酶如赖氨酰 氧化酶。细胞在组织生长过程中所经历的机械条件将 显著地有助于组织工程的最终性质， 构建体研究机械环境对组织的影响 形成工程血管移植物，我们将设计一个脉动流 生物反应器可以模拟体内经历的机械条件。 组织工程构建体将暴露于不同水平的 生理流与控制的壁剪切应力和循环 株我们将研究动态力学环境对 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、交联和组织化; 和血管活性基因的表达。