ELASTOMERIC POLYPEPTIDE VASCULAR MATERIALS

弹性多肽血管材料

• 批准号: 3358775
• 负责人: DAN W URRY
• 金额: $ 15.33万
• 依托单位: UNIVERSITY OF ALABAMA AT BIRMINGHAM
• 依托单位国家: 美国
• 财政年份: 1988
• 资助国家: 美国
• 起止时间: 1988-07-01 至 1991-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3358775
• 关键词: antithrombogenic surface; biomaterial development /preparation; biotransformation; blood vessel prosthesis; calcification; cell adhesion; cell migration; chemotaxis; cow; crosslink; elastin; elastomers; extracellular matrix; mechanical stress; peptide chemical synthesis; thermodynamics; vascular endothelium; vascular smooth muscle

The long term objective of this research program is to develop a new class of materials, elastomeric polypeptide biomaterials, for use as vascular prostheses. The specific aims are: 1) to design polypeptide elastomers which match the compliance of the small vessels to be replaced, 2) to identify and suitably incorporate chemotactic peptides for vascular endothelial and smooth muscle cells, 3) to identify and covalently incorporate cell attachment sequences for vascular endothelial and smooth muscle cells into the elastomeric vascular prosthesis and 4) to achieve this within a biocompatible and appropriately biodegradable elastomeric matrix. The basic elastomeric polypeptide is (Val-Pro-Gly-Val-Gly)n or simply (VPGVG)n. For the bulk of the synthetic vessel the repeating hexapeptide, (Val-Ala-Pro-Gly-Val-Gly)n or simply (VAPGVG)n, will be added to modulate elastic modulus and to give strength and satisfactory handling characeristics. The general formula will be ((VPGVG)m-(VAPGVG)n) with molecular weights of greater and 50,000 Daltons. Cell attachment sequences for vascular endothelial and smooth muscle cells will be incorporated within the polypentapeptide at appropriate ratio of cell attachment sequence to pentamer sequence. Chemotactic peptides will be included in such a way as to provide the requisite concentration gradient for chemotaxis. The experimental design and methods involve four major categories: 1) design and preparation of elastomeric matrices by means of peptide synthesis of multicomponent high polymers and gamma-irradiation cross-linking with the capability of making cell specific vessel wall layering, 2) physical characterization of the synthetic high polymers by spectroscopic, compositional and relaxational analyses and of the cross-linked matrices by means of mechanical studies, primarily stress/strain for determination of elastic modulus, hysteresis and fatiguing and temparature dependence of force at fixed length and of length fixed force, 3) chemotaxis and cell adhesion studies on vascular endothelial and smooth muscle cells involving standard assays and the prepared matrices, and 4) additional site specific interactions for vascular prostheses including assessment of calcification potential, assessment of in vivo thromboembolic potential (by collaboration) and biocompatibility and in vivo biodegradability (by collaboration). Animal implant studies to assess rate of cell migration into the material, rate of matrix component synthesis by the cells, rate of degradative removal of synthetic matrix, etc., will be pursued by means of collaboration once adequate perspective is obtained regarding on going development of the material and which elements a given collaborator would determine.

该研究计划的长期目标是开发一种 新型材料，弹性多肽生物材料，用于 用作血管假体。 具体目标是：1）设计 与小分子的顺应性相匹配的多肽弹性体 要更换的容器，2) 识别并适当合并 血管内皮和平滑肌趋化肽 细胞，3) 识别并共价结合细胞附着 血管内皮细胞和平滑肌细胞的序列 弹性血管假体和4）在短时间内实现这一目标 生物相容性且可适当生物降解的弹性体 矩阵。 基础弹性体多肽是(Val-Pro-Gly-Val-Gly)n或 简单地说（VPGVG）n。 对于大部分合成容器来说 重复六肽，(Val-Ala-Pro-Gly-Val-Gly)n 或简单地 (VAPGVG)n，将被添加以调节弹性模量并给出 强度和令人满意的操控特性。 将军 分子式为 ((VPGVG)m-(VAPGVG)n)，分子量为 大于 50,000 道尔顿。 细胞附着序列 血管内皮细胞和平滑肌细胞将被纳入 聚五肽内以适当的细胞比例 与五聚体序列的连接序列。 趋化性 肽将以这样的方式包含在内以提供必需的 趋化性的浓度梯度。 实验设计和方法主要涉及四个方面 类别：1) 弹性体基质的设计和制备 多组分高聚物的肽合成方法和 具有制造细胞能力的伽马射线交联 特定的血管壁分层，2) 的物理特征 通过光谱、成分和方法合成高聚物 松弛分析和交联矩阵的方法 机械研究，主要是确定应力/应变 弹性模量、滞后和疲劳以及温度 固定长度力和长度固定力的依赖性，3) 血管内皮细胞的趋化性和细胞粘附研究 平滑肌细胞涉及标准测定和制备 矩阵，以及 4) 血管的其他位点特异性相互作用 假体，包括评估钙化潜力， 体内血栓栓塞可能性评估（通过合作） 以及生物相容性和体内生物降解性（通过 合作）。 评估细胞率的动物植入研究 迁移到材料中，基质成分合成速率 通过细胞，合成基质的降解去除率， 等，一旦足够，将通过合作的方式进行 获得了关于当前发展的观点 材料以及特定合作者会使用哪些元素 决定。