IN VIVO TESTING OF AN IMPROVED VASCULAR PROSTHESIS

改进的血管假体的体内测试

• 批准号: 3508646
• 负责人: DAVID L CLAPPER
• 金额: $ 25.07万
• 依托单位: SURMODICS, INC.
• 依托单位国家: 美国
• 财政年份: 1990
• 资助国家: 美国
• 起止时间: 1990-09-30 至 1994-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3508646
• 关键词: antithrombogenic surface; biomaterial development /preparation; biomaterial evaluation; blood vessel prosthesis; cell adhesion molecules; cell growth regulation; dogs; extracellular matrix proteins; heparin; hirudins; laboratory rat; polymers; vascular endothelium

No adequate small diameter vascular prostheses are now commercially available, with the major reasons for loss of patency being thrombus formation and neointimal fibrous hyperplasia. This project is designed to improve prosthesis function by covalently immobilizing cell adhesion proteins onto the prosthesis lumen. The proteins are expected to improve initial endothelial cell attachment (EC) attachment, subsequent EC growth, and ultimately promote the establishment of a stable and non-hyperplastic neointima. Phase I results showed that proprietary BSI photoimmobilization technology covalently immobilized active fibronectin and type IV collagen onto four vascular prosthesis materials, with the coated materials showing greatly improved attachment and growth of EC's. Phase II proposes to : 1) optimize protein coatings (as evaluated by promotion of EC cell attachment and growth in vitro) and then 2) evaluate coated prostheses in vivo for improved patency when implanted intrafemorally in dogs. The dog implants will be conducted with and without autologous seeded endothelial cells. Also, antithrombic agents (heparin and hirudin) will be immobilized along with the cell adhesion proteins and evaluated for effectiveness at inhibiting thrombus formation and improving the in vivo development of a stable endothelial layer. small diameter prostheses with greatly improved patency rates would be used for both coronary and peripheral artery reconstructions.

目前商业上没有足够的小直径血管假体 可用，通畅性丧失的主要原因是血栓 形成和新生内膜纤维增生。 该项目旨在 通过共价固定细胞粘附改善假体功能 将蛋白质转移到假体腔上。 蛋白质有望改善 初始内皮细胞附着（EC）附着，随后的EC生长， 并最终促进建立稳定且非增生的 新生内膜 第一阶段的结果表明，专有的BSI光固定 共价固定化活性纤维连接蛋白和IV型胶原技术 在四种人造血管材料上，涂层材料显示 大大改善了EC的附着和生长。 第二阶段建议：1） 优化蛋白质涂层（通过促进EC细胞附着来评估 和体外生长），然后2）在体内评价涂层假体， 犬股内植入时的通畅性改善。 狗植入 将使用和不使用自体接种的内皮细胞进行。 此外，抗血栓剂（肝素和水蛭素）将沿着 与细胞粘附蛋白，并评估有效性， 抑制血栓形成和改善血栓形成的体内发展， 稳定的内皮层。 小直径假体， 通畅率将用于冠状动脉和外周动脉 重建。