Elastic, Degradable Vascular Grafts with Helical Microfibers

具有螺旋微纤维的弹性、可降解血管移植物

• 批准号: 10685260
• 负责人: Edith Tzeng
• 金额: $ 62.28万
• 依托单位: CORNELL UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-08-15 至 2025-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10685260
• 关键词: Acceleration; Address; Affect; Aging; Animal Model; Architecture; Arteries; Arteriovenous fistula; Atherosclerosis; Autologous; Autologous Transplantation; Automobile Driving; Biological; Bioreactors; Blood Vessels; Blood flow; Bypass; Caliber; Cardiovascular Diseases; Cardiovascular system; Carotid Arteries; Cells; Clinical; Coronary; Data; Deposition; Development; Devices; Diabetes Mellitus; Diameter; Elasticity; Elastomers; Elderly; Extracellular Matrix; Fiber; Goals; Harvest; Human; Immune response; Impairment; Implant; In Situ; Infiltration; Inflammation; Interleukin-10; Intervention; Kidney Failure; Knee; Knowledge; Limb structure; Modeling; Morbidity - disease rate; Non-Insulin-Dependent Diabetes Mellitus; Operative Surgical Procedures; Pathology; Patients; Performance; Process; Property; Proteins; Rattus; Research; Rodent; Route; Sheep; Site; Source; Speed; Sprague-Dawley Rats; Stromal Cells; Systemic disease; Technology; Testing; Tissues; Vascular Graft; Vein graft; age effect; aged; artery occlusion; biodegradable scaffold; cell motility; clinical translation; comorbidity; controlled release; cost; cytokine; design; diabetic; effectiveness evaluation; elastomeric; endothelial stem cell; graft failure; graft function; improved; infection risk; insight; non-diabetic; patient population; pre-clinical; reconstruction; scaffold; stem cell population; wound healing

Elastic, Degradable Vascular Grafts with Helical Microfibers When an artery occludes, rerouting blood flow with a vascular graft can save lives or limbs. Autologous grafts are the preferred conduit for replacing small-diameter vessels. However, not all patients have suitable donor vessels, and the wound healing complications associated with the harvest can be severe. Synthetic grafts can be used but the foreign material does not degrade or integrate with the host, leading to graft failure and risk of infection. These grafts function best in large caliber arterial reconstruction but perform poorly in smaller arteries such as in the coronary and below the knee arteries. We will overcome this challenge by using a degradable graft made of elastomeric microfibers arranged in helices mimicking extracellular matrix fibers in the artery. Our preliminary data in rats show these grafts remodel into compliant, elastic vascular conduits resembling the native arteries. The proposed research will address two key questions for clinical translation: 1) will host cells fully populate the long grafts needed for human applications and 2) will the same transformation occur in aged patients and those with systemic diseases such as diabetes? Correspondingly, Specific Aim 1 will investigate host remodeling of 7-inch-long interposition grafts in a sheep carotid artery. Aim 2 will assess graft remodeling in Zucker Diabetic Sprague-Dawley rats, a new polygenetic model of Type 2 diabetes. Aim 3 will evaluate the effectiveness of controlled release of cytokines in the graft to overcome the limitations caused by aging. Upon completion of this project, we expect to have a graft design ready for clinical translation. The knowledge gained will have impact beyond vascular substitutes in the development of other cardiovascular devices.

具有螺旋微纤维的弹性、可降解血管移植物 当动脉闭塞时，用血管移植物重新引导血流可以挽救生命或肢体。 自体移植物是替代小直径血管的首选导管。然而，并非所有 患者有合适的供体血管，并且与移植相关的伤口愈合并发症 收获可能会很惨重。可以使用合成移植物，但异物不会降解或 与宿主融合，导致移植失败和感染风险。这些移植物在以下情况下功能最佳 大口径动脉重建，但在较小动脉（例如冠状动脉）中表现不佳 以及膝盖以下的动脉。我们将通过使用由以下材料制成的可降解移植物来克服这一挑战 排列成螺旋状的弹性微纤维模仿动脉中的细胞外基质纤维。我们的 大鼠的初步数据显示这些移植物重塑为顺应的弹性血管导管 类似于天然动脉。拟议的研究将解决临床的两个关键问题 翻译：1）宿主细胞将完全填充人类应用所需的长移植物，2） 同样的转变会发生在老年患者和患有全身性疾病的患者身上吗？ 糖尿病？相应地，Specific Aim 1将研究7英寸长的主机改造 绵羊颈动脉的介入移植物。目标 2 将评估 Zucker 糖尿病患者的移植物重塑 Sprague-Dawley 大鼠，一种新的 2 型糖尿病多基因模型。目标 3 将评估 移植物中细胞因子受控释放的有效性，以克服由移植物引起的局限性 老化。该项目完成后，我们预计将有一个可供临床使用的移植物设计 翻译。所获得的知识将产生超越血管替代品的影响 其他心血管设备的开发。