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四肢。 自体移植物是替代小直径血管的首选管道。但并非所有 患者有合适的供体血管，与供体血管相关的伤口愈合并发症 收获可能很严重。可以使用合成移植物，但异物不会降解， 与宿主结合，导致移植失败和感染的风险。这些移植物的功能最好， 大口径动脉重建，但在较小的动脉，如冠状动脉， 以及膝盖以下的动脉我们将通过使用一种可降解的移植物来克服这一挑战， 以螺旋状排列的弹性微纤维模仿动脉中的细胞外基质纤维。我们 大鼠的初步数据显示，这些移植物重塑成顺应性，弹性血管导管 类似于天然动脉。这项研究将解决两个关键问题， 翻译：1）宿主细胞是否会完全填充人类应用所需的长移植物，以及2） 同样的转变是否会发生在老年患者和患有全身性疾病的患者身上， 糖尿病？相应地，具体目标1将研究7英寸长的 在羊颈动脉中插入移植物。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 在移植物中控制释放细胞因子的有效性，以克服 衰老在这个项目完成后，我们希望有一个移植设计准备临床 翻译.所获得的知识将产生超出血管替代物的影响， 其他心血管设备的开发。