Elastic, Degradable Vascular Grafts with Helical Microfibers

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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.