VS5 Human Tissue-Engineered Grafts for Hemodialysis: Development, Preclinical Data, and Early Investigational Human Implant Experience

Abstract

Current synthetic grafts have high rates of failure, due primarily to thrombosis and intimal hyperplasia. We have developed a tissue-engineered vascular graft that consists of human extracellular matrix and is similar in strength to native human vein and artery. This investigational graft is currently in clinical studies for evaluation of safety and efficacy in hemodialysis vascular access in patients with end-stage renal disease. In this presentation, we describe the development, preclinical experience, and early human implant experience for these tissue-engineered vascular grafts. A video is presented on the first case in the United States in which a human tissue-engineered vascular graft was implanted into a patient for hemodialysis access. Perspective is presented on the key developmental milestones that led to the first clinical implantation. These milestones include graft growth, animal studies, and clinical implantation of the graft. Banked human aortic smooth muscle cells were cultured in bioreactors in vitro to produce vascular tissue grafts, and a decellularization process was subsequently used to remove immunogenic cellular antigens. Arteriovenous grafts were implanted into nonhuman primates for up to 6 months and were evaluated for patency, durability, cannulation, rejection, and cellular repopulation. In addition, these grafts were evaluated for long-term arterial reconstruction in a canine model, using canine-derived grafts. In animal studies, histologic analysis demonstrated evidence of host vascular cell migration into grafts and endothelialization. Little intimal hyperplasia was observed in animal studies. These preclinical studies supported initiation of clinical trials.