Engineering Collagen-Based Vascular Substitutes That Recapitulate Native Vessel Structural and Functional Properties

Abstract

Autologous vein grafts remain the gold standard in small diameter bypass grafting for the surgical management of peripheral arterial and coronary artery disease. Yet outcomes remain compromised by low patency rates. Tissue-engineering strategies have been explored as alternatives, however, a clinically available tissue engineered vascular graft (TEVG) remains an elusive reality. In the present study we report a novel fabrication method for the generation of TEVGs. A microfluidic strategy is employed for the rapid and continuous formation of ultrathin, highly aligned and compacted collagen sheets with tunable properties. In turn, these collagen sheets were used to fabricate TEVGs yielding tubular structures comprised of circumferential human aortic smooth muscle cell layers alternating with layers of compact, aligned and genipin-crosslinked collagen fibrils. The resulting TEVGs recapitulated aspects of both the microstructure and mechanical properties of native arteries. The maximum burst pressure and suture retention strength averages achieved were 2,645 ± 346 mm Hg and 153.5 ± 37.4 gF, respectively. Importantly, the present TEVG approach does not make use of synthetic polymers or prolonged bioreactor incubation times, hence being a more cost-effective and scalable solution.