Multilayer Hybrid Construct for Vascular Tissue Engineering

Vascular grafts are often used as blood vessel substitutes. Until now, synthetic materials have not matched the efficacy of native tissues, particularly in the applications of small-diameter vascular grafts (<6mm) such as bypass grafts for arthrosclerosis and vascular access graft for hemodialysis. There is a considerable need for alternatives to the autologous veins or arteries. Many patients do not have an autologous vessel suitable for use due to preexisting pathological conditions or previous surgical harvest. Recent developments in vascular tissue engineering demonstrate the possibility of a biodegradable graft material containing living cells to mimic the structure and function of native vessels. However, fabrication of biomimetic grafts is often time and labor intensive, and subsequently requires complicated storage. This demands technology advancements in producing vessel mimetic grafts, considering their availability in addition to efficacy. To this end, new approaches to constructing small-diameter grafts that are of immediate availability and capable of regenerating biomimetic blood vessels in vivo may address the unmet demand in this area. We have designed a novel multilayer vascular construct which is made up of a nanofibrous “intima-equivalent” with thrombus-resistant vessel lumen and a porous biopolymer matrix as “media-equivalent” to allow smooth muscle cells (SMC) from native artery to grow and remodel the tissue. In this study, various layering strategies have been explored. To evaluate the resultant multilayer construct, structural, biochemical and biomechanical characterizations, as well as cell assays and short-term animal studie have been performed.