Investigating an Electrospun Nanofibrous Platform of Degradable Polar Hydrophobic Ionic Polyurethane/Polycarbonate for Applications in Small-Diameter Vascular Graft Engineering
Katya D'Costa (1, 2), Xiaoqing Zhang (1, 2), J.Paul Santerre (1, 2, 3)
(1) Institute of Biomaterials and Biomedical Engineering
(2) Ted Rogers Centre for Heart Research, Translational Biology and Engineering Program, University of Toronto
(3) Faculty of Dentistry
One of the main factors that contributes to cardiovascular disease (CVD) the leading cause of death in North America, is peripheral arterial disease (PAD). PAD pertains to the health and integrity of blood vessels in the extremities, the lack of which would cause increased cardiac stress and lead to tissue death due to ischemia. The current gold standard to treat CVD is autologous grafts from the saphenous vein or internal thoracic artery, however, harvesting these tissues is invasive and may not always result in successful grafts as such patients are predisposed to compromised vascular health. The low long-term patency rates and poor mechanical compliance of current commercial grafts stresses the need for a small diameter graft (<6mm) that can provide a tenable solution for arterial reconstruction or bypass surgeries. The objective of this study was to investigate the feasibility of an electrospun degradable polar hydrophobic ionic polyurethane/polycarbonate (D-PHI) scaffold for use as a small diameter vascular graft. This material has previously demonstrated biocompatibility with vascular smooth muscle cells (VSMC), endothelial cells, monocytes, stem cells and gingival fibroblasts. It can be tuned for controlled biodegradation and has demonstrated immunomodulatory properties that reduce inflammatory macrophage activation. Previous investigations utilized a porous disc D-PHI scaffold, however, the mechanical properties in the model were well below physiological requirements. Therefore, this study will involve the translation of the same co-culture system, comprised of patient-derived VSMCs and monocytes cultured on to a nanofibrous electrospun D-PHI membrane. The culture will be supplemented with ascorbic acid and sodium ascorbate, which have been employed to boost extracellular matrix deposition thereby enhancing cell adherence and viability. Gene expression levels of early, middle and late stage VSMC genes (α-SMA, SM22α, calponin, caldesmon, SM-MHC, smoothelin, myocardin) and total DNA, elastin and collagen content are to be measured for comparison against data previously gathered from the porous D-PHI system. This direct comparison study of the porous disc and fibrous sheet D-PHI platforms aims to prove that the latter can support cell proliferation and ECM development to a greater degree while providing superior mechanical strength.