Basement Membrane of Small Diameter Xenogeneic Extracellular Matrix Scaffolds Modulate Quiescent Human Endothelial Cell Monolayer Formation

Abstract

Off-the shelf small diameter vascular grafts are an attractive alternative to eliminate the need and shortcomings of autologous tissue for vascular grafting. Bovine saphenous vein (SV) extracellular matrix (ECM) scaffolds are potentially ideal small diameter vascular grafts, due to their inherit architecture and signaling molecules capable of driving proper cell behavior and regeneration. However, harnessing this potential is predicated on the ability of the scaffold generation technique to maintain the delicate structure, composition and associated function of native vascular ECM. Previous decellularization methods have been uniformly demonstrated to distupt the delicate basement membrane (BM) components of native vascular ECM. Here we demonstrate bovine SV ECM scaffolds generated using the novel antigen removal (AR) approach results in retention of native BM protein composition (e.g., Collagen IV and laminin), structure and cell modulatory function. Presence of BM proteins in AR vascular ECM scaffolds increases endothelial cell migration and proliferation, appropriate formation of adherence junction and apicobasal polarization, increased secretion of nitric oxide, and modulates endothelial cell quiescence. We conclude that presence of intact native vascular BM in AR SV ECM scaffolds modulate human endothelial cell behaviors which are essential for vessel homeostasis.