Project Summary
This project proposes to investigate the role of surface topography in endothelialization by decoupling it from
surface chemistry using reactive ion plasma (RIP) of peripheral vascular graft (PVG) biomaterials, including a
promising material: polyvinyl alcohol (PVA). Over half of PVGs made from synthetic materials fail within two
years of implantation and therapies to reduce the factors contributing to graft failure have shown no benefit in
lower extremity PVG outcomes. Because the two predominant failure modes of PVGs are thrombosis (blood
clotting) and intimal hyperplasia (tissue build-up inside the graft), an ideal PVG biomaterial should be resistant
to both. The primary attributes of such a material are that it 1) have comparable compliance to the native
vasculature, 2) be non-thrombogenic, and 3) encourage endothelialization. RIP-treated PVA is a promising
PVG material which we have shown previously 1) is easily manufactured with compliance ranging from that of
venous to arterial vasculature, 2) is less thrombogenic than the current clinical standard PVG material, and 3)
allows endothelial progenitor cells (EPCs) to proliferate on the surface for at least 48 hours in vitro. Progress in
manufacturing endothelializable PVGs has been hampered because the approaches predominantly involve
conjugation of small molecules onto the PVG material, which have limitations associated with cost, stability,
reproducibility, and scalability and despite significant attention have yet to be translated into the clinic.
Our project is focused on using RIP treatment, a common and scalable manufacturing process, of PVA to
decouple the two surface properties known to be important in the endothelialization process: surface chemistry
and topography, in order to understand the fundamental factors that promote endothelialization and to achieve
our long-term goal of manufacturing an improved PVG. We have shown that RIP-treatment introduces
reactive surface chemistry necessary for cell adhesion in the form of surface nitrogen, as well as nanotexture
to PVA and to varying degrees for different RIP treatments. While most of the reactive surface chemistry
introduced by RIP is still apparent after 230 days in storage, the surface becomes smooth and EPCs no longer
adhere or proliferate after storage. We will first characterize the changes in surface chemistry and topography
during storage in order to understand the nature of the material surface as the topography relaxes (Aim 1). We
will then decouple the effects of surface chemistry and topography on endothelial cell (EC) and EPC
attachment, proliferation, and migration (Aim 2) as well as EC and EPC function with and without exposure to
fluid flow (Aim 3). This understanding will allow us to determine the effect of surface chemistry and topography
on the important processes of endothelialization and engineer a rapidly endothelializable PVG which remains
patent longer than current clinical materials. Our studies will afford a more detailed understanding of the factors
which govern endothelialization of synthetic biomaterials, provide a platform to understand EC biology, and
improve translation of PVGs which can be applied to other biomaterials to improve their biointegration.
