| Cardiovascular biomaterials suffer from well-known problems associated with surface induced thrombosis such as thrombosic occlusion and thromboembolism. Endothelialization of a biomaterial surface is one approach for improving a material's blood compatibility. Unfortunately, most current biomaterials that can promote EC growth and adhesion exhibit significant cell loss under dynamic flow conditions, which exposes the underlying thrombogenic biomaterial. In vivo, the interaction of ECs with their extracellular matrix (ECM) is of critical importance for cell adhesion, differentiation, and effective anti thrombotic function. Thus, a stable biomaterial surface design that mimics the ECM should promote cell adhesion, growth, migration and maintenance of a healthy confluent EC monolayer under both static and dynamic flow conditions. To explore this hypothesis, we have developed novel “ECM-like” biomimetic surfactant polymers that consist of a poly(vinyl amine) (PVA) backbone with pendant oligosaccharides and oligopeptides. The peptide sequences include RGDS, which binds to EC integrin receptors and peptides derived from the heparin-binding domain of fibronectin (HBP). Human endothelial cell adhesion and growth were examined as a function of RGDS:oligosaccharide ratios as well as on surfaces containing two different HBPs. Surfaces with 50% RGD peptide or greater, and both HBPs were initially able to promote receptor specific EC adhesion, stress fiber, and focal adhesion formation. However, over time, only the RGD containing surfaces facilitated long term EC survival. Consequently, EC migration was examined as a function of RGD surface peptide density, and demonstrated that surfaces with high peptide density (100% RGD) showed the slowest migration, while moderate density surfaces (50%RGD, 75% RGD) promoted increased migration rates. The results of these migrational studies were utilized in the development of a mathematical model to describe this behavior. Finally, a rotating disk system was implemented to examine the effects of shear stress on endothelialized biomimetic surfaces, with the most adhesive surface (100% RGD) displaying the best shear stability. These studies demonstrated that we could engineer surfaces to control EC adhesion and behavior through alterations in peptide content and composition. Moreover, they provide insights that will contribute to advances in tissue engineering of blood vessels and other cardiovascular devices. |
