Peptide Modified PDMS: Surface Modification For Improved Vascular Cell Interactions

Abstract

Many of the materials used today for cardiovascular implants exhibit good bulk mechanical properties but fail to provide desirable surface properties for reducing thrombogenicity and promoting tissue integration. In fact, biological responses at the blood-material interface, including non-specific protein adsorption, coagulation, and platelet adhesion and activation significantly limit the use of currently available materials in many blood contacting applications. As our understanding of the biological responses to foreign materials has grown, so too has the potential for creating 'bioactive' materials capable of inducing and directing beneficial cellular processes. One promising technique for circumventing undesirable blood-biomaterial interactions involves seeding vascular endothelial cells (ECs) onto synthetic vascular grafts as a means of exploiting the physiological anticoagulant characteristics of the endothelium. Methods for improving cell retention on these constructs include immobilization of cell recognition motifs on the biomaterial surface in order to improve interactions between cells and the synthetic substrate. However, there remains the need to better understand the interactions between surface bound ligands and cells, and the role of linker molecule chemistry on ligand bioactivity and cellular response. In the current work, a novel method was optimized for modifying poly (dimethylsiloxane) (PDMS) with cell adhesion peptides tethered via a heterobifunctional allyl-, NSC-terminated polyethylene oxide (PEO) linker molecule. These novel surfaces combine the protein repellant property of PEO with the cell binding property of cell adhesion peptides. It was found that surfaces modified in this manner reduced protein adsorption to PDMS while increasing cell adhesion. Therefore the use of a generic PEO linker molecule was shown to be a very promising method of reducing non-specific protein interactions while maintaining ligand bioactivity. Silicone surfaces were also modified with diaminobutane (DAB) dendrimers in an attempt to increase the surface capacity for attachment of biomolecules and to compare the effect of surface peptide density with ligand mobility. Grafting cell adhesion peptides via surface bound dendrimers was found to increase the surface peptide density when compared to peptides grafted via the PEO spacer alone. However, cell adhesion was not significantly improved on the dendrimer-peptide modified surfaces compared to PDMS controls. This observation provides evidence that the properties of the linker molecule used for attachment of cell adhesion peptides to a biomaterial surface may be a critical factor in determining peptide bioactivity. In this case the peptides bound to the surface via the highly mobile linear PEO linker showed increased cell adhesion when compared to peptides linked via the rigid, highly branched dendrimer. It is therefore hypothesized that ligand mobility on a biomaterial surface may significantly influence ligand-cell receptor interactions to an even greater extent than surface peptide density.