(276d) Surface Functionalization for Selective Cell Attachment
AIChE Annual Meeting
Tuesday, November 18, 2008 - 1:15pm to 1:35pm
A common approach to direct cell and tissue responses at synthetic surfaces is to modify the material to mimic the extracellular matrix. Typically, short recognition sequences presenting cell binding motifs found in components of the extracellular matrix (e.g., the RGD or the YIGSR peptides) are immobilized on the material to promote cell adhesion via ligand-receptor interactions. Although surface functionalization remains one of the most promising strategies, the clinical utility of this approach is limited by the need to develop materials that are optimized to promote adhesion of a specific cell type. Towards this end, we designed and implemented a high-throughput protocol for screening a phage display peptide library to identify and select novel peptide ligands that bind with high affinity and specificity to human blood outgrowth endothelial cells (HBOEC). Here we demonstrate the use of the phage display-selected-HBOEC-specific peptides as a tool to direct and modulate endothelial cell (EC) behavior with a focus on designing functional biomaterials intended for use in cardiovascular applications. First, we ensured that our peptide ligands did not interfere with EC function as tested by proliferation, migration, tube formation, and response to vascular endothelial growth factor. Second, peptides that supported EC function were incorporated into methacrylic terpolymers via chain transfer free radical polymerization. The HBOEC-specific peptide, TPSLEQRTVYAK, when covalently coupled to a terpolymer matrix, retained binding affinity towards HBOEC in a serum-free medium. Under the same binding conditions, the attachment of human umbilical vein endothelial cells (HUVEC) was limited, thus establishing HBOEC specificity. The findings from this work could facilitate the development of autologous cell therapies with which to treat cardiovascular disease.