(276e) Polymeric Biomaterial Tuned to the Adhesion of Human Blood Outgrowth Endothelial Cells

Thrombus undermines the function of many blood contacting biomedical devices. We hypothesize that a surface which specifically adheres human blood outgrowth endothelial cells (HBOECs) will scavenge these adult stem cells from circulation and lead to the development of a confluent, functioning, and blood compatible endothelial cell layer. A biostable methacrylic terpolymer synthesized from hexyl methacrylate (HMA), methyl methacrylate (MMA), and methacrylic acid (MAA) was used in this research [1]. The mechanical properties of the material were modulated by controlling the molar ratio of HMA and MMA in the polymer while MAA provided acid functionality for post-synthesis derivitizations [2,3]. The biological properties of the base polymer have been enhanced through the introduction of topography [4], peptide ligands [2,3,5], and non-fouling character. Electrospinning generated fibrous terpolymer constructs with random or aligned fiber orientations [4]. Peptide ligands which specifically bind HBOECs were discovered through phage display screening and have been covalently incorporated into the biomaterial [5,6]. Resistance to protein adsorption and unwanted cell adhesion will be achieved through copolymerization of methacrylate monomers with non-fouling pendant groups: poly(ethylene oxide) (PEO), phosphorylcholine (PC), and quaternary ammonium/sulfonic acid (QS).

Electrospinning was used to generate fibrous terpolymer constructs with both random and aligned fiber orientations with the electrospinning enhancing the cytocompatibility of the material as observed through increased cell adhesion [4]. The HBOEC-specific ligands have been incorporated into the polymer through novel chain transfer chemistry [5]. The peptide ligand TPSLEQRTVYAK retained its biofunctionality after covalent attachment to the polymer and was illustrated to increase the adhesion of HBOECs on films in media not enriched with serum [6]. Currently we are creating polymers with higher ligand densities to maximize the cellular response. Polymers containing PEO pendant groups have been synthesized as well as the QS-methacrylate monomer. Results on non-fouling polymers will be presented.

In conclusion, a polymer system with tunable mechanical properties has been synthesized. This material has been electrospun into random and aligned fiber constructs and biofunctionalized with cell-specific peptide ligands. The topography introduced through the electrospinning process and the covalently incorporated ligands have each increased the cytocompatibility of the material towards HBOECs. Currently we are maximizing HBOEC specificity through increasing the density of ligands in the material and by incorporating non-fouling character to inhibit the adsorption of unwanted proteins and the adhesion of undesired cell types. These results support the use of this polymer system as a cardiovascular biomaterial.

References

[1] Veleva AN, et al, JBMR. 2005; 74A: 117 – 123.

[2] Fussell GW, et al, Biomaterials. 2004; 25: 2971 – 2978.

[3] Fussell GW, et al, JBMR. 2004; 70A: 265 – 273.

[4] Veleva AN, et al, JBMR. Submitted.

[5] Veleva AN, et al, Biotechnology and Bioengineering. 2007; 98.1: 306 – 312.

[6] Veleva AN, et al, Biomaterials. Submitted.