(601b) Peptide Modified Polymers for the Adhesion of Human Blood Outgrowth Endothelial Cells

Thrombus formation 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 can be 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 cell adhesion properties of the base polymer have been enhanced through the introduction of topography and cell specific ligands.

Electrospinning was used to generate fibrous terpolymer constructs with both random and aligned fiber orientations. It was found that the molar ratio of HMA and MMA in the polymer greatly affected the scaffold morphology. HMA-rich materials produced scaffolds with fused fibers and low void percents (18%) while MMA-rich materials produced scaffolds with discrete fibers and much higher void percents (85%). Endothelial cells exhibited increased proliferation and spreading on the HMA-rich electrospun fibers in comparison to films of the same material or the MMA-rich electrospun scaffolds. Furthermore, scaffolds with aligned fibers were able to induce the adherent endothelial cells to elongate in the direction of fiber orientation thus guiding the cells into morphology more similar to what is seen in vivo [4].

Previously we have discovered novel peptide ligands which specifically bind to human blood outgrowth endothelial cells (HBOECs) through phage display technology [5]. We have illustrated that the ligands can be covalently incorporated into the polymer though chain transfer chemistry and that these ligands retain their bioactivity upon incorporation into the polymer as observed by an increase in the initial adhesion of the desired cell population. Furthermore, we have illustrated that the ligands are not chemically degraded through the electrospinning process allowing us to generate bioactive and three dimensional scaffolds.

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] Heath DE, et al, JBMR. In preparation.

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