(549g) Methacrylic Terpolymers with Non-Fouling Interfacial Properties

Non-specific interactions occurring between a biomaterial and the host environment can result in suboptimal performance or failure of medical devices. For instance, thrombus formation can result in the occlusion of small diameter vascular grafts or the impaired movement of artificial heart valves. Thrombus develops due to these non-specific interactions between the biomaterial and blood proteins and platelets. An attractive strategy for suppressing these undesired interactions is to engineer surfaces which possess non-fouling characteristics resisting the adsorption of biomacromolecules and the attachment of cells.

In previous work, we have developed a biostable methacrylic terpolymer copolymerized from hexyl-methacrylate (HMA), methyl methacrylate (MMA), and methacrylic acid (MAA) [1]. The physical properties of the biomaterial system can be tailored by controlling the molar ratio of HMA to MMA incorporated into the polymer backbone. MAA was incorporated in small quantities (2 mole %) to allow post synthesis derivatizations [2, 3]. The biological properties of the polymer system were modified through the incorporation of topography using electrospinning and the covalent attachment of cell specific ligands [4, 5]. Endothelial cells seeded onto electrospun scaffolds possessed higher proliferation capacities and increased cell spreading. Furthermore, cells seeded onto aligned fiber scaffolds achieved an elongated morphology more similar to what is seen in vivo [4]. Polymers functionalized with the RGD peptide ligand were more favorable to the attachment and growth of human umbilical vein endothelial cells (HUVECs) while polymers functionalized with novel human blood outgrowth endothelial cell (HBOEC) specific ligands selectively fostered a larger population of the adult stem cells [5, 6].

In this presentation we describe the incorporation non-fouling character into the polymer through copolymerization of methacrylate monomers which possess hydrophilic and electrically neutral pendant groups. Materials containing 5, 15, and 25 mole % poly(ethylene glycol) methacrylate (PEGMA) were synthesized. Polymers containing > 15 mole % PEGMA showed excellent resistance to fibrinogen adsorption and HUVEC and platelet adhesion. Furthermore, these materials were electrospun into fibrous scaffolds which retained their non-fouling character.

Though excellent at suppressing non-specific biological interactions, PEG undergoes degradation in vivo limiting its application in long-term medical implants. Therefore, new non-fouling groups are required. Whitesides illustrated that self assembled monolayers expressing zwitterionic groups were also useful in creating non-fouling surfaces [7]. We have synthesized a quaternary amine/sulfonic acid methacrylate (QSMA) zwitterionic monomer and incorporated it into our polymer material through copolymerization. Finally we are incorporating HBOEC-specific ligands into the PEGylated polymer to enhance the specificity of the surface towards this desired stem cell population.

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 DH, et al, JBMR. In preparation.

[5] Veleva AN, et al, Biomaterials. 2008; 29: 3656 - 3661

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

[7] Holmlin RE, et al, Langmuir. 2001; 17: 2841 ? 2850.