Promotion of cellular adhesiongrowth

The development of a uniform cellular layer on the implanted biomaterial has been proposed to enhance biocompatibility. These cells, while providing structural stability via material incorporation into the surrounding tissue, maintain hemostasis, prevent infection, and synthesize bioactive mediators. This type of cellular incorporation does not occur in actuality, thereby predisposing these biomaterials to infection [109,110] and thrombosis [111,112]. Thus, failure of appropriate cell-type growth and development to these biomaterials significantly limits their expanded use.

Cellular adhesion to biomaterials using cell-seeding techniques has been extensively employed [113, 114]. Adhesive proteins such as fibronectin, fibrinogen, vitronectin, and collagen have served well in graft-seeding protocols [115]. The cell-attachment properties of these matrices can also be duplicated by short peptide sequences such as RGD (Arg-Gly-Asp) [116]. These adhesive proteins, however, have several drawbacks: (1) bacterial pathogens recognize and bind to these sequences [117]; (2) non-endothelial cell lines also bind to these sequences [118]; (3) patients requiring a seeded material such as a vascular graft have few donor endothelial cells, therefore cells must be grown in culture [119]; and (4) endothelial cell loss to shear forces from flowing blood remains a significant obstacle [120].

Modification of the surface has also been employed to modify host response to the foreign body, serving as an approach for improving cellular adherence. Cells that have been seeded have been shown to attach and grow better on a variety of protein substrates coated onto the biomaterial [121]. Bioactive oligopeptides [122] and cell-growth factors [123] have been immobilized onto various polymers and shown to effect cell adherence and growth. Additional studies have described the incorporation of growth factors into a degradable protein mesh, resulting in the formation of capillaries into the material [124]. Utilizing these techniques to incorporate growth factors, however, does have limitations: (1) growth factor is rapidly released from the matrix; (2) matrix degradation re-exposes the thrombogenic surface, thus endothelialization is not uniform; and (3) release of non-endothelial specific growth factor is not confined to the biomaterial matrix, thereby exposing the "normal" distal artery to the growth factor.

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