The effect of peptide surface density on mineralization of a matrix deposited by osteogenic cells.

The density of Arg-Gly-Asp-containing peptides covalently grafted to solid materials has been shown to affect adhesion, spreading, and focal contact formation. The objective of this study was to examine the effect of ligand density on mineralization of the extracellular matrix deposited by osteoblasts. In particular, RGD-modified quartz surfaces with ligand densities varying over two orders (0.01-3.6 pmol/cm(2)) of magnitude were prepared to assess the long-term function of osteoblasts on peptide-derivatized surfaces. After 3 weeks in culture, surfaces modified with a 15 amino acid peptide (Ac-Cys-Gly-Gly-Asn-Gly-Glu-Pro-Arg-Gly-Asp-Thr-Tyr-Arg-Ala-Tyr-NH(2) ) at a density > or =0.62 pmol/cm(2) significantly (p<0.05) enhanced mineralization compared with a RGD surface density of 0.01 pmol/cm(2), RGE surfaces, or clean surfaces adsorbed with serum proteins. These results suggest that regulation of the surface density of adhesive ligands on biomaterial surfaces is a critical determinant in a strategy to alter the degree of extracellular matrix maturation in contact with solid surfaces (e.g., implants). Further studies are required to elucidate the intracellular signal transduction pathways that mediate long-term matrix mineralization through the initial engagement of these adhesive ligands.