Surface engineering approaches using biomimetic peptides provide promising strategies to improve the bioactivity of materials. In this study, to improve the bioactivity of hydroxyapatite (HA), a recombinant osteopontin fragment (rhOPN) was devised so as to retain its specific binding domains to HA, as well as to cells, in order that it function as a bridge between the two. A protein adsorption assay was performed to determine the optimal coating conditions, and the bioactivity of rhOPN coated HA was evaluated by conducting various in vitro cellular assays, such as the evaluation of cellular attachment, proliferation and differentiation. The rhOPN was adsorbed to the HA by an electrostatic attraction which was facilitated by the formers HA binding domain. The osteoblast-like cell attachment was significantly simulated through the RGD-integrin interaction. Moreover, HOS cells attached to the adsorbed rhOPN ligands on the HA surfaces showed significantly enhanced proliferation and differentiation behaviors (P < 0.05). These enhanced cellular responses can be attributed to changes in gene expression via the signal transduction cascade initiated by the RGD-integrin interaction. (C) 2005 Springer Science + Business Media, Inc.