Functional response of bone and bone cells to biomaterials coated with integrin-stimulating small peptides

Implant characteristics such as surface chemistry, charge, texture and porosity can be used to influence bone response. The author´s research is targeted at understanding how small peptide, integrin-stimulating coatings influence bone formation. The composition of bone extracellular proteins and their corresponding integrin receptors provides a rational basis for designing bone-active surface coatings. The organic component of bone is comprised of numerous extracellular matrix (ECM) proteins including fibronectin, thrombospondin, osteopontin, type I collagen, osteonectin, and bone sialoprotein. These ECM proteins contain the arginine-glycine-aspartic acid (RGD) sequence and interact with heterodimeric integrin receptors found on osteoblasts. Integrins use multiple intracellular signalling pathways to control cell adhesion, gene/protein expression and apoptosis. The author´s laboratory has developed a model system to evaluate the biological activity of peptide modified biomaterials using self-assembled monolayer technology. Briefly, peptides with terminal cysteine groups (C=cysteine which contains free thiol side groups for gold binding) added to gold-coated surfaces form bioactive substrates. Using surface plasmon resonance and other surface analytical techniques (ESCA, SIMS), the author has demonstrated the formation of stable self assembled monolayers of cysteine terminated peptides on electron-beam deposited gold surfaces. Such surfaces are functionally stable for at least 30 days in vitro as demonstrated by osteoblast focal adhesion formation (the site of integrin clustering). A series of in vitro studies have also shown that rat calvarial osteoblasts cultured on RGDC coated surfaces show significantly greater spreading, surface area and number of focal adhesions in a peptide dose-dependent fashion