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

摘要

Implant characteristics such as surface chemistry, charge, textureand porosity can be used to influence bone response. The author'sresearch is targeted at understanding how small peptide,integrin-stimulating coatings influence bone formation. The compositionof bone extracellular proteins and their corresponding integrinreceptors provides a rational basis for designing bone-active surfacecoatings. The organic component of bone is comprised of numerousextracellular matrix (ECM) proteins including fibronectin,thrombospondin, osteopontin, type I collagen, osteonectin, and bonesialoprotein. These ECM proteins contain the arginine-glycine-asparticacid (RGD) sequence and interact with heterodimeric integrin receptorsfound on osteoblasts. Integrins use multiple intracellular signallingpathways to control cell adhesion, gene/protein expression andapoptosis. The author's laboratory has developed a model system toevaluate the biological activity of peptide modified biomaterials usingself-assembled monolayer technology. Briefly, peptides with terminalcysteine groups (C=cysteine which contains free thiol side groups forgold 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 selfassembled monolayers of cysteine terminated peptides on electron-beamdeposited gold surfaces. Such surfaces are functionally stable for atleast 30 days in vitro as demonstrated by osteoblast focal adhesionformation (the site of integrin clustering). A series of in vitrostudies have also shown that rat calvarial osteoblasts cultured on RGDCcoated surfaces show significantly greater spreading, surface area andnumber of focal adhesions in a peptide dose-dependent fashion