| The long-term success of medical and dental implants can be enhanced by engineering surfaces with built-in specificity towards certain cells or proteins surrounding the implant. One approach to engineering a surface has been the use of biologically relevant molecules as coatings on the biomaterial. This thesis utilized cell adhesion signals found in bone sialoprotein to modify the surfaces of model biomaterials. In particular, the sequence Arg-Gly-Asp (-RGD-), known to be involved in integrin-mediated osteoblast adhesion, and Phe-His-Arg-Arg-Ile-Lys-Ala (-FHRRIKA-), shown in this project to be involved in cell-surface proteoglycan-mediated osteoblast adhesion, and combination of these sequences were used as suitable bioactive molecules for immobilization on model surfaces. A simple three-step immobilization protocol was developed to covalently link synthetic peptide(s) containing a terminal cysteine residue to modified quartz, silicon, and titanium surfaces. Established surface characterization techniques (dynamic contact angle measurements, X-ray photoelectron spectroscopy, and spectroscopic ellipsometry) were used to confirm the presence of the peptides and quantify the density of the immobilized peptides. A cell detachment assay was developed to quantify the adhesive nature of the peptide-modified surfaces towards osteogenic cells.; The engineered surfaces containing RGD and FHRRIKA, in the ratio of 75:25 or 50:50, enhanced initial osteoblast-like adhesion, spreading, and long-term mineralization of the synthesized matrix. Initial osteoblast-like cell adhesion to RGD-grafted surfaces was primarily through the integrin receptors alpha vbeta3 and alpha2beta1 whereas attachment to heparin-binding peptide was mediated through cell surface proteoglycans. Moreover, the surface density of the RGD peptide affected the kinetics of matrix mineralization. Peptide surfaces with a surface density ≥0.62 pmol/cm 2 enhanced the kinetics of mineralization compared to RGD surfaces with a surface density ≤0.01 pmol/cm2.; The results of this dissertation demonstrate that surface modification using monolayer coating of biologically relevant molecules with the appropriate surface density can alter the kinetics of bone formation, and offer a strategy to reduce the healing period required following implant surgery. |
