The influence of RGD peptide surface modification on the fixation of orthopaedic implants

Early osseointegration of cementless implants is fundamental for the longevity of the implant. The discovery of the RGD peptide, as an important mediator of osteoblast adhesion to implants, has lead to a new approach in designing biomaterials for use in orthopedic surgery. Implants can be biologically modified by covalent immobilization of RGD peptide on the surface of the implant. Immobilized RGD peptides facilitate osteoblast adhesion, spreading and differentiation in vitro. Only few in vivo studies have investigated the effect of RGD peptide in bone. This thesis includes three papers based on four experimental animal studies and one in vitro study. All in vivo studies involved titanium alloy implants inserted in cancellous bone sites. The study design was paired, so that identical implants with and without immobilized RGD peptide were compared in the same animal. Implants were evaluated by push-out test and histomorphometry after four weeks of observation. In study I, implants were inserted without load in the proximal tibia, and with load in the medial femoral condyle. A critical gap surrounded the implants in both cases. Push-out test showed that RGD coated implants with load had 2 to 3 fold higher median values for all mechanical parameters compared to the controls. A significant difference was only seen for total energy absorption. For unloaded RGD coated implants, apparent shear stiffness was significantly higher compared to the controls. No difference was found in energy absorption and shear strength for unloaded implants. Only half of the loaded and unloaded RGD coated implants had bone ongrowth. Fibrous tissue dominated the interface for both RGD coated and control implants. Unloaded RGD coated implants had significantly more bone in the inner half of the gap while no difference of bone in the inner gap was observed for loaded implants. RGD coated implants had significantly less fibrous tissue in the inner half of the gap in both models. Loaded RGD coated implants also had significantly more bone marrow in the inner half of the gap. No difference in bone, bone marrow or fibrous tissue volume was observed in the outer half of the gap. In study II, the implants were unloaded and inserted as press-fit in the proximal tibia. All parameters of mechanical fixation were higher in the RGD coated group compared with the control implants, with significantly higher apparent shear stiffness for RGD coated implants. A significant increase in bone ongrowth and bone volume in a 0-100 μm circumferential zone was found for RGD coated implants. A significant decrease in fibrous tissue ongrowth was also found for the RGD coated implants. In study III, an in vitro analysis of RGD coated titanium alloy discs with X-ray Photoelectron Spectroscopy verified that the RGD molecules were not organized randomly and that they did have the preferred orientation for cell adhesion as the phosphonate anchor was closer to the titanium surface than the RGD peptide. The in vivo study included loaded, press-fit implants inserted in the medial femoral condyle. No difference was seen in mechanical fixation. This was a predictable result because the implants were inserted with a tight pressfit. A significant increase in bone ongrowth and bone volume in a 0-100 μm circumferential zone was observed for RGD coated implants. Fibrous tissue ongrowth was not seen on any of the implants. In conclusion, these studies demonstrated that biological modification of implants with RGD