Investigation of exogenous growth factors; platelet derived growth factor, insulin-like growth factor binding protein and fibroblast growth factor, and their influence on in vivo bone repair.

This research investigated if exogenous growth factors (GFs), in particular platelet derived growth factor (PDGF), has an in vivo effect on the healing response of normal healthy bone. The research was orientated to study whether a clinical beneficial effect could be demonstrated. To achieve this two animal models were utilised, namely, a rabbit tibial osteotomy model and an ovine tibial defect and porous implant ingrowth model. The rabbit model comprised of a unilateral V-shaped tibial osteotomy, stabilised with an absorbable intramedullary pin and figure-of-eight tension band suture, with a 3 week survival period. The GFs tested in this model were 3 concentrations of PDGF, a single dose of insulin-like growth factor binding protein (IGF-BP) and a combination of the two. Each osteotomy was injected with a single bolus of collagen (control) or collagen containing GF (treatment) during surgery. After sacrifice tibiae were CT-scanned in situ, harvested and subject to 4-point bend testing. The callus, underlying bone and contralateral bone's greyscales and mechanical testing results were used for comparative analysis. The ovine model consisted of implanting 6 small rectangular shaped titanium alloy porous implants and one empty defect bilaterally in sheep's tibiae, for 4 and 6 weeks. The sheep were injected with tetracycline bone marker at 2 week intervals. The model's characteristics and any positional effects were initially investigated. Followed by an investigation into the influence of various exogenous GFs on the healing response and ingrowth characteristics of bone into the porous implants. The GFs investigated were PDGF, IGF-BP and fibroblast growth factor impregnated into the porous implants in a collagen carrier. Comparative analysis was done on results from 3-point bend testing of the bone/implant interface, image analysis to quantify percentage of bone, from scanning electron microscopy images of implant sections and confocal microscopy images of tibial defect sections. Analyses indicate that the GFs investigated have a direct and quantifiable positive in vivo effect. The more significant finding is that the growth factors have a potent systemic effect. These results were confirmed by both the sheep porous bone plug model and the rabbit tibial osteotomy model used within this research