Local application of IGF-I and TGF-β1 from a biodegradable poly(D,L-lactide) coating of implants accelerates fracture healing

In vitro and in vivo studies have demonstrated an osteoinductive effect of growth factors like IGF-I and TGF-PI. However, for therapeutic use in fracture treatment, the local application of these bioactive molecules is still an unsolved problem. The controlled release of growth factors from a biodegradable coating of osteosynthetic implants could stimulate fracture healing locally. Coated implants could stabilise the fracture and work as a local drug delivery system. Previous studies demonstrated a high mechanical stability of a thin 10 mu m poly(D,L-lactide) (PDLLA) coating on metallic implants that withstands even an intramedullary insertion process. After an initial peak, 80% of incorporated growth factors IGF-T and TGF-beta 1 were continuously released within 42 days. The effect of locally applied IGF-I and TGF-beta 1 from a biodegradable PDLLA coating of intramedullary implants on fracture healing were investigated in a rat model. A fracture of the right tibia of 5-month-old female Sprague-Dawley rats was stabilised with coated versus uncoated titanium K-wires. X-ray examinations and blood analysis were performed, body weight and body temperature monitored throughout the experimental period. After 42 days both tibiae were dissected for mechanical torsional testing and histomorphometric analyses. The results demonstrate a nearly completely consolidated fracture in the X-ray examinations, a significant higher maximum load and torsional stiffness in the biomechanical tests and a progressed remodeling in the histological and histomorphometric analyses after 42 days in the group treated with growth factors compared to the controls. Interestingly, the PDLLA coating itself had a positive effect on fracture healing even without incorporated growth factors. No systemic change of serum parameters including IGF-I and IGF binding proteins and no differences in body weight and body temperature were seen in any group. These findings suggest that the local application of growth factors from a biodegradable poly(D,L-lactide) coating of osteosynthetic implants accelerates fracture healing significantly without systemic side effects.