Local application of IGF-I and TGF-beta 1 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 fract ure treatment, the local application of these bioactive molecules is still an unsolved problem. The controlled release of growth factors from a biodeg radable 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 stabi lity of a thin 10 mu m poly(D,L-lactide) (PDLLA) coating on metallic implan ts that withstands even an intramedullary insertion process. After an initi al peak, 80% of incorporated growth factors IGF-T and TGF-beta 1 were conti nuously released within 42 days. The effect of locally applied IGF-I and TG F-beta 1 from a biodegradable PDLLA coating of intramedullary implants on f racture healing were investigated in a rat model. A fracture of the right t ibia of 5-month-old female Sprague-Dawley rats was stabilised with coated v ersus uncoated titanium K-wires. X-ray examinations and blood analysis were performed, body weight and body temperature monitored throughout the exper imental period. After 42 days both tibiae were dissected for mechanical tor sional testing and histomorphometric analyses. The results demonstrate a ne arly completely consolidated fracture in the X-ray examinations, a signific ant higher maximum load and torsional stiffness in the biomechanical tests and a progressed remodeling in the histological and histomorphometric analy ses 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 chan ge of serum parameters including IGF-I and IGF binding proteins and no diff erences in body weight and body temperature were seen in any group. These f indings suggest that the local application of growth factors from a biodegr adable poly(D,L-lactide) coating of osteosynthetic implants accelerates fra cture healing significantly without systemic side effects.