Local application of growth factors (insulin-like growth factor-1 and transforming growth factor-beta 1) from a biodegradable poly(D,L-lactide) coating of osteosynthetic implants accelerates fracture healing in rats

In vitro and in vivo studies have demonstrated an osteoinductive effect of growth factors such as insulin-like growth factor-1 (IGF-1) and transformin g growth factor-beta1 (TGF-beta1) However, for therapeutic use in fracture treatment, questions remain with regard to the local application of these p roteins. A controlled, local release of growth factors from a biodegradable polylactide coating of osteosynthetic implants may have a stimulating effe ct on fracture healing, Such implants could stabilize the fracture and thei r bioactive surface could function simultaneously as a local drug-delivery system. Previous studies have demonstrated the high mechanical stability of an approximately 10-14-mum-thick poly(D,L-lactide) (PDLLA) coating on meta llic implants, which can even withstand the process of intramedullary inser tion, Following an initial peak, 80% of incorporated growth factors IGF-1 a nd TGF-beta1 were continuously released within 42 days, The effect of local ly applied IGF-1 and TGF-beta1 from a biodegradable PDLLA coating of intram edullary implants on fracture healing was investigated in a rat model. Mids haft fractures of the right tibia of 5-month-old female Sprague-Dawley rats (n = 127) were stabilized with coated vs, uncoated titanium Kirschner wire s. X-ray examinations and blood analyses were performed, and body weight an d body temperature measurements were taken throughout the experimental peri od. After 28 and 42 days, respectively, tibiae were dissected for mechanica l torsional testing and histomorphometrical analyses. X-rays demonstrated a n almost completely consolidated fracture, biomechanical testing showed a s ignificantly higher maximum load and torsional stiffness, and histological and histomorphometric analyses demonstrated progressed remodeling after 28 and 42 days in the group treated with growth factors as compared with contr ols. Interestingly, the PDLLA coating itself revealed a positive effect on fracture healing even without incorporated growth factors. No systemic chan ges of serum parameters, including IGF-1 and IGF binding proteins, and no d ifferences in body weight and body temperature were observed within and bet ween groups. These findings suggest that the local application of growth fa ctors from a biodegradable PDLLA coating of osteosynthetic implants acceler ates fracture healing significantly without systemic side effects. (C) 2001 by Elsevier Science Inc, All rights reserved.