Long‐term effects of local growth factor (IGF‐I and TGF‐β1) treatment on fracture healing . A safety study for using growth factors

Previous studies showed that growth factors dramatically stimulate healing processes in bone. However, the long‐term effect of locally applied growth factors on fracture healing remains unclear. In considering the safety of using growth factors, it is necessary to elucidate that after initial stimulation, the effect stops and the result is a normally healed tissue. Therefore, the purpose of the present study was to investigate the long‐term time course of healing processes during growth factor (GF) stimulated and unstimulated fracture healing in a closed tibial fracture model in rats. A well established local drug delivery system was used. IGF‐I (50 μg) and TGF‐β1 (10 μg) were locally applied using a 10 μm thin polylactide (PDLLA) coating on intramedullary implants. The biomechanical and histomorphometrical results demonstrated a significant stimulation of the fracture healing due to the locally applied growth factors compared to control at days 28 and 42 in agreement with the literature. At the last time point, 84 days after fracture, no differences were measurable in the biomechanical testing and the callus composition between the groups. The callus was consistently in the late phase of remodeling with no remaining cartilage. In conclusion, local growth factor application enhances the healing in the early phase without alteration of the normal healing process. © 2003 Orthopaedic Research Society. Published by Elsevier Ltd. All rights reserved.

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