title: Long-term effects of local growth factor (IGF-I and TGF-beta 1) treatment on fracture healing. A safety study for using growth factors.
abstract: 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 microg) and TGF-beta 1 (10 microg) were locally applied using a 10 microm 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.
authors.affiliation: Department of Trauma and Reconstructive Surgery, Humboldt University of Berlin, Charité, Campus Virchow Clinic, Augustenburger Platz 1, Berlin D-13353, Germany. gerhard.schmidmaier@charite.de
authors.forename: Gerhard
authors.initials: G
authors.lastname: Schmidmaier
authors.forename: Britt
authors.initials: B
authors.lastname: Wildemann
authors.forename: Daniel
authors.initials: D
authors.lastname: Ostapowicz
authors.forename: Frank
authors.initials: F
authors.lastname: Kandziora
authors.forename: Richard
authors.initials: R
authors.lastname: Stange
authors.forename: Norbert P
authors.initials: NP
authors.lastname: Haas
authors.forename: Michael
authors.initials: M
authors.lastname: Raschke
mesh_terms: D000818:Animals; D001696:Biomechanical Phenomena; D016723:Bone Remodeling; D005260:Female; D017102:Fracture Healing / Q000187:drug effects* / Q000502:physiology; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D016212:Transforming Growth Factor beta / Q000494:pharmacology*; D053773:Transforming Growth Factor beta1
chemical_list: C508962:Tgfb1 protein, rat; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D007334:Insulin-Like Growth Factor I