title: Insulin-like growth factor-1 and transforming growth factor-beta1 accelerates osteotomy healing using polylactide-coated implants as a delivery system: a biomechanical and histological study in minipigs.
abstract: Stimulation of bone healing and bone formation through local application of growth factors from implants may improve the clinical outcome in fracture treatment. Previous studies demonstrated a high mechanical stability of a thin poly(D,L-lactide) (PDLLA) coating on metallic implants that can withstand the process of intramedullary insertion. Following an initial peak, 80% of incorporated insulin-like growth factor-1 (IGF-1) and transforming growth factor-beta1 (TGF-beta1) were released continuously, within 42 days. The goal of the present study is evaluation of the coated implants on fracture healing in a large animal model. A midshaft osteotomy (1 mm gap) of the right tibia of Yucatan minipigs was stabilized with uncoated vs. coated titanium interlocking nails (5 mm). X-ray examinations and blood analyses (including IGF-1 and IGF-binding proteins) were performed, and body weight and body temperature were taken throughout the experiment. After 28 days, both tibiae were dissected for mechanical torsional testing and histomorphometric analyses. No differences were found in the blood analyses, body weight, or temperature due to the coating or the incorporated growth factors between the groups. X-ray examinations revealed a faster consolidation of the osteotomy in the growth factor-treated group. Biomechanical testing showed a significantly higher torsional stiffness and maximum load. Progressive remodeling was observed in the histological and histomorphometric analyses with a larger callus volume in the growth factor group compared with the control groups. We conclude that local application of growth factors from a biodegradable PDLLA coating of intramedullary implants accelerates bone healing in a large animal model without systemic side effects.
authors.affiliation: Department of Trauma and Reconstructive Surgery, Charité, Humboldt University of Berlin, Berlin, Germany. michael.raschke@charite.de
authors.forename: M
authors.initials: M
authors.lastname: Raschke
authors.forename: B
authors.initials: B
authors.lastname: Wildemann
authors.forename: P
authors.initials: P
authors.lastname: Inden
authors.forename: H
authors.initials: H
authors.lastname: Bail
authors.forename: A
authors.initials: A
authors.lastname: Flyvbjerg
authors.forename: J
authors.initials: J
authors.lastname: Hoffmann
authors.forename: N P
authors.initials: NP
authors.lastname: Haas
authors.forename: G
authors.initials: G
authors.lastname: Schmidmaier
mesh_terms: D000818:Animals; D001696:Biomechanical Phenomena; D002146:Bony Callus / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D016503:Drug Delivery Systems; D004343:Drug Implants; D005260:Female; D005594:Fracture Fixation, Intramedullary; D017102:Fracture Healing / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000008:administration & dosage / Q000494:pharmacology*; D010027:Osteotomy; D011091:Polyesters; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000494:pharmacology; D013552:Swine; D013556:Swine, Miniature; D013978:Tibial Fractures / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology / Q000601:surgery; D016212:Transforming Growth Factor beta / Q000008:administration & dosage / Q000494:pharmacology*; D053773:Transforming Growth Factor beta1; D014945:Wound Healing / Q000187:drug effects / Q000502:physiology
chemical_list: D004343:Drug Implants; D011091:Polyesters; D011994:Recombinant Proteins; C508960:TGFB1 protein, human; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; C033616:poly(lactide); D007334:Insulin-Like Growth Factor I