title: Effects of low dose FGF-2 and BMP-2 on healing of calvarial defects in old mice.
abstract: There is an age-associated reduction in the bone healing activity of bone morphogenetic protein-2 (BMP-2) that is currently addressed by administering higher doses of BMP-2 in elderly patients. The unwanted medical complications from high dose BMP-2 motivated this investigation to determine whether the addition of a low dose of fibroblast growth factor 2 (FGF-2) could enhance the ability of a lower dose of BMP-2 to heal calvarial bone defects in old mice (18-20 months old). FGF-2 (5 ng) and BMP-2 (2 μg) were administered by a controlled release two-phase biomaterial scaffold placed into the bone defect. FGF-2 released more rapidly and completely in vitro than BMP-2 (40% vs 2%). In vivo, both BMP-2 and FGF-2+BMP-2 groups formed more new bone in calvarial defects than scaffold alone (p < 0.001) or FGF-2 only groups (p < 0.01). The overall total volume of new bone was not statistically increased by the addition of FGF-2 to BMP-2 as measured by microCT, but the pattern of bone deposition was different. In old mice, but not young, there was enhanced bony fill in the central bone defect area when the BMP-2 was supplemented with FGF-2. Histological analysis of the center of the defect revealed an increased bone volume (%BV/TV (p = 0.004)) from the addition of FGF-2. These studies suggest that combining a low dose of FGF-2 with a low dose of BMP-2 has the potential to increase bone healing in old mice relative to BMP-2 alone.
authors: Department of Reconstructive Sciences, University of Connecticut Health Center, Farmington, CT 06030, USA.
authors: Lyndon F
authors: LF
authors: Charles
authors: Department of Reconstructive Sciences, University of Connecticut Health Center, Farmington, CT 06030, USA.
authors: Jessica L
authors: JL
authors: Woodman
authors: Unit of Oral and Maxillofacial Implantology, Tsurumi University School of Dental Medicine, Yokohama, Japan.
authors: Daisuke
authors: D
authors: Ueno
authors: Department of Surgery, University of Connecticut Health Center, Farmington, CT 06030, USA.
authors: Gloria
authors: G
authors: Gronowicz
authors: Department of Medicine, University of Connecticut Health Center, Farmington, CT 06030, USA.
authors: Marja M
authors: MM
authors: Hurley
authors: Department of Reconstructive Sciences, University of Connecticut Health Center, Farmington, CT 06030, USA. Electronic address: lkuhn@uchc.edu.
authors: Liisa T
authors: LT
authors: Kuhn
mesh_terms: D000375:Aging; D000818:Animals; D055396:Bone Morphogenetic Protein 2 / Q000494:pharmacology*; D001861:Bone Regeneration / Q000187:drug effects*; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology*; D051379:Mice; D008807:Mice, Inbred BALB C; D010012:Osteogenesis / Q000187:drug effects; D012886:Skull / Q000000981:diagnostic imaging / Q000473:pathology*; D014945:Wound Healing / Q000187:drug effects; D055114:X-Ray Microtomography
chemical_list: D055396:Bone Morphogenetic Protein 2; D016222:Fibroblast Growth Factor 2