title: Revascularization and bone remodeling of frozen allografts stimulated by intramedullary sustained delivery of FGF-2 and VEGF.
abstract: Frozen bone allografts are susceptible to nonunion and fracture due to limited revascularization and incomplete bone remodeling. We aim to revascularize bone allografts by combining angiogenesis from implanted arteriovenous (AV) bundles with delivery of fibroblast growth factor (FGF-2) and/or vascular endothelial growth factor (VEGF) via biodegradable microspheres. Rat femoral diaphyseal allografts were frozen at -80°C, and heterotopically transplanted over a major histocompatibility mismatch. A saphenous AV bundle was inserted into the intramedullary canal. Growth factor was encapsulated into microspheres and inserted into the graft, providing localized and sustained drug release. Forty rats were included in four groups: (I) phosphate-buffered saline, (II) FGF-2, (III) VEGF, and (IV) FGF-2 + VEGF. At 4 weeks, angiogenesis was measured by the hydrogen washout method and microangiography. Bone remodeling was evaluated by quantitative histomorphometry and histology. Bone blood flow was significantly higher in groups III and IV compared to control (p < 0.05). Similarly, bone remodeling was higher in VEGF groups. FGF-2 had little effect on allograft revascularization. No synergistic effect was observed with use of both cytokines. Delivered in microspheres, VEGF proved to be a potent angiogenic cytokine, increasing cortical bone blood flow and new bone formation in frozen allografts revascularized with an implanted AV bundle.
authors: Microvascular Research Laboratory, Department of Orthopedic Surgery, Mayo Clinic, 200 First Street SW, Rochester, Minnesota 55905, USA.
authors: Wouter F
authors: WF
authors: Willems
authors: Mikko
authors: M
authors: Larsen
authors: Guilherme
authors: G
authors: Giusti
authors: Patricia F
authors: PF
authors: Friedrich
authors: Allen T
authors: AT
authors: Bishop
mesh_terms: D000818:Animals; D001861:Bone Regeneration / Q000187:drug effects*; D016025:Bone Transplantation; D015925:Cryopreservation; D004337:Drug Carriers; D004359:Drug Therapy, Combination; D005260:Female; D005269:Femur / Q000098:blood supply* / Q000637:transplantation; D016222:Fibroblast Growth Factor 2 / Q000008:administration & dosage*; D008863:Microspheres; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D051381:Rats; D014184:Transplantation, Homologous; D042461:Vascular Endothelial Growth Factor A / Q000008:administration & dosage*
chemical_list: D004337:Drug Carriers; D042461:Vascular Endothelial Growth Factor A; D016222:Fibroblast Growth Factor 2