title: Site-specific delivery of acidic fibroblast growth factor stimulates angiogenic and osteogenic responses in vivo.
abstract: A major clinical problem in orthopedics is the healing of nonunion fractures. Limitations of this bone repair process include insufficient angiogenesis and mineralization. Integrating appropriate biomaterials with site-specific neovascularization and osteogenesis at the wound site has been the focus of several clinically relevant therapeutic strategies. As an extracellular protein, acidic fibroblast growth factor (FGF-1) induces, coordinates, and sustains site-specific molecular responses associated with angiogenesis and osteogenesis. To establish the ability of this growth factor to coordinate bone regenerative process in vivo, site-specific delivery of FGF-1, entrapped in a fibrin/hydroxyapatite composite, was evaluated. Kinetic analysis in vivo revealed the biocomposite was capable of delivering biologically active FGF-1. Release kinetics revealed an initial delivery of 87.5 ng/h of active FGF-1 in the first 20 h, followed by a reduced delivery of 28 ng/h during the next 20 h. In situ immunohistological analyses demonstrated that FGF-1-containing implants induced increased angiogenesis and infiltration of cells expressing osteogenic related markers (i.e., osteopontin, osteocalcin). Collectively, these efforts support that site-specific delivery of active FGF-1 in a fibrin/hydroxyapatite composite is competent to induce not only angiogenesis but also osteogenic cellular responses.
authors.affiliation: Department of Surgery, The University of Alabama at Birmingham, Birmingham, AL 35294-0007, USA. skelpke@uab.edu
authors.forename: S S
authors.initials: SS
authors.lastname: Kelpke
authors.forename: K R
authors.initials: KR
authors.lastname: Zinn
authors.forename: L W
authors.initials: LW
authors.lastname: Rue
authors.forename: J A
authors.initials: JA
authors.lastname: Thompson
mesh_terms: D043925:Angiogenesis Inducing Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000494:pharmacology*; D000818:Animals; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D016503:Drug Delivery Systems; D016220:Fibroblast Growth Factor 1 / Q000008:administration & dosage* / Q000009:adverse effects / Q000494:pharmacology*; D007150:Immunohistochemistry; D007249:Inflammation / Q000139:chemically induced; D008297:Male; D051379:Mice; D008855:Microscopy, Electron, Scanning; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D010012:Osteogenesis / Q000187:drug effects*; D051381:Rats
chemical_list: D043925:Angiogenesis Inducing Agents; D016220:Fibroblast Growth Factor 1