Site-specific delivery of acidic fibroblast growth factor stimulates angiogenic and osteogenic responses in vivo

Journal of Biomedical Materials Research. Part a
S S KelpkeJ A Thompson

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 si...Continue Reading

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