Control of basic fibroblast growth factor release from fibrin gel with heparin and concentrations of fibrinogen and thrombin

Basic fibroblast growth factor (bFGF) has been known to stimulate the regeneration of a number of tissues including cartilage, nerve, skin, liver, and blood vessel. Delivery of bFGF for a long period in a controlled manner would enhance stimulative effects. The purpose of the present study is to test the hypothesis that the kinetics of bFGF release from fibrin gels could be controlled with heparin and concentrations of fibrinogen and thrombin. The kinetics of bFGF release from fibrin gels with various concentrations of fibrinogen, thrombin, and heparin was determined. The bioactivity of bFGF released from fibrin gels was assessed using dermal fibroblast cell culture. To examine the therapeutic potential of the bFGF delivery system, bFGF-loaded fibrin gels were injected into mouse ischemic limbs. The addition of heparin to fibrin gels decreased the bFGF release rate. As the thrombin content in fibrin gels increased, the bFGF release rate significantly decreased. Similarly, increased concentration of fibrinogen in fibrin gels decreased the bFGF release rate. Basic FGF released from fibrin gels exhibited significantly higher extents of fibroblast growth than bFGF added in a free form daily into the culture medium, suggesting that the fibrin gels may stabilize the bFGF bioactivity. Immunohistological analysis of mouse ischemic limbs indicated that the microvessel density was much higher in the ischemic limbs treated with injection of bFGF-loaded fibrin gels than in the ischemic limbs with no treatment. This study showed that the rate of bFGF release from fibrin gels can be controlled and that the bFGF delivery system has therapeutic potentials for angiogenesis.