Specific Effects of Fibrinogen and the γA and γ′-Chain Fibrinogen Variants on Angiogenesis and Wound Healing

In a newly formed wound, the natural fibrin network provides the first temporary matrix for tissue repair. Topical application of fibrin to a new wound may improve wound healing. A matrix of the common natural γ' fibrin variant may further improve wound healing because it is expected to have a different architecture and this will influence angiogenesis, because it possesses increased thrombin and factor XIII binding and decreased platelet binding, when compared with the common γA fibrin matrix. Our objective was to determine the effect of fibrinogen and its γA and γ' variants on angiogenesis and wound healing. We used in vitro angiogenesis models and an in vivo rat full-thickness excisional wound healing model. When comparing γA and γ' fibrin in vitro, more tube-like structures were formed on day 7 in γA fibrin than in γ' fibrin (13.83±6.12 AU vs. 6.1±1.46 AU). Wounds treated with fibrin demonstrated improved healing in vivo with more perfusion (47%±3% vs. 26%±4%, p<0.01 in placebo) and higher CD34 density score (2.0±0.4 vs. 2.8±0.1, p<0.01) on day 21 with fibrin matrices when compared with placebo-treated wounds. Increased perfusion was observed in γA fibrin-treated wounds on day 21 (53%±10% vs. 41%±7% for γ' fibrin). The other parameters showed slightly improved (not significant) wound healing with γA fibrin compared with γ' fibrin matrices. In conclusion, the use of fibrin and fibrin variant matrices offers an interesting methodology to stimulate the wound healing process.