Role of angiogenesis and angiogenic factors in acute and chronic wound healing

Angiogenesis plays a crucial role in wound healing by forming new blood vessels from preexisting vessels by invading the wound clot and organizing into a microvascular network throughout the granulation tissue. This dynamic process is highly regulated by signals from both serum and the surrounding extracellular matrix environment. Vascular endothelial growth factor, angiopoietin, fibroblast growth factor and transforming growth factor-beta are among the potent angiogenic cytokines in wound angiogenesis. Specific endothelial cell ECM receptors are critical for morphogenetic changes in blood vessels during wound repair. In particular integrin (αvβ3) receptors for fibrin and fibronectin, appear to be required for wound angiogenesis: αvβ3 is focally expressed at the tips of angiogenic capillary sprouts invading the wound clot, and any functional inhibitors of αvβ3 such as monoclonal antibodies, cyclic RGD peptide antagonists, and peptidomimetics rapidly inhibit granulation tissue formation. In spite of clear knowledge about influence of many angiogenic factors on wound healing, little progress has been made in defining the source of these factors, the regulatory events involved in wound angiogenesis and in the clinical use of angiogenic stimulants to promote repair.