[Implication of hyaluronic acid in normal and pathological angiogenesis. Application for cellular engineering]

Angiogenesis is a physiological process that allows the formation of new blood vessels, either from the local vascular structures, or from circulating endothelial progenitor cells, mobilized from the bone marrow, and attracted to the neovascularization site. This mechanism is controlled by pro-angiogenic molecules. It is crucial to supply oxygen and nutrients to tissues during growth, embryonic development or tissue regeneration in response to injuries. Thus, the dermis part of the skin is highly vascularized by a dense network of small and medium arteries and of capillaries and venules. In case of injury, rapid tissue repair is possible through this vascular network. However, once the vascularization is restored in tissue repair, the process of angiogenesis is negatively regulated by anti-angiogenic molecules. Controling the balance between pro-and anti-angiogenic agents is crucial and its deregulation leads to serious disease. The extracellular matrix plays an important role in controlling angiogenesis, allowing at least, the distribution of growth factors and the regulation of endothelial cell migration. Among these matrix components, hyaluronic acid plays a major role in the mechanical properties of connective tissues in ensuring their hydration. This glycosaminoglycan is a large size polymer, whose breakdown products strongly act on angiogenesis, especially in pathological situations (cancer, inflammation). Regarding its biological and mechanical properties, hyaluronic acid is used as matrix in tissue engineering, for improving the revascularization of tissues like skin.