Exogenous hyaluronic acid and wound healing: an updated vision.

Hyaluronic acid (HA), an endogenous substance whose concentration increases during the process of wound repair, can be manufactured in order to use it as an exogenous intervention able to reduce the time to wound repair and improve the quality of the scar. The role of HA as a key component of the extracellular matrix structure has been recognized for many decades, while its actions on cells involved in the process of tissue repair has been partly clarified only in the last few years. Fibroblasts, endothelial cells and macrophages are key players in the tissue repair process and a concerted activation of specific functions of these cells may substantially improve the process of wound closure. Hyaluronan, as well as its degradation products that are generated in the wounds, are capable to activate specific responses in all the cells involved in the process; in particular, fibroblast proliferation and new vessel formation have been extensively studied. The molecular patterns leading to cell activation have been substantially clarified and it is now widely accepted that cellular actions of hyaluronic acid are mediated by specific surface receptors, including CD44, RHAMM and toll like receptors. Elucidation of the mechanisms of cellular activation will allow an optimal use of exogenous hyaluronan and its derivatives in the wound care setting.