Validation of human ex-vivo models for studies on wound healing process in microgravity conditions

3 1. INTRODUCTION 1.1 The wound healing process: an overview The wound healing process is a complex biological phenomenon involving not only the skin, which is the largest organ by surface on human body, but also all biological tissues. Not all tissues are composed of cells with a high proliferative activity, which, combined with the ability to connect with connective tissue structures, ensures wound repair. In fact, a distinction is made between labile, stable and perennial tissues, according to their regenerative capacities (Bizzozero, 1989). Labile tissues, consisting of actively proliferating cells (high presence of stem cells) are the lining epithelia, mucosecreting epithelia and haematopoietic cells; stable tissues, on the other hand, consist of cells that are normally quiescent but capable of re-starting proliferation, such as the parenchymal cells of glandular organs (liver, kidneys, pancreas), mesenchymal cells (fibroblasts and smooth muscle cells), and vascular endothelia; perennial cells are cells that once specialised abandon their cell cycle and their proliferative capacity, such as neurons, skeletal and cardiac striated muscle cells. In the central nervous system, damaged neurons are replaced by the proliferation of glial cells, while in the striated muscle a modest proliferative activity is maintained by peripheral satellite cells (stem cells) that provide repair with the formation of a fibrous scar. The injury of the soft structures, i.e. the wound, is repaired through scarring, an event represented by the neoformation of a connective structure different from the original one, the scar, aimed at filling the injury due to loss of substance to restore tissue integrity. The wound is always composed of a margin, perilesional skin and a lesional bottom. Healing can take place in three different ways which differ not in the healing mechanisms involved, but only in the extent of the reparative phenomena: - Stab wounds, such as accidental or surgical wounds which are suturated, not infected and have sharp margins, heal 'by first intention'. Through the juxtaposition of the wound flaps, the loss of substance is minimised. In this way, healing takes place rather quickly, promoting the filling of the wound by granulation tissue, i.e. the connective structure representing neoangiogenesis. - Unsuturated wounds, which have jagged margins, e.g. burns, infected and necrotic wounds, heal 'by second intention'. It is a process in which the granulation tissue, which forms at the bottom of the wound, needs a rather long time to repair the loss of substance up to the surface.