Wound healing is our body's ability to repair damaged tissue. It can take place by regeneration (damaged cells are replaced by cells of the same type), or by substitution with connective tissue (fibrosis). In the first case, in general, the repair does not give rise to significant scarring, while in the second case there is the formation of a permanent scar. Apart from very few tissues almost exclusively consisting of non-proliferating cells, the vast majority of other tissues are made up of different cellular populations, some of which are actively proliferating, others are quiescent but which can enter into proliferation, and others still absolutely incapable of proliferation.
The ability of labile and stable cells to proliferate does not in itself imply the reconstitution of normal tissue architecture during the repair process. This depends on the fact that, in order to restore a normal cytoarchitecture, it is necessary that the proliferating cells can establish an intimate relationship with the connective structures, and in particular with the basement membrane, in the case for example of epithelial tissues. The destruction of the basement membrane profoundly alters the growth polarity and the reciprocal relationships of the epithelial cells, and this makes it very difficult to restore the original tissue architecture. In the case of perennial cells (and tissues), a modest proliferative activity is present in the skeletal striated muscle, by peripheral satellite cells, but there is rarely an efficient regeneration. Damage is frequently repaired with the formation of a fibrous scar. In the central nervous system finally the damaged neurons are replaced by the proliferation of the glial cells.
In wound healing there is always the more or less extensive formation of a fibrous scar, due precisely to the pivotal role of the connective tissue in restoring the interrupted tissue continuity. The wound healing modality will determine whether the scar will be more or less wide, more or less visible to the external inspection, or more or less damaging to the mechanical properties of the tissue. As we will see later, wound repair is a process closely related to the inflammatory response (indeed some consider it a kind of "physiological inflammation"), whose resolution (including scarring) is inevitably influenced by intensity, duration and from the dominant cellular elements. The biochemical and molecular mechanisms are always the same qualitatively, and the biological significance is also the same: to re-establish tissue integrity, first temporarily and then permanently.
In the overall repair process, three components can be recognized that are in part functionally and temporally separate: the phase of hemostasis, the phase of inflammation and that of regeneration. However, it is important to stress that these components can only be separated very schematically, and that in most cases they are on the contrary intimately interconnected. Historically the habit (probably to be traced back to the medieval medical-surgical tradition) of identifying two ways of healing wounds: by first intention or second intention (where the intention is ideally "manifested" by the wound following one or the other way). It is important to stress that these two modalities essentially differ for the extent of the reparative phenomena, but not for the mechanisms involved, which are fundamentally the same.
Healing by first intention is by far the most favorable: the wound is clean (not infected), with clear margins, close together, juxtaposed, with little loss of substance. In the case of surgical wounds or sutured accidental wounds, the margins are carefully matched with the use of stitches, a procedure that further facilitates repair.
Secondary healing is typical of those wounds characterized by extensive loss of substance or bacterial infections. In this case an intense inflammatory response is evoked, and there is a massive production of granulation tissue to repair the extensive loss of substance. Both these phenomena profoundly alter the normal reparative process and cause significant scarring.
