Maturation phase
During the maturation phase of wound healing, unnecessary vessels formed in granulation tissue are removed by apoptosis, and type III collagen is largely replaced by type I. Collagen which was originally disorganized is cross-linked and aligned along tension lines. This phase can last a year or longer. Ultimately a scar made of collagen, containing a small number of fibroblasts is left. Tissue damaged by inflammation
After inflammation has damaged tissue (when combatting bacterial infection for example) and pro-inflammatory eicosanoids have completed their function, healing proceeds in 4 phases. Recall phase
In the recall phase the adrenal glands increase production of cortisol which shuts down eicosanoid production and inflammation. Resolution phase
In the Resolution phase, pathogens and damaged tissue are removed by macrophages (white blood cells). Red blood cells are also removed from the damaged tissue by macrophages. Failure to remove all of the damaged cells and pathogens may retrigger inflammation. The two subsets of macrophage M1 & M2 plays a crucial role in this phase, M1 macrophage being a pro inflammatory while as M2 is a regenerative and the plasticity between the two subsets determine the tissue inflammation or repair. Regeneration phase
In the Regeneration phase, blood vessels are repaired and new cells form in the damaged site similar to the cells that were damaged and removed. Some cells such as neurons and muscle cells (especially in the heart) are slow to recover. Repair phase
In the Repair phase, new tissue is generated which requires a balance of anti-inflammatory and pro-inflammatory eicosanoids.
Alongside most cells there is either a basement membrane or a collagenous network made by fibroblasts that will guide the cells growth. Since ischaemia and most toxins do not destroy collagen, it will continue to exist even when the cells around it are dead. Example
Acute tubular necrosis (ATN) in the kidney is a case in which cells heal completely by regeneration. ATN occurs when the epithelial cells that line the kidney are destroyed by either a lack of oxygen (such as in hypovolemic shock, when blood supply to the kidneys is dramatically reduced), or by toxins (such as some antibiotics, heavy metals or carbon tetrachloride).Although many of these epithelial cells are dead, there is typically patchy necrosis, meaning that there are patches of epithelial cells still alive. In addition, the collagen framework of the tubules remains completely intact.The existing epithelial cells can replicate, and, using the basement membrane as a guide, eventually bring the kidney back to normal. After regeneration is complete, the damage is undetectable, even microscopically.Healing must happen by repair in the case of injury to cells that are unable to regenerate (e.g. neurons). Also, damage to the collagen network (e.g. by enzymes or physical destruction), or its total collapse (as can happen in an infarct) cause healing to take place by repair. Genetics
Many genes play a role in healing. For instance, in wound healing, P21 has been found to allow mammals to heal spontaneously. It even allows some mammals (like mice) to heal wounds without scars.