• See also Healing, North East Lincolnshire

Healing is the process where the cells in the body regenerate and repair to reduce the size of a damaged or necrotic area.

Healing incorporates both the removal of necrotic tissue (demolition), and the replacement of this tissue.

The replacement can happen in two ways:

• by regeneration - this is when the necrotic cells are replaced by what was there in the first place.
• by repair - this is when the injured tissue is replaced with scar tissue .

Most organs will heal using a mixture of both mechanisms.

Healing by regeneration

In order for an injury to be healed by regeneration, the cell type that was destroyed must be able to replicate. Most cells have this ability, although it is believed that cardiac muscle cells and neurons are two important cells that cannot divide.

As well as the ability to replicate, there must still be a collagen framework for the cells to grow on. Alongside most cells there is either a basement membrane, or a collagenous network made by fibroblasts that will guide the cells as to where they should grow. As collagen will not be destroyed by ischaemia or most toxins, it will survive even when the cells around it are dead.

Example of regeneration

An example of healing completely by regeneration is in acute tubular necrosis (ATN) in the kidney.

ATN is 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 well and truly dead, there is typically patchy necrosis. This means that there are patches of epithelial cells still alive. As well as this, the collagen framework of the tubules is 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, it is impossible to tell, even microscopically, that there has ever been damage.

Healing by repair

If the injury occurred in cells that can't regenerate (e.g. cardiac muscle or neurons), or if the collagen network has been damaged (e.g. by enzymes or physical destruction), or even if the collagen has collapsed (as can happen in an infarct), healing must happen by repair.

Repair starts happening soon after necrosis of the tissues, and ultimately results in a scar made of collagen, containing a small number of fibroblasts.

The first thing that happens is that the dead tissue is removed by macrophages. This is the process of demolition. As well as phagocytosis the tissue, macrophages release chemical factors that encourage fibroblasts and new capillaries to form.

Immature granulation tissue is the next thing to form. This contains plump active fibroblasts, producing lots of type III collagen very quickly. There are many new capillaries that are leaky and dilated, that are necessary to supply nutrients to the new cells.

Granulation tissue moves, as a wave, from the border of the injury towards the centre of the necrotic area. As the granulation tissue matures the fibroblasts produce less collagen, and are much more spindly in appearance. The collagen they produce is the much stronger type I collagen. Some of the fibroblasts contain actin and myosin bundles, like smooth muscle which enables them to contract.

Eventually, the vessels of granulation tissue disappear, and there is a lot of type I collagen with a few spindly fibroblasts. This, and contraction of the myofibroblasts, has left a small white scar on the tissue.

Specific examples of healing

• Skin healing - this is important cosmetically and functionally, as scar formation, especially at a joint, can impair movement.
• Bone healing - the healing of a fracture takes a lot of time, has a lot of potential problems, and a lot can be done surgically to overcome these problems.
• Brain healing - Such as in a cerebral infarct (a stroke). Not only can neurons not divide, but a collagen scar will not form.
• Nerve healing - Even though neurons cannot replicate, a nerve is often just a collection of axons, and the cell itself doesn't die.