Professor Keith Harding on the physiology of the wound

The ability of the body to repair itself following injury is, at a cellular and molecular level, very complex. In trying to get across a series of complex cellular processes, it's probably best to divide the wound healing process into four components. Following injury, whether it is a surgical incision, whether it is trauma or whether it is the initial breakdown of the skin following pressure or other causes of skin breakdown. The first thing you need is to stop bleeding. So the first phase is haemostasis. It's the normal blood clotting mechanism where the blood clots, stops you bleeding to death, limits the degree of tissue damage, and then over a period of a few hours, one or two days, that clot then starts to resolve. That then triggers the second phase of wound healing, which is inflammation. For wounds to heal, the body needs to put in a series of inflammatory cells, the neutrophils and the macrophages in main, which will come in, help break up the clot, help deal with any foreign body, deal with any bacteria or any infections there. It then triggers the next phase of wound healing which is the ability for that tissue to proliferate which is mainly the ingrowth of blood vessels, the delivery of oxygen to the tissue and the deposition of what we call extracellular matrix protein which which is mainly collagen, which fills the hole. The final phase of wound healing that then follows on from proliferation is maturation, where you get epithelialization of the residual defect and maturation of that scar tissue. That process can last for up to two years after wound closure has occurred. What you want the body to do is to heal as quickly as possible, to restore normal function as far as you can, and to minimize scarring. When all of those four processes work in a coordinated fashion, that is what you hope will occur. But because of the integration of these four processes, because of the potential for these processes to be delayed or diverted in one way or another, that is the reason why wound healing may be delayed in many of the patients that we see with chronic wounds. When I first got into wound healing 20, 30 years ago, it was seen that one of the biggest challenges was the body's ability to deposit new protein, the extracellular matrix protein, within the wound. It is now recognized that the body, even in patients with chronic wounds, is probably working as hard as it can, and as quickly as it can, to deposit that new protein. But in a wound that's not healing, it's not the deposition of the protein that's the problem, it's the overexpression of degrading enzymes, the proteases, which chew up that protein, which we don't see happening at the macroscopic level, we just see a wound that's not healing. So you need a balance between synthesis and degradation, particularly in the proliferative phase of wound healing, where you're trying to fill that defect with new tissue. Growth factors and cytokines are basically the same family of proteins. The differentiation is based on the molecular size of those proteins. So small growth factors are cytokines, large molecular weight proteins are growth factors. You need an awful lot of cytokines to stimulate that inflammatory response. You need an awful lot of growth factor release to provide the nutrients and the signals for cells and tissue to be laid down in that wound. Because of the multiple cytokines and multiple growth factors involved in this complex process, it is understandable why many people have been looking at the value of giving that patient or delivering to that wound cytokines or growth factors which may have a stimulatory effect don't wound healing.