There are many intrinsic and extrinsic factors leading to delayed wound healing. Among them we find: smoking, malnutrition, stress, age, poor blood circulation, but also pain.
Wounds are naturally colonized with matrix metalloproteases (MMPs), which are eliminated once healing has taken place. But on chronic wounds there is a phenomenon of self-maintenance of these MMPs, which colonize the wound and prevent it from healing. In this case, it must be thoroughly and vigorously cleaned and these MMPs eliminated.
The conditions required for rapid healing go through a good nutritional state and systemic factors (good vascularization, absence of pathogenic germs, good general condition). Despite careful local care, healing may not succeed. Various factors can lead to delayed healing. They can be intrinsic, specific to the individual and modifiable (tobacco, undernutrition, obesity, etc.), or extrinsic and non-modifiable (age, ischemia, anti-cancer treatment).
Obesity Poor vascularization of adipose tissue
Poor circulation (V/A) Hypoperfusion
Malnutrition Poor collagen synthesis
Irradiations Narrowing of the vascular lumen
Immunosuppressants Reduced collagen synthesis
Stress Cortisol decreases lymphocytes
Corticosteroids Slow epithelialization
It is necessary to add the pain which involves a vasoconstriction in distal and thus a prejudicial hypo perfusion to the cicatrization.
There is another, less well-known factor that delays wound healing: matrix metalloproteinases (MMPs). These are proteases involved in cell reconstruction. They act by activating growth factors and degrading the protein: they cut it into pieces. Their presence is normal during the inflammation phase.
HOW ARE THEY PRODUCED?
By activated inflammatory cells.
By wound cells.
The amount of MMP is considerable in chronic wounds
THEIR ROLE :
Metalloproteases eliminate the damaged extracellular membrane, exert an action on the biofilm (more or less complex, often symbiotic multicellular community of micro-organisms), allow angiogenesis, help scar contraction (during the remodeling phase ). They therefore find their usefulness during the first phase.
WHEN HEALING IS COMPLETE
And in the absence of complications, there is normal production of MMP inhibitors. But on the chronic wound, the abundant exudate and the fibrin (or necrosis) maintain the phenomenon of MMP, which proliferate. They continue their "cleaning" action, maintaining a wound that can no longer heal.
When they are present in too large a quantity, the MMPs destroy in a non-selective way the growth factors or receptor of the extracellular membrane. The secretion of an MMP inhibitor decreases, leaving them open field. The bacteria present on the wound also produce MMPs: it is a vicious circle which is a major factor in delayed wound healing and chronicization of a wound.
THE IMBALANCE DUE TO MMPs
In normal wound healing, there is a balance between MMPs and growth factors. When the wound becomes chronic, there is an increased activity of metalloproteases.
EXAMPLES:
Leg Ulcers/Diabetes Wound: MMP-1 X 65 (relative to normal).
Bedsore exudate: MMP-9 X 25. A constant decrease in growth factors is found in chronic wounds.
Some laboratories have manufactured and integrated MMP inhibitors (eg Urgostart®) which activate healing.
