Why do chronic wounds persist? How do we best treat this type of wound? It may be possible that wound is stuck in the inflammatory phase, where enzymes that should have long ago disappeared are still present. These enzymes are possibly destructive, and include the following types:
– Elastase: secreted by neutrophilis, this enzyme is simply not useful at this stage in a wound’s life. Elastase destroys elastin, and other enzymes too – even those that could be useful to the wound, such as tissue inhibitors of matrix metalloproteinases (TIMPs).
– Matrix Metalloproteases (MMPs): MMPs are proteases that are associated with metal ions, and the worst of them are specific to collagen (or fragments of collagen). They seek out collagen molecules and chemically break them down.
TIMPs are thought of as “anti-MMPs” and must outnumber the MMPs (conceptually speaking) for the wound to heal normally. In a chronic wound, the MMP to TIMP ratio is in favor of MMPs—the collagen-destroying enzymes.
One place to start is to bring fibroblasts to the wound bed. An effective method is to plant native collagen dressings that will bind with the MMPs, keeping the MMPs occupied in the activity of breaking down the dressing material instead of the new (de novo) collagen made by the fibroblasts that are working hard in a challenging environment.
Enzymes are concentrated in the dressing, where collagen is plentiful, instead of in the tissue, where the fibroblasts are putting out the body’s own collagen at low concentrations. Denatured collagen, available in some wound care products today, is processed chemically to the extent that it has lost the sophisticated triple helix structure of collagen is particularly attractive to fibroblasts.
Fibroblasts also thrive in structures in which they can spread out three-dimensionally (as they would in real-life wound environment) and essentially “be themselves.” In other words, they like to be doing the things they should be doing, like secreting collagen and other important materials of the extracellular matrix. So, using a collagen product with a noticeable three-dimensional structure allows the fibroblasts to act as normally as they possibly can.
Why native collagen-based dressings interact with the destructive elastase enzyme to the extent that they seem to do is still under investigation. Binding of a dressing material to elastase obviously reduces the concentration of the elastase in the wound bed, which means that less of the wound bed’s elastin is destroyed. But— perhaps more importantly— elastase is known to play a role in creating the final destructive form of MMPs. Taking elastase out of the equation dramatically reduces the potential of MMPs being freshly and efficiently created in the wound bed. Elastase is also known to destroy the beneficial TIMP enzymes that keep the MMP in check. A reduced elastase level allows the TIMP concentration to reach a level that keeps MMP activity low in the wound bed.
But what happens to the dressing once applied to the chronic wound? Essentially it is “taken apart” (in a chemical sense) by the MMPs to which it was bound. The byproducts of this binding are collagen fragments, which are consumed by the fibroblasts. The fibroblasts will synthesize “fresh” collagen (or the body’s own de novo collagen) and secrete it out into an environment relatively free of MMPs. Without their removal, the newly synthesized collagen would have been destroyed.
Even after trying everything else to treat a chronic but infection-free wound— by taking these findings into consideration and practice, there’s a good chance that the chronic wound will proceed to heal.