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Wound Healing Biology

Normal wound healing occurs in four overlapping phases. The first involves formation of a plug consisting of platelets and a network of fibers (fibrin, fibronectic, vitonectin and thrombospondin) to rapidly cover the wound and protect it from bacteria.  The plug also releases cytokines that recruit white blood cells to the wound, thereby triggering the next phase. The second, inflammatory phase starts with the migration of macrophages and other white blood cells into the wound.  There, they destroy bacteria and remove cell debris.  After about 1-2 days, keratinocytes at the wound margins and beneath the wound also migrate over and upwards the wound during the third, proliferative phase.  During this phase, the formation of new blood vessels starts. The fourth, remodeling phase uses multiple cytokines and other growth factors such as TGF-b, VEGF and PDGF secreted by the macrophages to attract fibroblasts, endothelial cells and other connective tissue cells to the wound.  Dermal cells surrounding the wound produce matrix proteins such as collagen to create a temporary matrix for the continued migration of keratinocytes throughout the healing wound.  Meanwhile, macrophages and fibroblasts produce growth factors that promote the development of new blood vessels and permanent structure.  In addition, proteases are working to remove the clot and assist in wound healing and scar prevention.  All of these processes conducted by the various cell types must proceed correctly if the wound is to heal normally resulting in strong new skin.  Unfortunately, there are many circumstances that inhibit or prevent the normal healing process and instead healing is stalled.  The failure to repair wound may result in a chronic open wound.

Diabetic Wound Biology

When diabetics have injuries to their feet, they must be aggressive at detecting this early and make a strenuous effort to promote rapid healing.  Unfortunately, 15-20% of all diabetics will develop  chronic foot wounds (also called diabetic foot ulcers, DFU) that will not heal.  Diabetics’ chronic wounds have unique issues because the wound healing appears to stagnate partway through the process, frequently in the inflammatory phase.  Because the wounds don’t appear to move on to the rebuilding phases and instead remain open, the patient’s foot and lower limb is in danger from infection often leading to amputation.  It is believed that the wound healing becomes stalled due to causes traced to the diabetes as well as external causes.  In poorly controlled diabetes, constant elevated blood glucose levels are toxic to many cells and cause the patient to develop a wide variety of side effects.  Patients will frequently develop neuropathy (loss of nerves and normal pain sensations) and peripheral vascular disease (abnormal blood vessels and blood supply) in their feet and lower limbs.  This results in the patients not noticing open wounds or serious injuries.  Once injured, the patients’ feet and lower limbs are susceptible to infections, callus formation and excessive pressure on an unhealed wound.

Health Crisis >>  Wound Biology 
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