Emerging Treatments in Diabetic Wound Care

Thanh Dinh, DPM;1 Hau Pham, DPM;1 Aristidis Veves, MD2


Treatment of diabetic foot ulceration is much more complex than simply putting a dressing over a wound. Diabetic foot ulceration is a significant cause of morbidity and is the most common reason for hospital admission in diabetic patients. Annually, two to three percent of diabetic patients1,2 will develop foot ulcers, and up to 15 percent of diabetic patients will develop chronic ulcers during their lifetimes.3 In those who require lower-limb amputation, 70 to 90 percent will be preceded by a foot ulceration.

Physiology of Wound Healing

The three general phases involved in wound healing are the acute inflammatory phase, the proliferative phase, and the maturation phase. The initiation and transition of these phases have no clear-cut boundaries but are descriptors on a continuum of events. The initial phase, inflammation, involves transient vasoconstriction of local arterioles and capillaries followed by an influx of inflammatory cells and plasma proteins to mediate the repair process. The next phase is proliferation, where fibroblastic activity and angiogenesis by the endothelial cells begin. The maturation phase may last for up to two years and involves collagen synthesis and breakdown.

Developments in Physiological Aspects of Wound Healing

Chronic diabetic foot ulcers have been shown to result from a number of causes, one of which involves faulty wound healing. The normal wound healing process entails a complex interplay between connective tissue formation, cellular activity, and growth factor activation. All three of these physiologic processes are altered in the diabetic state and contribute to the poor healing of diabetic foot ulcers. More specifically, the chronic diabetic foot ulcer is stalled in the inflammation phase of the normal wound healing process.4 During this delay, there is a cessation of epidermal growth and migration over the wound surface.5,6 Analyses of fluid from chronic wounds have demonstrated elevated levels of matrix metalloproteinases (MMPs) directly resulting in increased proteolytic activity and inactivation of the growth factors that are necessary for proper wound healing. A number of recent studies have investigated these alterations in an attempt to better understand the wound healing abnormalities in diabetes and to target therapy specifically aimed at correcting these deficiencies, as described below.

Collagen. Collagen, the most abundant protein in connective tissue, is an integral component of dermis, bones, tendons, and ligaments. Collagen synthesis and degradation in wound repair are complex processes that continue at the wound site long after the injury. The resulting scar tissue following wound repair never fully regains the tensile strength of the original intact skin. Instead, scar collagen retains only 70- to 80-percent tensile strength of the original collagen.7 The balance between collagen synthesis and degradation in wound repair is tenuous, and disease states, such as diabetes, can shift the balance to one side, disrupting the wound healing process.

In diabetes, collagen synthesis is markedly decreased, resulting in chronic connective tissue complications. The defect in collagen metabolism in diabetes is present at both the collagen peptide production level as well as the posttranslational modification of collagen degradation. The resultant collagen production deficits can be observed in several systems, including thickening of the vascular basement membrane, limited joint mobility, and poor wound healing.

Cellular activity. The inflammatory stage of wound repair involves an orchestrated interaction of resident cells, such as epithelial cells, fibroblasts, dendritic cells, and endothelial cells, with biochemical activity. In addition to these resident cells, platelets, neutrophils, T-cells, natural killer cells, and macrophages are recruited to the wound site.



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Mia Tigahsays: August 13.2010 at 10:33 am

The greatest benefit for many of these dermal replacements would be: IF they can improve the tensile strength of these wound sites. Healing these wounds is not the issue. KEEPING them healed IS. Unless the biomechanical components are addressed as a FIRST THOUGHT, money spent on the modalities listed here is a waste of limited health care $$$ resources. Management of Diabetes / Neuropathic foot wounds is first and foremost a biomechanical issue, until such time when neuropathy can ever be prevented or reversed.
The components of Diabetes foot/Neuropathic wound healing presented here do not include information regarding management of repeated high pressure and gait related shearing, which are fundamentally major issues in the acquisition, treatment and prevention of neuropathic DM Foot wounds. Also omitted is mention of the management of commonly seen foot deformities and offloading strategies, which are integral to a successful Neuropathic / DM Foot Treament plan. There are emerging strategies in the biomechanical field, which if considered, eliminate the need for many of the most costly options included in this article.

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says: October 2.2011 at 21:47 pm

If there is an infection present and it is chronic then the microorganism responsible has to be identified. Typically this is done by taking tissue and fluid samples and growing the bacteria in a petri dish with media, a procedure familiar to every medical student. However there are many cases in which laboratories are unable to grow bacteria, so the doctor has to guess as to what antibiotic treatment might be suitable. It is not clear why the failure to grow bacteria happens even in reputable laboratories while other laboratories can be successful. It is possible, if you can find a research laboratory, to have a different than standard way to grow the bacteria, in a nutrient broth rather than in the typical petri dish media. This is not high throughput, requires more expertise, but is also more reliable. Knowing the nature of the bacteria is important, people have spent many weeks on antibiotic therapies that did not work. Once the organism has been grown and identified, a susceptibility test should be done. The usual test is the standard MIC test, basically worthless for chronic infections. The MIC test tries therapies against free floating, disorganized, easy to kill bacteria. In a chronic wound the bacteria have organized to defend themselves in a biofilm and are far harder to kill off. The same compound that works to kill unorganized bacteria can fail to kill a biofilm. Sometimes a combination of antibiotics are needed. This is new technology. Search for "biofilm susceptibility testing" to get the most recent news on what is available and what the stage of development is.

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says: March 15.2012 at 13:30 pm

I have been a diabetic for a good while and recently have developed a callus on the bottom of my forefoot. It has become inflamed and the medicine prescribed for it did not agree with me; besides, the side effect were frightening. I stopped taking this medicine because I thought that I had experienced some of them. I don't know what this callus can develop into and I am really very concerned that it could become very serious or that I may not get the proper treatment for it. It is the result (the callus) of a bunion on the large toe and then the friction and the pressure to the forefoot. How can I get my foot back to normal and where should I go that could make a real difference in terms of outcomes? I love your article as it provides information to me. Thank you for allowing me to make this comment, I appreciate your information.

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