Exploring The Potential Of Advanced Wound Care Products For Diabetic Wounds

E. Giannin Perez, DPM, MS, and Khurram H. Khan, DPM, FACFAS

Wound healing is a challenging task for any podiatric physician, especially for our high-risk patients with diabetes. Uncontrolled diabetes has consequences for all aspects of the body but is especially detrimental to wound healing. Patients with diabetes have a 15 to 25 percent lifetime risk of developing foot ulcers and their annual treatment costs are estimated to be about $30,000.1

   The normal physiology of wound healing encompasses three phases. The inflammatory phase occurs right after the initial insult. Platelets adhere to form a hemostatic plug and release alpha granules containing platelet-derived growth factor (PDGF). The alpha granules act to recruit and activate pro-inflammatory cells such as fibroblasts, macrophages, neutrophils and monocytes. These in turn secrete transforming growth factor beta (TGF-β), fibroblast growth factor (FGF), endothelial growth factor (EGF) and vascular endothelial growth factor (VEGF). Platelets also release TGF-β themselves and platelet-derived angiogenesis factor (PDAF).

   In the epithelialization phase, epidermal cells proliferate and migrate, depositing basement membrane components. Neovascularization causes the formation of granulation tissue. Fibroblasts are key to orchestrating the reorganization of the extracellular matrix. Growth factors and VEGF support wound healing and angiogenesis.

   During the remodeling phase, fibroblasts assist in wound contraction and matrix metalloproteinases (MMPs) continuously remodel collagen until wound re-epithelialization has occurred.

   There are numerous bioengineered alternative tissues (BATs) available to the podiatric physician but there are basic principles of wound care that physicians must follow prior to recruiting BATs.2 These principles include:

• removal of non-vital tissue via enzymatic, mechanical, biologic or surgical debridement, including hydrosurgical debridement;
• maintenance of moist wound healing environment;
• avoidance of excessive cytotoxic therapies (povidone-iodine or silver agents);
• assessment of micro- and macrovascular disease;
• offloading pressure sites; and
• aggressive treatment of infection.

   A chronic non-healing wound, as defined by Medicare and based on the research of Sheehan and colleagues, is a wound that does not heal by at least 50 percent after receiving basic wound care for 30 days.3-5 This definition is necessary to establish an endpoint at which more expensive biological therapies may be warranted.2

   Remember that chronic wounds are those in which there is an imbalance of the phases of wound healing. Although MMPs are present and important at every stage of wound healing, chronic diabetic wounds contain higher levels of MMPs in comparison to acute wounds, and this increase plays an inhibitory role at the wound base. Fibroblasts produce tissue inhibitors of metalloproteinases (TIMPs) that regulate MMPs. Interestingly, research has shown that diabetic wounds have decreased levels of TIMPs, suggesting even less regulation of MMPs.6,7

A Pertinent Overview On Bioengineered Alternative Tissues

Physicians have adopted the term bioengineered alternative tissue recently mainly because it is more descriptive than previous terms. The old terms, such as “tissue-engineered skin,” “biologic skin substitutes,” etc., caused much confusion.

   Bioengineered alternative tissues are not autogenous skin and we should not treat them as such. All BATs are not created equal. It is imperative that one understands the capabilities and limits of these BATs in order to prevent misuse.

   Just like in bone healing with reference to osteoinductive and osteoconductive properties of bone fillers, the terms “dermoinductive” and “dermoconductive” can apply to BATs.8

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