Optimal wound healing requires adequate nutrition. Nutrition deficiencies impede the normal processes that allow progression through stages of wound healing. Malnutrition has also been related to decreased wound tensile strength and increased infection rates. Malnourished patients can develop pressure ulcers, infections, and delayed wound healing that result in chronic nonhealing wounds. Chronic wounds are a significant cause of morbidity and mortality for many patients and therefore constitute a serious clinical concern. Because most patients with chronic skin ulcers suffer micronutrient status alterations and malnutrition to some degree, current nutrition therapies are aimed at correcting nutrition deficiencies responsible for delayed wound healing. This review provides current information on nutrition management for simple acute wounds and complex nonhealing wounds and offers some insights into innovative future treatments.

Modern advances in nutritional therapies have led to the specific use of arginine supplementation for protein synthesis, cell signaling through the production of nitric oxide, and cell proliferation through its metabolism to ornithine and to polyamines. Arginine is classified as a nonessential amino acid that becomes a conditionally essential substrate in stressed adults. Arginine has been shown to enhance wound strength and collagen deposition in artificial incisional wounds in rodents and humans. A role for dietary intervention in the form of arginine supplementation has been proposed to normalize or enhance wound healing in humans. Although this hypothesis is frequently discussed, the therapeutic effect of arginine supplementation on chronic wound healing in humans is still undetermined and requires further objective evidence. Well-designed clinical trials are required to determine whether arginine supplementation is effective in enhancing healing of acute and chronic wounds in humans and how much arginine is recommended to meet metabolic needs during the phases of wound healing.

Many chronic wounds fail to heal with conventional therapy, resulting in disability and impaired quality of life. New technologies using recombinant growth factors, autologous growth factors, or bioengineered skin-tissue substitutes have been shown to be effective, but these treatments are costly. An effective, low-cost treatment to improve healing of chronic wounds is needed. The molecular environment of chronic wounds, like many other chronic inflammatory diseases, contains abnormally high levels of proinflammatory cytokines (tumor necrosis factor [TNF]-alpha and interleukin [IL]-1beta]) and matrix metalloproteinases (MMPs), which impair normal wound healing. In animal models and clinical studies of ulcerative diseases, doxycycline, an inexpensive and Food and Drug Administration (FDA)-approved antibiotic, appears to inhibit members of the MMP superfamily like MMPs and TNF-alpha-converting enzyme (TACE). This article provides an overview of the roles of MMPs and intrinsic tissue inhibitors of metalloproteinases (TIMPs) in wound healing and the damaging effects of chronically elevated levels of MMPSs in chronic wounds. It also explores the use of topical doxycycline, a synthetic MMP inhibitor (MMPI), to enhance healing of chronic wounds.

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