Delayed wound healing in diabetes: considering future treatments

Abstract

Diabetic foot ulcers result from multiple risk factors including peripheral neuropathy, arterial insufficiency and foot deformities. Recent investigation has also revealed a chronic wound environment with diminished expression of growth factors and cytokines integral to the wound healing process. Current accepted standard of care for the treatment of diabetic foot ulcerations focuses on periodic debridement of the wound, appropriate topical wound therapy, pressure off-loading and treatment of infection. Owing to increased cost and equivocal effectiveness, topical growth factors, bioengineered living skin equivalents, hyperbaric oxygen therapy and negative pressure wound therapy are proposed as adjuncts to standard of care and may be added to the treatment regimen when healing of the wound has stalled. Other future therapies currently under investigation include stem cell therapy, platelet-rich plasma, extracorporeal shock-wave therapy and laser treatment. These modalities continue to be developed and tested, and may offer promise as effective therapies in the future for the chronic diabetic foot ulcer.

The Treatment of Impaired Wound Healing in Diabetes: Looking among Old Drugs

“…Impaired healing in diabetes is the result of a complex pathophysiology involving vascular, neuropathic, immune, and biochemical components [3]. Hyperglycemia correlates with stiffer blood vessels which cause slower circulation and microvascular dysfunction, causing reduced tissue oxygenation [2]. Blood vessel alterations observed in diabetic patients also account for reduced leukocyte migration into the wound, which becomes more vulnerable to infections [3].…”

“…In fact, as a consequence of hyperglycemia, diabetic patients are at increased risk for comorbid conditions affecting several organs [1]. One of the main consequences of diabetes is the impairment of self-repairing abilities [2].…”

Use of Oral Anticoagulation and Diabetes Do Not Inhibit the Angiogenic Potential of Hypoxia Preconditioned Blood-Derived Secretomes

“…The persistent hyperglycemic state in diabetic patients results in endothelial dysfunction and smooth muscle abnormalities, followed by vasoconstriction due to the reduction of vasodilators [ 20 ]. Moreover, hyperglycemia correlates with stiffer blood vessels, which causes alterations in blood flow and, consequently, reduced tissue oxygenation [ 8 , 18 , 21 ]. Vascular pathology also contributes to reduced leukocyte migration into the wound, which becomes more vulnerable to infections [ 18 , 22 ].…”

Generation of bioactive prolyl‐hydroxyproline (Pro‐Hyp) by oral administration of collagen hydrolysate and degradation of endogenous collagen

“…The generation of Pro-Hyp at the site of wound healing in db/db mice, a diabetic model mouse, is lower compared to that of the normal mice. Delayed wound healing in diabetic patients is well known (Dinh et al, 2011). If the amount of Pro-Hyp generated at the site of wound healing in a diabetic patient is insufficient, it may hinder wound healing.…”