Angiogenic-Inducing Hydrogels for Improved Wound Repair of Diabetic Foot Ulcers

Rishabh Shah

Introduction. Diabetes mellitus is the most common metabolic disease related to impaired wound-healing conditions.1 2-3% will develop a diabetic foot ulcer (DFU) each year, and 15% will develop a foot ulcer during their lifetime.2 Even with extensive treatment, 24% to 30% of DFUs heal within 12 to 20 weeks.3  In a large study in European specialized foot centers, 23% of patients with diabetic foot ulcers lost at least part of their foot despite treatment.2 Methods. Alginate, a natural hydrophilic polymer, can be encapsulated with growth factors to form an injectable Arginine-glycine-aspartic acid (RGD)-Alginate microgel. A skin incision was made in an anesthetized female mouse at 5 weeks of age, the femoral artery and its branches were ligated. The femoral artery was excised from its proximal origin. Blood flow of the ischemic limb versus the normal limb was measured before and after surgery. At one week after the induction of ischemia, mice were intramuscularly treated with PBS, RGD-alginate microgels only, growth factors only, outgrowth endothelial cells (OECs) only, RGD-alginate microgels with OECs, and RGD-alginate microgels with OECs and growth factors.4 For the Collagen-glycosaminoglycan (GAG) study, punch holes were made in a rabbit ear. The wounds were treated with the in-situ forming hydrogel collagen-GAG scaffold. The variables were untreated wounds, acellular in-situ forming hydrogel collagen-GAG scaffold, in-situ forming scaffolds containing xenofibroblasts, and in-situ forming scaffolds containing IDO-expressing fibroblasts.5  The Acellular dermal matrix (ADM) is a bioprosthetic mesh made up of a mixture of dermal elastin and collagen that is free of cellular components. The control group received standard split-thickness skin graft (STSG) treatment while the experimental group received the STSG with the ADM. Patients were followed for 12 months after graft surgery to estimate the physical appearance, quality of healing, and recurrence rate.2 Results. Enhanced tube formation is seen based on paracrine effects from OECs and growth factors that are encapsulated in RGD-alginate microgels.4 In the GAG system study, the use of the GAG system showed significant decreased in scar elevation.5 In the ADM study, the experimental group that received ADM as an added treatment produced a lower Manchester Scar Scale score.2 Conclusion. The delivery of nutrients through angiogenesis is essential to prevention and repair of chronic wounds. These hydrogels facilitate wound repair by increasing the half-life of growth factors to promote angiogenesis and facilitating the direct transmission of growth factors to the wound site.

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