Evaluation of Topical Reconstituted HDL as a Treatment for Diabetic Wounds in Murine and Porcine Models

Chronic, non-healing foot ulcers are the most common complication of diabetes and are associated with high morbidity, mortality, and substantial health-care costs. Impaired wound healing in diabetes results from a complex pathophysiology involving persistent inflammation, interrupted re-epithelialization, impaired neovascularization, and defective granulation tissue formation. Reconstituted high-density lipoprotein (rHDL), with its antioxidant and anti-inflammatory properties, may counteract these processes and thereby promote wound repair. We investigated the effect of topical administration of rHDL in full thickness excisional wounds in murine and porcine diabetic models. rHDL significantly enhanced wound closure in diabetic mice in a dose-dependent manner as compared to phosphate-buffered saline (PBS) control. Histological and immunohisto-chemical analysis showed that rHDL-treated wounds had increased collagen deposition, a higher number of alpha-smooth muscle actin-positive cells, greater macrophage infiltration, and decreased neutrophil infiltration compared to PBS controls. In contrast, in the porcine model no wound healing improvement was observed after daily topical application of rHDL. Administration of rHDL enhances wound closure in a murine model of diabetic wound healing by promoting collagen production and modulating inflammation. However, lack of efficacy in a more physiologically relevant pre-clinical porcine model under the experimental conditions tested does not support further development of a topical rHDL formulation for diabetic wound healing indications.