Abstract

Background. Diabetic foot ulcers (DFUs) are a serious health problem. Nitric Oxide (NO) has been found to be an effective modulator in wound healing if administered externally. While NO is a promising therapy for DFUs, the current delivery of gaseous NO is cumbersome. The present work explores a novel gel that releases NO when in contact with wound exudates. Material and methods. Efficacy of the gel was assessed using a 1 cm2 full-thickness dorsal wound model on diabetic type 2 mice (Lepr db/db). The wounds were treated with NO-releasing gel at two concentrations: 100 μM (Gel 100) and 1000 μM (Gel 1000). A Gel-control group and an untreated group were included for comparison. Planimetry was employed for wound size dynamics up to day seven. H&E and IHC staining were used to quantify granulation tissue, CD31, and α-SMA expressions. Results. While the current experiment found no difference in wound healing kinetics between the groups, histological evaluation showed a significant increase in granulation tissue thickness in both Gel 100 and Gel-control groups compared to the other two groups (p < 0.05). Furthermore, Gel 100 significantly impacted the expression of angiogenesis marker CD31 and α-SMA compared to the other groups (p < 0.05). Conclusions. This preliminary study showed that the NO gel used has a dose-dependent effect on CD31, α-SMA resulting in regulation of granulation tissue formation during wound healing in diabetic murine models. While these preliminary studies show the potential of this treatment, further studies to optimize these compounds are needed.

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