A poly(lipoic acid)-based elastomer adhesive with synergistic activity of microenvironment regulation and peripheral neuropathy repair facilitates infectious diabetic wound healing.

Abstract

Diabetic wounds are notorious for their difficulty in healing and high recurrence rate, due to their harsh inflammatory microenvironment and the peripheral neuropathy caused by a hyperglycemic condition. However, current research often overlooks the impact of diabetic peripheral neuropathy on hindering wound healing. Here, we develop an adhesive elastomeric wound dressing by combining the natural active molecule lipoic acid (LA) with the clinically applied hypoglycemic drug metformin (Met), integrating the characteristics of remodeling the wound microenvironment and restoring peripheral nerve function, while stabilizing polyLA through the formation of strong salt bridge hydrogen bonds between guanidyl and carboxyl. The surface of the elastomeric dressing rich in adhesive carboxyl groups can achieve effective sealing protection for diabetic wounds by forming multiple hydrogen bonds or electrostatic interactions with the tissues, thereby resisting harmful bacterial invasion. The sustained targeted release of LA and Met at the wound site can effectively reduce local oxidative stress, increase collagen deposition and angiogenesis, and significantly upregulate neuroendocrine chemicals and nerve fiber markers, promoting the recovery of peripheral nerves around the lesion. In the diabetic infection model in rats, the polyLA-Met patch shows a significantly superior wound healing effect compared to the commercial 3M dressing.