Bio-Inspired Adaptable Indwelling Microneedles for Diabetic Ulcers Treatment.

Microneedles provide an effective strategy for transdermal drug delivery. Many endeavors have been devoted to developing smart microneedles that can respond to and interact with pathophysiological environments. Here, we present novel bio-inspired adaptable indwelling microneedles with therapeutic exosome encapsulation for diabetic wound healing by a combined fabrication strategy of template replication and three-dimensional transfer printing. Such microneedles are composed of mesenchymal stem cell (MSC)-exosomes encapsulated adjustable polyvinyl alcohol (PVA) hydrogel needle tips and detachable medical 3 M tape supporting substrate. As the mechanical strength of the PVA hydrogel is ionic responsive due to Hofmeister effects, the hardness of the resultant microneedle tips could be up-regulated by sulfate ions to ensure skin penetration and be softened by nitrate ions after tip-substrate detachment to adapt to the surrounding tissue and release exosomes. Because the MSC-exosomes can effectively activate fibroblasts, vascular endothelial cells and macrophages, the indwelling microneedles are demonstrated with the function of promoting tissue regeneration and diabetic wound healing in full-thickness cutaneous wounds of diabetic rat models. These features indicate that the bio-inspired adaptable indwelling microneedles are with practical values and clinical prospects in tissue and wound regeneration. This article is protected by copyright. All rights reserved.