Abstract
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, novel bioinspired adaptable indwelling microneedles with therapeutic exosome encapsulation are presented for diabetic wound healing by a combined fabrication strategy of template replication and 3Dtransfer printing. Such microneedles are composed of mesenchymal stem cell (MSC)-exosomes-encapsulated adjustable poly(vinyl alcohol) (PVA) hydrogel needle tips and detachable 3M medical tape supporting substrate. As the mechanical strength of the PVA hydrogel is ionically responsive due to Hofmeister effects, the hardness of the resultant microneedle tips can be upregulated 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 bioinspired adaptable indwelling microneedles are with practical values and clinical prospects in tissue and wound regeneration.
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