Biomimetic Triplet Messenger RNA Formulation in MXene Hydrogel Microneedles forWound Healing

Abstract

Messenger RNA (mRNA) has demonstrated immense potential in disease therapeutic applications. The current direction is focused on imparting mRNA with competitive synthetic functions and delicate carrier systems. Here, inspired by the collaborative regulation of growth factors by the cellular microenvironment, we present novel transitionmetal carbide/nitride (MXene) hydrogel microneedles loaded with a biomimetic triplet mRNA formulation (TM) for diabetic wound treatment. Such microneedles were composed of TM, MXene, and hyaluronic acid hydrogel. The presence of MXene imparted the microneedles with great photothermal responsiveness properties, thus realizing controlled active release by the shrinkage/swelling of hydrogel. With the effective release of TM, the microneedles were proven to enhance endothelial cell migration, growth, and angiogenesis. Through in vivo animal experiments, we have confirmed that TM-microneedles (TM-MNs) can promote tissue regeneration and collagen deposition more effectively than intravenous and intradermal administration. Thus, we believe that the proposed TM-MNplatform with precise delivery and controllable release of TMwill show great potential for promoting the healing of clinic diabetic wounds.

Keywords

growth factor / microneedles / mRNA therapeutics / MXene / wound healing

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RIGHTS & PERMISSIONS

2024 The Author(s). Aggregate published by SCUT, AIEI, and John Wiley & Sons Australia, Ltd.