Biomimetic Triplet Messenger RNA Formulation in MXene Hydrogel Microneedles for Wound 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 transition metal 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 photo‐thermal 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‐MN platform with precise delivery and controllable release of TM will show great potential for promoting the healing of clinic diabetic wounds.