Paquinimod-hydrogel hybrid microneedle array patch alleviates hypertrophic scar via inhibiting M1 polarization.

Hypertrophic scar (HS) is one of the most common complications of skin injuries, with a lack of effective therapeutic approaches to date. Most current research has focused on the dysfunction of hypertrophic scar fibroblasts (HSFBs) and dermal vascular endothelial cells (HDVECs), neglecting the crucial role of the inflammatory microenvironment that causes them to be abnormal. In this study, we first discovered and validated that the S100A8/9 specific inhibitor Paquinimod could inhibit macrophage polarization toward M1, and further suppress the proliferation, migration, collagen formation, and angiogenesis of HSFBs and HDVECs in vitro. This mechanism has also been validated in a rat model of HS. Then, we developed a good biocompatibility and penetrability Paquinimod-Hydrogel Hybrid Microneedle Array Patch (PHMAP) for HS treatment. With the advantages of excellent penetrability, surface sealing, sustained release, and precise uniform distribution, PHMAP exhibited superior therapeutic efficacy over intravenous and intradermal injections. These results suggest that PHMAP can be a promising and advanced solution for HS prevention and therapies.