Multifunctional Microneedles Based on Metal-Phenolic Network and Applications to Oral Ulcer Treatment

Oral ulcer is a common and painful oral mucosal disease that severely impairs patients' quality of life. Conventional topical therapies often suffer from limited retention and inadequate efficacy due to the unique oral microenvironment. In this study, a multifunctional microneedles (MNs) patch based on metal-phenolic network (MPN) was developed for the treatment of oral ulcer. The MPN was formed by coordinating zinc ions (Zn 2+ ) with epicatechin (EC), resulting in the formation of ZnEC nanoparticles (ZnEC NPs), which were incorporated into a dissolvable gelatin methacryloyl (GelMA) hydrogel matrix to construct the MNs. The developed ZnEC/Gel MNs exhibited excellent mechanical, adhesive, degradation, and penetration properties. Meanwhile, the MNs enabled targeted delivery and controlled release of EC and Zn 2+ directly into the ulcer site, effectively scavenging reactive oxygen species (ROS). In addition, the ZnEC/Gel MNs exhibited significant antibacterial efficacy against common oral pathogens in vitro compared to the commercial propolis oral film (POF). Moreover, in vitro cytocompatibility assessment showed that ZnEC/Gel MNs significantly improved the proliferation and migration of human oral keratinocytes (HOKs), outperforming the POF. These results demonstrated that this MPN-based microneedles patch offered an effective management for oral ulcer, with potential for extension to other mucosal diseases.