Spatiotemporal bilayer microneedle patches enable bacterial control and ROS-driven immunomodulation for infected
Dingqi Tang1,2, Junzhe Fu1,2, Fan Jia1,2
1MOE Key Laboratory of Macromolecular Synthesis and Functionalization, Department of Polymer Science and Engineering, Zhejiang University, Hangzhou 310027, P. R. China. jijian@zju.edu.cn.
Abstract:
Infected wounds are characterized by bacterial colonization and inflammatory dysregulation. Existing therapies often fail to match the spatiotemporal demands of infected wound healing, which requires bacterial control followed by timely immunomodulation. Herein, we propose a spatiotemporal bilayer microneedle patch to match the spatial heterogeneity and temporal immune requirements of infected wounds. Through the formation of boronic ester bonds, epigallocatechin gallate (EGCG) serves simultaneously as an anti-inflammatory agent and a cross-linker to form reactive oxygen species (ROS)-responsive gel needle tips. Ciprofloxacin (CIP)-loaded polyvinylpyrrolidone (PVP) constitutes needle tails. Upon insertion, the PVP needle tails rapidly dissolve to release CIP for early bacterial control, whereas the gel needle tips partially retain EGCG and subsequently enable ROS-triggered EGCG release for immunomodulation. This spatiotemporally differentiated delivery enables early antibacterial intervention followed by microenvironment-responsive immunomodulation, attenuating sustained M1 macrophage activation and promoting a shift toward M2 phenotype. In vitro studies indicated that this patch responded to ROS and released EGCG within 48 h. In vivo, it effectively reduced bacterial burden, facilitated a subsequent shift toward M2 macrophage phenotype, and enhanced angiogenesis. This spatiotemporally programmed strategy provides a promising platform for coordinated antibacterial and immunomodulatory therapy.
