Abstract

Current biodegradable meshes for pelvic floor repair are constrained by a limited ability to actively modulate the hostile immune microenvironment following implantation. To address these challenges, we developed a functionalized degradable silk fibroin mesh (SFM) integrated with a reactive oxygen species (ROS) responsive nanocomposite hydrogel. The resulting composite mesh, SFM@Gel NP, features a "hydrogel mesh hydrogel" sandwich structure, wherein the hydrogel layers are loaded with self-assembled nanoparticles (NP H CRFP) for the co-delivery of the STING inhibitor H 151 and the ROS scavenging agent catechin. This design provides immediate mechanical reinforcement while enabling microenvironment-triggered drug release. In vitro, NP H CRFP demonstrated efficient cellular uptake, significant ROS clearance, and effective attenuation of macrophage inflammation and apoptosis. In vivo, SFM@Gel NP remodeled the local immune milieu by inhibiting the ROS/cGAS STING/NF {kappa}B axis, thereby promoting a shift from pro-inflammatory M1 toward pro-regenerative M2 macrophage polarization. This immunomodulatory effect, coupled with enhanced and well-organized collagen deposition, particularly of early type III collagen, resulted in improved tissue integration and repair. This work presents a novel strategy that combines structural reinforcement with active immune regulation, offering a promising next generation solution for durable and functional pelvic floor reconstruction.