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.
Shen, Z., Li, Y., Chen, X., Tuo, D., Li, Y., Tang, M., Wang, S., Xiao, B., Wang, J., Wang, G., Wu, X., Zhang, Y., Zheng, S., Huang, X., Jia, D., Sun, X., Wang, J.
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