A novel barrier membrane with long-term ROS scavenging function for complete prevention of postoperative adhesion

Abstract

Local oxidative stress induced by surgical trauma has been recognized as one of pathogenesis for postsurgical adhesion tissue formation. Herein, tannic acid (TA) based metal-phenolic networks (MPNs) was assembled via chelating with Fe3+, and acted as a novel bio-filler for nanofibrous polycaprolactone (PCL) barrier membrane to endow it with reactive oxygen species (ROS) scavenging capacity. By chelating with Fe3+, the release of TA could last for more than 20 days, rendering the membrane with continuous ROS scavenging capacity. The modified membrane could effectively inhibit fibroblasts adhesion and proliferation, as well as immune cells recruitment, infiltration, and expression of pro-inflammatory cytokines. Consequently, a complete prevention of peritoneal adhesion formation was obtained in a rat model of sidewall defect-cecum abrasion, far better than commercial Poly lactic acid (PLA) membrane. Systematic biological mechanism investigations revealed that the enhanced anti-adhesion function was mainly ascribed to its robust ROS scavenging capacity, through which the PI3K-Akt signaling pathway was blocked, leading to repress of downstream NF-κB-TGFβ1-SMAD signaling pathway, finally inhibiting the bioactivity of fibroblasts and immune cells. This work provided a new strategy for the design of advanced barrier membrane, demonstrated its efficacy and mechanism on preventing postoperative adhesion, holding great promise for future clinical application.