A Biocompatible CMCHMA/F127DA Hydrogel with ROS-Scavenging Activity Prevents Postoperative Peritoneal Adhesions

Postoperative peritoneal adhesion (PPA) is a prevalent complication of abdominal surgery with limited effective preventive approaches. To tackle this critical unmet clinical need, a CMCHMA/F127DA composite hydrogel was developed via photo-cross-linking-induced polymerization of carboxymethyl chitosan methacryloyl (CMCHMA) and Pluronic F127 diacrylate (F127DA). Our results demonstrated that the CMCHMA/F127DA hydrogel exhibited a tensile modulus of 43 kPa, matching the mechanical properties of abdominal soft tissues, rapid gelation within 5-10 s, and a high shear strength of 56 kPa, which outperforms many previously reported antiadhesive hydrogels. In vitro experiments verified excellent biocompatibility, as NIH-3T3 cell viability exceeded 95% following coincubation with the hydrogel. In vivo safety evaluations in SD rats showed no obvious toxicity to major vital organs, including the heart, liver, and kidneys. Utilizing a rat cecal abrasion model, the hydrogel markedly reduced intra-abdominal adhesions at 14 days postoperatively. The histological and molecular analyses revealed that the hydrogel inhibited inflammatory cell infiltration, reduced collagen deposition, and suppressed myofibroblast activation. Mechanistically, the hydrogel scavenged excessive reactive oxygen species (ROS) and targeted the NF-κB signaling pathway, downregulating pro-inflammatory cytokines (IL-1β and TNF-α) while upregulating the anti-inflammatory cytokine IL-10, thus mitigating inflammation and excessive fibrosis. In conclusion, the CMCHMA/F127DA hydrogel integrates mechanical adaptability, rapid gelation, and biocompatibility with a dual antiadhesive mechanism involving a physical barrier effect and regulatory roles in inflammation and fibrosis. Thus, it holds substantial clinical translation potential as a novel, effective, and safe approach for PPA prevention.