Microenvironment-Responsive Hydrogel Enclosed with Bioactive Nanoparticle for Synergistic Postoperative Adhesion Prevention

Postoperative adhesion (PA) is a severe complication of abdominal surgery caused by the inability of clinical physical barriers to cope with diverse pathological factors in the process of PA formation. Herein, we described a multifunctional hydrogel composed of bioactive nanoparticles (BNs) and dual-responsive hydrogel to serve as a combination of physical and pharmacological therapy for preventing PA. Specifically, BNs with pro-inflammatory cell-targeted aggregation were designed by integrating hyaluronic acid onto the polydopamine (PDA)-coated hollow ZrO₂ nanoparticles loaded with antimicrobial peptides and platelet lysates that can eliminate bacterial infection and promote tissue repair. PDA can remove the excessive reactive oxygen species (ROS) and thus suppress the oxidative stress damage and accompanying inflammation in the presence of high ROS. The dynamically cross-linked host hydrogel presents injectable yet microenvironment-responsive properties, which enables complete coverage of the uneven tissue and instantly forms a physical barrier to effectively isolate injured tissues and neighboring organs, and synchronously acts as a niche to deliver the BNs in a controlled way. The hydrogel demonstrates a remarkable antiadhesion effect in a rat cecum-abdominal wall adhesion model. Together, this "all-in-one" composite hydrogel strategy capable of a physical barrier capability and pharmacological effects represents a promising clinical solution to prevent PA.