Microenvironment-Responsive\nHydrogel Enclosed with\nBioactive Nanoparticle for Synergistic Postoperative Adhesion Prevention

Postoperative\nadhesion (PA) is a severe complication of abdominal\nsurgery caused by the inability of clinical physical barriers to cope\nwith diverse pathological factors in the process of PA formation.\nHerein, we described a multifunctional hydrogel composed of bioactive\nnanoparticles (BNs) and dual-responsive hydrogel to serve as a combination\nof physical and pharmacological therapy for preventing PA. Specifically,\nBNs with pro-inflammatory cell-targeted aggregation were designed\nby integrating hyaluronic acid onto the polydopamine (PDA)-coated\nhollow ZrO<sub>2</sub> nanoparticles loaded with antimicrobial peptides\nand platelet lysates that can eliminate bacterial infection and promote\ntissue repair. PDA can remove the excessive reactive oxygen species\n(ROS) and thus suppress the oxidative stress damage and accompanying\ninflammation in the presence of high ROS. The dynamically cross-linked\nhost hydrogel presents injectable yet microenvironment-responsive\nproperties, which enables complete coverage of the uneven tissue and\ninstantly forms a physical barrier to effectively isolate injured\ntissues and neighboring organs, and synchronously acts as a niche\nto deliver the BNs in a controlled way. The hydrogel demonstrates\na remarkable antiadhesion effect in a rat cecum-abdominal wall adhesion\nmodel. Together, this “all-in-one” composite hydrogel\nstrategy capable of a physical barrier capability and pharmacological\neffects represents a promising clinical solution to prevent PA.