Engineered honeysuckle extracellular vesicles loaded in ROS response hydrogel for inhibition of postoperative abdominal adhesion

Abdominal adhesions are a common complication following abdominal surgery, often resulting in inflammation, pain, and dyskinesia, which significantly impair treatment outcomes and hinder patient recovery. Hydrogel-based materials have been extensively investigated to prevent postoperative adhesions due to their excellent biocompatibility, biodegradability, moisture retention, and drug-loading capacity. However, conventional hydrogels still suffer from insufficient anti-inflammatory and anti-adhesion properties, underscoring the need for more advanced biomaterials to address these challenges. In this study, a reactive oxygen species (ROS)-responsive hydrogel (CS-Linker-HA) was developed by crosslinking chitosan (CS) and hyaluronic acid (HA) through an ROS-sensitive linker, serving as a controlled drug delivery system. Additionally, for the first time, honeysuckle-derived extracellular vesicles engineered with puerarin (HEVs-P) were incorporated into the hydrogel (CS-Linker-HA@HEVs-P) to enhance its anti-inflammatory and anti-adhesion properties. The results indicated that this multifunctional hydrogel not only exhibited effectively ROS scavenging ability and anti-swelling properties but also possessed the ROS-triggered controlled release of HEVs-P, the synergism of which would further inhibit postoperative adhesions, promote the healing of abdominal and cecal injury in both murine and rabbit models. Therefore, the therapeutic strategy combined the multifunctional hydrogels with puerarin-engineered honeysuckle extracellular vesicles, providing a promising approach in peritoneal surgery aimed at preventing postoperative adhesions and promoting postoperative recovery.