Sprayable zwitterionic self-assembling powder for postoperative adhesion prevention.

Postoperative adhesions, a common complication resulting from surgical trauma, can lead to severe adverse outcomes. Current drug treatments and physical barriers are failed to solve adhesions due to their inherent limitations. In this study, we developed a novel sprayable powder-based drug delivery system, which could self-assemble into dynamically cross-linked zwitterionic hydrogels through the strong electrostatic interactions between polysulfobetaine (pSB) powder and polysulfobetaine-grafted hydroxypropyl-β-cyclodextrin (HCP) nanogel powder. HCP nanogels with hydrophobic cavities are used to load curcumin and also serve as crosslinkers to reinforce the hydrogel. As the hydrogel degrades, HCP@Cur nanogels are gradually released, significantly prolonging the release duration of curcumin. The combination of drug therapy and barrier effect demonstrates superior anti-adhesion efficacy. In a rat abdominal wall-caecum injury model, the hydrogel powder demonstrated significantly superior anti-adhesive performance compared to commercial HA hydrogel. Genomic analysis revealed that the hydrogel powder primarily prevents postoperative adhesions through its dual anti-inflammatory and antioxidant mechanisms, highlighting its significant potential for clinical applications.