An anti-inflammatory and anti-fibrotic Janus hydrogel for preventing postoperative peritoneal adhesion

Abstract

Postoperative peritoneal adhesion (PPA) is pathological tissue hyperplasia between surgical wounds and nearby organs. Currently, traditional double-sided bioadhesives are limited in preventing PPA due to the indiscriminate adhesive properties and the poor interaction with wet tissues. Herein, we developed a Janus hydrogel, named PAA-Cos, by using the polycationic carbohydrate polymer of chitooligosaccharide (Cos) and the polyanionic polymer of polyacrylic acid (PAA). The adhesive layer of Janus hydrogels could adhere to wet tissue tightly due to surfaces composed of carboxyls, and the positively charged biomaterial (Cos) neutralized carboxyls on one side of PAA hydrogel to form Janus hydrogels. Moreover, PAA-Cos can further load with ligustrazine hydrochloride (Ligu), a pharmaceutical compound with anti-inflammatory and anti-fibrotic effects, finally obtaining PAA-Cos@Ligu. After the application of PAA-Cos@Ligu on the surgical trauma, the bottom surface can adhere to wet tissues robustly to restore the wound, while the top surface acts as a physical barrier with antiadhesive effects to avoid PPA. PAA-Cos@Ligu also exhibited anti-inflammatory effects by promoting M2 macrophage polarization, inhibiting the myofibroblast-like differentiation of peritoneal mesothelial cells, and blocking the TGF-β/Smad2/3 signaling pathway to hinder collagen deposition. Our findings suggest that PAA-Cos@Ligu has great potential as an anti-adhesion candidate with biocompatibility and ease of preparation. A) Schematic illustration of the fabrication of the Janus hydrogel PAA-Cos@Ligu. B) The Janus bioadhesives hydrogel PAA-Cos@Ligu prevents PPA by regulating macrophage polarization and suppressing epithelial-mesenchymal transition. C) Molecular mechanism of the Janus hydrogel PAA-Cos@Ligu suppressing epithelial-mesenchymal transition through the TGF-β/Smad signaling pathway.

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