A rapid crosslinking injectable polygalacturonic acid barrier modified with zwitterion bottlebrush for preventing postoperative adhesion

Abstract

Postoperation adhesion, as a worldwide problem, are often accompanied by serious complications and cause severe pain to patients, and traditional medicines and commercial anti-adhesion barriers have limited protective effects. So, we designed a novel injective, antifouling and photo-crosslinked polygalacturonic acid (PGA) hydrogel barrier composed of PGA methacrylate (PGAMA) and 2-methacryloyloxyethyl phosphorylcholine (MPC) with excellent effect of covering the wound and preventing adhesion. The product termed, as PGAMA-MPC, enhanced hydration as expected with the introduction of abundant MPC, showing an obvious resistance to protein, cell, and microorganism. Simultaneously, as injectable medical materials, stable attachment to the wound and low invasiveness for tissue were provided by photo-crosslinking of PGAMA-MPC hydrogel during Minimally invasive surgery. In the rat model of cecal injury, the PGAMA-MPC hydrogel effectively prevented the postoperative peritoneal adhesion, showing an obvious protective effect within 7 d and the excellent ability to repair of cecum and abdominal wall after 14 d. Compared with the control group, the rats treated with PGAMA-MPC3 almost recovered to the level of the normal level. Furthermore, we found that PGAMA-MPC3 hydrogel significantly reduced the expression of inflammation and deposition of fibrin. The underlying mechanism of anti-adhesion was subsequently confirmed by analyzing the signaling pathway TGF-β1. The PGA-MPC3 hydrogel promoted fibrinolysis by blocking the activation of TGF-β1/Smad3 pathway. In conclusion, we developed an available polysaccharide hydrogel for rapid repair of peritoneum and prevention of postoperative adhesion, possessing an extensive application as medical materials.