Zwitterionic biodegradable physical hydrogel based on ATRP technology for effective prevention of postoperative tissue adhesion

Abstract

Postoperative adhesions are one of the most common complications post intraperitoneal surgery. Even after the adhesiolysis, the recurrence of adhesions is as high as 85%. Although zwitterionic-based materials have been reported for the application, unlike the conventional zwitterionic hydrogel, a series of poly (sulfobetaine methacrylate) grafted dextran derivatives (Dex-g-PSBMA) were synthesized by atom transfer radical polymerization (ATRP) reaction, making it fined controllable copolymer by its living polymerization property. Intriguingly, the Dex-g-PSBMA copolymer can self-assemble into a physical hydrogel under physiological conditions. When injected at the site of the lesions, it can immediately cover the wound area, and as the ion concentration increases, the chemical bonds dissociate and the hydrogel may degrade completely. In the abdominal wall-cecum injury adhesion model in rats, Dex-g-PSBMA hydrogel showed excellent anti-adhesion ability, effectively preventing postoperative abdominal wall-cecum adhesion. The mechanism exploration revealed that Dex-g-PSBMA hydrogel can take an effect on the TGF-β/Smad signaling pathway, which can inhibit the Smad3 and activate the Smad7 pathway, thereby reducing the probability of tissue fibrosis, reducing fibrin deposition, and resisting fibroblast adhesions. In conclusion, these findings demonstrated that this Dex-g-PSBMA physical hydrogel is a promising candidate for completely preventing post-surgical adhesions.