A self-healing pH-responsive injectable zwitterionic hydrogel for the prevention of postoperative adhesions

Postoperative adhesions remain a significant challenge in clinical surgical procedures. In this study, PGA-DMAPS-APBA was synthesized via free radical addition and amidation reactions of zwitterion [2-(methacryloyloxy) ethyl] dimethyl-(3-sulfopropyl) ammonium hydroxide (DMAPS), 3-aminophenylboronic acid (APBA), and polygalacturonic acid (PGA). Then, an injectable, self-healing, and antifouling hydrogel (PPDA) was fabricated through the dynamic boronate ester bonds between PGA-DMAPS-APBA and polyvinyl alcohol (PVA). The optimized PPDA hydrogel composed of 3 wt% PGA-DMAPS-APBA and 2 wt% PVA exhibited excellent injectability (20 N) and rapid self-healing in approximately 13.5 s. Importantly, the zwitterionic modification greatly improved the antifouling performance of the hydrogel. Compared with the non-zwitterionic control, protein adsorption of PPDA-3 was reduced by 50% to 19.4 μg/mL, and its fibroblast adhesion decreased by nearly 75%. At the same time, acting as an effective drug carrier, the pH-sensitive boronate ester bonds of the hydrogel could respond to the local acidic microenvironment at injury sites, and continuously release the loaded drug quercetin (Que) for 120 h. This hydrogel effectively prevented postoperative adhesions in a rat model of cecum-abdominal wall injury and facilitated tissue repair. Subcutaneous implantation tests confirmed that it had no organ toxicity and completely degraded within 120 days. This study demonstrates the potential of dynamic zwitterionic hydrogels as a promising anti-adhesion barrier for postoperative treatment.