In Situ Clickable Purely Zwitterionic Hydrogel for Peritoneal Adhesion Prevention

Intraperitoneal adhesions are common and serious complications after surgery. Deposition of proteins and inflammatory response on an injured cecum are the main factors resulting in the formation of adhesion. In this study, purely zwitterionic hydrogels (Z-hydrogels) are developed using thiolated poly(sulfobetaine methacrylate-co-2-((2-hydroxyethyl)disulfanyl)ethyl methacrylate) [poly(SBMA-co-HDSMA)] as the network backbone and divinyl-functionalized sulfobetaine (BMSAB) as the zwitterionic cross-linker via the thiol–ene click reaction. To improve the anti-inflammatory activity, cefoxitin sodium is loaded into Z-hydrogels (Z/C-hydrogel) to construct the physical barrier/drug system. The gelation time, mechanical behavior, and swelling ratio of the prepared Z-hydrogel can be modulated via adjusting the SBMA/HDSMA ratio in the copolymer. Moreover, they not only exhibit excellent resistance to protein and fibroblast adhesion but also show good biocompatibility and hemocompatibility. To assess its anti-adhesion effects in vivo, the Z-hydrogel is injected on the injured cecum surface using a rat model of sidewall defect-cecum abrasion. The results show that the Z-hydrogel can completely cover the irregular cecum surface and effectively suppress the formation of postoperative adhesion via reducing protein deposition and resisting fibroblast adhesion. Moreover, the introduction of cefoxitin sodium decreases the inflammatory response after surgery, thus further improving the anti-adhesion effect. Overall, we suggest that the Z-hydrogel is a promising candidate for the prevention of a postsurgical peritoneal adhesion.