In Situ Clickable Purely Zwitterionic Hydrogel for Peritoneal Adhesion Prevention

Abstract

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.

Functional hydrogels for diabetic wound management

“…(b) A zwitterionic hydrogel crosslinked via the thiol–ene click reaction resisted adhesion of protein and cells. 73 Reproduced with permission from Guo et al , Chem. Mater.…”

“…2(b) ]. 73 The antiadhesive feature of such hydrogels, although having limited contribution to wound healing, largely reduces patients' pain upon change of dressings. Additionally, the antiadhesive hydrogels reduce secondary tissue damage so that the healing process would not be disrupted.…”

Biodegradable Zwitterionic Cream Gel for Effective Prevention of Postoperative Adhesion

“…[ 18–21 ] Comparatively injectable hydrogels, mostly under development, can be straightforwardly applied: the injected pre‐gel solution is typically fluid‐like and can completely cover the injured surface. [ 22–24 ] This is followed by an in situ polymerization, Michael addition thiol–ene reactions [ 25,26 ] or Schiff base amino‐aldehyde reactions, [ 18,27,28 ] to form a chemically crosslinked hydrogel. Nevertheless, a dual valve applicator must be in place to separate the reactive components before they are mixed and extruded through the syringe.…”

“…Nevertheless, a dual valve applicator must be in place to separate the reactive components before they are mixed and extruded through the syringe. The applied pre‐gel solution also requires one to several minutes to completely cure, [ 18,25–28 ] which presents a burden in surgical duration and risk of infection. Certain chemical hydrogels require an ultraviolet source for curing, [ 29,30 ] which poses further concerns on irradiation safety.…”

Recent advancement in medical antifouling hydrogel coatings

“…Figure7(Color online) Antibacterial amphoteric hydrogel poly(SBMA-co-HDSMA) prevents peritoneal adhesion[82].…”