Dextran-based in situ cross-linked injectable hydrogels to prevent peritoneal adhesions

Peritoneal adhesions are serious sequelae of surgery, and can cause significant morbidity and/or mortality due to pain, infertility, and bowel obstruction. We have designed and synthesized novel dextran (DX)-based injectable hydrogels for adhesion prevention, which are formed by mixing hydrazide-modified carboxymethyldextran (CMDX–ADH) with aldehyde-modified DX (DX–CHO) or carboxymethylcellulose (CMC–CHO). At high polymer concentrations, hydrogels formed very quickly upon mixing, e.g. 5% CMDX–ADH with 6% DX–CHO (CMDX–DX; 1.8 s) and 5% CMDX–ADH with 6% CMC–CHO (CMDX–CMC; 5.8 s). CMDX–DX shrank after gelling, while CMDX–CMC swelled. CMDX–ADH and CMC–CHO showed minimal to mild cytotoxicity to mesothelial cells and macrophages in vitro, while DX–CHO was very cytotoxic. However, all cross-linked gels had very mild cytotoxicity. When applied in a rabbit sidewall defect-bowel abrasion model of adhesion formation, CMDX–CMC greatly reduced the formation of adhesions while CMDX–DX worsened them.