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

Abstract

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.