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

Biomaterials . 2007 Aug;28(23):3418-26. Epub 2007 Apr 18. [Link]

Taichi Itoa, 1, Yoon Yeoa, Christopher B. Highleya,
Evangelia Bellasa and Daniel S. Kohaneb

  • aDepartment of Chemical Engineering, Massachusetts Institute of Technology, 45 Carleton St. Cambridge, MA 02142, USA
  • bLaboratory for Biomaterials and Drug Delivery, Division of Pediatric Intensive Care, Bartlett Extension 413, Massachusetts General Hospital, Harvard Medical School, 55 Fruit St., Boston, MA 02114, USA


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.

Keywords: Post-operative adhesion; Dextran; Carboxymethyl dextran; Carboxymethyl cellulose; In situ cross-linking hydrogel; Rabbit sidewall defect-cecum abrasion model