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.
Ito
Taichi
T
Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02142, USA.
Yeo
Yoon
Y
Highley
Christopher B
CB
Bellas
Evangelia
E
Kohane
Daniel S
DS
D000818:Animals; D001672:Biocompatible Materials / Q000008:administration & dosage* / Q000737:chemistry; D002460:Cell Line; D045744:Cell Line, Tumor; D003432:Cross-Linking Reagents / Q000737:chemistry; D003911:Dextrans / Q000737:chemistry; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D020100:Hydrogels / Q000008:administration & dosage* / Q000737:chemistry; D007274:Injections, Intraperitoneal; D008264:Macrophages / Q000187:drug effects; D008654:Mesothelioma / Q000473:pathology; D051379:Mice; D010532:Peritoneal Diseases / Q000473:pathology / Q000517:prevention & control*; D011183:Postoperative Complications; D011817:Rabbits; D000267:Tissue Adhesions / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*
D001672:Biocompatible Materials; D003432:Cross-Linking Reagents; D003911:Dextrans; D020100:Hydrogels