The prevention of peritoneal adhesions by in situ cross-linking hydrogels of hyaluronic acid and cellulose derivatives.
Post-operative peritoneal adhesions can cause pelvic pain, infertility, and potentially lethal bowel obstruction. We have designed and synthesized injectable hydrogels that are formed by mixing hydrazide-modified hyaluronic acid (HA) with aldehyde-modified versions of cellulose derivatives such as carboxymethylcellulose (CMC), hydroxypropylmethylcellulose (HPMC), and methylcellulose (MC). Gelation of these hydrogels occurred in less than 1 min, and had higher shear moduli than that of HA-HA gel (HAX). Hydrogels degraded in the presence of hyaluronidase in vitro, with HA-MC and HA-HPMC degrading more slowly than HAX and HA-CMC. The aldehyde-modified cellulose derivatives showed dose-dependent mild-to-moderate cytotoxicity to mesothelial cells and macrophages in vitro, but all were biocompatible in the murine peritoneum, causing no adhesions for 3 weeks. All the cellulose-derived gels showed efficacy in reducing the area of adhesion formation in a rabbit sidewall defect-bowel abrasion model.
Ito
Taichi
T
Department of Chemical Engineering, Massachusetts Institute of Technology, 45 Carleton St., Cambridge, MA 02142, USA.
Yeo
Yoon
Y
Highley
Christopher B
CB
Bellas
Evangelia
E
Benitez
Carlos A
CA
Kohane
Daniel S
DS
D000818:Animals; D001672:Biocompatible Materials / Q000009:adverse effects / Q000737:chemistry; D002482:Cellulose / Q000009:adverse effects / Q000737:chemistry*; D003432:Cross-Linking Reagents / Q000737:chemistry; D006820:Hyaluronic Acid / Q000009:adverse effects / Q000737:chemistry*; D020100:Hydrogels / Q000009:adverse effects / Q000737:chemistry*; D008422:Materials Testing; D051379:Mice; D010532:Peritoneal Diseases / Q000139:chemically induced / Q000473:pathology* / Q000517:prevention & control*; D010537:Peritoneum / Q000187:drug effects* / Q000473:pathology*; D011817:Rabbits; D000267:Tissue Adhesions / Q000139:chemically induced / Q000473:pathology
D001672:Biocompatible Materials; D003432:Cross-Linking Reagents; D020100:Hydrogels; D002482:Cellulose; D006820:Hyaluronic Acid