The prevention of peritoneal adhesions by in situ cross-linking hydrogels of hyaluronic acid and cellulose derivatives

Biomaterials. 2007 Feb;28(6):975-83. doi: 10.1016/j.biomaterials.2006.10.021. Epub 2006 Nov 15.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biocompatible Materials / adverse effects
  • Biocompatible Materials / chemistry
  • Cellulose / adverse effects
  • Cellulose / chemistry*
  • Cross-Linking Reagents / chemistry
  • Hyaluronic Acid / adverse effects
  • Hyaluronic Acid / chemistry*
  • Hydrogels / adverse effects
  • Hydrogels / chemistry*
  • Materials Testing
  • Mice
  • Peritoneal Diseases / chemically induced
  • Peritoneal Diseases / pathology*
  • Peritoneal Diseases / prevention & control*
  • Peritoneum / drug effects*
  • Peritoneum / pathology*
  • Rabbits
  • Tissue Adhesions / chemically induced
  • Tissue Adhesions / pathology

Substances

  • Biocompatible Materials
  • Cross-Linking Reagents
  • Hydrogels
  • Cellulose
  • Hyaluronic Acid