title: The prevention of peritoneal adhesions by in situ cross-linking hydrogels of hyaluronic acid and cellulose derivatives.
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.
authors.affiliation: Department of Chemical Engineering, Massachusetts Institute of Technology, 45 Carleton St., Cambridge, MA 02142, USA.
authors.forename: Taichi
authors.initials: T
authors.lastname: Ito
authors.forename: Yoon
authors.initials: Y
authors.lastname: Yeo
authors.forename: Christopher B
authors.initials: CB
authors.lastname: Highley
authors.forename: Evangelia
authors.initials: E
authors.lastname: Bellas
authors.forename: Carlos A
authors.initials: CA
authors.lastname: Benitez
authors.forename: Daniel S
authors.initials: DS
authors.lastname: Kohane
mesh_terms: 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
chemical_list: D001672:Biocompatible Materials; D003432:Cross-Linking Reagents; D020100:Hydrogels; D002482:Cellulose; D006820:Hyaluronic Acid