Reducing the Oxidation Level of Dextran Aldehyde in a Chitosan/Dextran-Based Surgical Hydrogel Increases Biocompatibility and Decreases Antimicrobial Efficacy

Int J Mol Sci. 2015 Jun 16;16(6):13798-814. doi: 10.3390/ijms160613798.

Abstract

A highly oxidized form of a chitosan/dextran-based hydrogel (CD-100) containing 80% oxidized dextran aldehyde (DA-100) was developed as a post-operative aid, and found to significantly prevent adhesion formation in endoscopic sinus surgery (ESS). However, the CD-100 hydrogel showed moderate in vitro cytotoxicity to mammalian cell lines, with the DA-100 found to be the cytotoxic component. In order to extend the use of the hydrogel to abdominal surgeries, reformulation using a lower oxidized DA (DA-25) was pursued. The aim of the present study was to compare the antimicrobial efficacy, in vitro biocompatibility and wound healing capacity of the highly oxidized CD-100 hydrogel with the CD-25 hydrogel. Antimicrobial studies were performed against a range of clinically relevant abdominal microorganisms using the micro-broth dilution method. Biocompatibility testing using human dermal fibroblasts was assessed via a tetrazolium reduction assay (MTT) and a wound healing model. In contrast to the original DA-100 formulation, DA-25 was found to be non-cytotoxic, and showed no overall impairment of cell migration, with wound closure occurring at 72 h. However, the lower oxidation level negatively affected the antimicrobial efficacy of the hydrogel (CD-25). Although the CD-25 hydrogel's antimicrobial efficacy and anti-fibroblast activity is decreased when compared to the original CD-100 hydrogel formulation, previous in vivo studies show that the CD-25 hydrogel remains an effective, biocompatible barrier agent in the prevention of postoperative adhesions.

Keywords: antimicrobial; biocompatibility; chitosan; hydrogel; oxidized dextran.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aldehydes / chemistry
  • Anti-Infective Agents / chemistry*
  • Anti-Infective Agents / pharmacology
  • Biocompatible Materials / chemistry*
  • Biocompatible Materials / pharmacology
  • Cell Line
  • Chitosan / chemistry*
  • Dextrans / chemistry*
  • Fibroblasts / drug effects
  • Humans
  • Hydrogels / chemistry*
  • Hydrogels / pharmacology
  • Oxidation-Reduction

Substances

  • Aldehydes
  • Anti-Infective Agents
  • Biocompatible Materials
  • Dextrans
  • Hydrogels
  • Chitosan