title: Reducing the Oxidation Level of Dextran Aldehyde in a Chitosan/Dextran-Based Surgical Hydrogel Increases Biocompatibility and Decreases Antimicrobial Efficacy.
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.
authors.affiliation: Department of Microbiology & Immunology, University of Otago, 9054 Dunedin, New Zealand. m.chan@massey.ac.nz.
authors.forename: Maggie
authors.initials: M
authors.lastname: Chan
authors.affiliation: Department of Microbiology & Immunology, University of Otago, 9054 Dunedin, New Zealand. heather.brooks@otago.ac.nz.
authors.forename: Heather J L
authors.initials: HJ
authors.lastname: Brooks
authors.affiliation: Department of Chemistry, University of Otago, 9054 Dunedin, New Zealand. smoratti@chemistry.otago.ac.nz.
authors.forename: Stephen C
authors.initials: SC
authors.lastname: Moratti
authors.affiliation: Department of Chemistry, University of Otago, 9054 Dunedin, New Zealand. lhanton@chemistry.otago.ac.nz.
authors.forename: Lyall R
authors.initials: LR
authors.lastname: Hanton
authors.affiliation: Department of Chemistry, University of Otago, 9054 Dunedin, New Zealand. jcabral@chemistry.otago.ac.nz.
authors.forename: Jaydee D
authors.initials: JD
authors.lastname: Cabral
mesh_terms: D000447:Aldehydes / Q000737:chemistry; D000890:Anti-Infective Agents / Q000737:chemistry* / Q000494:pharmacology; D001672:Biocompatible Materials / Q000737:chemistry* / Q000494:pharmacology; D002460:Cell Line; D048271:Chitosan / Q000737:chemistry*; D003911:Dextrans / Q000737:chemistry*; D005347:Fibroblasts / Q000187:drug effects; D006801:Humans; D020100:Hydrogels / Q000737:chemistry* / Q000494:pharmacology; D010084:Oxidation-Reduction
chemical_list: D000447:Aldehydes; D000890:Anti-Infective Agents; D001672:Biocompatible Materials; D003911:Dextrans; D020100:Hydrogels; D048271:Chitosan
keywords: antimicrobial; biocompatibility; chitosan; hydrogel; oxidized dextran