Author(s): Pereira, Isabel Sofia Melo ; Fraga, Sónia ; Silva, Susana ; Teixeira, João Paulo ; Gama, F. M.
Date: 2019
Persistent ID: https://hdl.handle.net/1822/59640
Origin: RepositóriUM - Universidade do Minho
Subject(s): Adipic acid dihydrazide (ADH); Aldehyde-modified polysaccharide; Ames test; Comet assay; Cytokinesis-block micronucleus (CBMN) assay; Dextrin; Hydrogel; TK6 cells
Hydrogels are threedimensional, crosslinked networks of hydrophilic polymers swollen with a large amount of water or biological fluids, without dissolving. Dextrin, a lowmolecularweight carbohydrate composed by glucose residues, has been used to develop an injectable hydrogel for biomedical applications. Dextrin was first oxidized to introduce aldehyde groups, which then reticulate with adipic acid dihydrazide, forming the dextrinbased hydrogel (HG). The HG and its components were tested for cyto and genotoxicity according to the International Standard ISO 109933 on the biological evaluation of medical devices. To assess genotoxicity, a battery of in vitro genotoxicity tests employing both eukaryotic and prokaryotic models was performed: comet assay, cytokinesisblock micronucleus assay and Ames test. Our data revealed that the HG (IC50 = 2.8 mg/mL) and oxidized dextrin by itself (IC50 = 1.2 mg/mL) caused a concentrationdependent decrease in cellular viability of human lymphoblastoid TK6 cells after 24 hours of exposure to the test agents. However, these concentrations are unlikely to be reached in vivo. In addition, no significant increase in the DNA and chromosomal damage of TK6 cells exposed to noncytotoxic concentrations of the HG and its isolated components was detected. Furthermore, neither the HG nor its metabolites exerted a mutagenic effect in different of Salmonella typhimurium strains and in an Escherichia coli mix. Our data demonstrated the genocompatibility of the HG (up to 3.5 mg/mL) for biomedical applications. To our best acknowledge, this is the first report with a detailed genotoxicity assessment of an aldehydemodified polysaccharide/adipic acid dihydrazide hydrogel.
