In vitro genotoxicity assessment of an oxidized dextrin‐based hydrogel for biomedical applications

Abstract

Hydrogels are three‐dimensional, crosslinked networks of hydrophilic polymers swollen with a large amount of water or biological fluids, without dissolving. Dextrin, a low‐molecular‐weight 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 dextrin‐based hydrogel (HG). The HG and its components were tested for cyto‐ and genotoxicity according to the International Standard ISO 10993‐3 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, cytokinesis‐block 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 concentration‐dependent 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 non‐cytotoxic 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 aldehyde‐modified polysaccharide/adipic acid dihydrazide hydrogel.

In vivo systemic toxicity assessment of an oxidized dextrin‐based hydrogel and its effectiveness as a carrier and stabilizer of granular synthetic bone substitutes

“…57 The radioactivity of the Dextrin-VA-SC16 nanogels was mainly located in the organs of the Mononuclear Phagocytic System (liver and spleen) and kidneys. The results herein obtained with blood cells are in agreement with in vitro findings in human lymphoblastoid TK6 cells exposed to different concentrations of the HG that revealed no DNA and chromosomal damage, as assessed by the micronucleus and comet assays, 23 supporting the view that the HG is genocompatible. Indeed, some renal uptake of the nanogels, and excretion in the urine was detected.…”

“…The comet assay results demonstrated that that HG did not induce DNA damage. The results herein obtained with blood cells are in agreement with in vitro findings in human lymphoblastoid TK6 cells exposed to different concentrations of the HG that revealed no DNA and chromosomal damage, as assessed by the micronucleus and comet assays, 23 supporting the view that the HG is genocompatible.…”

“…[12][13][14][15][16][17][18] One of the major advantages in using HGs is the possibility to develop injectable formulations of bone substitutes. [20][21][22][23] To obtain the HG, dextrin was first oxidized with sodium periodate to produce dialdehydes, which then reticulate with adipic acid dihydrazide (ADH). Using these flowable materials, complete filling of the defect site can be established by means of minimally invasive techniques.…”

“…9 Our research group has been developing and characterizing a fully resorbable and injectable dextrin-based HG which was intended to perform as a multifunctional platform, enabling the combination with stem cells and other bioactive agents, during clinical procedures. [20][21][22][23] To obtain the HG, dextrin was first oxidized with sodium periodate to produce dialdehydes, which then reticulate with adipic acid dihydrazide (ADH). 20 We proposed that in situ forming dextrin-based HG would be a suitable carrier for ceramic granules in clinical applications.…”

Injectable hydrogel as a carrier of vancomycin and a cathelicidin‐derived peptide for osteomyelitis treatment

“…32 We have previously developed a fully resorbable and injectable dextrin-based hydrogel (HG) intended to perform as a multifunctional platform for the delivery of stem cells and other bioactive agents. [33][34][35][36][37][38] We have demonstrated its in vitro and in vivo biocompatibility and safety. 36,37 This HG has been approved for an ongoing clinical study as a carrier of granular synthetic bone substitutes for alveolar bone repair (iBone Therapies: advanced solutions for bone regeneration; EUDAMED No.…”