DEXTRIN INJECTABLE HYDROGEL FOR TISSUE HEALING AND REGENERATION

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

Publication . Pereira, Isabel; Fraga, Sónia; Silva, Susana; Teixeira, João Paulo; Gama, Miguel

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.

2018-11-28Journal article

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

Publication . Pereira, Isabel; Fraga, Sónia; Maltez, Luís; Requicha, João; Guardão, Luísa; Oliveira, Joana; Prada, Justina; Alves, Helena; Santos, José Domingos; Teixeira, João Paulo; Pereira, José Eduardo; Soares, Raquel; Gama, Francisco Miguel

The worldwide incidence of bone disorders is raising, mainly due to aging population. The lack of effective treatments is pushing the development of synthetic bone substitutes (SBSs). Most ceramic-based SBSs commercially available display limited handling properties. Attempting to solve these issues and achieve wider acceptance by the clinicians, granular ceramics have been associated with hydrogels (HGs) to produce injectable/moldable SBSs. Dextrin, a low-molecular-weight carbohydrate, was used to develop a fully resorbable and injectable HG. It was first oxidized with sodium periodate and then cross-linked with adipic acid dihydrazide. The in vivo biocompatibility and safety of the dextrin-based HG was assessed by subacute systemic toxicity and skin sensitization tests, using rodent models. The results showed that the HG did not induce any systemic toxic effect, skin reaction, or genotoxicity, neither impaired the bone repair/regeneration process. Then, the HG was successfully combined with granular bone substitute, registered as Bonelike (250-500 μm) to obtain a moldable/injectable SBS, which was implanted in tibial fractures in goats for 3 and 6 weeks. The obtained results showed that HG allowed the stabilization of the granules into the defect, ensuring effective handling, and molding properties of the formulation, as well as an efficient cohesion of the granules.

2019-04-12Journal article

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