Reduced graphene oxide facilitates biocompatibility of alginate for cardiac repair
Negar Karimi Hajishoreh, Nafiseh Baheiraei, Nasim Naderi, Mojdeh Salehnia
Abstract
The benefits of combined cell/material therapy appear promising for myocardial infarction treatment. The safety of alginate, along with its excellent biocompatibility and biodegradability, has been extensively investigated for cardiac tissue engineering. Among graphene-based nanomaterials, reduced graphene oxide has been considered as a promising candidate for cardiac treatment due to its unique physicochemical properties. In this study, the reduced graphene oxide incorporation effect within alginate hydrogels was investigated for cardiac repair application. Reduced graphene oxide reinforced alginate properties, resulting in an increase in gel stiffness. The cytocompatibility of the hydrogels prepared with human bone marrow–derived mesenchymal stem cells was assessed by the 3-(4,5dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromide) assay. Following reduced graphene oxide addition, alginate-reduced graphene oxide retained significantly higher cell viability compared to that of alginate and cells cultured on tissue culture plates. Acridine orange/propidium iodide staining was also used to identify both viable and necrotic human bone marrow–derived mesenchymal stem cells within the prepared hydrogels. After a 72-h culture, the percentage of viable cells was twice as much as those cultured on either alginate or tissue culture plate, reaching approximately 80%. Quantitative reverse transcription polymerase chain reaction analysis was performed to assess gene expression of neonatal rat cardiac cells encapsulated on hydrogels for TrpT-2, Conx43, and Actn4 after 7 days. The expression of all genes in alginate-reduced graphene oxide increased significantly compared to that in alginate or tissue culture plate. The results obtained confirmed that the presence of reduced graphene oxide, as an electro-active moiety within alginate, could tune the physicochemical properties of this material, providing a desirable electroactive hydrogel for stem cell therapy in patients with ischemic heart disease.