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Our previous studies revealed that graphene had anticancer properties in experiments in vitro with glioblastoma multiforme (GBM) cells and in tumors cultured in vivo. We hypothesized that the addition of arginine or proline to graphene solutions might counteract graphene agglomeration and increase the activity of graphene. Experiments were performed in vitro with GBM U87 cells and in vivo with GBM tumors cultured on chicken embryo chorioallantoic membranes. The measurements included cell morphology, mortality, viability, tumor morphology, histology, and gene expression. The cells and tumors were treated with reduced graphene oxide (rGO) and rGO functionalized with arginine (rGO + Arg) or proline (rGO + Pro). The results confirmed the anticancer effect of graphene on GBM cells and tumor tissue. After functionalization with amino acids, nanoparticles were distributed more specifically, and the flakes of graphene were less agglomerated. The molecule of rGO + Arg did not increase the expression of TP53 in comparison to rGO, but did not increase the expression of MDM2 or the MDM2/TP53 ratio in the tumor, suggesting that arginine may block MDM2 expression. The expression of NQO1, known to be a strong protector of p53 protein in tumor tissue, was greatly increased. The results indicate that the complex of rGO + Arg has potential in GBM therapy. [ABSTRACT FROM AUTHOR]

Graphene oxide (GO) and reduced graphene oxide (RGO), due to their large active surface areas, can serve as a platform for biological molecule adhesion (both organic and inorganic). In this work we described methods of preparing composites consisting of GO and RGO and inorganic nanoparticles of specified biological properties: nanoAg, nanoAu, nanoTiO2 and nanoAg2O. The idea of this work was to introduce effective methods of production of these composites that could be used for future biomedical applications such as antibiotics, tissue regeneration, anticancer therapy, or bioimaging. In order to characterize the pristine graphene materials and resulting composites, we used spectroscopic techniques: XPS and Raman, microscopic techniques: SEM with and AFM, followed by X-Ray diffraction. We obtained volumetric composites of flake graphene and Ag, Au, Ag2O, and TiO2 nanoparticles; moreover, Ag nanoparticles were obtained using three different approaches. [ABSTRACT FROM AUTHOR]

The potential therapeutic applications of mesenchymal stem/stromal cells (MSCs) and biomaterials have attracted a great amount of interest in the field of biomedical engineering. MSCs are multipotent adult stem cells characterized as cells with specific features, e.g., high differentiation potential, low immunogenicity, immunomodulatory properties, and efficient in vitro expansion ability. Human umbilical cord Wharton's jelly-derived MSCs (hUC-MSCs) are a new, important cell type that may be used for therapeutic purposes, i.e., for autologous and allogeneic transplantations. To improve the therapeutic efficiency of hUC-MSCs, novel biomaterials have been considered for use as scaffolds dedicated to the propagation and differentiation of these cells. Nowadays, some of the most promising materials for tissue engineering include graphene and its derivatives such as graphene oxide (GO) and reduced graphene oxide (rGO). Due to their physicochemical properties, they can be easily modified with biomolecules, which enable their interaction with different types of cells, including MSCs. In this study, we demonstrate the impact of graphene-based substrates (GO, rGO) on the biological properties of hUC-MSCs. The size of the GO flakes and the reduction level of GO have been considered as important factors determining the most favorable surface for hUC-MSCs growth. The obtained results revealed that GO and rGO are suitable scaffolds for hUC-MSCs. hUC-MSCs cultured on: (i) a thin layer of GO and (ii) an rGO surface with a low reduction level demonstrated a viability and proliferation rate comparable to those estimated under standard culture conditions. Interestingly, cell culture on a highly reduced GO substrate resulted in a decreased hUC-MSCs proliferation rate and induced cell apoptosis. Moreover, our analysis demonstrated that hUC-MSCs cultured on all the tested GO and rGO scaffolds showed no alterations of their typical mesenchymal phenotype, regardless of the reduction level and size of the GO flakes. Thus, GO scaffolds and rGO scaffolds with a low reduction level exhibit potential applicability as novel, safe, and biocompatible materials for utilization in regenerative medicine. [ABSTRACT FROM AUTHOR]

Cell-based therapies have recently emerged as promising strategies for the treatment of cardiovascular disease. Mesenchymal stem cells (MSCs) are a promising cell type that represent a class of adult stem cells characterized by multipotency, high proliferative capacity, paracrine activity, and low immunogenicity. To improve the functional and therapeutic efficacy of MSCs, novel biomaterials are considered as scaffolds/surfaces that promote MSCs growth and differentiation. One of them are graphene-based materials, including graphene oxide (GO) and reduced graphene oxide (rGO). Due to the unique physical, chemical, and biological properties of graphene, scaffolds comprising GO/rGO have been examined as novel platforms to improve the differentiation potential of human MSCs in vitro. We verified different i) size of GO flakes, ii) reduction level, and iii) layer thickness to select the most suitable artificial niche for MSCs culture. The results revealed that graphene-based substrates constitute non-toxic substrates for MSCs. Surfaces with large flakes of GO as well as low reduced rGO are the most biocompatible for MSCs propagation and do not affect their proliferation and survival. Interestingly, small GO flakes and highly reduced rGO decreased MSCs proliferation and induced their apoptosis. We also found that GO and rGO substrates did not alter the MSCs phenotype, cell cycle progression and might modulate the adhesive capabilities of these cells. Importantly, we demonstrated that both materials promoted the cardiomyogenic and angiogenic differentiation capacity of MSCs in vitro. Thus, our data indicates that graphene-based surfaces represent promising materials that may influence the therapeutic application of MSCs via supporting their pro-regenerative potential. • GO and rGO represent novel surfaces for culture of hUC-MSCs which constitute promising population of cells in tissue repair • GO and rGO with a low reduction level represent surfaces enhancing cardiomyogenic and angiogenic potential of hUC-MSCs • Novel approaches using combined graphene-based surfaces and hUC-MSCs may provide promising solutions for tissue regeneration [ABSTRACT FROM AUTHOR]