Graphene Nanomaterials: Synthesis, Biocompatibility, and Cytotoxicity

Abstract

Graphene, graphene oxide, and reduced graphene oxide have been widely considered as promising candidates for industrial and biomedical applications due to their exceptionally high mechanical stiffness and strength, excellent electrical conductivity, high optical transparency, and good biocompatibility. In this article, we reviewed several techniques that are available for the synthesis of graphene-based nanomaterials, and discussed the biocompatibility and toxicity of such nanomaterials upon exposure to mammalian cells under in vitro and in vivo conditions. Various synthesis strategies have been developed for their fabrication, generating graphene nanomaterials with different chemical and physical properties. As such, their interactions with cells and organs are altered accordingly. Conflicting results relating biocompatibility and cytotoxicity induced by graphene nanomaterials have been reported in the literature. In particular, graphene nanomaterials that are used for in vitro cell culture and in vivo animal models may contain toxic chemical residuals, thereby interfering graphene-cell interactions and complicating interpretation of experimental results. Synthesized techniques, such as liquid phase exfoliation and wet chemical oxidation, often required toxic organic solvents, surfactants, strong acids, and oxidants for exfoliating graphite flakes. Those organic molecules and inorganic impurities that are retained in final graphene products can interact with biological cells and tissues, inducing toxicity or causing cell death eventually. The residual contaminants can cause a higher risk of graphene-induced toxicity in biological cells. This adverse effect may be partly responsible for the discrepancies between various studies in the literature.

Graphenic Materials for Biomedical Applications

“…Previous studies have shown that the information obtained on the in vitro and in vivo toxicity of GBMs due to their dimensions and variation in oxidation states is far from complete [60]. The interactions of living cells with GBMs depends on their hydrophilicity, surface chemistry, purity, lateral dimensions, layer number, and dose [61][62][63][64]. These properties vary greatly according to their synthesis eventually to methods of functionalization.…”

“…GBMs can affect cell membranes and damage them with subsequent cytotoxic effects. Cell membranes contain phospholipids, which are composed of a head group based on phosphate and two chains of fatty acids [61]. The head groups are formed by phosphatic acid modified also by small molecules such as glycerol, inositol, ethanolamine, serine, or choline, which give rise to the phospholipid distinctive properties.…”

“…Pristine GR is not able to electrostatically bind phospholipids, due to lack of charge in its lattice, but it can hydrophobically interact with long chains of the fatty acids. Membranes can be also damaged by withdrawing cholesterol molecules from the membrane [61]. On the opposite side, GO can electrostatically interact with membrane lipids due to the presence of oxygen-containing functional groups on its surface, contributing to a high negative charge density.…”

Combined Application of Graphene‐Family Materials and Silk Fibroin in Biomedicine

“…As stated earlier, graphene‐family materials can promote cell adhesion and proliferation of some types of cells, and SF has good biocompatibility and can provide a scaffold for cell growth ,. So, a combination of the two materials can mimic the natural environment for cell culture.…”

Antibacterial Activity against Staphylococcus Aureus of Titanium Surfaces Coated with Graphene Nanoplatelets to Prevent Peri-Implant Diseases. An In-Vitro Pilot Study

“…Moreover, GNPs possess the typical anti-adhesion property of graphene, because the absence of basal plane functional groups inhibits the cell adhesion over substrate, and there is also a lower potential for cytotoxicity than graphene oxide, because the absence of oxygen-containing functional groups on the basal plane does not generate reactive oxygen species (ROS) which produce oxidative stress [30,31]. However, regarding the biocompatibility and cytotoxicity of graphene-related materials, conflicting results have been reported in the literature because the response of living cells to these nanomaterials depends greatly on their layer number, lateral size, purity, dose, surface chemistry, and hydrophilicity [32][33][34]. Nevertheless, in a previous study, Zanni et al [35] evaluated the nanotoxicology of GNPs using the model system Caenorhabditis elegans, which is an excellent indicator of nanotoxicology that has highlighted no toxic impact on this animal, nor on its vitality and reproduction capability.…”