# Expanding Horizons: Taking Advantage of Graphene's Surface Area for Advanced Applications
## 6 Toxicity Related to Graphene Derivatives  
Most graphene research highlights its positive physical and biological traits. Studies often emphasize biocompatibility and cell growth. However, the negative impacts of graphene appear less investigated and should be considered as well. The primary research highlights the good biocompatibility of various graphene derivatives (GDs) across different cell lines, including fibroblasts, osteoblasts, cervical carcinoma cells, vascular smooth muscle cells, and mesenchymal stem cells. Multiple studies [103; 104] demonstrated that GD-like graphene paper, graphene oxide-hydroxyapatite nanocomposites, chitosan-based graphene oxide scaffolds, and poly-sulfone/GO membranes generally support cell attachment and proliferation and even enhance cell viability without inducing significant cytotoxicity. While the focus is largely on positive outcomes, literature note that biocompatibility can vary depending on the specific properties of GD, such as surface chemistry, morphology, and synthesis route, emphasizing the need for comprehensive material characterization and standardized production methods. Despite the overall positive trend, this section implicitly acknowledges the importance of further investigation into potential negative outcomes, as most research has historically emphasized the beneficial aspects of graphene [105; 106].  
Controlling the potential toxicity of GD involves a multifaceted approach focusing on material design, processing, and application. Careful control over the synthesis process to  
\begin{table}
\begin{tabular}{c c c c} \hline \hline
**References** & **Modification Method** & **Increased Surface Area** & **Key Findings** \\ \hline
[2] & Exfoliation method & 1100 m\({}^{2}\)/g & - \\ \hline
[68] & Hydrothermal method & 165.95 m\({}^{2}\)/g & Higher specific capacitance with CoFe\({}_{2}\)O\({}_{4}\) \\  & & & addition to rGO \\ \hline
[95] & Hydrothermal carbonization & 2106 m\({}^{2}\)/g & High packing density and capacitance \\ \hline
[96] & Carbon nanoparticle functionalization & 1256 m\({}^{2}\)/g & High specific capacitance of 324.6 F/g \\ \hline
[97] & Tape casting & \textgreater{}400 m\({}^{2}\)/g & High electrical conductivity and tensile strength \\ \hline
[98] & Hydrazine reduction & 745 m\({}^{2}\)/g & High electrical conductivity and specific capacitance \\ \hline
[99] & Chemical reduction & 195.97 m\({}^{2}\)/g & Low-cost production method \\ \hline
[100] & Hydrazine reduction with rGO & 891 m\({}^{2}\)/g & Useful for supercapacitors \\ \hline
[101] & Active rGO method & 1000 to 3000 m\({}^{2}\)/g & Increased surface-to-volume ratio \\ \hline
[102] & GO reduction & 670.98 m\({}^{2}\)/g & Increased surface-to-volume ratio provides high electric conductivity \\ \hline \hline \end{tabular}
\end{table}
Table 1: Summary of the different methods used to increase the surface area of graphene.  
minimize impurities and tailor the size, shape, and surface functionalization of graphene materials is crucial, as these properties significantly influence their biological interactions. Surface modification with biocompatible coatings or functional groups can reduce direct cellular interactions and enhance dispersibility, preventing agglomeration, which can lead to localized toxicity [107]. Rigorous in vitro and in vivo testing using standardized protocols is essential to thoroughly evaluate the toxicological profile of specific graphene derivatives under relevant exposure conditions, ultimately guiding the safe development and application of these promising materials [108].