N-Doped Graphene for Biomedical Applications: A Comparative Biocompatibility Assessment of Green and Chemical Exfoliation

Abstract

Graphene-based nanomaterials have transformed biomedical applications due to their exceptional physicochemical properties, and nitrogen (N)-doping further enhances the electrocatalytic activity of graphene. Driven by the demand for safer and more sustainable nanomaterials, in this work, we compared eco-friendly produced N- doped graphene (bD) with conventionally synthesized N- doped graphene (cD) in three different cell lines. Across all cell types and assays, cD was more toxic than bD. In NIH/3T3 fibroblast cells, cD activated the Nrf2 signaling pathway, whereas in HaCaT keratinocytes, it triggered oxidative stress responses and increased the apoptotic population. High doses of cD also affected THP-1-derived macrophages by inducing apoptosis and arresting the cell cycle in the G0/G1 phase. Although high doses of bD were also cytotoxic, overall, its effects were milder than cD. Our results confirm that green exfoliation of N- doped graphene retains its desirable biomedical properties while enhancing its biocompatibility, making bD a safer choice for future biomedical applications.