Green synthesis of relevant and sustainable bio-applications of few-layer graphene: A multi-faceted review and future perspectives

Graphene and graphene-based nanomaterials have gained remarkable attention owing to their outstanding physicochemical characteristics and versatile functional properties. This review aims to provide a comprehensive overview that integrates graphene production, comparing chemical versus green synthesis routes from waste materials, with a discussion of their potential health-related applications. Top-down and bottom-up synthetic approaches, along with several industrial routes, are discussed. The bottom-up method remains the most efficient for high-quality graphene production; however, scale-up limitations, batch-to-batch variability, and cost-effective industrial scalability continue to represent major research challenges. Sustainability metrics (E-factor, energy consumption, and solvent footprint) are essential for a complete evaluation of FLG synthesis routes. Increasing global focus has shifted toward sustainable, eco-friendly production routes. In this context, the upcycling of plastic waste into value-added products such as graphene represents a promising and environmentally sound strategy for large-scale production. Few-layer graphene (FLG) and graphene quantum dots (GQDs) have demonstrated considerable potential in biomedical applications including drug delivery, tissue engineering, biosensing, bioimaging, antiviral, and anticancer therapy. However, these applications are largely preclinical, and translation to clinical practice remains limited by variability in material quality, incomplete long-term toxicity and immunogenicity data, and challenges in achieving scalable, GMP-compliant production. The global graphene market is also reviewed, revealing that most commercially available graphene-based materials are applied in energy storage, electronics, and sports composites, whereas biomedical applications remain underrepresented. Addressing these translational barriers through standardized synthesis, thorough safety evaluation, and regulatory harmonization will be essential to fully realize the biomedical potential of graphene, and future research should focus on scalable green production, detailed in vivo safety studies, and clinical translation of graphene-based therapeutics.