Synthesis and Functionalization of Graphene Materials for Biomedical Applications: Recent Advances, Challenges, and Perspectives

Since its discovery in 2004, graphene is increasingly applied in various fields owing to its unique properties. Graphene application in the biomedical domain is promising and intriguing as an emerging 2D material with a high surface area, good mechanical properties, and unrivalled electronic and physical properties. This review summarizes six typical synthesis methods to fabricate pristine graphene (p-G), graphene oxide (GO), and reduced graphene oxide (rGO), followed by characterization techniques to examine the obtained graphene materials. As bare graphene is generally undesirable in vivo and in vitro, functionalization methods to reduce toxicity, increase biocompatibility, and provide more functionalities are demonstrated. Subsequently, in vivo and in vitro behaviors of various bare and functionalized graphene materials are discussed to evaluate the functionalization effects. Reasonable control of dose (<20 mg kg(-1)), sizes (50-1000 nm), and functionalization methods for in vivo application are advantageous. Then, the key biomedical applications based on graphene materials are discussed, coupled with the current challenges and outlooks of this growing field. In a broader sense, this review provides a comprehensive discussion on the synthesis, characterization, functionalization, evaluation, and application of p-G, GO, and rGO in the biomedical field, highlighting their recent advances and potential.