Current tissue engineering approaches combine different scaffold materials with living cells to provide biological substitutes that can repair and eventually improve tissue functions. Both natural and synthetic materials have been fabricated for transplantation of stem cells and their specific differentiation into muscles, bones, and cartilages. One of the key objectives for bone regeneration therapy to be successful is to direct stem cells' proliferation and to accelerate their differentiation in a controlled manner through the use of growth factors and osteogenic inducers. Here we show that graphene provides a promising biocompatible scaffold that does not hamper the proliferation of human mesenchymal stem cells (hMSCs) and accelerates their specific differentiation into bone cells. The differentiation rate is comparable to the one achieved with common growth factors, demonstrating graphene's potential for stem cell research.

Graphene, with its excellent physical, chemical, and mechanical properties, holds tremendous potential for a wide variety of biomedical applications. As research on graphene-based nanomaterials is still at a nascent stage, due to the very short time span since its initial report in 2004, a focused review on this topic is timely and necessary. In this feature review, we first summarize the results from toxicity studies of graphene and its derivatives. Although literature reports have mixed findings, we emphasize that the key question is not how toxic graphene itself is, but how to modify and functionalize it and its derivatives so that they do not exhibit acute/chronic toxicity, can be cleared from the body over time, and thereby can be best used for biomedical applications. Next, we discuss in detail the exploration of graphene-based nanomaterials for tissue engineering, molecular imaging, and drug/gene delivery applications. The future of graphene-based nanomaterials in biomedicine looks brighter than ever, and it is expected that they will find a wide range of biomedical applications with future research effort and interdisciplinary collaboration.

Nanotechnology has witnessed tremendous advancement over the last several decades. Zinc oxide (ZnO), which can exhibit a wide variety of nanostructures, possesses unique semiconducting, optical, and piezoelectric properties hence has been investigated for a wide variety of applications. One of the most important features of ZnO nanomaterials is low toxicity and biodegradability. Zn2+ is an indispensable trace element for adults (~10 mg of Zn2+ per day is recommended) and it is involved in various aspects of metabolism. Chemically, the surface of ZnO is rich in -OH groups, which can be readily functionalized by various surface decorating molecules. In this review article, we summarized the current status of the use of ZnO nanomaterials for biomedical applications, such as biomedical imaging (which includes fluorescence, magnetic resonance, positron emission tomography, as well as dual-modality imaging), drug delivery, gene delivery, and biosensing of a wide array of molecules of interest. Research in biomedical applications of ZnO nanomaterials will continue to flourish over the next decade, and much research effort will be needed to develop biocompatible/biodegradable ZnO nanoplatforms for potential clinical translation.

Herein we demonstrate that nano-graphene can be specifically directed to the tumor neovasculature in vivo through targeting of CD105 (i.e. endoglin), a vascular marker for tumor angiogenesis. The covalently functionalized nano-graphene oxide (GO) exhibited excellent stability and target specificity. Pharmacokinetics and tumor targeting efficacy of the GO conjugates were investigated with serial non-invasive positron emission tomography (PET) imaging and biodistribution studies, which were validated by in vitro, in vivo, and ex vivo experiments. The incorporation of an active targeting ligand (TRC105, a monoclonal antibody that binds to CD105) led to significantly improved tumor uptake of functionalized GO, which was specific for the neovasculature with little extravasation, warranting future investigation of these GO conjugates for cancer-targeted drug delivery and/or photothermal therapy to enhance therapeutic efficacy. Since poor extravasation is a major hurdle for nanomaterial-based tumor targeting in vivo, this study also establishes CD105 as a promising vascular target for future cancer nanomedicine.

Graphene-based nanomaterials have attracted tremendous attention in the field of biomedicine due to their intriguing properties. Herein, we report tumor vasculature targeting and imaging in living mice using reduced graphene oxide (RGO), which was conjugated to the anti-CD105 antibody TRC105. The RGO conjugate, 64Cu-NOTA-RGO-TRC105, exhibited excellent stability in vitro and in vivo. Serial positron emission tomography (PET) imaging studies non-invasively assessed the pharmacokinetics and demonstrated specific targeting of 64Cu-NOTA-RGO-TRC105 to 4T1 murine breast tumors in vivo, compared to non-targeted RGO conjugate (64Cu-NOTA-RGO). In vivo (e.g., blocking 4T1 tumor uptake with excess TRC105), in vitro (e.g., flow cytometry), and ex vivo (e.g., histology) experiments confirmed the specificity of 64Cu-NOTA-RGO-TRC105 for tumor vascular CD105. Since RGO exhibits desirable properties for photothermal therapy, the tumor-specific RGO conjugate developed in this work may serve as a promising theranostic agent that integrates imaging and therapeutic components.