Graphene for Biomedical Applications

Graphene is a material formed from carbon in a honeycomb structure with one-atom thickness. It provides distinctive optical, thermal, electronic and mechanical properties. The material can be manufactured into sheets, flakes and graphene oxide to provide a variety of applications to the field of biomedicine.

Current research is developing practical applications of graphene for use in drug delivery, as a material for building biosensors, as a potential antibacterial agent and as a scaffold for tissue engineering.

Graphene for drug delivery

One of the earliest biomedical applications of graphene was for improved drug delivery. Graphene oxide, produced by the oxidation of graphite, was first reported as a suitable nanocarrier for drug delivery in 2008. The large, planar surface structure and enriched oxygen-containing groups provide biocompatibility and solubility, properties which are appropriate for delivering drugs within the body.

Graphene oxide contains COOH and OH groups which will readily allow for the attachment to various biomolecules. Studies have explored the use of graphene oxide for the delivery of cancer treatments and anti-inflammatory drugs. Chemo-photothermal therapy for cancer treatment has shown promise through a graphene oxide delivery system, with high uptake in tumors reported indicating targeted delivery of the therapy.

Graphene for use as a biosensor

Biosensors are utilized for the detection of biological molecules and events through the production of a measurable signal. Single-layer graphene sheets are particularly suitable for use as a biosensor material because its properties include high mechanical strength and thermal conductivity, along with a tunable electronic band gap. Graphene can also be easily functionalized to enable a biocompatible surface through both the covalent and non-covalent bonding of small molecules. Biosensors produced from graphene include enzymatic electrochemical biosensors which work by immobilizing enzymes onto the electrode surface in order to detect biological molecules.

Graphene has also been used in the development of electrochemical immunosensors, where antigen-antibody complexes are detected on an electrode surface, useful for diagnosing diseases via a portable device. A technique for detecting an important cancer biomarker, alpha-fetoprotein (AFP), has been produced by forming an immunosensor on a graphene surface. The graphene surface enhanced performance was formed through the construction of an improved pathway for electron transfer, caused by the AFP immunocomplex.

Graphene as a biological agent

With the increasing risk imposed by antibiotic resistance, the development of new types of antibacterial agent is vital. Early results produced by utilizing graphene oxide paper suspended by vacuum filtration found an antibacterial effect. A more recent study explored the underlying mechanism of the antibacterial effect produced by graphene. Raman spectroscopy, a method used to provide a chemical fingerprint for identifying molecules, was applied to a sample expressing the antibacterial ability of graphene oxide.

The spectroscopic signatures of biomolecules such as DNA nucleobases and proteins were analyzed and compared between Escherichia coli and Enterococcus faecalis cultures with different concentrations of graphene oxide. The larger spectroscopic signature of nucleobases and proteins produced from cultures treated with graphene oxide indicate the underlying mechanism of the antibacterial effect. This is because larger concentrations of the biomolecules which were analyzed are associated with induced bacterial death, further confirmed through observation using traditional microscopy. The study indicates that methods employing graphene will have future importance in the development of new antibacterial agents in a post-antibiotic era.

Graphene for tissue engineering          

The ability to engineer tissue will increase the potential for regenerative medicine, through the use of new materials which enhance cell adhesion, growth and differentiation. Graphene has been shown to display biocompatibility with mammalian cells necessary for use as a scaffold structure for tissue engineering.

In particular, graphene-based film accelerates stem cell differentiation, with a study developing bone cells from undifferentiated stem cells using osteogenic inducers on a graphene scaffold. Graphene also has the mechanical strength to support the growth of bone cells such as osteoblasts, making it a suitable material for engineering bone tissue. This technology may be used in the future during hard tissue surgery, particularly for reinforcing artificial bone implants.

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Sources:

1. University of Manchester: Biomedical Applications of Graphene. http://www.graphene.manchester.ac.uk/explore/the-applications/biomedical/
2. Shen, H. et al. 2012. Biomedical Applications of Graphene, Theranostics, 2, pp. 283-294. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3311234/
3. Su, B. et al. 2010. Graphene and Nanogold-Functionalized Immunosensing Interface with Enhanced Sensitivity for One-Step Electrochemical Immunoassay of Alpha-Fetoprotein in Human Serum, Electroanalysis, 22, pp. 2720-2728. http://onlinelibrary.wiley.com/doi/10.1002/elan.201000324/abstract
4. Nanda, S.S. et al. 2016. Study of antibacterial mechanism of graphene oxide using Raman spectroscopy, Nature Scientific Reports, 6, e28443. https://www.nature.com/articles/srep28443
5. Shin, S.R. et al. 2016. Graphene-based materials for tissue engineering, Advanced Drug Delivery Reviews, 105, pp. 255-274. https://www.sciencedirect.com/science/article/pii/S0169409X1630093X