An Interview with Alexander Seifalian: Graphene for Medical Applications

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This is an interview taken by Liam Critchley, an NGA advisory board member, with Professor Alexander Seifalian, CEO of NanoRegMed Ltd, at the 5th NANOMED Conference held in Manchester, UK, between 26-28th June 2018.

About Professor Alexander Seifalian

Alexander Seifalian, Professor of Nanotechnology and Regenerative Medicine worked at the Royal Free Hospital and University College London for over 27 years. During this time, he spent a period at Harvard Medical School looking at the causes of cardiovascular disease, and a year at Johns Hopkins Medical School looking at liver treatments. He has published more than 647 peer-reviewed research papers and has registered 14 UK andInternational patents. He is currently the CEO of NanoRegMed Ltd (short for Nanotechnology Regenerative Medicine) and is now working on the commercialization of his research.

During his career Prof. Seifalian has led and managed many large projects with successful outcomes – in terms of commercialization and translation to patients. In 2007, he was awarded the top prize in his field for the development of nanomaterials and technologies as cardiovascular implants by Medical Future Innovation, and in 2009 he received a Business Innovation Award from UK Trade & Investment (UKTI). He was the European Life Science Awards’ Winner of Most Innovative New Product 2012 for the “synthetic trachea”. Prof. Seifalian also won the NANOSMAT Prize in 2013. In 2016, he received the Distinguished Research Award in recognition of his outstanding work in regenerative medicine from Heals Healthy Life Extension Society.

Prof. Seifalian’s achievements include the development of the world first synthetic trachea, lacrimal drainage conduit, and vascular bypass graft using nanocomposite materials, bioactive molecules and stem cell technology. He has had over 15,000 media reports cover his achievements, include the BBC, ITV, WSJ, CNN, and many more. He is currently working on the development and commercialization of human organs using graphene-based nanocomposite materials and stem cell technology. He has developed two families of graphene-based, non-biodegradable nanocomposite materials for applications such as heart valves, blood vessels and bioabsorbable materials for the development of guided conduits in nerve regeneration and heart patches to regenerate damaged heart muscles.

The Interview

So, could you tell me a little bit about your research?

So, at the university I was initially working on a range of areas from liver transplants to cardiovascular research. I was working with nanotechnology-based materials and stem cells to grow organs, such as the trachea, nose and blood vessels. Since I started up the company with Hana Salussolia (a financial expert who worked for Goldman Sachs), we now base the research around carbon and carbon nanoparticles for medical applications.

Our frontrunner is graphene oxide. We take graphene oxide and we functionalize it, and conjugate it, with a base polymer. The polymers we choose need to be compatible for medical applications, because we make surgical implants such as the ear, nose, heart valves, tendons and bone. We make these by using the graphene oxide and the polymer as a type of composite – we take the polymer solution and we make thermoplastic and fibrous polymers depending on the application. The polymers we use must also have anti-infection and anti-biofilm properties because they are implanted. To do this we make the material have either a hydrophobic or a hydrophilic nanotopography.

So, where do you source your graphene oxide?

We found that everyone made graphene platelets or graphite, we did initially have some trouble sourcing graphene oxide. We were going to make our own graphene oxide, but then we found out about a lot of people making it, and we now get it either for free or for very cheap. So, there’s no point in us making it ourselves. We obtained quite a few samples from a few companies, but then we settled for just one company, an American company [didn’t disclose the name]. However, we are not just dependent on them, as there’s a UK company as well, and we’re always on the lookout for other companies.

Is there any reason why you chose graphene oxide over the other forms of graphene (such as pure graphene, graphene nanoribbons, graphene nanoplatelets etc)? Does it bind better with the Polymer?

No, well the name is a bit of a gray area anyway, and there’s a lot of overlapping between the different types. Our patent does cover a wide range of carbon materials – graphene, carbon nanotubes etc, and we have synthesized composites using different carbon materials. We just happened to use graphene oxide more because it’s more popular and most people have graphene oxide. But we do play around with different materials.

What effect does the graphene have on the composite?

We synthesize the composite using poly(urethane-carbonate) because it has certain beneficial mechanical properties. However, some of the other mechanical properties are not as strong and it doesn’t have any antibacterial properties. We first mixed the graphene oxide as a filler and there was a bit of improvement, but not much. By conjugating and bonding the graphene oxide to the rest of the polymer chain, the mechanical properties are significantly improved. For example, in some medical applications such as the blood vessel, the composite needs to be very elastic; whereas in other applications such as bone, the composite needs to be hard. We can control the amount of graphene oxide we put in, to tailor the properties of the composite to be either hard or viscoelastic, depending on the application. On average, you need about 80 kg of force (80 MPa) to tear the composite.

Some people have problems dispersing graphene and incorporating it in a specific way. Have you ever come across any problems with that? Does the orientation of the graphene oxide within the polymer matrix matter?

We actually synthesize our material inside a high-frequency ultrasonic cell, and we have done a lot of tests, such as XPS, on the distribution of graphene within the polymer. But yes, and we can control it. Because we conjugate, rather than disperse, the graphene oxide, it is looking to attach to a specific site and not just fill a hole in the matrix.

Do you ever have any problems with using different sets of graphene? [i.e. graphene from different suppliers]

Yes, I think the problem is that there are no standards as such. There needs to be a standard for graphene, there needs to be a purification process for graphene, there needs to be an exact definition for different graphene derivatives – so that when you say graphene oxide, someone will know exactly what graphene oxide means. In the form of a formal definition, XPS or spectrum curve, there needs to be something, because when you get the material, it sometimes doesn’t do what it is supposed to do.

There are people, such as the NGA in the US, who are working toward creating better graphene standards. But, from an application perspective, does the quality of the graphene affect the quality of the end product?

As a medical application, you synthesize using GMP, knowing the source and knowing the safety aspects, and different qualities can affect the polymer and the application. However, we try to minimize the effects of that (when we get the graphene in) by washing the graphene, sonicating it and functionalizing it with different groups. We also do a quality control and send it off for XPS tests.

After processing the graphene, do you find that you get a consistent standard?

The company we have been getting it from in the US have been good. We had some from Europe, in Spain, alongside some from China. But they weren’t as good. It’s hard to say, ‘how not as good’. But, even after we purified them, they weren’t as pure as some of our other sources. Again, for medical applications, it is important. For industry, if you want to license or commercialize, you need to have more than one source of graphene, but they all need to be of the same quality. If there are any differences, you need to prove that there is no effect on the quality of the product.

Could that be a potential barrier to commercializing these medical technologies?

Of course. But it’s a little bit lesser of a problem for ours as we conjugate it with the polymer. However, for example, you take a biosensor or drug delivery that require high quality materials, it is a lot more of a barrier. But for medical applications on the whole, there needs to be standards.

Obviously, you’re doing implants (things that are going to go into the body). There are studies out there say that graphene can have adverse effects on the body, have you found any adverse with putting graphene composites into the body.

No, because we conjugate the graphene with the polymer into a non-biodegradable composite, the graphene does not come out of the composite, and it cannot get to the point where it could be toxic to the surrounding environment [I was shown a sample and failed to tear it]. If you were injecting graphene nanoparticles into patients without any functionalization, it would be toxic – we tried this test on rats and it was toxic to the kidneys, the liver etc. But, when you functionalize it, the toxicity goes away. That is quite important.

How far is this from being used commercially?

Well, when I was giving a talk at a previous conference, someone came along and said, “what about fouling/antifouling?”. We went away and did some tests and it proves to be good materials for anti-fouling applications. We’ve been getting some money from Innovate UK and industry for anti-fouling applications, such as for making anti-fouling fishing nets. So, we’ve been a bit side-tracked with this. But the money from that has been feeding into the medical applications as well. I personally think that we’ll be starting on our first patient in 2-3 years (for the more basic procedures, such as the ear). We have also just started our pre-clinical animal work for cardiovascular applications.

On a final note, you’re currently looking at doing the ear, the nose and the trachea. Anything else you are looking at?

We’re also looking at the urethra, catheter and wound patches. We want to keep with simple areas, such as facial organs. Initially, we are looking at the simpler organs, but there are other areas, such as heart valves and bone that we have done some work on. But those areas will take more time and money.

About the Author:

Liam Critchley is a writer, journalist and communicator who specializes in chemistry and nanotechnology. Liam sits on the advisory board for the National Graphene Association (NGA) and is currently the Senior Science Communications Officer for the Nanotechnology Industries Association (NIA) in Europe. Liam also writes for many nanotechnology-focused media websites and has over 300 articles published to date. Liam will be attending the Global Graphene Expo & Conference held in Austin, TX in October, and will be looking to take interviews with participants.

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