Suspended manufacture of a 3D iPSC-derived blood brain barrier with Sam Moxon

In this interview with Sam Moxon (University of Manchester, UK), 3DMedNet takes a closer look at bioprinting tissue for studying the blood-brain barrier and the neurovascular unit.

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I am Sam Moxon. I am a post-doc at the University of Manchester (UK) working in an Alzheimer’s research group.

I started as an undergraduate in genetics and my PhD focused on biomaterials and trying to develop ways of regenerating osteochondral tissue – that’s where bioprinting first came in. I was trying to create a structure that can mimic the fact that, for example in knee tissue, there are two layers of different matrix and different cell types: there is a gradient and the best way to try and replicate that is with bioprinting, so we developed a bioprinting platform to be able to replicate heterogeneity.

Today, I am applying those same principles to try and look at the brain where you also see those changes in biological and mechanical properties.

Could you tell us about any current (or recent) projects?

The main project involving bioprinting tissue surrounding the blood brain barrier. In the brain, there are millions and millions of blood vessels and they supply the brain with its vital oxygen nutrients, but they also control what goes in and out of the brain. There is a layer of endothelial cells and then other cell types interact with that on different levels and with Alzheimer’s disease, you see that breakdown. We want to try and replicate that complex structure because a lot of models don’t manage to mimic that complexity. So bioprinting-wise, we are hoping to try and create a more reflective model of what the blood-brain barrier and the bigger structures - the neurovascular unit - looks like inside the brain and by doing so, we can try to work out what happens when that goes wrong.

We are also working on other projects surrounding Alzheimer’s disease, but this one is the one that is more bioprinting focused.

How are 3D printing and bioprinting technologies involved with your group’s work?

The team is using bioprinting to try to improve on the complexity of models. A lot of models that you see are often based on one cell type and even if it’s 3D, again, it’s one cell type or you have a mixture of cells in one and that doesn’t really reflect the fact that they are actually in precise locations. 

For us, bioprinting is all about trying to get a more clinically relevant orientation of cells, in different types of matrices.

What challenges with fabricating blood brain barriers do 3D printing and bioprinting technologies help to overcome? 

The main challenges are trying to control cell interaction because one of the big arguments people always say is, ‘why don’t you just use an animal, they have got a perfect representation of what it is that you are looking at?’.

The problem is when you do that, you can get some viable data but there is also the fact that you are looking at an entire organism, so it is very difficult to pick apart how each individual cell type plays a role because you have everything present at once.

With bioprinting, you can tailor what biological interactions you want to look at by printing different cell types and retracting different cell types. It really helps to pick apart complex areas and control which areas you want to look at to help get a better understanding.

In the brain, every cell type talks to every cell type, so being able to choose which ones you look at really helps you understand what’s going on.

How do you see your work translating into the medical field?

We are making strides towards something that’s more tissue-like but actually getting it to the clinic is always the difficult part.

Clinical trials are like the limiting step: we can have stuff that goes through years of clinical trials, only to fail.

I think we are getting closer, but I think we are still talking maybe at least 5–10 years before we start to see our projects translated into a clinical environment. We have previously seen 3D platforms get to the clinic and then be retracted from the clinic, so it is challenging, but I also think that there has never been a better time to try and push forwards with the technologies we have.

What’s next with your research? What should we be looking out for?  

Well, we are hoping within the next 6–8 months to publish something on our blood brain barrier model and also move towards something that is more automated and more bioprinting focused. So hopefully within next 6–12 months, you will start to see some published data on how you can use bioprinting for modeling the brain.

Where do you see bioprinting in the medical field in 5–10 years’ time? 

I would like to bioprinting become more scalable economically and practically. This would include increased access to bioprinters to be able to do more for less money because at the moment, the cost is reducing but some of the top-end bioprinters are still costing hundreds of thousands of pounds.

I would also like to see bioprinting integrating more into biology labs. At the moment, it is often restricted to engineering labs and we need to get more crosstalk between engineers, biologists and clinicians.

Do you have any final comments about medical 3D printing, bioprinting, bioengineering and/or their applications to neuroscience you would like to share? 

I think the main message is that it is a challenge, but the technologies we have now we are in a much better place than they were 10 years ago, and there has never been a better time to try and push for these kinds of technologies.

With the way science is changing and also with the way the society is becoming more ethical, there are more campaigns for reducing animal models - I think bioprinting is going to become a big technology both scientifically and ethically, in response to these campaigns.

It is a good time to capitalize on bioprinting and we are trying to make most of it.

The opinions expressed in this feature are those of the interviewee/author and do not necessarily reflect the views of 3DMedNet or Future Science Group.

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