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Origami Organs: Medicine’s Next Big Thing? – In-Depth Expert Interview

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Ramille Shah, PhD, Professor of Material Science and Engineering in Surgery, Transplant Division, expertise in Biomaterial Engineering and Regenerative Medicine, Simpson Querrey Institute for BioNanotechnology, Northwestern University, talks about using 3D printing technology with a focus on creating a tissue paper made from cells that may one day eventually help surgeons repair organs.

Interview conducted by Ivanhoe Broadcast News in December 2017.

If you could tell us what you and your colleagues look at?

Shah: My lab really focuses on developing new biomaterial platforms that can be compatible with 3D printing. Several years ago 3D printing (really probably in 2009) just started in the tissue engineering field. When I bought my 3D printer for my lab, it was part of my faculty start up package; it was probably the best investment I made. But it was just being investigated as a tool for tissue engineering applications. It really expanded our ability to create more sophisticated and more mimetic devices for these applications. We soon found out that there were a very limited number of biomaterials that were compatible with 3D printing and ones that we can tune especially with regard to mechanical and biological properties. There really wasn’t much out there that we can use for different tissue indications so this motivated us to come up with these basic material platforms that can really expand the number of different materials that we can print and use for biomedical and now non-biomedical applications.

Tell me a little bit about tissue paper.

Shah: The tissue paper was really an exciting discovery in the sense where in the process of developing a new type of 3D printable ink, my then post doc Adam he was working with the ink and spilled a little bit becoming a 2D substrate paper-like material. Within that material it had extra cellular matrix derived from natural tissue. So this was basically a tissue that we processed to remove cells and the remaining tissue is called extra cellular matrix. It was processed and incorporated into the ink so it had a lot of different biological signaling that is specific to a particular tissue. When he showed it to me it was very flexible and easy to make because you can just make ink and then cast it into any 2D container. We can make a lot of different types of tissue papers for different uses.

Could you go a little bit more in depth as to what the potential uses are in humans?

Shah: I think the more immediate use of these types of materials could be for high throughput screening. So these are applications that are used outside the body. Drug screening for drug testing, so we can take say a patient’s cells cultured in a dish with the papers that are specific for a particular tissue type, for example liver or cardiac, and we can see how the patient’s cells respond on that substrate and in that environment in the presence of drugs. The tissue paper can serve as a more biomimic substrate for cells to grow and function before they do the drug testing to better predict how the drugs would work in the patient. Because we can make different tissue papers that are tissue specific, it really expands what researchers and scientists can do for testing different drugs. It also can be used for wound healing applications, whether that be externally or internally. For example, it could be used on the skin or internally as a cardiac patch; anywhere where you need to tissue to regenerate. Because it is highly surgically friendly surgeons can cut it to size, they can suture it to material, it’s flexible. It really can revolutionize what surgeons have in their tool box, to be able to regenerate tissue. Long term I think these sub straights can also be integrated into some of the more sophisticated scaffolding devices that we’re producing in our lab to create more complex constructs for multi-tissue regeneration.

You talked about the cells remodeling and the paper actually biodegrading, can you explain again how this would work within the system? So basically the paper goes away and then the cells are signaling it to start to grow and be part of your body?

Shah: Right, exactly. For tissue engineering in general the main goal is to provide a substrate or scaffolding so the cells can adhere and grow. They then degrade and interact with the material. The material itself sends the appropriate signaling and the cells then start to proliferate or expand in number, migrate, and start to deposit matrix of their own. In that process of remodeling you have degradation of the scaffold and signaling of cells to produce a specific biological response. Then over time the ultimate goal is to have that material completely replaced by natural functioning tissue.

Could it down the road go so far as to regenerate a whole organ, or is that something else?

Shah: For the tissue papers themselves most likely not because these are more 2D sub straights. But we have efforts in my lab to 3D print these tissue paper inks. And that can be then integrated into a more three-dimensional structure that is more indicative of 3D organs. Hearts, livers, kidneys; again when you think about trying to bioengineer a whole organ you can imagine how complex it can be. It is very complex and so it most likely will have to be a combination of different types of materials because there are different types of cells that respond differently to different types of signals. I imagine this technology being able to be integrated within those more complex devices.

How long before you think you will see this in humans?

Shah: I would say for the less complicated uses; for example wound healing, again as patches, I think within five to ten years. It really depends on the regulatory path and funding of course; and doing the necessary studies to prove its efficacy. For the more complex structures, definitely past the ten maybe twenty year mark. But the sky is the limit as far as where we can use these materials because of its versatility. Not just the different tissues we can use for biological signaling but also we can change mechanical properties that can then influence also the biology. There’s probably a lot of different multiple uses that we still haven’t even imagined that we can use this for.

Is there anything I didn’t ask you that you want people to know?

Shah: I think one of the major goals, as I mentioned, is to expand the number of materials that are compatible with simple extrusion based 3D printing platform. I think one of the things that this technology can do is really give access to different 3D printable functional biomaterials to a lot of people. Whether those are researchers or industry partners that want to integrate it into their product line, I think the versatility of these particle-based inks as well as in the hydrogel-based platforms that we’re developing in our lab really focuses on that. Really trying to give people a toolbox so they then can do their own research and find different applications and different conditions that are most effective. That really hasn’t been done before especially in this field of 3D printing, creating multiple different platforms that are very, very versatile. Also they can be integrated with each other so we can do multi-material printing with them which has been difficult in the past; creating different inks that can be printed together and as I mentioned you most likely need that capability for more complex tissue targets.

END OF INTERVIEW

This information is intended for additional research purposes only. It is not to be used as a prescription or advice from Ivanhoe Broadcast News, Inc. or any medical professional interviewed. Ivanhoe Broadcast News, Inc. assumes no responsibility for the depth or accuracy of physician statements. Procedures or medicines apply to different people and medical factors; always consult your physician on medical matters.

If you would like more information, please contact:

Kristin Samuelson

Kristin.Samuelson@northwester.edu

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