Innovating and developing tissue engineering beyond replacement: a podcast with Guillermo Ameer

[00:06] Kadeja Johnson: Hi, I’m Kadeja, a digital editor of RegMedNet and today I’m joined by Guillermo Ameer,  Professor of Biomedical Engineering at Northwestern University. Thank you for agreeing to undertake this podcast interview with RegMedNet. Before we start, please, would you mind introducing yourself and telling us a little bit about the research you focus on?

[00:29] Guillermo Ameer: Sure. I am Guillermo Ameer. I am a professor at Northwestern University in the Department of Biomedical Engineering and the Department of Surgery. I run a lab on regenerative engineering, biomaterials, drug delivery.  I’m also in charge, or I’m the director, of a new initiative here. It’s a university-wide effort. It’s called the Querrey Simpson Institute for Regenerative Engineering at Northwestern University, or RENU. And I’m also the director of several other programs that try to foster and disseminate the new field of regenerative engineering.

[01:04] Kadeja Johnson: Thank you for sharing that. It’s great to hear about your experience and the initiatives that you have started and curating. You have a lab, Ameer Lab, that has pioneered the development of citrus-based antioxidant biomaterials for applications like regenerative engineering, drug delivery, and cell delivery. Could you provide a refresher on how this technology works and elaborate on its versatility across these applications?

[01:31] Guillermo Ameer: Sure. So the foundation of my lab, my laboratory, is the development of new materials, new biomaterials, that will help promote our body’s ability to heal on its own. So when I first started 20-something years ago, there were no materials that were, for example, elastic or rubber-like. Rubbers are permanent. They don’t biodegrade. And back then, the field of tissue engineering was relatively new and growing. And the premise behind that field is that you use a temporary scaffold, you seed it with cells, and you provide certain signals, biological signals, to then be able to regrow a particular tissue or organ, either in the lab and then implant it into the body, or maybe perhaps use the body as the environment to grow that tissue or organ.

The challenge back then, however, was that because I was interested in tissues that are normally elastic, such as, for example, tendon, muscle, skin, in fact, most of our body is elastic, and there were no materials that had those properties. I had to be creative and come up with new materials that could do this. And we did this by using this molecule called citric acid, which happens to be very ubiquitous or very common throughout our body. It’s involved with our energy metabolism. It’s actually involved in many things that we do in our daily lives. It’s been around for thousands of years and used by humans.

We use it in food products, hair products, beverages, skin products, and so forth. So it was very safe. And that was the core discovery, that we could use that molecule, react it with pretty much an infinite range of other molecules, referred to as alcohols, could be vitamins, amino acids, and then we create materials that have these unique properties that include antioxidant properties. And, in fact, it’s very similar to vitamin C or vitamin E, which we take as a supplement to try to stay healthy, especially during a cold. We can now do this with materials that we use to design devices that would go into our bodies. And these devices are places where we allow our tissues to grow and become targeted organs.

[03:45] Kadeja Johnson: Thank you for explaining that so well. What do you see as the most exciting advancements in the field and how is your lab contributing to these innovations?

[03:54] Guillermo Ameer: Sure. So, as you know, one of the challenges in healthcare or in society is the lack of organs for people who need organs. It’s a long list of people waiting for an organ replacement. There’s also trauma. There’s also cancer. There are many diseases that damage your tissues and your body. So, this field of regenerative engineering is an interesting new way to look at this problem in order to develop technologies and potentially products that can help us overcome some of these challenges. So, for example, our work has been applied to bone regeneration, cartilage regeneration. Cartilage, obviously, as you get older, your knee joints start to suffer. You know, cartilage starts to degrade. It doesn’t come back. So, it would be nice if you had ways to be able to replace that cartilage with cartilage material rather than plastics and metals, right, as in artificial knees or artificial hips. So, we can have an impact in musculoskeletal tissue reconstruction surgeries.

We’ve shown also that our materials can have an impact in vascular or heart applications where you want to basically either create or use a new blood vessel in order to allow your blood flow to restore, your blood vessels to restore perfusion to a particular part of your body, or you need to prevent your heart from becoming too large after a heart attack, which could lead to chronic heart failure. So, we’ve given examples throughout the years of how our materials and others as well can use these type of concepts to help slow the progression of disease or straight up replace tissues and organs where needed. We’ve also been successful at doing this for kids potentially. We haven’t done it in humans yet, but we have data, and we’ve shown that we can regenerate bladder tissue.

That would impact kids that have, for example, a disease called spina bifida where they have a congenital defect in their spinal cord when they’re born as babies, and then when you do that repair surgery, you can unfortunately affect the lower part of their bodies, including their bladder, which does not grow the way they should. And a lot of these kids can be a very devastating disease where they need catheters to urinate and so forth. They have to use intestinal tissue to reconstruct their bladders, make it larger.

So, we’re hoping to eliminate those procedures where you have to take one part of your body to repair another part, leaving you basically defective or with a lot of pain in that donor site. We want to be able to have materials that the surgeon can actually use off the shelf and get that tissue to regrow for that particular purpose. So, that’s the potential impact that this field can have in terms of health.

[06:41] Kadeja Johnson: That’s fantastic. Thank you for giving so many examples and for doing a really deep dive into that. It’s so extensive what we can do. And as you said, you want to prevent that donor discomfort by completely replacing it. So, it’s amazing. It’s incredible. What are some of the biggest challenges in developing biomaterials for regenerative applications? And you touched on it before, but how is your lab addressing them?

[07:10] Guillermo Ameer: Yeah. So, the biggest challenge for the field of regenerative medicine in general, so that when you go to the doctor, you need a ligament, you can give your a tissue-like ligament rather than harvest it from your own body or a cadaver ligament, is that the regulatory process, right? You have to get regulatory approval for these products. It’s a very extensive, very costly process. It takes a very long time to get that done. And it’s very difficult to get new materials through the regulatory bodies because there’s a lot of scrutiny to make sure it’s safe and effective, which is important. So, that’s a big barrier, right? Also, investment.

Investment that’s required into companies that are trying to develop these sort of new technologies is pretty high. And it’s not like AI or IT or social media type platforms where you don’t require a lot of funding, but you can get a lot of return for your money. That’s what you’re competing against, right? So, the investment profile is very, very different for our field. That can be a challenge. And that’s how do they pay for healthcare, right? In the US, it’s mostly driven by private insurance, right? So, that’s problematic. If the insurance company does not want to recover or pay for that particular product that can do these things, then the product is not going to be developed, right? So, there are many challenges, not just technical, but from a societal infrastructure point of view that must be taken into account.

[08:43] Kadeja Johnson: Thank you for sharing that. I think it’s so important that you mentioned the societal impact on it. Oftentimes, we talk about the technical challenges. So, it’s great to hear a different perspective on the socioeconomic impact that will have. It’s clear that you put a lot of thought into it. And also, the considerations that go throughout this whole process, it’s not just one, it’s multiple. So, leading off from that, how important is interdisciplinary collaboration in your research? And can you share an example of where such collaboration led to valuable progresses?

[09:21] Guillermo Ameer: Oh, yeah. So, interdisciplinary or cross-disciplinary collaboration is integral to what we do. So, in fact, regenerative engineering is a field defined as a convergence of advances in material sciences, stem cell and developmental biology, physical sciences, translational medicine, right? All coming together to develop the tools that will enable your body to regenerate tissues and complex tissues, organs, and improve your quality of life, right? So, that idea of convergence is intrinsically built into the definition of the field.

And what is convergence, right? It’s a deep integration of very different fields or disciplines that come together to address a grand challenge, a very big societal problem. So, I work with people that are in electrical engineering departments, that are material sciences departments. But most important, I also work with clinical scientists or clinical practitioners as well, people who see patients. And I talk with them. I understand what are their concerns, what are their problems. They also often come to me with problems that they see every day in their practice and try to understand how can we address those problems using technology.

So, those types of cross-disciplinary or interdisciplinary collaborations are important. But most importantly is this concept of convergence. So, really fully understanding the questions and the problems that each field has and understanding the benefits or the advantages that we can bring together in order to tackle that problem.

So, as an example, we published with Nature last year a device. I call it the electric nose. But it’s basically a device that can sense vapors, water vapor or organic compounds that come out of your skin.

It’s very, very sensitive. That was developed in the lab of Professor John Rogers. He’s a pioneer of bioelectronics, happens to be here at Northwestern University. With my background in regenerative engineering and applying these types of materials and bioelectronics technologies to medicine, we came together, our students came together, had discussions as a group. And again, coming from very different backgrounds, we were able to develop this device that now we can use to sense it. For example, there’s bacterial contamination in a wound, in a diabetic foot ulcer.

So, unfortunately with diabetic foot ulcers, which you often get if you’re diabetic at some point in your life, by the time you see the infection, it’s too late oftentimes. Now you have to deal with an infected wound. Wouldn’t it be nice if you could come to the doctor, come to the hospital, have a device at home that would sense that infection very early on and give you a warning, an alarm, something to go see your nurse, go see your doc, call someone.

So now that’s an example of an application of that type of technology, that device that came out of this interdisciplinary convergence approach to research.

[12:17] Kadeja Johnson: That’s fantastic. Wow. We never really see the behind the scenes of a lot of these research that gets published. And often it’s always labelled as a collaborative study, but we’re never really deep diving into just how collaborative it is. And for you to mention that you talk to clinical practitioners as well as like other interdisciplinary teams, it’s amazing to see how these great minds come together to tackle the problem. So thank you so much for going into detail and for providing that perspective for us. I appreciate your insight. And as a professor, how do you inspire your students and members of your lab to think creatively and push boundaries in their research?

[13:00] Guillermo Ameer: Well, I kind of hopefully inspired them by doing so. I try to do the best I can to walk my talk and do the best to show that when you reach out to colleagues that are in other fields and have these discussions and come up with creative ideas that you do as a trainee, you can do the same. You can reach out to other people that are training in other fields and talk to them, have these discussions about important problems that you might be able to solve together. So that’s step number one, for them to see that you’re doing it yourself.

And then, of course, step two is to show examples, to give them successful examples of other groups, other teams that are doing this type of collaborative convergence research. But most importantly, I think when you hear from potential patients, people who hear about your research and say, hey, I have this problem with diabetic foot ulcers and I’ve had an infection for six months. It doesn’t heal. Can you help me? Or you hear from the parent with a kid that has spina bifida with this bladder problem that I told you about. It says, you know, they tried everything. Now they have to do this surgery, you know, to cut them open and use intestinal tissue. When is your product going to be ready? Right. So that sort of thing, you know, hearing from the potential users, the people who need these types of solutions, I think often inspires the trainees to do their best and think creatively outside of the box.

[14:26] Kadeja Johnson: I really appreciate your answer and I love how you made it patient focused to really think about who is benefiting from the work that you’re doing. And I think that’s inspiration enough to always have the patient in mind. So thank you so much. And I’d love to hear more, which leads me to ask, what advice would you give students or young researchers who are interested in pursuing a career in biomedical engineering, particularly areas like regenerative medicine or biomaterials? What advice would you give them?

[14:59] Guillermo Ameer: I would say to them, you know, these are very exciting times with the types of advanced technologies that are being developed in these other adjacent fields that we borrow from or we work with to move our field forward. I mean, things are moving so fast. You always have to learn things every almost every other week or so you hear about a new technique or a new instrument that does something fantastic. So I think that that’s an exciting point, but also this idea of working together in teams with people from different backgrounds is a fantastic opportunity for you to not just learn from maybe only your field of interest, but you get to learn from other very smart people in their areas of interest.

So my advice is to, you know, ask the right questions, talk to people, talk to your colleagues. Always do your best to be excellent at everything you do. Just don’t do things halfway or just because you can barely get it done. And you have to be aggressive. You have to you have to you have to be creative. You have to be dedicated. You have to be first because it’s a crowded area. We’re not the only ones doing this kind of work. It is a worldwide effort. China is very strong as well in this kind of work. Japan, Europe is trying. So it’s a worldwide community. Right. So we have to be always thinking about doing our best and pushing ourselves. So to the younger people, I would say, you know, definitely is an exciting area because you can have impact.

We have products in the market that are in the bodies of thousands of people where you have to reattach a ligament or a tendon to bone, for example. Right. And these are progenitive materials, devices that did not exist, you know, three, four years ago. So this is brand new technology. So it is possible to see your concepts and ideas go from the lab or academic environment to a actual patient we can help. So we’ve helped athletes get back and do their best at what they do in terms of sports. People have torn their Achilles tendon, you know, or their ACL, for example. And then eventually we have products that are going to be helping you with the rotator cuff repair surgeries. Right. So I think it’s a it’s a it’s an exciting time where people recognize that there is a need for this sort of work and there’s a path forward to have an impact on people.

[17:57] Kadeja Johnson: Fantastic. Thank you so much for joining us. It was an incredible conversation that we’re having. And I’m so glad you decided to take part in this podcast interview with us. Thank you so much.