Dr. Maribel Vazquez is a biomedical engineering professor at Rutgers New Brunswick. She researches microfluidic devices and how to apply them to the nervous system, most specifically to the retina.
Q: Just in simpler terms for our viewers, can you give an overview of your research and its applications in the medical field?
A: I’m a mechanical engineer by training, even though I’ve been a professor of biomedical engineering for 20 plus years. So we build in vitro and ex vivo systems to study how we can develop new therapies or increase the efficacy of existing therapies. I basically make devices out of plastic. These microfluidic systems are defined as systems that have one side that’s less than one millimeter, which is 1000 micrometers. To give a scale, one human hair is about 80 micrometers thick.
We make devices that mimic the retina in terms of scale. So they’re shaped in the same size as the retina. And we apply different types of chemical, mechanical and electrical fields across retinal cells in these devices to see how they behave. We are particularly looking at how these cells communicate with one another. So how they cluster and how they adhere to different types of matrix that are biomaterials that can be used for transplantation of stem cells. We also observe how they respond to electric fields being whether they become more active and there are different types of signaling talking to one another or to the matrix. And if that can help their migration as they’re transplanted into the eye to get to where they need to go to reactivate the circuit to.
What we hope to have is to cure blindness. That is the goal. We work on age-related conditions, specifically diabetic retinopathy and macular degeneration, often age-related macular degeneration, AMD, which are two of the most common sight threatening diseases in the United States and worldwide. I think everyone deserves the privilege of vision.
Q: It is obvious that you’re very passionate about your work, and it has so many possible applications. But what is your next step?
A: So we are currently working on two different projects. One is to study diabetic retinopathy, in which we have some therapies that work remarkably well for some patients, but not at all for others. Those are intravitreal injections of vascular endothelial growth factor. It’s used off-label in the eye. It was developed to stop abnormal blood vessel growth in different parts of the body. And in the eye, when we have too much, when we have high glucose, in the case of diabetes or chronic conditions over a lifetime, doesn’t happen in one year, about a third of all adult diabetics will develop some type of diabetic retinopathy because of the chronic conditions of high blood glucose. So in this project, we’re trying to understand how molecules, whether it’s pharmacology or sugar or different molecules, transport from the blood into the retina and how those molecules then affect the different types of retinal cells that are supposed to fix the retina, which are called glia, or the actual neurons themselves to continue the neuronal circuit for vision. We work with collaborators from the medical field for live animals and hopefully humans eventually to make a nice microfluidic device to study the transport molecules from one cell type to another under different types of flows.
But to get that really into the clinic, we need to work with ophthalmologists who actually deliver these injections.So if they do a surgery, once they put the incision, how can we put an electrode there that won’t hurt the patient, and actually improves the therapy?
For the other side of the run, I’m looking at macular degeneration. So this is when the cells die and we’re transplanting stem cells. Same thing. We really need to work with surgeons because there’s only so much we can do in vitro. So we’re doing things in glass to mimic the eye. And then eventually we actually enucleate the eyes of different animal models, starting with rodents, to see if the results can be mimicked with an actual eyeball. We need an ophthalmologist with the surgery to help us see what’s possible and what electrodes we can implant. We have to make them, can we buy them? What electric fields can we use in the eye without hurting the rest of the patient?
What is interesting here is that there is a lot more non-human testing required. A lot of other research has much more direct paths to human testing due to lack of capability to test in other methods, or previous research confirming safety. Dr Vazquez’s work is extremely innovative, but must be approached carefully because of the lack of precedent.
Q: What is the main technology involved in your research?
A: Essentially, the same process is used for computer chips, just photolithography, is the one we use. And that, of course, gives you very nice features that are very small, close to one micron. And now over the last 20 years, we’ve developed different types of technology for microfabrication. So we don’t need the expensive clean rooms. We can do this out of polymers. PDMS is a big one because cells can survive on it. But even more recently now in my lab, we’ve been able to make things out of acrylic and actually laser print things on acrylic. So it’s much faster, much cheaper, much safer for the researchers to actually make the devices. You can go from a device in your head to sketching it out and doing the equations to getting the right sizes to then just 3D printing it and testing it and then maybe making it an acrylic or making it a different polymer without having to go into the clean room and use this series of horrible acids that can hurt you.
Q: Do you face challenges working with the nervous system and eye?
A: What’s very cool about the eye is that it is immune-privileged. The very back is the retina, which is connected to the brain through the optic nerve making it separate from the nervous system. We can actually do many different therapies. We can survive if our eyes are removed. We can. So it’s not life-critical. Plus, we have imaging, in which we can actually see what’s happening in the back of our eyes with blood vessels and other things. It’s not the same as, let’s say, getting something delivered into the frontal cortex of the brain. So that eliminates a lot of issues in terms of the brain science working for the eye.
This is very interesting to consider when looking back at our interview with Dr. Cynthia Chestek. While she worked with interfaces connected directly to the brain, which led to higher risks and much higher chances of incompatibility with metals from interfaces, Dr. Vazquez’s research is much lower risk even though it involves the nervous system.
Q: How is your work compatible with the body?
A: So we’re using plastics to study the effects of the external fields on the cells. When we are implanting or transplanting, it is with biomaterials. So it is things like laminin, hyaluronic acid, things that are already in our bodies, collagen, so that you have a higher chance that it will not be rejected by the body.
Dr. Vazquez mentions that working with such small and easily printable systems, a lot of devices must be printed for her work. However, in the case of failure, it is easy to redesign and print new devices due to low printing costs.
She proceeds to explain the difficulties of transplanting cells, saying “you can put a million cells in the eye, and they did this about 15 years ago and 99 % of them died. Then you have just a few of them that migrate in the retina and that’s not enough to return vision. So how do we get the cells to survive when you put them in the eye and then migrate out so they’re in the actual eye, not just in the biomaterial that you use to transplant them. And that goes a lot to understand what the adult environment is rather than the stem cell environment. Our eyes are very different as young adults and beyond than when we’re in utero. And when our nervous system is developing. So we’re taking these developing cells and putting them in an adult retina, seeing completely different signals than what it’s used to and how that cell responds. We still don’t know.”
This next section addresses the humanitarian and societal impacts and factors of Dr. Vazquez’s research. Let’s dive in!
The reason that I am a professor of biomedical engineering is because I wanted to use my technology for impacting human health. When I was in industry, my technology was just cheaper, better, faster, and shipped out more computer chips to get slightly more money from stocks of the company. That, to me, was not satisfying. When I was in my 20s, I said, “This is fun, but after a few years, I want to do more with this technology”. So the health disparities angle for me is why I became a biomedical engineer.
Health disparities are defined as differences in health outcomes between certain groups, dependent on nonmedical factors. So things like income, socio economic status, whether biological sex, age, things like that. And so what I found, and I started becoming a biomedical engineer, particularly in vision loss. Vision loss is very complex and you can lose vision from different parts of the eye and different people lose vision from different parts of the eye. So I mentioned it’s typically age related. If you’re older, it has to do with chronic degeneration. But there are certain diseases that affect women way more than men, biological women and biological men.
What we’re studying is if this is a factor of changes in estrogen. Is this a factor of not having a Y-chromosome? And so I study the health disparities from a biological angle of can we have an engineering system that is very specific to a group of patients that are being underserved. Why are we making a therapy for everyone who has vision loss when different groups suffer from different diseases disproportionately? And some therapeutics who are great for one group but not for another. There’s a lot of research in social science and community health to uncover societal factors, but there’s not much for the medical factors and the biology factors.
This is an extremely interesting point Dr. V brings up, and we agree. Why is it that medicine does not target the struggles faced by specific groups and rather tries to create a one fits all medicine? Is this something you as an audience would like to learn more about?
There’s a lot of excellent work from other collaborators and colleagues looking at sex differences in not only the cells, but in the extracellular matrix in our bodies. And so we’re just starting to understand how the lack of the Y-chromosome would lead to different markers and different responses in cells than if you have the Y-chromosome. And so it’s… For the sex based differences, it really is saying, okay, it’s looking at what everyone is doing and saying, hey, I need these types of cells for my system. And we’re certainly getting there for development of pharmacological things or developing a treatment regimen using perhaps the same pharmacology. In terms of the transplantation for the stem cells as well. What do we consider for stem cells? There have to be other factors in the stem cell that would integrate into an older woman rather than a younger man, for example.
Q: What has been the response you have had from the medical sector?
We absolutely need the physicians, we need the surgeons for this. You don’t want me near your eye at all. I should not be cutting your eye in any shape or form. I think the medical community, particularly ophthalmology, has always been very receptive to new technologies of all the medical fields. Ophthalmology has been one of the first to say, let’s try this new type of imaging and look at that. It works really great. And so they’re very receptive to it. But making that transition is finding ophthalmologists who are clinical and also do research.
If you have to find someone who really has a balance in research and clinical, and that’s hard across every field. But because of the way health care is in our country, it’s particularly difficult in ophthalmology given the age related diseases.
Q: What about patient response?
A: Unfortunately, the medical field has a bad history of using electric shock therapy for different patients. So it’s changing. But I think because we’re all very comfortable with small electrodes now. You can buy electrodes and put them on your hand to fix scarring and things like that. The more people are exposed to conventional things, commercial devices that they can buy and say, Okay, that didn’t hurt me. They said, Okay, now with a surgeon doing a surgery, he said, This doesn’t hurt you. You can buy it yourself from CVS. It’s very similar. Now we can put this in your eye.
Q: Finally, How do you involve students in your work and foster the next generation of researchers?
A: Students do the majority of the benchtop experiments. I just write the grants to get funding so that we can do research. I’m the mentor. So I help the students learn how to make the devices, how to validate the devices, how to design the devices, and how to do experiments with the devices. In my lab, I have PhD students all the way down to undergraduates who just learned how to culture cells, how to make the devices in plastic, how to laser print devices, and how to image them in a microscope.
It’s more of the interest in these particular types of cells and what stimulus do we want to do? Do you like electric fields? Do you like doing different cocktails of chemicals? Or do you like making new biomaterials? Do you like changing the biomaterial? That’s more the question of where my students are, where their interests go in the project.
Dr. Vazquez ends her extremely informative interview with a message that resonates with our mission. For high schoolers, you have to get your hands wet and try different things. See what you like, and explore what research can be. We hope these stories that we bring motivate you to try a new form of research, and we look forward to what you innovate!