Engineering Vasculatures: Interview w/ Dr. Jordan Miller

Jordan Miller is an Assistant Professor of Bioengineering at Rice University and Co-Founder of Volumetric, a Houston-based startup focused on next-generation biomaterials and biofabrication technologies. Miller received his bachelor’s degree in Biology from MIT in 2003 and earned his Ph.D. in Bioengineering from Rice University in 2008. His primary interests combine synthetic chemistry, 3D printing, microfabrication, and molecular imaging to direct cultured human cells to form more complex organizations of living vessels and tissues for research in regenerative medicine. Precisely engineered in vitro systems at the molecular, micro- and meso-scale are well suited to decouple the relationship between tissue architecture and cell function. These systems are now permitting comprehensive closed-loop design and optimization of large-scale engineered tissues through refinement with computer models of mass transport and assessment of their therapeutic potential in vivo. Dr. Miller will be speaking at the upcoming 3DHEALS2020.

Jenny: What inspired you to start your career in bio-fabrication?

Dr. Miller: My first love in school was Biology, and I worked in all kinds of research labs to try to figure out what I wanted to focus on — ophthalmology research at Cedars-Sinai, fluid dynamics of fish swimming at MIT, and viral pathogenesis at Harvard Medical School. As an undergrad at MIT, I saw an intriguing talk by Professor Ioannis Yannas on how he was able to take collagen from cow skin and process it into a skin substitute for human patients with major burns over their body. The natural response to large area skin burns is the formation of scar (if you are lucky enough to survive the injury and can get enough graft material).

Professor Yannas’ work showed that his skin substitute could not only provide a near-limitless supply of skin substitute for human patients, but his engineered collagens completely prevented scar formation to dramatically improve the lives of burn victims. I was completely captivated; I approached him after the talk and asked if I could join his lab. I worked with him for two years in the Department of Mechanical Engineering and completed a small undergraduate thesis project on some of the pathophysiologies of scar tissue formation in response to injury. I was completely hooked on this idea of biofabrication — making novel materials and structures in the lab that can seamlessly integrate with the body and replace damaged tissues simply by encouraging resident cells to take a regenerative, rather than a reactive, response to the injury at hand. I’ve remained enamored with this idea ever since, and have built my career on this pursuit.

Jenny: How did you first encounter bioprinting? What was that experience like? What were you thinking at that moment?

Dr. Miller:

During my Bioengineering Ph.D. at Rice University, I learned about hydrogels — water-swollen polymer networks that closely matched the mechanics and water content of human tissue. The fact that they can be photopolymerized — converted from liquid to solid simply by shining the right color of light at the right intensity — I knew I wanted to study that phenomenon for my doctoral work. Our field was recognizing that the adage of “genotype leads to phenotype” — a cell’s genetic makeup leads to the cell’s behavior — is not a constant, but that cells are continuously sampling their surrounding environment or “microenvironment” and responding based on what they are able to sense. So, using my experience with confocal microscopy, we were the first group to utilize multiphoton polymerization to structure and pattern hydrogels containing living cells. It was an extremely powerful and high-precision technique, but I realized it wouldn’t have the fabrication throughput to build entire human organ replacements. So, I began looking to develop simpler techniques that were radically lower in cost, much higher in throughput and could work within the short timescales needed to keep human cells alive.

Photo Credit: Jordan Miller

Jenny: What motivates you the most for your work?

Dr. Miller: The fact that we have a national organ donation waitlist whose prospects continue to worsen has been a major motivator for my life. When I was 16 and went to get my driver’s license in California, I had to answer the question “do you wish to register to be an organ and tissue donor?” This one question changed my entire outlook. The realization that more than 100,000 sick people are waiting, often for someone else to die, so that they can receive an organ donation to live was shocking and transformative to my young mind. I described this in more detail in a TEDx talk in 2012, and it remains a constant drive in my life.

A more recent review paper highlights that if a ready supply of replacement organs was available, it could not only clear the 100,000 people on the organ donation waitlist, but millions of people worldwide that are not currently sick enough or able to qualify to be on that list, yet could medically benefit from an organ transplant, could be treated. The technologies we are developing have a real potential to extend human life expectancy worldwide.

Jenny: What are the biggest challenges in your current work? What are the potential solutions?

Dr. Miller: I laid out many of the biggest challenges in a recent open-access perspective article, and they still remain. One of the biggest challenges we have been focusing on is how to make a complete blood vessel network to keep millions, and eventually billions, of human cells alive. It’s akin to the challenge of designing a city for people to live in: we must architect discrete regions where the residents can live, but we also must build the fluid conduits — roadways for cities and blood vessels for living human tissue — that can be used to deliver nutrients and remove waste. We have invented advanced 3D printing approaches to address this challenge and are now able to make large scale tissue constructs for the first time.

Jenny: What do you think are the biggest challenges facing the bio-printing industry? What do you think the potential solution(s) is (are)?

Dr. Miller: 3D printing of plastics is already having a tremendous impact on the medical space — everything from custom braces for broken bones, prosthetic devices, medical implants, and anatomical models to help with surgical planning.

For Bioprinting, which is more in its infancy, the challenges are finding the right way to bring the technology to market given that human clinical trials are probably still at least 5-10 years away. No one is doing large animal studies with whole organ bioprinting yet, because that large yet intricate structure simply cannot be built just yet. However, I believe the technology we and others are developing are now at the maturity where most of the research is done. We are more at the development stage, pushing current technologies to larger tissue volumes, with higher speed, and higher precision than was possible just 5 years ago.

We have to find the right cell sources that can be seeded into these tissue constructs or entrapped directly, but a lot of people working with iPS cells are doing just that. Finally, the prospect of building 3D printed tissues with human cells has a unique opportunity to engage with regulatory bodies such as the Food and Drug Administration (FDA) that will ultimately oversee and ensure the safety of human recipients.

The hyphae crispata 1 from the ‘Growing Objects’ exhibition that inspired Jordan Miller | Credits: Nervous System

Jenny: If you are granted three wishes by a higher being, what would they be? 

Dr. Miller:

An end to disease and suffering. Achieving the full potential of each individual, and indeed all of humanity is held back by biological and social issues that if obviated would bring about a dramatic acceleration of our collective progress. Volumetric’s technology is most directly applicable to this goal.

Plentiful and low-cost of clean energy. Access to energy will further underlie humanity’s access to education, healthcare, and quality of life. And clean energy may provide for such progress without a heavy toll on the worldwide ecosystem.

Interplanetary travel for humans. Exciting progress is being worked on in this space right now!

Jenny: What advice would you give to a smart driven college student in the “real world”? What bad advice did you hear that they should ignore?

Dr. Miller: I often share with trainees the wisdom of Professor Bob Langer: the single most important subjects to study are the fundamentals of your chosen major. If you become deeply specialized too early, it not only limits your future career options, it also can limit your ability to think critically and solve problems creatively or efficiently. For these reasons, I believe that often complained-about “breadth” classes are just as important as “depth” classes in college, as well as at later stages of education like graduate school. Even if you are a senior executive in a highly specialized field, it’s still important to keep up to date on what’s happening in other fields because their approach to problem-solving may help you break through your own perceived roadblocks.

Jenny: If you could have a giant billboard to promote a message to millions and even billions of people in our community (i.e. 3DHEALS community), what message would that be?

Dr. Miller: Register to become an organ donor today. 3D bioprinted organ replacements are still 5-10 years away from a first-in-human safety study, and there are more than 100,000 people in need right now. Checking one little box can positively impact the lives of up to eight other people in need.

Jenny: What were/was the best investment you made in 3D printing/bio-printing/bio-fabrication?

Dr. Miller: Diving into the RepRap project back in 2009 was my single best investment of time and money. I learned all about the power of open-source hardware and software, and I engaged with a worldwide community of thinkers and tinkerers who were able to help us progress our work on 3D bioprinting. We continue to be actively engaged with the worldwide open-source community, and this ethos is even permeating back into basic Science with the so-called “Open-Science” movement. The term “Open-Science” should be redundant… Science is supposed to be open! It’s very exciting to see the scientific community embracing this area and making their data available for others to review.

Jenny: What were/was the worst investment you made in 3D bio-printing/bio-fabrication?

Dr. Miller: We have generally steered away from what I would consider poor investments in this space – we buy open technology platforms, not appliances. The field is way too new for closed systems to provide the fuel we need to progress the field. Volumetric is listening to user feedback, and we have open-sourced our software platform to help provide for the future of this amazing field.

Jenny: What was/is the biggest risk you took in your career?

Dr. Miller: Moving from Biology to Bioengineering was a big risk for me at the time, not many people make that jump successfully. But I believed in myself and followed my interests and passions, and I remain captivated each and every day by the power of applying engineering principles to solving some of the biggest challenges in Biology and Medicine today.

Jenny: What do you enjoy in your spare time? What are you passionate about outside of your work/3d printing?

Dr. Miller: 3D printing! Designing and visualizing new blood vessel structures is actually a hobby of mine, and 3D rendering and animation with the open-source program Blender have helped us to communicate our work to a much larger audience. I also enjoy the outdoors — hiking, swimming, exploring so much of what Nature has to offer.

Jenny: What is your favorite quote? Why?

Dr. Miller: “The best way to predict the future is to invent it” — Alan Kay. This quote says to me that there’s no point in sitting back in an armchair and trying to be a prognosticator. It’s much more effective to actually work at the cutting edge of technology and become a driver for the future of humanity through personal effort and innovation. Teams working together towards a shared vision can do this even more effectively. I’ve been lucky enough to participate in several widely regarded innovations in my career thus far, and it’s been extremely gratifying to see our hard work extrapolated into new futures that couldn’t be imagined before, but now we and others believe are within our grasp.

Jenny: What does the word “3DHEALS” mean to you?  =)

Dr. Miller: The human body contains the most complicated structures in the known universe. These structures, such as the intricate three-dimensional blood vessel networks of the body, critically underlie human physiology. I see 3DHEALS as a summary that the best way to heal the human body is to better understand this 3D architecture and replicate it in a laboratory and, eventually, a clinical setting. If we can make replacement organs for people, made from their own cells, we can treat literally millions of people worldwide and extend overall human life expectancy. 3DHEALS will move the current medical paradigm of “one size fits all” to a highly personalized experience of precision medicine where “one size fits one”.

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