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Aric Lu on Breaking Biology by Bioprinting Complex Tissue

The Humans of the Wyss (HOW) series features members of the Wyss community discussing their work, the influences that shape them as scientists, and their collaborations at the Wyss Institute and beyond. 

Like each cell in the body, each paddler in a dragon boat plays a specific role. In both cases, each has different characteristics and strengths, but all must work together in tandem for the boat, or the body, to function. Aric Lu knows all of this from firsthand experience. Not only does he enjoy racing dragon boats in his spare time, at the Wyss he is using genetic engineering and bioprinting to form complex tissues made up of the large variety of cells found in humans. Learn more about Aric and his work in this month’s Humans of the Wyss.

What are you working on?

Aric Lu on Breaking Biology by Bioprinting Complex Tissue
Aric Lu, Ph.D. Student. Credit: Wyss Institute at Harvard University

We’re using genetic engineering and bioprinting, in a method we’re calling orthogonally induced differentiation, to form tissues that have the various types of cells you’d find in the human body. To do this, we are using induced pluripotent stem cells or iPSCs, which are derived from adult cells and engineered to take on the properties of stem cells, so they can be transformed into different types of cells. Current protocols using iPSCs rely on signaling molecules and can only give us a certain number of cell types. Without all types of cells, tissues lack some of the key processes necessary for organs to form and function. To overcome that barrier, we’re using genetic engineering to force iPSCs to become even more types of cells, like endothelial cells or neurons.

Next, the bioprinting comes in. We can create different printing “inks” made of living cells that are genetically engineered to become the cell types we want. Then, we use multi-material bioprinting to print all of these inks together to create specific patterns within tissues.

What real-world problem does this solve?

If we could one day use genetic engineering and 3D bioprinting to create tissue to repair or replace an organ, that would be incredibly valuable for people with a variety of diseases, including those waiting on transplant lists. However, to get to the point, we need printed tissue that can behave like human tissue.

This image shows an organoid structure generated from iPSCs using orthogonally induced differentiation that were programmed to create an organized structure with a vascular network (red) and neuronal cells (blue) similar to those found in the brain cortex. Credit: Wyss Institute at Harvard University

Some of the cell types missing from current iPSC protocols, like endothelial cells, are critical for organ function. Prior to our current work, when we created neural tissue, we’d get no endothelium. The endothelium makes up the inner cellular lining of blood vessels and lymphatic vessels – it’s necessary to form the capillary network that’s required to sustain the tissue and keep it alive. By using orthogonally induced differentiation, we can actually create these networks. In the future, we could use them to push blood or lymphatic fluid through these vessels to deliver crucial nutrients to tissues. We’re not at that point yet, but this is a huge step towards making functional tissue.

How do you get into this field?

My undergraduate degree is in electrical engineering. During my studies, I was 3D printing electronic components, like antennas, and using electronic metal inks to create devices. When it came time for graduate school, I had a really cool opportunity to apply for something that was, at the time, called the Draper Fellowship (now Draper Scholarship). They invited me to switch from electrical engineering to bioengineering because of my 3D printing experience. I agreed, and that’s how I ended up getting into tissue engineering and 3D bioprinting.

What continues to motivate you?

There’s lots of interesting challenges that arise in using 3D printers and building tissues. I come across so many different problems, and it’s fascinating to tease apart all the factors that go into making these tissues function. For instance, how do we get all the cells to stick together? How do we build other systems to culture these tissues once we can make them? Searching for these solutions is what gets me in the lab every day.

What excites you the most about your work?

We’re kind of breaking biology with what we’re doing. It’s not so much that the cells can’t do it, but we’re trying to use biology in ways that don’t happen naturally. We’re using genetic engineering to force a cell to become a specific cell type instead of letting it go through the natural development process. The biology is there, but we’re also creating something new. That’s incredibly interesting and motivating.

We’re kind of breaking biology with what we’re doing. It’s not so much that the cells can’t do it, but we’re trying to use biology in ways that don’t happen naturally.

Aric Lu

What are some of the challenges that you face?

Coming from an electrical engineering background, I learned how to do cell biology and cell culture later in my academic career. I had to teach myself what all of these different experiments are looking at and how to incorporate them into my research. Then, it’s another challenge to bridge my 3D printing experience with the fields of genetic engineering and biofabrication. Where does the genetic engineering inform the 3D printing? Where does the 3D printing inform the genetic engineering approaches we can use? I’m finding a way to create something that’s more than just the sum of its parts.

What is unique about the Wyss and how has it impacted your work?

Before I applied for graduate school, I’d never heard of the Wyss Institute. Once I joined Jennifer Lewis’ lab, I was exposed to this whole ecosystem. I’ve collaborated with members of George Church’s lab on the genetic engineering aspect of my work, and I’ve gotten to see the dynamic environment here through events like the Wyss Retreat.

Being part of the Wyss exposes me to a variety of ways of thinking about engineering and biology.

Aric Lu

In addition to providing opportunities to collaborate, being part of the Wyss exposes me to a variety of ways of thinking about engineering and biology. It’s great to see all the projects happening and try to understand the science behind them and their potential impact. There is always somebody here that’s doing something totally different than what I’m doing that I can talk to and learn from. Even if it’s not directly related to my work, it’s always good to have in the back of my head because I never know when I’ll face a similar problem that they can help me solve.

How have your previous experiences in electrical engineering and as part of the Society of Asian Scientists and Engineers (SASE) shaped your approach to your work today?

Because my undergraduate degree was in electrical engineering, I’m always thinking about the physical nature of what we’re doing and I approach biology from an engineering mindset. I think of the cells as sort of a system. I can treat them with something – a molecule or genetic engineering, and that’s the input. Then I see what the result, or output, is. With that framing device, I try to understand how my input relates to my output.

When I was in undergrad, SASE was focused on developing Asian American talent in the sciences and in engineering with the goal of trying to train us and prepare us to become leaders in these technical communities. Part of the mission was to break the stereotype that Asian Americans are excellent at doing technical and scientific work but aren’t good at managing teams or leading projects. A lot of the activities involved getting us to connect with big companies, like General Electric or Raytheon, understand their management structures, and even get us into some of their leadership training programs once we joined the workforce. I chose to continue my studies, so some of that information on infrastructure isn’t quite relevant now, but what I think SASE did for me was gave me the confidence to pursue ambitious projects and lead them in directions that I think are best. For a few years, I volunteered with SASE to help students organize SASE chapters at their schools, and I remember many of the lessons I learned about organization and planning from that time. I’m still in touch with many of the friends I made in SASE!

When you’re not in the lab, how do you like to spend your time?

Aric Lu on Breaking Biology by Bioprinting Complex Tissue
Aric running a marathon in Washington, DC in 2022. Credit: Aric Lu

I ran my first marathon last October in Washington, DC and right now I’m training for another one. I want to see if I can improve my time from last year. Running is a nice, Zen moment where I can disconnect entirely from the world. I don’t usually bring my phone or listen to music. It’s nice to disconnect from your own mind and just take in what’s going on around you.

The other thing I enjoy doing is dragon boat racing. I’ve done it in the past with a friend’s company and this year I plan to join Harvard’s dragon boat team. A dragon boat is a long boat of traditional Chinese design that’s operated by a large crew of rowers. It’s typically designed to look like a dragon.

What is something fun about you that someone wouldn’t know from your resume?

There was a very short period of time, early in the pandemic, where I thought about becoming a Twitch streamer. I was stuck in my apartment doing nothing, and I thought it would be fun to go on Twitch, play video games, and engage with the community there.

If you had to choose an entirely different career path, what would it be?

My answer to this question changes anytime someone asks it, but right now I’d say being a video game developer or designer. When it’s raining outside and I cannot run, I play a lot of video games. I’ve always been really fascinated by the idea of making my own video game, building new worlds, and trying to create something that’s fun and engaging for other people.

What does it feel like to be working on cutting-edge technology that has the potential to have a real and significant impact on people’s lives and society?

I’m doing this work because I think it’s really engaging and technically interesting. What drives me is the day-to-day work and how we can continue to improve these technologies so they reach a point where we can start thinking about how to put them in a person. Right now, it’s not quite ready. My attention is on what steps we need to take to get there. However, it is cool to occasionally think about the fact that this could one day give someone an extra few years, or even decades, of life.

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