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Translational Science Q&A: Tissue regeneration and artificial airway design with Dr. Eben Alsberg

Eben Alsberg, Richard and Loan Hill Chair Professor in the biomedical engineering department has recently received several accolades, including induction into the National Academy of Inventors 2022 Class of Fellows, being selected for the Tissue Engineering and Regenerative Medicine International Society Senior Scientist Award and earning UIC’s 2022 Distinguished Researcher of the Year award in the Natural Sciences and Engineering.

His team, the Alsberg Stem Cell & Engineered Novel Therapeutics (ASCENT) Lab, focuses on engineering functional biologic replacements to repair damaged or diseased tissues in the body. In 2020, his tissue engineering work helped inform a CCTS pilot project, Engineering an in vitro high-throughput drug discovery platform for COVID-19. That proposal aimed to develop a laboratory generated airway wall model for drug development for COVID-19 and other respiratory diseases. The resulting technique has the potential to offer better protection from respiratory health problems to people around the world, and it opened the door to entirely new areas of research in the lab.

Alsberg spoke about the work that laid the foundation for his CCTS pilot, shared his aspirations for future tissue engineering efforts, and imparted some lessons he has learned along the way.

The ASCENT lab

Q: Your COVID-19 drug discovery project sprang from your existing work in tissue regeneration and artificial airway design. Why does the world need artificial tracheas?

There are thousands of people worldwide who experience trachea damage each year. This damage can lead to stenosis, a condition where the trachea narrows and a person struggles to breathe. If the damage is substantial, it can lead to a very limited quality of life or even death. There are a few surgical procedures- like laser-assisted tissue removal, insertion of an airway stent, or tracheal dilation- that can provide short-term relief, but often the trachea closes off again over time and requires additional treatment. Tracheal resection and construction provides a successful long-term solution, but it is not an option if the tracheal tissue damage is extensive.

We are always very excited to try to engineer technologies and strategies to regenerate and replace tissues for those that have lost them due to injury, disease or congenital conditions. Those who need artificial tracheas are a more limited population compared to some of our other work, but if you are among the thousands who are suffering from this condition, you could benefit greatly from an actual living tissue replacement.

Q: You were studying the use of 3D printing for tissue generation for some time. How did this inform your work in airway modeling? How did other knowledge from previous projects help kickstart your COVID drug discovery project?

Our lab had focused some of effort into engineering model tissue systems, and we thought we were getting to a stage where we might be able to use either healthy tissues or pathologic tissue models to study drug therapeutics.

At first, we were trying to engineer tissue for tracheal replacement in adults and children. Our initial strategy involved making donut shaped cell condensation tissues using molds and then assembling them into multi-tissue type tubes. This work was funded by an R01 grant that ended this year. About 6 years ago we developed a strategy that may enable us to use 3D printing technology to make these cell condensation constructs. 3D printing is easier and faster, enabling higher throughput, while also enabling spatial control over the architecture of the tissues we are engineering. Therefore, recently we’ve been applying the new 3D printing strategy to engineering the trachea. We also have a couple of additional other model systems we’ve been developing for engineering the trachea.

When the COVID-19 pilot call came from the CCTS, I thought this would be a great opportunity apply aspects of these systems for drug screening. It would have been difficult to make a compelling story for a pilot project without having quite a bit of preliminary data, so we took the technologies and models that we had in hand to try to apply it to this problem.

Q: Where does the study stand now? What are the next steps in translation?

Having better tissue models that can be fabricated easily and in high throughput will enhance the ability to test drugs to treat diseases such as COVID and beyond, which would substantially impact the health of people around the world.

We are still strongly pursuing our tracheal engineering models, both for studying development and disease therapeutics in vitro, but also as a tissue replacement therapy. We received a grant this year from the Department of Veterans Affairs to fund our trachea bioprinting research. With this funding, we are planning to try some of our 3D printed cell condensation constructs in a rabbit model to determine the efficacy in restoring and maintaining an open airway for extended periods of time.

Once we have a promising preclinical in vivo animal model data, we will either create a startup company or identify a larger venture to license the technology and pursue clinical trials to get this technology to patients.

Q: Challenges are inevitable in any project. What issues have you encountered and how did you overcome them?

A common challenge within academia is continuity and technology transfer within the lab. Finding someone who can step in and continue to operate within the timeframe attached to a grant is very difficult to address. Staff turnover led to a change in direction midway through the project. The project lead got an incredible position at a startup company and needed to transition away. The team member who stepped into this vacated role had been focusing on different strategies that we thought might have advantages over our original approach. I was thrilled that the departing researcher had secured an exciting new professional opportunity, and while we miss having him in our group, the transition forced us think about the project direction in a different way. While we collaborate with labs across the country and internationally, we also collaborate within our own team to not only bring in a variety of expertise and ideas, but to ensure that more than one person is acquainted and knowledgeable about the different projects. In this way, there is always someone who can continue to push our discoveries forward if there are changes in team personnel.

Q: On the topic of lessons learned, what advice would you give to another translational scientist?

I would say, identify a problem you are interested in and can be passionate about and dive into it. Find the right collaborators to pursue the problem and surround yourself with varied expertise. Regenerative medicine and tissue engineering are very multidisciplinary. These fields involve diverse areas, such as cell and developmental biology, genetics, material science and polymer chemistry, mechanical engineering, bio-transport,  and AI and machine learning. There is no need for any individual to become an expert in all these different areas. Rather, find people who would make good team members and fill the gaps within your strategy to make things work.

There is very little science out there that is entirely novel; we are all standing on the shoulders of others. So, build upon the most promising strategies to take things to the next level and hopefully obtain a strategy that works and could lead to the next generation of therapeutics.