Every human body is a city, brought to life by trillions of cells working in a range of jobs. The heart cells keep oxygen flowing; the brain cells wire thousands of instructions; the liver cells filter out toxic materials. However, a trait all cells share is that—like a city’s people—they rarely work their jobs alone; bundled together as tissues, they accomplish more working together than they would as individuals.
For biologists, the differences between how cells behave on their own versus how they behave as tissues can add layers of complexity to studies that attempt to model human physiology in the lab. As such, tissue engineers like Wai Hon Chooi work to develop the biomaterials needed to artificially construct tissue models that accurately mirror those in living bodies. These innovations are also paving the way for regenerative treatments that replace the worn-out natural tissues behind many human health disorders.
Formerly a Senior Scientist at A*STAR’s Institute of Molecular and Cell Biology (IMCB), Chooi now holds an assistant professorship at the Duke-NUS Medical School at National University of Singapore (NUS), where he continues his work in developing 3D tissue models of the human nervous system. For this A*STAR alumni feature, A*STAR Research spoke with Chooi to learn more about his research on biomaterials at the agency and beyond.
Tell us about your journey in research.
I completed my bachelor's degree in bioengineering at Nanyang Technological University (NTU) and subsequently obtained my PhD degree in biomedical engineering at the University of Hong Kong, focusing on tissue engineering for bone and cartilage. Following this, I undertook a postdoctoral position at NTU, where I developed scaffold-mediated gene delivery platforms for nerve regeneration.
Along the way, I met fantastic mentors, supportive colleagues and talented researchers who inspired me to combine and apply my training to developing neural organoid models. It was a major focus during my time at IMCB and continues to be so to this day.
What was your time at A*STAR like?
At IMCB, I joined Shi-Yan Ng’s lab, where I not only worked with a group of motivated and talented people, but was given a lot of freedom to explore my ideas. Outside the lab, A*STAR and IMCB were also very supportive of early-career researchers, providing various opportunities for us to explore new ideas through grant support and exposure.
From my personal experience, A*STAR offered a wealth of opportunities for postdocs; in particular, the Career Development Fund provided me with added avenues to secure funding and hone grant management skills as a principal investigator. The agency also reviewed my grant proposal and provided me with feedback when I was applying for the Young Individual Research Grant (YIRG) by the National Medical Research Council (NMRC).
Besides these, A*STAR’s culture encouraged collaborations among junior researchers, fostering many interesting ideas and potential long-term partnerships, which I continue to enjoy. Furthermore, I benefited from A*STAR's training workshops and career events, as well as their efforts to increase the visibility of early-career researchers. These experiences not only honed my skills as a scientist, but also strengthened my credentials and helped build my repute as a researcher.
What have you been up to since leaving A*STAR?
I now hold an assistant professorship (non-tenure track) at Duke-NUS Medical School, where I work in Hongyan Wang's research group. Besides guiding junior lab members, my role is primarily research-focused. I’m using organoid models to understand neurodevelopmental diseases, with the aim of shedding light on underexplored pathways in brain development. Although it's still early days, my role makes me eligible to apply for higher-tier research grants as a faculty member, for which I am preparing.
Additionally, I’m continuing my NMRC YIRG-funded project, where I collaborate with Zibiao Li at A*STAR’s Institute of Materials Research and Engineering (IMRE) to develop organoid-hydrogel models to study the ageing process.
How could biomaterials be used in ageing research?
The field excites me because of its interdisciplinary nature: it combines biology, chemistry and engineering to solve challenging biomedical problems. Over the years, this field has advanced towards clinical translation, with tissue-engineered products already available in clinics to replace tissues such as bone and cartilage.
As people age, tissue damage becomes more common due to wear-and-tear or ageing-related diseases. Besides direct cell transplants, researchers have been attempting to create tissues from cells as a long-term solution for tissue replacement. By design, tissue engineering strategies that combine cells with biomaterials and signals offer advantages by closely mimicking native tissues. This mimicry not only improves tissue regeneration and transplant grafting, but protects the transplanted cells. Excitingly, many of these advanced approaches are currently in clinical trials.
Besides this, tissue engineering and biomaterials have greatly improved the in vitro models we can create. In 2D or animal models, it can be difficult to observe the intricate and complex ways that our intercellular and cell-extracellular matrices interact, yet these may hold the keys to understanding ageing processes on a tissue level. But now, we can produce 3D models that are more representative of human tissue, opening the door to clearer views of tissue development, ageing, degeneration and disease; and paving the way for effective therapeutics.
What was a memorable biomaterials project you worked on at A*STAR?
One of my most memorable projects involved developing defined hydrogels for spinal cord organoid (SCO) cultures to improve their reproducibility and reduce costs. SCOs are tiny, artificially-grown tissues that mimic key spinal cord’s structures and functions; they’re useful for studying neurological development and disorders. Most SCO cultures currently use Matrigel™ as a substrate, but it’s a somewhat poorly-defined substrate derived from mouse tissues, which can create differences between batches of organoid cultures.
Our findings showed that simple and low-cost hydrogels could serve as ideal substitutes for Matrigel™ in generating SCOs, especially when trying to create a xeno-free (i.e., free of cells from a different species) and fully-defined 3D culture. The use of alginate reduced the expression of non-specific markers that could introduce variability and obscure meaningful results. We also validated our model using a disease model, indicating its suitability for spinal cord disease modelling and drug screening.
This project was particularly significant as it opened up funding opportunities and collaborations for us with principal investigators from NUS and A*STAR’s IMRE. Building on this work and its partnerships, we’re expanding our research to incorporate synthetic hydrogels; we aim to further improve reproducibility and develop new ageing-related models by manipulating organoids and their microenvironments. Notably, we were surprised to find that many popular synthetic hydrogel systems are cytotoxic to our model, suggesting that each cellular model might have unique features to consider and test individually.
What do you find challenging in your field of research?
An interdisciplinary field like tissue engineering presents a unique challenge due to the vast breadth and depth of knowledge required. Since it’s impossible to know everything, it’s essential to collaborate with colleagues from different fields. For example, in organoid model development projects, we work with chemists to develop new materials, and with developmental biologists to understand stem cell and tissue development.
Sometimes, this in turn poses a different kind of challenge, due to the diverse backgrounds and views within the team. However, with constant communication, I find that engaging in the role of a bridge between chemists, biologists and engineers has been both challenging and fulfilling, especially when we can resolve our differences and work towards a common goal.
What advice do you have for STEM peers looking at their next big career step?
As postdoctoral researchers, it’s easy to become too focused; we can get lost in projects and daily research work. However, it’s crucial—even essential—to be proactive not only in making career plans, but also in executing those plans. This includes learning what’s needed to take the next steps, such as securing additional grants, fostering collaborations and building networks. These efforts, though often behind the scenes, will give us a competitive advantage and better prepare us for the future stages of our careers.
