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The Building Blocks for Tissue Engineering: New Study Shows an Automated and Rapid Method to Assemble Cell Spheroids

An overview of new research led by Reza Rasouli, a PhD Student in the Biomat'X Research Laboratories of Prof. Maryam Tabrizian

A new study published in Small is the result of research conducted by Reza Rasouli, a PhD Student in Biological & Biomedical Engineering, under the supervision of Prof. Maryam Tabrizian. The research focuses on acoustic formation of cell spheroids, a type of three-dimensional cell modeling that better simulate a live cell's environmental conditions compared to a two-dimensional cell model. The findings have broad implications for tissue engineering and 3D  bioprinting.

We asked Reza to explain his research, how it was conducted, and the implications for the future:

Q: What’s really new in this paper?

In this paper, we developed an acoustic-based microfluidic platform to rapidly form cell spheroids. In 10 seconds, this platform can trap, compress, and congregate cells in the vortices that are formed by acoustic waves. Simultaneously, Collagen I, which is a natural ECM, glues the cells together to form coherent 3D cell spheroids. Once the spheroid with the size of interest is formed, the acoustic waves can be turned off and the flow guides the spheroids to the Petri dish.

Q: How does it add to what was already known?

3D cell spheroids have numerous applications in biomedical science, from being excellent models for drug screening to tissue engineering. One of the challenges in making spheroids is the reliance on cells to gradually secrete binding proteins and form coherent clusters which not only can be time-consuming, but is also not applicable to all cell types. The controlled vortex in our platform accelerates this process without harming cell viability, while incorporation of ECM makes this method applicable to more cell types.

Q: How did you discover it? What led you to ask the question and explore it this way?

We used acoustic microstreams earlier for another project which included nanoparticle synthesis. As I was developing the platform, I realized the forces and mechanism show interesting interactions with particles such as trapping. At the same time, some of my lab mates were working on the formation of Pancreatic islets and, when I observed the challenges in spheroid formation, I saw the potential to develop a mechanism to accelerate the process and minimize manual handling.

Conceptual illustration of acoustic spheroid formation mechanism by collagen assembly
Conceptual illustration of acoustic spheroid formation mechanism by collagen assembly

Q: Why is this finding important?

I believe one of the important aspects of this system is its continuous flow nature which allows it to function as a spheroid assembly line. This gives the method adaptability and potential for automation where cells can be infused, attached, packed with collagen, and finally moved to the collecting chamber - all without external interaction.

Q: What are the practical implications?

The automated and rapid spheroid formation system can lay the groundwork for numerous bio-applications, particularly when incorporated as a module to complex machines. For instance, in this paper we showed the spheroid made with the acoustic platform has a high tendency to merge together. One interesting application would be the integration of this device to a 3D bioprinter to continuously form spheroids as building blocks for tissue engineering.

Q: What challenges did you face? How did you overcome them? Who supported you in overcoming the challenges?

Well, as any researcher would tell you, the initial experiments almost always find a whimsical way to not work as planned. Between adapting the system to the cellular environment and optimizing the biomaterial for continuous flow, every step raised another challenge which sometimes required late-evening experiments on winter night. But over time you learn to address the challenges one at a time, and it gradually builds a confidence to be a problem solver, which I believe is a key skill to develop as a researcher.

Q: What questions might other scientists raise about this study?

Since we published the study, I was contacted by a number of researchers from very diverse fields (to my surprise). The most frequently asked question was about the versatility and compatibility of the method for their specific applications. I particularly receive questions about the different bio-materials that can be used in the acoustic spheroid formation method, and various cell-specific requirements, which shows there are diverse perspectives to explore using this method.

Q: What are the next steps/future directions for this research?

Continuing from the previous question, it would be particularly interesting to see how much we can push this device in terms of using different biomaterials and spheroid production throughput for various applications. Another promising step would be the automation of the device to realize the potential of 3D constructs as building blocks for the fascinating field of tissue engineering.

Q: How is the McGill experience (or people in the McGill community) helping you to pursue/develop your passion/research? Is there anyone here who has supported or mentored you?

Certainly! When I started my Ph.D., I was really passionate about acoustofluidics but I also had my reservations, since it was still an emerging field with very limited people working on that subject. However, my supervisor, Dr. Tabrizian, was the big influence as she not only encouraged me to explore this topic, but also her excitement toward this project and her support were always inspiring. Moreover, McGill is full of world-leading scientists and there is a strong collaborative atmosphere within the community which always helped me to find someone who could help answer my questions. Not to forget, the friendly administrative staff and advisors at BME were always supportive and helpful.

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