Episode 7: Key biomaterial parameters found for optimal organoid morphogenesis

In this podcast episode, MRS Bulletin’s Laura Leay reports on the quantified relationship between rheology of a granular biomaterial and tissue self-organization, a study conducted by research groups at the University of California, the Chan Zuckerberg Biohub in San Francisco, Stanford University, and Cedars-Sinai in Los Angeles. The collaborators developed a 3D-bioprinter with a piezoelectric print head to control mechanical forces and a composite extracellular matrix for the biomaterial. One aim of the research was to demonstrate a print medium that could be used to produce a wide variety of biological structures. This work was published in a recent issue of Nature Materials. 

Transcript

LAURA LEAY: Welcome to MRS Bulletin’s Materials News Podcast, providing breakthrough news & interviews with researchers on hot topics in materials research. My name is Laura Leay. 

In vitro tissue growth has achieved some great things for science and medicine but challenges remain when it comes to controlling aspects such as uniformity and complexity of tissues. Using 3D printing along with a new extracellular matrix while also controlling mechanical stress can open opportunities to learn more about fundamental biology and applications.

In vitro techniques need to replicate initial conditions seen in vivo, and this includes rheological cues related to movement within a biological system as organs grow. Collaborative work between groups at the University of California, the Chan Zuckerberg Biohub in San Francisco, Stanford University, and Cedars-Sinai in Los Angeles has quantified the relationship between rheology of a granular biomaterial and tissue self-organization. They found that even when characteristics of the biomaterial such as storage modulus are similar at short timescales, quantifiable aspects of tissue morphogenesis such as the crypt morphology of intestinal organoids can differ. This difference is governed by the rate and extent of stress relaxation at longer timescales. These findings apply when large deformations or high strain are applied.

These finding were determined using a composite extracellular matrix for the biomaterial. Matrigel, was used as its chemical composition supports morphogenesis of most epithelial organoids. This was combined with a granular phase of alginate microgels which would facilitate self-organization. Altering the ratios of these components meant that the rheological properties of the matrix could be tuned.

One aim of the research was to demonstrate a print medium that could be used to produce a wide variety of biological structures. Lead author of the study, Dr. Austin Graham, a post-doctoral researcher at both University of California and the Chan Zuckerberg Biohub, explained to MRS Bulletin that they wanted to kick-start imaginations. They printed a wide variety of structures from both human and mouse biology, demonstrating that their findings and the new print medium could open a lot of doors for other researchers.

A bespoke bioprinter was also developed, which uses a piezoelectric print head to control mechanical forces. Prof. Michelle Khoo, from the Chan Zuckerberg Biohub, explained that early tests to reproduce what they had seen in the literature using this type of print head were challenging, but with the newly developed matrix, the quality and reproducibility of the results is very high. The bioprinter is engineered to work with low sample volumes and achieves high accuracy. A future paper will focus on this open source platform, allowing other researchers to benefit. 

Professor Zev Gartner, also affiliated with both the University of California and the Chan Zuckerberg Biohub and one of the corresponding authors of the study, is excited for what they – and others – can achieve next. Now that initial boundaries are established, his team can start thinking about living systems and how cells sculpt themselves into organs. This advance was made possible because of the collaboration between groups with complementary expertise. 

The platform also has applications in areas such as drug screening. Where large arrays of organoids are used for high throughput screening, the bioprinter and composite matrix led to a level of reproducibility and statistical power that surprised the research team. When compared to organoid arrays produced using manual methods, the printed arrays showed greater uniformity in morphology and so led to statistically significant results with incredibly small p-values for the same number of organoids produced: over a million times smaller than the usual p-value of 0.05. For the research team, this is just one avenue to explore using their newly developed platform that can open up opportunities for understanding and utilizing tissue morphogenesis.

This work was published in a recent issue of Nature Materials. 

My name is Laura Leay from the Materials Research Society. For more news, log onto the MRS Bulletin website at mrsbulletin.org and follow us on X, @MRSBulletin. Don’t miss the next episode of MRS Bulletin Materials News – subscribe now. Thank you for listening.