Tiny Brains Grown in 3D-Printed Bioreactor

(CN) — Cutting edge technology has allowed scientists to grow and observe miniature organoid brains in a 3D-printed vessel, paving the way for important research about both organoids and neuroscience.

In a study published Tuesday in AIP Publishing's Biomicrofluidics, researchers from MIT and the Indian Institute of Technology Madras demonstrate how their design for a 3D-printed bioreactor provides a successful avenue for the growth of organoids and organic tissue — one that is much more effective and affordable than the previously accepted method.

Organoids are miniscule organs grown in a controlled environment capable of performing the same functions of a full-sized organ. They are achieved when tissue derived from stem cells is made to self-organize and form three-dimensional cell structures, ranging anywhere from less than the width of a human hair to just under an inch wide.

Organoids open up countless opportunities in medicine by allowing experts to get up close and personal with living replicas of organs. By testing organoids, scientists can see firsthand how an organ grows and develops, how mutations and diseases occur in specific organs, how certain drugs interact with different parts of the body, and more. 

The standard mode of growing and observing organoids is limited by available technology, and is typically done in culture dishes and then viewed under a microscope. The problems with this method are that the culture plates requires must have numerous wells and glass bottoms for viewing under a microscope, they are expensive and can only fit under certain microscopes, and they do not provide optimal flow of nutrients into the live tissue, resulting in much trial and error and cell death.

The study’s authors utilized recent findings in the field of microfluidics, otherwise known as the manipulation of fluids on an incredibly small scale. In this technique, small tubes are used to allow a “nutrient medium” to travel to a small area or chip, but the process is difficult and costly.

The method proposed in the new study offers a much more affordable solution, using 3D-printing to construct a platform that not only fits the needs of organoid growth and observation, but also costs about $5 to create. The team printed a platform that is reusable, easily adjusted, heated for optimal temperatures, and contains the necessary wells and microfluidic channels to promote organoid health.

The 3D-printed vessel was composed of a biocompatible resin, which the authors say is commonly used in dental surgery. Part of the device includes a chip cured by UV light and sterilized so that the live cells can be placed in the wells on top of it. The wells are then sealed with a glass slide for viewing, and a nutrient medium and subsequent drugs can be administered through small openings.

"Our design costs are significantly lower than traditional petri dish- or spin-bioreactor-based organoid culture products," said study author Ikram Khan. "In addition, the chip can be washed with distilled water, dried, and autoclaved and is, therefore, reusable."

To test their device, the researchers inserted tissue obtained from human brain cells and watched through the glass with a microscope as the organoid grew over the course of seven days. Within the week, the brain tissue formed a ventricle surrounded by a structure that resembled a neocortex in development, otherwise known as the set of layers in the cerebral cortex responsible for complex brain functions.

This week-long experiment with the 3D-printed vessel resulted in a much smaller percentage of cell death within the core of the organoid than what was seen with standard culture plates. The authors are confident that this is a sign that their design better protects the miniature brains.

"One advantage offered by our microfluidic device is that it allows constant perfusion of the culture chamber, which more closely mimics a physiological tissue perfusion than conventional culture, and thus reduces cell death at the organoid core," said Khan.

This research is significant for the studies of mutations and disorders within the brain. Researchers at Harvard University look to organoid research as a way to finally crack the science behind commonly misunderstood neurological diseases, such as schizophrenia and autism. These disorders occur from mutations that take place very early on in the development of the brain. Its difficult to pinpoint the exact cause of neuro-disorders or how to prevent them, but if scientists were able to see a brain organoid develop and mutate in real time, they could may be able to answer those difficult questions.

Moving forward the team would like to increase the number of available wells in their device to produce more organoids at a time, as well as improve the design to allow more instruments to be included.

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