A team of researchers from Tsinghua University have 3D bioprinted brain-like tissue structures capable of nurturing neural cells. They tested the fabricated structures by extracting a group of primary neural cells from the cortex of a rat and integrating them into the printed structures. Interestingly, after several weeks of in vitro nurturing, the primary neural cells had formed a complex neural circuit capable of responding to external stimuli.
A living 3D model
3D bioprinting, while advanced, is not yet capable of fabricating useful whole organs – at least not for transplantation. Fortunately, smaller and less complex tissue structures have their uses in health monitoring and drug testing. For example, medical professionals are able to collect neural cells from an individual and grow them into larger cultures on 3D printed lattice-like structures. These 3D structures do a good job of mimicking the pathways found in real brain tissue, so the neural cells treat them as such and, with the right nutrition, grow along them.
The resulting neural circuits behave as a miniature brain would – a petri dish brain if you will. Once complex enough to respond to stimuli, the cultures are exposed to experimental drugs and their neural responses are documented, giving us an idea of how an actual brain might respond if a human were to trial the drug.
Bioprinting the brain
The researchers had to go through a few phases of trial and error before they got the structures right. They found the optimum nozzle diameter and print rate to be 0.51 mm and 5 μL/s respectively. The resulting structures had an elastic modulus of approximately 6 kPa and immunostaining imaging was used to track the growth of the neural cells on the printed structures.
To test the electrical stimulus response of the neural networks, the team cultured them directly in a 4×4 electrode array. An electric field was generated and the neurons were observed, showing sensitive activity. Tetrodotoxin was then used to test the drug sensitivity of the cultures, indicating that the 3D printed structure has “great potential as a drug testing model”.
Finally, the survival rate of the neural cells were studied when printed in 2D and 3D formations. Impressively, the 3D structures were kept alive for four whole weeks, with an initial 85% of cells surviving the bioprinting process. Comparatively, the 2D structures only had a survival rate of 25%, validating the superiority of the Tsinghua scientists’ method of 3D bioprinting brain tissue.
Further details of the study can be found in the paper titled ‘Engineering of brain-like tissue constructs via 3D Cell-printing technology’. It is co-authored by Yu Song, Xiaolei Su, Kevin F. Firouzian, Yongcong Fang, Ting Zhang, and Wei Sun.
There are a number of different methods of bioprinting, all with their unique strengths and weaknesses. One of the most popular methods is the Kenzan method, whereby a culture of cells called spheroids are skewered on an array of microneedles (the Kenzan) until they fuse. A recent progress report published in the journal Advanced Healthcare Materials details the results of various experiments that have utilized the Kenzan method of 3D bioprinting. Early results of these studies indicate great potential for the future of 3D printed tissue transplants.
Elsewhere, in Korea, a 3D bioprinting startup has developed a respiratory epithelium model using its own cell printing technology. The company intends to use the model to research viruses and their interaction with cells in the respiratory tract – a more than relevant mission given the state of the global pandemic.
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Featured image shows testing of the 2D and 3D formations with an electrode array. Image via Tsinghua University.