3D Bioprinting Models of Neural Tissue: The Current State of the Field and Future Directions

By Shesha Taylor

Advances in bioprinting have opened various doors in the interdisciplinary field of tissue engineering. Using different combinations of bioinks- organic and inorganic scaffolds, and tissues can be printed. This can be used for drug screening, studying biological mechanisms, and eventually, to reduce organ shortages through patient specific tissue transplants. For now, however, engineering neural cells remain a challenge due to the brain’s complexity.

To successfully culture neural cells, hydrogels (a category of bioink) are often used to mimic the cell’s environment and provide them with supporting nutrients and growth factors. The two types of hydrogels are: natural and synthetic based. Natural hydrogels have been used successfully with other tissue types and allow for the growth of vascularized structures which is important in the neural network. On the other hand, synthetic hydrogels can be altered for different cell types and are highly customizable in terms of cross-linking and stability. However, synthetic hydrogels are harder to use in the bioprinting process even though they provide more control over the 3D construct in terms of gelation and degradation time.

Bioprinting neural tissues presents opportunities to accurately model neurodevelopment, diseases and neural networks among other things. The current bioprinting process has two steps in which scaffolds are 3D printed followed by cell seeding within it, and a single step process where the cells are imbedded within the bioink. Cell-laden fibers are bioprinted in layers to create the full 3D construct. Recent advances in neural tissue bioprinting include the combination of biomaterials, for example neural mini tissue constructs (nMTC) using human neural stem cells in an agarose bioink (Gu et al. 2016). Another study used a non-ionic crosslinking material for bioprinting human iPSCs (Li et al., 2018). Bioinks continue to evolve as bioprinting advances increase rapidly. One interesting application of neural tissue printing is developing brain tumor models. The 2D animal cell culture models commonly used in modeling are often too simple to fully capture the complexity of a brain tumor. Therefore, being able to recreate the tumor in a controlled 3D environment allows us to glean much more information about potential drug targets, cellular cancer mechanisms, etc.

There are also alternative methods for generating 3D neural tissues which can be used if the standard method does not work in a particular situation. One method is forming cell aggregates that self-assemble into spheroids, which can then be used to model neural tissue (Chatzinikolaidou, 2016; Ungrin et al., 2008). Spheroid-based methods can require less resources in comparison to 3D bioprinting as it is a scaffold free differentiation method. Another promising method of engineering 3D neural tissue are brain organoids which can be created from induced pluripotent stem cells.

Future goals for the field of bioprinting are to continue the development of more accurate and complex nervous system models. These models will benefit from recent advances as bioprinting tissues with high degrees of complexity while improving their reproducibility is becoming the norm. Additionally, the potential to bioprint patient derived neural tissues opens a pathway for personalized medicine as doctors could tailor their treatments to their patients. 3D bioprinting neural tissues has tremendous promise for finding better treatments for a range of neurological diseases and disorders.