Described in Nature Communications, the work ultimately saw the Oxford team implanting the 3D printed structures into mouse brain slices. According to the researchers, the host and implanted brain tissues exhibited ‘strong integration’, including the migration of neurons and signalling activity that correlated with that of the host cells. It’s hoped the first-of-its-kind study could pave the way for personalised treatments of stroke, brain trauma, and recovery from brain tumour surgery.
“This advance marks a significant step towards the fabrication of materials with the full structure and function of natural brain tissues,” said lead author Dr Yongcheng Jin, from Oxford’s Department of Chemistry. “The work will provide a unique opportunity to explore the workings of the human cortex and, in the long term, it will offer hope to individuals who sustain brain injuries.”
The cortical structure was made from human induced pluripotent stem cells (hiPSCs), which have the potential to produce the cell types found in most human tissues. HiPSCs can be easily derived from cells harvested from patients themselves, thereby avoiding an immune response.
The hiPSCs were differentiated into neural progenitor cells for two different layers of the cerebral cortex by using specific combinations of growth factors and chemicals. These cells were then suspended in solution to generate two bioinks, which were then printed to produce a two-layered structure.
When implanted into the mouse tissue, the 3D printed cells were observed communicating with the mouse cells, demonstrating functional as well as structural integration of the tissues. The researchers now intend to further refine the droplet printing technique to create complex multi-layered cerebral cortex tissues that more realistically mimic the human brain’s architecture. Alongside potential for treating brain injuries, the technology could be used in drug evaluation, studies of brain development, and to improve our understanding of cognition.
“Human brain development is a delicate and elaborate process with a complex choreography,” said senior author Professor Zoltán Molnár, from Oxford’s Department of Physiology, Anatomy and Genetics.
“It would be naïve to think that we can recreate the entire cellular progression in the laboratory. Nonetheless, our 3D printing project demonstrates substantial progress in controlling the fates and arrangements of human iPSCs to form the basic functional units of the cerebral cortex.”
The research was supported by a European Research Council Advanced Grant (SYNTISU) and the Oxford Martin School Programme on 3D Printing for Brain Repair.