A new technique developed by University of Oxford researchers could one day provide tailored repairs for those who suffer brain injuries.
The research team demonstrated for the first time that neural cells can be 3D printed to mimic the architecture of the cerebral cortex.
Brain injuries, including those caused by trauma and stroke typically result in significant damage to the cerebral cortex, leading to difficulties in cognition, movement and communication.
The are currently no effective treatments for severe brain injuries, which lead to serious impacts on quality of life.
Tissue regenerative therapies, especially those in which patients are given implants derived from their own stem cells, could of a promising route to treat brain injuries in the future.
But up until now, there has been no method to ensure that implanted stem cells mimic the architecture of the brain.
In the new study, the University of Oxford researchers fabricated a two-layered brain tissue by 3D printing human neural stem cells.
After being implanted into mouse brain slices, the cells showed convincing structural and functional integration with the host tissue.
Lead author Dr Yongcheng Jin of the University of Oxford Department of Chemistry, said: “This advance marks a significant step towards the fabrication of materials with the full structure and function of natural brain tissues.
“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 using human induced pluripotent stem cells (hiPSCs), which have the potential to produce the cell types found in most human tissues.
A key advantage of using these cells for tissue repair is that they can be easily derived from cells harvested from patients themselves, and therefore would not trigger an immune response.
The hiPSCs were differentiated into neural progenitor cells for two different layers of the cerebral cortex, using specific combinations of growth factors and chemicals.
The cells were then suspended in solution to generate two ‘bioinks’, which were then printed to produce a double-layered structure.
In culture, the printed tissues maintained their layered cellular architecture for weeks, as shown by the expression of layer-specific biomarkers.
When the printed tissues were implanted into mouse brain slices, they showed strong integration, as shown by the projection of neural processes and the migration of neurons across the implant-host boundary.
The implanted cells also demonstrated signalling activity, which correlated with that of the host cells.
This finding indicates that the human and mouse cells were communicating with each other, demonstrating functional as well as structural integration.
The scientists 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.
As well as their potential for repairing brain injuries, these engineered tissues might be used in drug evaluation, studies of brain development, and to improve our understanding of the basis of cognition.
The new research builds on the team’s decade-long track record in inventing and patenting 3D printing technologies for synthetic tissues and cultured cells.
Senior author Dr Linna Zhou, also of the university’s Department of Chemistry, said: “Our droplet printing technique provides a means to engineer living 3D tissues with desired architectures, which brings us closer to the creation of personalised implantation treatments for brain injury.”
