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University of Oxford has announced that researchers at the institution have developed a ‘breakthrough’ 3D printing technique that it says could one day provide tailored repairs for those who suffer brain injuries. The researchers demonstrated that neural cells can be 3D printed to mimic the architecture of the cerebral cortex.
Brain injuries, including those caused by trauma, stroke and surgery for brain tumours, typically result in significant damage to the cerebral cortex, which is the outer layer of the human brain, leading to difficulties in cognition, movement, and communication.
The researchers involved in the project say that tissue regenerative therapies, especially those in which patients are given implants derived from their own stem cells, could be a promising route to treat brain injuries. The team says that up to now however, there has been no method to ensure that implanted stem cells mimic the architecture of the brain.
The researchers fabricated a two-layered brain tissue by 3D printing human neural stem cells. When implanted into mouse brain slices, the cells showed convincing structural and functional integration with the host tissue according to the university.
“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,” said Dr. Yongcheng Jin of the Department of Chemistry at the University of Oxford, and lead author on the study.
Yongcheng Jin, University of Oxford
Droplets containing human iPSC-derived neural progenitors were 3D-printed to form 2-layer cerebral cortical tissue, which was cultured before implantation into a mouse brain slice. DNPs: deep-layer neural progenitors; UNPs: upper-layer neural progenitors.
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. A key advantage of using hiPSCs for tissue repair according to the researchers is that they can be easily derived from cells harvested from patients themselves, and would not trigger an immune response.
When the printed tissues were implanted into mouse brain slices, they showed strong integration, demonstrated by the projection of neural processes and the migration of neurons across the implant-host boundary. The implanted cells also showed signalling activity which correlated with the host cells, demonstrating functional and structural integration.
The university says that the researchers 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 having potential for repairing brain injuries, the engineered tissues could be used in drug evaluation, studies of brain development, and to improve understanding of the basis of cognition according to the researchers.
Yongcheng Jin, University of Oxford
3D-printed two-layer cerebral cortical tissue visualised within a mouse brain slice. The implanted neural cells were labelled with fluorescent markers (blue and red in the image)
“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,” said Senior author Dr. Linna Zhou, also from the University of Oxford’s Department of Chemistry.
Senior author Associate Professor Francis Szele, Department of Physiology, Anatomy and Genetics added: “The use of living brain slices creates a powerful platform for interrogating the utility of 3D printing in brain repair. It is a natural bridge between studying 3D printed cortical column development in vitro and their integration into brains in animal models of injury.”
Professor Zoltán Molnár, Department of Physiology, Anatomy and Genetics at the University and Senior author on the study said: “Human brain development is a delicate and elaborate process with a complex choreography. 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 hiPSCs to form the basic functional units of the cerebral cortex.”
Senior author Professor Hagan Bayley, Department of Chemistry said: “This futuristic endeavour could only have been achieved by the highly multidisciplinary interactions encouraged by Oxford’s Martin School, involving both Oxford’s Department of Chemistry and the Department of Physiology, Anatomy and Genetics.”
