An innovative technique developed by researchers at the University of Oxford could one day provide tailor-made repairs for those suffering from brain injuries. Researchers have demonstrated for the first time that neural cells can be 3D printed to mimic the architecture of the cerebral cortex.
The results of the study were published in the magazine Nature Communications.
Brain injuries: this is how the new 3D technique works
Brain injuries, including those caused by trauma, stroke, and brain tumor surgery, typically cause significant damage to the cerebral cortex (the outer layer of the human brain), leading to difficulties with cognition, movement, and communication.
For example, each year, approximately 70 million people worldwide suffer from traumatic brain injury (TBI), of which 5 million are severe or fatal. There are currently no effective treatments for severe brain injuries, which have serious repercussions on quality of life.
Regenerative tissue therapies, particularly those in which patients are given implants derived from their own stem cells, could represent a promising avenue for treating brain injuries in the future. Until now, however, there was no method to ensure that implanted stem cells mimic the architecture of the brain.
In this new study, researchers at the University of Oxford fabricated a two-layer 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.
In this new study, researchers at the University of Oxford fabricated a two-layer 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.
Lead author Dr Yongcheng Jin (Department of Chemistry, University of Oxford) said: “This progress marks a significant step towards fabricating materials with the full structure and function of natural brain tissues. The work will provide a unique opportunity to explore how the human cortex works and, in the long term, offer hope to people who suffer brain injuries.”
The cortical structure was built 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 is that they can easily be derived from cells harvested from patients themselves and therefore would not trigger an immune response.
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 two-layer structure. In culture, the printed tissues maintained their layered cellular architecture for weeks, as indicated by the expression of layer-specific biomarkers.
When the printed tissues were implanted into mouse brain slices, they showed strong integration, as demonstrated by the projection of neural processes and the migration of neurons across the implant-host boundary. The implanted cells also showed signaling activity, related to that of the host cells. This indicates that human and mouse cells communicated with each other, demonstrating functional and structural integration.
The researchers now intend to further refine the droplet printing technique to create complex, multilayered cerebral cortex tissues that more realistically mimic the architecture of the human brain. In addition to their potential to repair brain injuries, these engineered tissues could be used in drug evaluation, brain development studies, and to improve our understanding of the basis of cognition.
The new advancement builds on the team’s decades of experience inventing and patenting 3D printing technologies for synthetic tissues and cultured cells.
Senior author Dr. Linna Zhou (Department of Chemistry, University of Oxford) said: “Our droplet printing technique provides a means to engineer living 3D tissues with desired architectures, which brings us closer to creating treatments of customized implant for brain injury”.
Senior author Associate Professor Francis Szele (Department of Physiology, Anatomy and Genetics, University of Oxford) added: “The use of living brain slices creates a powerful platform to interrogate the utility of 3D printing in brain repair . It is a natural bridge between the study Development of 3D printed cortical columns in vitro and their integration into the brain in animal injury models.”
Senior author Professor Zoltán Molnár (Department of Physiology, Anatomy and Genetics, University of Oxford) said: “Human brain development is a delicate and elaborate process with complex choreography. It would be naive to think that we could recreate the entire cellular progression in the laboratory. However, our 3D printing project demonstrates substantial progress in controlling the fate and arrangement of human iPSCs to form the basic functional units of the cerebral cortex.”
Senior author Professor Hagan Bayley (Department of Chemistry, University of Oxford) said: “This futuristic endeavor could only have been achieved thanks to the highly multidisciplinary interactions encouraged by the Martin School at Oxford, involving both the Department of Chemistry of Oxford and the Department of Physiology, Anatomy and Genetics.”
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