A pioneering Oxford Martin School Programme that explored whether 3D printed human neural tissues could one day help repair the injured brain has concluded after five years of major advances — but the collaboration it helped build is set to continue through new links between the Department of Physiology, Anatomy and Genetics (DPAG) and the Ellison Institute of Technology.
The Oxford Martin Programme on 3D Printing for Brain Repair, which ran from 2020 to 2026 (https://www.oxfordmartin.ox.ac.uk/news/can-3d-printing-help-repair-the-brain-oxford-martin-programme-reports-key-advances), brought together expertise in stem cell biology, tissue engineering, chemistry, developmental neuroscience and brain repair. Led by Professor Hagan Bayley from Oxford Chemistry, Professor Zoltán Molnár and Professor Francis Szele from DPAG, and Oxford Martin Fellow Dr Linna Zhou, the programme set out to tackle one of the most difficult challenges in modern neuroscience: whether structured human brain tissue can be engineered in the laboratory and used to understand, model and ultimately repair damage to the brain.
Brain injury caused by trauma, stroke or disease can have profound and lifelong consequences, affecting memory, movement, communication and independence. Despite decades of research, effective treatments for severe brain damage remain extremely limited. At the same time, the complexity of the human brain means that researchers still lack sufficiently realistic experimental systems to study how human brain cells develop, connect and respond to injury.
The Oxford Martin School Programme addressed these challenges through a bold interdisciplinary approach. The team developed methods to derive distinct types of neural cells from human induced pluripotent stem cells and organise them into layered structures resembling aspects of the cerebral cortex — the outer region of the brain responsible for many higher functions, including perception, cognition and voluntary movement. Using 3D printing and microfluidic technologies, the researchers were able to generate engineered tissues in which different neural progenitor populations were patterned into defined layers.
Over the course of the programme, the team showed that these printed tissues could maintain their structure in culture, develop early signs of organisation, and extend cellular processes across layers. In ex vivo mouse brain tissue, the engineered human cells showed encouraging evidence of integration, including movement into surrounding tissue, extension of processes and signalling activity consistent with interaction with the host brain environment. Further studies demonstrated that bilaminar constructs containing upper- and lower-layer human neurons could be implanted into young mouse brains, where the neurons developed connections to specific targets and showed functional interactions with host circuits.
A major advance came from incorporating astrocytes, the support cells that play essential roles in brain development, homeostasis and repair. Including astrocytes improved survival and maturation of the engineered tissue, strengthened connections and supported interactions with blood vessels. In models of traumatic brain injury, these combined constructs were associated with reduced lesion size, providing an important foundation for future research into brain repair strategies.
Although the Oxford Martin School Programme has now formally ended, the work will continue through a developing partnership between DPAG and the Ellison Institute of Technology. This continued collaboration is supported by the appointment of Dr Linna Zhou as a Research Lecturer in DPAG, alongside her role as Group Leader at the Institute of Materials & Devices for Life Sciences at the Ellison Institute of Technology, where she leads the Tissue Engineering Team (https://eit.org/people/linna-zhou).
Dr Zhou’s research focuses on engineering realistic 3D human tissues by combining stem cell technology with 3D printing and microfluidics. These patient-derived 3D tissues are being developed to model hard-to-treat diseases, test novel therapeutics and create soft implantable biomaterials that may one day help repair damaged tissues and organs. Her dual role will help maintain and strengthen the scientific links established during the Oxford Martin School Programme, while opening new routes for collaboration between Oxford neuroscience and advanced tissue engineering at EIT.
Dr Zhou said: “I am delighted to be able to maintain links with our Oxford Martin School collaborators at DPAG in this new position. We shall be building on the project that we have been developing over the last six years as an Oxford Martin School Programme. We are also very happy to have Dr Mona Barkat as a postdoctoral researcher in our team at the Institute of Materials & Devices for Life Sciences at EIT while she will keep association to DPAG. Dr Barkat recently completed her DPhil under the joint supervision of Professor Molnár, Professor Szele and Professor Swietach at DPAG.”
Professor Francis Szele said: “This collaboration opened up new possibilities to combine systems neuroscience with tissue engineering, and we value these excellent opportunities to continue our close collaboration.”
Professor Zoltán Molnár added: “The evolution of the mammalian brain took several millions of years, and we now dream big and try to reproduce some of the properties of key neuronal circuits using tissue engineering. These projects would not be possible without the combination of a large variety of methods and collaboration of the members of this consortium.”
The programme’s achievements also reflect the contributions of Oxford Martin personnel Dr Luana Campos Soares, Dr Mingyu Li and Dr Yufan Xu, as well as the wider collaborative network across DPAG, Oxford Chemistry, Ludwig Cancer Research and the Ellison Institute of Technology.
The next phase of work will build on the methods and insights generated by the Oxford Martin School Programme. By combining precise control over cell types, tissue architecture and biological environment, researchers are now better equipped to investigate how human brain tissue forms, matures and responds to damage. In the longer term, this approach could support research into traumatic brain injury, neurodegenerative disease and other conditions where new models and therapeutic strategies are urgently needed.
What began as an ambitious Oxford Martin School Programme has therefore laid the groundwork for a continuing collaboration at the interface of neuroscience, engineering and regenerative medicine. Through DPAG’s partnership with the Ellison Institute of Technology, the team will continue to explore how engineered human tissues can deepen understanding of the brain and help shape future approaches to repair.
Publications:
https://doi.org/10.1002/adma.202002183
https://www.nature.com/articles/s41467-023-41356-w
https://doi.org/10.1002/advs.202507423Digital Object Identifier (DOI)