3D printed brain organoids: Humanitas University and Politecnico di Milano together to research neuronal diseases

Developing increasingly complex and realistic 3D printed brain organoids that best reproduce the activity of our brain, contributing further to studying neuronal diseases. This is the aim of the project involving the Humanitas Neurodevelopment Laboratory, coordinated by Dr Simona Lodato, and the Mechanics and Chemistry Departments of the Politecnico di Milano, represented respectively by Professor Bianca Maria Colosimo and Professor Davide Moscatelli.

The project, funded by Cariplo with €250,000, was coordinated by the young researcher Mattia Sponchioni from Politecnico di Milano, in collaboration with the young researcher Monica Tambalo from Humanitas. The aim is to study the mechanisms underlying the Pitt-Hopkins Syndrome. This neurodevelopment rare genetic disease affects newly born children, leading to severe cognitive disabilities, recurrent epileptic seizures and respiratory complications.

“This project”, explains Dr Simona Lodato, “is part of an already active collaboration with the Politecnico di Milano in which we believe very strongly: bringing technological innovation within the medical and biological field represents an increasingly necessary knowledge transmission between different areas. In our Neurodevelopment laboratory we are able to produce brain organoids, i.e. three-dimensional cellular models from pluripotent stem cells derived from patients, which reproduce important characteristics of the developing human brain. For the Pitt-Hopkins syndrome, we use cells from biobanks that present the genetic mutation underlying the disease. We then make these cells differentiate into neural precursors capable of generating a wide diversity of neurons and glial cells of the human cerebral cortex; these cells, grown in suspension within the bioreactors, assemble spontaneously with each other to form spherical organoids containing active neural circuits. However, these organoids lack a vascularisation system and cannot faithfully reproduce the sophisticated architecture of the cerebral cortex. Our collaboration with the Politecnico di Milano will allow to meet the challenge of producing organoids that are not only increasingly similar to our brains, or other organs, but are also self-sufficient and more sophisticated”.

Researcher Monica Tambalo continues “Politecnico di Milano is indeed carrying out a research to identify biomaterials that are able to support the development of differentiated neurons starting from patients’ cells. In addition, our colleagues at the Polytechnic are equipped with 3D bioprinters which, unlike normal 3D printers, use ‘biomimetic inks’ as printing materials, i.e. compatible with a specific cellular component. We are working to ensure the multiple printing of different cellular components in the Bio-ink, loaded into the machine at high resolution, while preserving their viability and biological functions. What we aspire to obtain are ‘bio-printed organoids’, of the order of a few millimetres, equipped with a primordial vascularisation system, in which we can implement complex geometries that are increasingly suitable for studying organs/tissues’.

“The aim”, concludes Dr Simona Lodato, ‘is to create prototypes, in this case starting from the cells of patients suffering from the Pitt-Hopkins Syndrome, which can also be used to study other neurodevelopmental or neurological diseases. It is essential to develop a robust system that will allow us to acquire more and more information on a given disease. This will be done in order to try to identify its underlying altered mechanisms and, possibly, design new intervention strategies, reducing the distance between the knowledge obtained in the laboratory and clinical practice, with a view to improving the health and quality of life of patients”.