Scaff-Net: 3 Dimensional multiphoton polymerisation printed scaffolds for medium throughput recording from stem cell derived human cortical networks.

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A major growing threat to human health, quality of life and society is that of neurological and neurodegenerative diseases. The annual cost of treating brain conditions in the EU is estimated at ~798 billion Euros, with brain disorders such as depression, bipolar disorder, epilepsy and dementia affecting about 165 million Europeans or 1 in 3 people (European Commission).There is a need for drug treatments and therapies for such conditions, however, advance is hampered by the lack of suitable methods to test and screen potentially useful molecules. One major problem is that most research traditionally has been conducted using animal tissues such as rat or mouse brains or cultured neurons from these animals. However, it seems that human brain cells responses and their connections in many ways may be different to mouse neurons. Another problem is that although cells can be cultured and investigated over a period of weeks or months they are usually grown on flat surfaces for testing by scientists and the pharmaceutical industry, which is totally different to the way that they grow in the brain. The human brain consists of networks of neurons communicating with each through connections that radiate in all directions in 3 dimensions. The pattern of connections and its complexity is one of the fundamental features that enables human brains to function as they do. Cultures of neuronal networks grown on flat 2D surfaces cannot make the same connections as they would in the living brain, and therefore the activity that they produce will also be different. To be able to develop drugs and therapies for human conditions, the ideal cell system would be 3 dimensional cultures of human neuronal networks that we could record activity from and test drugs. It would also be ideal if many recordings could be done at the same time from different networks so that many drugs could be tested in a shorter time. This is what we will achieve with Scaff-Net. Using laser-based technology we will "print" small scaffolds that will support neuronal networks. To obtain human neuronal networks we will use human derived stem cells that come from skin samples. We will grow neurons from the stem cells and culture these on the scaffolds where they will form connected networks. Many of the 2D flat cultures grown today are grown on grids of many small electrodes to record activity. In Scaff-Net we will print a single scaffold and neuronal network on each single electrode of these grids of multi electrode arrays. This will mean that these electrode arrays will be transformed from being able to record at many sites on a single flat 2D culture to be able to record activity from many 3D networks on scaffolds (about 60!) at the same time. This will mean that the testing of drugs can be made quicker, and so therapeutic discoveries will be made quicker. In the future we would expect Scaff-Net devices to have a major impact on the way that drug discovery is conducted and transform the field.