Engineered Neural Networks

Introduction to Neuroengineering

The integration of neuroscience and engineering is a relatively new discipline where scientists aim to invent unique methods of aiding patients with neurodegenerative diseases, such as Alzheimer’s and Parkinson’s, in addition to various types of brain injury. Although the human brain possesses sensory, motor and cognitive capabilities, a major limitation is the ability to repair itself in response to strokes, chronic neurodegeneration etc. This ultimately leads to a persistence of functional deficits. In an attempt to enhance and restore human function, scientists are able to collaborate Neuroscience and Engineering by creating artificial devices including neuroprosthetics and brain-computer interfaces. Such devices directly interact with the nervous system and have been used to assist research related to the understanding of coding and processing of the sensory and motor systems in both healthy and pathological states.

Central nervous system (CNS) injuries induce tissue damage, creating barriers to regeneration. One of the main barriers is the glial scar, consisting predominately of reactive astrocytes and proteoglycans. Axons cannot regenerate beyond the glial scar, and they take on a dystrophic appearance of stalled growth.1 An example of neuroengineering in action includes some relatively recent research conducted at the Penn Medicine’s department by D. Kacy Cullen (assistant professor of Neurosurgery) and his team, involving the engineering of neural networks.

Neural Networks

An axon is one of the four distinct regions of a neurone – the functional unit that makes up the mammalian nervous system. The remaining 3 regions include the dendrites, cell body and the axon terminal (Figure 1). Dendrites are outward extensions of the cell body that are specialised to receive chemical signals from the terminals of other neurones. These signals are then converted into small electric impulses which are transmitted inwardly in the direction of the cell body. The impulses travel down the axon, specialised for the conduction of an electrical impulse called the action potential, at speeds of up to 100 metres per second. The length of the axon varies, with some reaching lengths of more than a metre long in humans. A single axon has the ability to communicate with multiple neurones throughout the CNS through sites called synapses, forming complex connections that regulate the body’s signal transmission.2

 

neuron.jpg

Figure1 – The information flow through neurones. http://www.uic.edu/classes/bios/bios100/lectures/nervous.htm

Populations of neurones are connected via axons, long projections that enable complex brain function to occur. When these axon pathways are broken or damaged, the effects on the human brain are detrimental. Previous regenerative medicine strategies produced to repair the CNS focus mainly on cell-based therapies. However, these therapies lack control of differentiation and specificity required for precise reconnection of long distance pathways.2 As a result, more unique approaches have been attempted using biomaterials and cellular scaffolds to enhance axonal regrowth as discussed below.

The research performed by Cullen et al. included working on pioneering developing technologies to restore neural circuits. They created replacement connections in a lab referred to as micro-tissue engineered neural networks (micro-TENNs). This novel class of preformed tissue engineered constructs were designed for both neuronal and axonal tract replacement upon transplantation and functional integration with the brain.3 The engineered tissue can be thought of as living scaffolds that allow the combination of neural cells and biomaterials to produce constructs with a 3D axonal cytoarchitecture. The aims of the micro-TENNs were to facilitate regeneration by directly replacing and modulating neural circuits, in order to restore nervous system function. They achieved this by mimicking the structure of broken axon pathways.

Although the team were the first to demonstrate successful integration of micro-TENNS into brain structures to reconstitute altered brain pathways, further improvement was required. The main issue was the method of delivery, with the current method being invasive. The team took this on board by developing a strategy that allowed the encapsulation of fully formed engineered neural networks to insert into the brain without the use of needles. Not only did this reduce the implant footprint, but it proved to be a more hospitable environment for implanted neurones to integrate within the CNS.

Summary

Cullen et al. produced a promising strategy capable of simultaneously restoring lost neuronal populations following CNS degeneration. Their current work provides a stepping stone for in vivo studies in the future regarding the treatment of a range of neurological disorders and neurodegenerative diseases through the application of engineering techniques into neuroscience. To read the article in more depth or gain access to more research on Neuroengineering, here’s a link to the journal by Cullen et al. published in the Journal of Neural Engineering: http://www.ncbi.nlm.nih.gov/books/NBK21535/

 

Author: Aisha Islam

References

1 – Silver J & Miller J.H. 2004. Regeneration beyond the glial scar. Nature Reviews Neuroscience. [Online]. 5, pp.146-156. [Accessed 20 September 2016]. Available from: http://www.ncbi.nlm.nih.gov/pubmed/14735117

2 – https://www.sciencedaily.com/releases/2016/01/160120201330.html

3 – Cullen D.K. & Harris J.P et al. 2016. Advanced biomaterial strategies to transplant preformed micro-tissue engineered neural networks into the brain. Journal of Neural Engineering. [Online]. 13(1). [Accessed 30 July 2016]. Available from: http://iopscience.iop.org/article/10.1088/1741-2560/13/1/016019/meta;jsessionid=72E9729F95579833734F65A02B388FE0.c2.iopscience.cld.iop.org

 

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