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Institute of Complex Systems
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Development of neuronal 3D cultures

Our research focuses on the development of 3D culture systems which potentially offer higher degrees of organization and advanced physiological characteristics, for instance mechanical properties as found in tissues and organs. This new culture system provides a valuable in vitro tool to investigate neural cell-cell and cell-substrate interactions in a three-dimensional environment and signal processing that will be of higher biological relevance.
In the human brain 86 billion neurons are located and interconnected forming a highly complex network. Most common experiments are based on 2D models, however to study complex neuronal networks and associated diseases, cells need an in vivo like environment to act physiologically. Especially cell survival and differentiation of neurons are highly sensitive to the mechanical properties of their surroundings (extracellular matrix = ECM). In general the ECM is composed of water, ions, glycoproteins, proteoglycans, hyaluronic acid and fibrous proteins. Naturally derived hydrogels, such as alginate, are able to mimic components of the native ECM and enhance the cell viability due to larger cell-surface contact area.


Development_of_Neuronal_3D_Cultures_2

The aim of our study is to establish a three dimensional alginate-based hydrogel with mechanical behaviors in the range of the brain, that enhances cell viability and enables the observation of in vivo like circuits of higher complexity. Alginate is a natural hydrophilic polysaccharide recovered from different types of brown seaweeds. Its molecular structure is composed of two repeating units: 164 linked -D-mannuronic acid (M) and -L-guluronic acid (G). These G-blocks form cavities which act as binding sites for Calcium ions, whereby Alginate polymerizes and forms a hydrogel. Alginate has an already proven biocompatibility, low immunogenicity and a high permeability.


Neural networks in this hydrogel can be studied in their formation (dendritic and axonal growth and maturation stages) and behavior (spontaneous activity, response to pharmaceuticals, etc.). By introducing e.g. cells affected on a single cell level by simulation neurodegenerative effects of the Parkinson disease dopaminergic neuron degeneration can be precisely analyzed. Platforms like microfluidic devices provide a defined structure, directed measurements and enable to mimic specific brain regions, where different cells are connected.


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