Engineered hydrogels supporting fast neurite extension

Society for Neuroscience Chicago 2015

Program#/Poster#: 46.08/D35
Topic: C.10. Trauma
Support: 3D NeuroN project in the European Union’s Seventh Framework Programme, Future and Emerging Technologies (grant agreement n° 296590) FIFA/F-MARC ETH funding

Title: Engineered hydrogels supporting fast neurite extension

Authors: *N. BROGUIERE, G. PALAZZOLO, M. ZENOBI-WONG; ETH Zürich, Zürich, Switzerland

Abstract: Animal derived matrices like fibrin, collagen and matrigel enable encapsulation of neurons with high viability and fast neurite extension. As a result, they have found widespread use as vehicles for the delivery of cells into severed tissues, for gap filling after trauma, and as 3D in vitro culture models. Their usefulness is nevertheless limited by their fast degradation, low tunability, poor definition, and/or by the costs and contamination/immunogenicity risks inherent to isolation of proteins from animal tissue. Matrices engineered from polysaccharides or synthetic polymers would be interesting alternatives. We systematically optimized 3 defined gels respectively based on polyethylene glycol (PEG), alginate, and hyaluronan to support similar fast neurite extension in defined, non-immunogenic matrices. Chick dorsal root ganglia (DRGs), rat primary cortical neurons and human induced pluripotent stem cell derived neurons were used as models, covering a wide range of species and neuron types. With all the gel systems and cell types, physical properties were found to be essential to recapitulate high viability and fast neurite extension, whereas specific biological cues such as growth factors and adhesion peptides were unexpectedly found to be unnecessary. In optimized conditions, 2 day viability reached more than 95%, and 3D neurite extension from encapsulated cells occurred at average rates of the order of 100 um/neuron/day. All gels could sustain cultures of cortical neurons for more than a month, yielding synaptically connected and electrically active 3D neural networks. Such neurite permissive hydrogels could find use in the treatment of spinal cord injury, as they are excellent supporting scaffolds for axonal regeneration. They would ideally be used in combination with current strategies to overcome growth inhibition, such as electrochemical stimulation, drug treatment, and stem cell delivery.

Disclosures: N. Broguiere: None. G. Palazzolo: None. M. Zenobi-Wong: None.

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