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NEURAXE

Oriented supramolecular gels as a guide for neural stem cells
Funder: French National Research Agency (ANR)Project code: ANR-15-CE07-0007
Funder Contribution: 412,131 EUR
Description

Cerebrovascular stroke or trauma lead to an important loss of neuronal tissue, leading to strong disability. A current challenge in the field of tissue engineering is to make implants which first ensure a good survival of implanted neuronal cells and furthermore, which allow to direct growth of these neuronal cells in a preferential direction, in order to organize the tissue reconstruction and to reconnect the two parts separated by the lesion. The objective of the project is to prepare and to inject in vivo biocompatible oriented gels charged with human neural stem cells. The aim is to demonstrate that these gels will guide the growth of neurons in a preferential direction and that they can improve the motor functional recovery and quality. For this purpose, a first step is to design and prepare new hydrogels for 3D cell culture, based on "Low Molecular Weight" (LMW) supramolecular hydrogelators. These gelators tend to form by self-assembly entangled fibers in water which support the formation of viscoelastic hydrogels. Their mechanical and rheological properties differ from polymer based hydrogels and can better mimic the properties of the extracellular matrix. In some cases, they also display fast gel recovery after shear as can do "self-healing" materials. For this reason, they could better fulfill the rheological requirements in their application as injectable matrices and could be more suitable for 3D cell cultures compared with polymer gels. Compared with few other LMW hydrogels already traded for 3D cell culture and injectability, based on quite expensive peptides, the objective is to design and synthetize of biocompatible "Low Molecular Weight" supramolecular hydrogelators belonging to other families of molecules. We will determine their biocompatibility and their rheological properties in relation with their use as in vitro 3D cell culture matrix and as injectable matrix for in vivo applications. In order to induce the oriented growth of neuronal cells, different methods for orienting the supramolecular fibers will be implemented. The objective is to better control the self-assembly of the "dissociated molecules" to fibers to get well-defined and well-organized fibrillar aggregates, and to get more particularly oriented fibers. The design of specific devices for controlling the alignment and the gelation triggers will be implemented. Finally, 3D in vitro neural cell cultures, including human neural stem cells, will be performed on the hydrogels, with or without orientation. Cytotoxicity, growth, adhesion and cell differentiation will be studied. Finally, the ability of hydrogels oriented to guide the growth of neurites in one preferred direction will be assessed. The final achievement will be to test, with the gels giving the best results in vitro, whether they can be injected and oriented in vivo. The results will be studied from the point of view of functional recovery and tissue reconstruction.

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