Blanc SIMI 7 - Sciences de l'information, de la matière et de l'ingénierie : Chimie moléculaire, organique, de coordination, catalyse et chimie biologique

Low Molecular Weight Gelators as versatile supramolecular scaffolds for stem cell culture and tissue engineering – GELCELLS

A multidisciplinary approach for the development of new gel matrices for applications in the field of regenerative medicine.

The work carried out in the framework of the «GelCells« project focuses on the physicochemical and biological properties of hydrogels formed from bio-inspired amphiphilic molecules. The work carried out under this program has highlighted a very good tolerance of the hydrogels in vivo and their absence of cytotoxicity in vitro. The new materials feature unique physicochemical and biological properties that are particularly suitable for tissue engineering.

Results

The new supramolecular hydrogels scafold feature remarkable properties such as cytocompatibility and biocompatibility, injectability, slow degradability and induction of differentiation in vitro and in vivo. The in vivo bone regeneration has been demonstrated from scaffolds resulting from supramolecular gels based on a glyco-nucleo-fluorocarbon compound. Recently, we demonstrated for the first time the possibility of controlling the fate of stem cells (ASC stem cells) using a non-polymeric supramolecular system (patent 2014 EP14290302.0). Research works linked to these discoveries are currently developped in collaboration with various startups and academic groups (Labex AMADEUS and Regenerative Medicine Pole Bordeaux).

Prospects

The proposed technology of supramolecular matrices ( patent 2014 EP14290302.0 ) allows new applications in the fields of tissue engineering and « bio printing «. Our technology is currently used in the context of several collaborations with various startups and academic groups ( Labex AMADEUS and Regenerative Medicine Pole of Bordeaux).

Scientific productions and patents

Brevet
1. «Glycosylated nucleo bola-amphiphlile as new LMWG for biomedical applications»
Barthélémy, P.; Ramin M.; Latxague L.; Appavoo A.; Chassande O. Erhret C. (2014), EP14290302.0.

Publications
1. « Controlling stem cell behavior by fine tuning the supramolecular assemblies of Low Molecular Weight Gelators »
Latxague L.; Appavoo A.; Chassande O. Erhret C. and Barthélémy, P. (2014), submitted.

2. « Decontamination of nanoparticles from aqueous samples using low molecular weight gels»
Patwa A. ; Labille, J. ; Bottero JY. ; Thiéry, A. ; and Barthélémy, P. (2014), submitted.

3. « Glycosyl-nucleolipids as new bioinspired amphiphiles »
Latxague L, Patwa A, Amigues E, Barthélémy P. (2013) Molecules, 18(10):12241-63. doi: 10.3390/molecules181012241.

4. « A thermosensitive low molecular weight hydrogel as scaffold for tissue engineering »
Ziane S, Schlaubitz S, Miraux S, Patwa A, Lalande C, Bilem I, Lepreux S, Rousseau B, Le Meins JF, Latxague L, Barthélémy P, Chassande O. Eur Cell Mater. (2012) 23;23:147-60.

5. « Glycoside Nucleoside Lipids (GNLs) : An intrusion into the glycolipids' world ? »
Latxague L, Dalila MJ, Patwa A, Ziane S., Chassande O., Godeau G. Barthélémy P. C. R. Chim., 15 (2012) 29-36.

6. « Glycosylated nucleoside lipid promotes the liposome internalization in stem cells »
Latxague L, Ziane S, Chassande O, Patwa A, Dalila MJ, Barthélémy P. Chem Commun (Camb). (2011) 21;47(47):12598-600

Submission summary

This proposal is foccused at developing a Low Molecular Weight Gel (LMWG) technology to serve as a smart scaffold for stem cell culture and in situ delivery systems. GELCELLS is based on the complementary chemistry/biology expertises of two partners. The methodology utilized in the proposed studies will marry the expertise of organic chemistry, physico-chemistry, cellular biology, stem cell cultures and a range of techniques to accomplish a comprehensive description of the systems developed.
To achieve this ambitious goal, the following tasks have been defined and are listed below. All the tasks can be achieved within the time frame of this project (see figure and table below for the link between the different workpackages of this program).

1. Coordination (INSERM U869, U. Bordeaux)
2. Synthesis of GNLs (INSERM U869, U. Bordeaux)
3. Physico-chemical studies (INSERM U869, U. Bordeaux). Identification of the key physical and structural characteristics of the LMWGs
4. Cells/hydrogel interaction studies in 2D and 3D systems (INSERM U577)
5. Study of nucleic acid entrapment and release (INSERM U869, U. Bordeaux)
6. Transfection assays with matricial systems (INSERM U577, INSERM U869, U. Bordeaux)

The following results will be used for patents and/or publications:
• Library of glycosylated GNLs
• A control of the molecular, supramolecular and physicochemical properties of the LMWG gel matrix and their influence on the cell fate
• Successful stem cell culture in LMWG systems
• Controlled entrapment and delivery of nucleic acids by the LMWGs matrices
• Successful in situ transfection in 2D and 3D matrix

Philippe Barthélémy (INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE - DELEGATION DE BORDEAUX) – philippe.barthelemy@inserm.fr

The author of this summary is the project coordinator, who is responsible for the content of this summary. The ANR declines any responsibility as for its contents.

U869 ARNA, équipe ChemBioMed INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE - DELEGATION DE BORDEAUX
INSERM U577 INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE - DELEGATION DE BORDEAUX

Help of the ANR 310,000 euros
Beginning and duration of the scientific project: - 36 Months

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