Category: A. Mehdi

Sol-gel synthesis of collagen-inspired peptide hydrogel

 Materials Today , Pages: Ahead of Print, Journal, 2017,  DOI: 10.1016/j.mattod.2017.02.001

C. Echalier, S. Jebors, G. Laconde, B. Guillaume, V. Luc, C. Pascal, B. Lea, A. Bethry, B. Legrand, H. Van Den Berghe, X. Garric, D. Noel, J. Martinez, A. Mehdi, G. Subra

Abstract

Conceiving biomaterials able to mimic the specific environments of extracellular matrixes are a prerequisite for tissue engineering applications. Numerous types of polymers (PEG, PLA, etc.) have been used for the design of biocompatible scaffolds, but they are still less efficient than natural biopolymers such as collagen exts. Chem. modified and loaded with different bioactive factors, biopolymers afford an environment favorable to cell proliferation and differentiation. Unfortunately, they present several drawbacks, such as weak batch-to-batch reproducibility, potential immunogenicity and high cost of prodn. Herein we propose a fully synthetic covalent hydrogel obtained by sol-gel polymn. of a silylated peptide. We selected a short and low mol. building-block derived from the consensus collagen sequence [Pro-Hyp-Gly]. Interestingly, the sol-gel process occurs in physiol. buffer, enabling the embedment of stem cells. This collagen-inspired hydrogel provides a cell-friendly environment comparable to natural collagen substrates, demonstrating its potency as a biomimetic scaffold.

-Modular bioink for 3D printing of biocompatible hydrogels: sol-gel polymerization of hybrid peptides and polymers

RSC Advances, 2017, Volume: 7, Issue: 20, Pages: 12231-12235, DOI: 10.1039/C6RA28540F

C. Echalier, R. Levato, M. A. Mateos-Timoneda, O. Castano, S. Dejean, X. Garric, C. Pinese, D. Noel, E. Engel, J. Martinez, A. Mehdi, G.Subra

RCS materials

Abstract

An unprecedented generic system allowing the 3D printing of peptide-functionalized hydrogels by soft sol-gel inorg. polymn. is presented. Hybrid silylated inorg./bioorg. blocks are mixed in biol. buffer in an appropriate ratio, to yield a multicomponent bioink that can be printed as a hydrogel without using any photochem. or org. reagent. Hydrolysis and condensation of the silylated precursors occur during the printing process and result in a covalent network in which mols. are linked through siloxane bonds. The viscosity of the colloidal soln. used as bioink was monitored in order to set up the optimal conditions for extrusion printing. Grid-patterned hydrogel scaffolds contg. a hybrid integrin ligand were printed using a pressure-driven rapid prototyping machine. Finally, they were seeded with mesenchymal stem cells, demonstrating their suitability for cell culture. The versatility of the sol-gel process and its biocompatibility makes this approach highly promising for the prepn. of tailor-made cell-laden scaffolds.

Unambiguous and Controlled One-Pot Synthesis of Multifunctional Silica Nanoparticles

Chemistry of Materials, 2016, Volume: 28, Issue: 3, Pages: 885-889, DOI: 10.1021/acs.chemmater.5b04398

J. Ciccione, T. Jia, J .L. Coll, K. Parra, M. Amblard, S. Jebors, J. Martinez, A. Mehdi, G. Subra 

Abstract

A method for obtaining in a single step well-defined tunable multifunctional fluorescent particles having their surface functionalized with multiple covalently linked ligands is reported.  The strategy relies on the synthesis of hybrid bioorg.-inorg. peptide ligands, greatly simplifying the design of multifunctional nanoparticles.  It was possible to tune the ratio of two grafted ligands on the surface of the SiNPs simply by adjusting the relative concn. of hybrid species in the starting soln.  An original fluorine NMR method was applied to the dissolved SiNPs to demonstrate our hypothesis.

Easy Synthesis of Tunable Hybrid Bioactive Hydrogels

Chemistry of Materials, 2016, Volume: 28, Issue: 5, Pages: 1261-1265,  DOI: 10.1021/acs.chemmater.5b04881

C. Echalier, C. Pinese, X. Garric, H. Van Den Berghe, E. Jumas Bilak, J. Martinez, A. Mehdi, G. Subra 

Abstract

Hydrogels are raising an increasing interest in the biomedical field and have found applications in tissue engineering and regenerative medicine.  In order to mimic the complexity of natural tissues, functionalization of hydrogels with bioactive mols. is of first importance.  In this context, we developed a bottom-up approach based on the synthesis of hybrid silylated blocks that can be combined to obtain covalently functionalized gels.  In this study, hybrid silylated PEG and hybrid silylated bioactive peptides were synthesized and mixed in desired ratio before being simply dissolved in phosphate buff-er at physiol. pH to form a gel.  The soln. turns quickly into a covalent functional gel at 37 °C.  Mech. properties of these hydrogels were studied and their biocompatibility was demonstrated.  Depending on the type of bioactive peptides introduced within the gels, they exhibited either antibacterial or cell adhesion properties demonstrating the potency of this sol-gel modular strategy for fine tuning of gel properties.

Selective homodimerization of unprotected peptides using hybrid hydroxydimethylsilane derivatives

RSC Advances, 2016, Volume: 6, Issue: 39, Pages: 32905-32914, DOI: 10.1039/C6RA06075G

C. Echalier, A. Kalistratova, J. Ciccione, A. Lebrun, B. Legrand, E. Naydenova, D. Gagne, J. A. Fehrentz , J. Marie, M. Amblard, A. Mehdi, J. Martinez, G. Subra 

Abstract

We developed a simple and straightforward way to dimerize unprotected peptide sequences that relies on a chemoselective condensation of hybrid peptides bearing a hydroxydimethylsilyl group at a chosen position (either C-ter, N-ter or side-chain linked) to generate siloxane bonds upon freeze-drying. Interestingly, the siloxane bond sensitivity to hydrolysis is strongly pH-dependent. Thus, we investigated the stability of siloxane dimers in different exptl. conditions. For that purpose, 29Si, 13C and 1H NMR spectra were recorded to accurately quantify the ratio of dimer/monomer. More interestingly, we showed that 1H resonances of the methylene and Me groups connected to the Si can be used as sensitive probes to monitor siloxane hydrolysis and to det. the half-lives of the dimers. Importantly, we showed that the dimers were rather stable at pH 7.4 (t1/2 ≈ 400 h) and we applied the dimerization strategy to bioactive sequences. Once optimized, three dimers of the growth hormone releasing hexapeptide (GHRP-6) were prepd. Interestingly, their pharmacol. evaluation revealed that the activity of the dimeric ligands could be switched from agonist to inverse agonist depending on the position of dimerization.

A new way to silicone-based peptide polymers

Angewandte Chemie, 2015, Volume: 54, Issue: 12, Pages: 3778-3782,  DOI: 10.1002/anie.201411065

S. Jebors, J. Ciccione, S. Al-Halifa, B. Nottelet, C. Enjalbal, C. M’Kadmi,  M. Amblard, A. Mehdi, J. Martinez, G. Subra

Abstract

We describe a new class of silicone-contg. peptide polymers obtained by a straightforward polymn. in water using tailored chlorodimethylsilyl peptide blocks as monomeric units.  This general strategy is applicable to any type of peptide sequences, yielding linear or branched polymer chains composed of well-defined peptide sequences.