CECILE ECHALIER
Assistant professor, Faculty of Pharmacy, University of Montpellier
Cécile Echalier is a researcher at the Institute of Biomolecules Max Mousseron and temporary lecturer at the University of Montpellier with expertise in biomaterials and chemical biology.
She studied organic and biomolecular chemistry at the University of Montpellier. There, she dedicated her PhD to the synthesis and evaluation of biomimetic materials for tissue engineering applications. Her PhD work was recognized with a L’Oréal-UNESCO For Women in Science fellowship. After her PhD, she joined the European Molecular Biology Laboratory (EMBL) in Heidelberg, Germany. In collaboration with GlaxoSmithKline, she developed chemical tools to elucidate the mode of action of drug candidates. In 2019, she joined the Stevens group at Imperial College London, UK. She was awarded a Scientia fellowship through the Marie Sklodowska-Curie Actions to develop an islets-on-chip platform with integrated biosensors in collaboration with the University of Oslo, Norway. She recently returned to Montpellier to resume her research on biomimetic hybrid materials for regenerative applications.
Her accomplishments include the development of a novel and modular method to prepare hydrogels by the sol-gel process. In particular, she demonstrated that the sol-gel process can be used both for crosslinking and covalent functionalization of hydrogels. She rendered the process fully biocompatible, enabling living cells encapsulation, and reported the very first example of sol-gel ink for extrusion-based 3D printing.
Her current research interests focus on the design of biomaterials that can recapitulate the complexity of native tissues for applications in tissue engineering. To achieve this, she develops new crosslinking chemistries and uses different 3D printing techniques.
5 major publications
(1) Montheil, T.; Simon, M.; Noël, D.; Mehdi, A.; Subra, G.*; Echalier, C*. Silylated Biomolecules: Versatile Components for Bioinks. Frontiers in Bioengineering and Biotechnology 2022, 10:888437. https://doi.org/10.3389/fbioe.2022.888437
(2) Echalier, C.; Rutkowska, A.; Kojic, A.; Thomson, D. W.; Edwards, L. J.; McKay, B. S. J.; Mülbaier, M.; Schultz, C.; Bergamini, G. AmTCO, a New Trans-Cyclooctene Derivative to Study Drug-Target Interactions in Cells. Chem. Commun. 2021, 57 (14), 1814–1817. https://doi.org/10.1039/D0CC06709A.
(3) Echalier, C.; Levato, R.; Mateos-Timoneda, M. A.; Castaño, O.; Déjean, S.; Garric, X.; Pinese, C.; Noël, D.; Engel, E.; Martinez, J.; Mehdi, A.; Subra, G. Modular Bioink for 3D Printing of Biocompatible Hydrogels: Sol–Gel Polymerization of Hybrid Peptides and Polymers. RSC Adv. 2017, 7 (20), 12231–12235. https://doi.org/10.1039/C6RA28540F.
(4) Echalier, C.; Jebors, S.; Laconde, G.; Brunel, L.; Verdié, P.; Causse, L.; Bethry, A.; Legrand, B.; Van Den Berghe, H.; Garric, X.; Noël, D.; Martinez, J.; Mehdi, A.; Subra, G. Sol–Gel Synthesis of Collagen-Inspired Peptide Hydrogel. Materials Today 2017, 20 (2), 59–66. https://doi.org/10.1016/j.mattod.2017.02.001.
(5) Echalier, C.; Pinese, C.; Garric, X.; Van Den Berghe, H.; Jumas Bilak, E.; Martinez, J.; Mehdi, A.; Subra, G. Easy Synthesis of Tunable Hybrid Bioactive Hydrogels. Chem. Mater. 2016, 28 (5), 1261–1265. https://doi.org/10.1021/acs.chemmater.5b04881.
Simple and Specific Grafting of Antibacterial Peptides on Silicone Catheters
Advanced Healthcare Materials 5: 3067–3073, 2016. https://doi.org/10.1002/adhm.201600757
Abstract
To fight against nosocomial infection initiated by colonization of medical devices, a strategy enabling the direct and fast functionalization of silicone surfaces is proposed. This strategy proceeds in a site-specific way using original hybrid silylated antibacterial peptides. This safe and up-scalable method guarantees a covalent and robust immobilization with the correct orientation of the bioactive moiety. Importantly it also avoids multi-step chemical modifications of the surface or multi-layer polymer coatings. As proof of concept, antibacterial silicone catheter has been prepared whose immediate and long term efficiency is superior by comparison to similar silver-embedded materials.
Direct Synthesis of Peptide-Containing Silicones: A New Way to Bioactive Materials
Chemistry A European Journal, 26:12839-12845, 2020. https://doi.org/10.1002/chem.202001571
Abstract
A simple and efficient way to synthesize peptide-containing silicone materials is described. Silicone oils containing a chosen ratio of bioactive peptide sequences were prepared by acid-catalyzed copolymerization of dichlorodimethylsilane, hybrid dichloromethyl peptidosilane, and Si(vinyl)- or SiH-functionalized monomers. Functionalized silicone oils were first obtained and then, after hydrosilylation cross-linking, bioactive polydimethylsiloxane (PDMS)-based materials were straightforwardly obtained. The introduction of an antibacterial peptide yielded PDMS materials showing activity against Staphylococcus aureus. PDMS containing RGD ligands showed improved cell-adhesion properties. This generic method was fully compatible with the stability of peptides and thus opened the way to the synthesis of a wide range of biologically active silicones.
Silylated biomolecules: Versatile components for bioinks
Abstract
Physical hydrogels prepared from natural biopolymers are the most popular components for bioinks. However, to improve the mechanical properties of the network, in particular its durability for long-lasting tissue engineering applications or its stiffness for bone/cartilage applications, covalent chemical hydrogels have to be considered. For that purpose, biorthogonal reactions are required to allow the inclusion of living cells within the bioink reservoir before the 3D printing procedure. Interestingly, such reactions also unlock the possibility to further multifunctionalize the network, adding bioactive moieties to tune the biological properties of the resulting printed biomaterial. Surprisingly, compared to the huge number of studies disclosing novel bioink compositions, no extensive efforts have been made by the scientific community to develop new chemical reactions meeting the requirements of both cell encapsulation, chemical orthogonality and versatile enough to be applied to a wide range of molecular components, including fragile biomolecules. That could be explained by the domination of acrylate photocrosslinking in the bioprinting field. On the other hand, proceeding chemoselectively and allowing the polymerization of any type of silylated molecules, the sol-gel inorganic polymerization was used as a crosslinking reaction to prepare hydrogels. Recent development of this strategy includes the optimization of biocompatible catalytic conditions and the silylation of highly attractive biomolecules such as amino acids, bioactive peptides, proteins and oligosaccharides. When one combines the simplicity and the versatility of the process, with the ease of functionalization of any type of relevant silylated molecules that can be combined in an infinite manner, it was obvious that a family of bioinks could emerge quickly. This review presents the sol-gel process in biocompatible conditions and the various classes of relevant silylated molecules that can be used as bioink components. The preparation of hydrogels and the kinetic considerations of the sol-gel chemistry which at least allowed cell encapsulation and extrusion-based bioprinting are discussed.
3D high-precision melt electro written polycaprolactone modified with yeast derived peptides for wound healing
Abstract
In this study melt electro written (MEW) scaffolds of poly(ε-caprolactone) PCL are decorated with anti-inflammatory yeast-derived peptide for skin wound healing. Initially, 13 different yeast-derived peptides were screened and analyzed using both in vitro and in vivo assays.
The MEW scaffolds are functionalized with the selected peptide VLSTSFPPW (VW-9) with the highest activity in reducing pro-inflammatory cytokines and stimulating fibroblast proliferation, migration, and collagen production. The peptide was conjugated to the MEW scaffolds using carbodiimide (CDI) and thiol chemistry, with and without plasma treatment, as well as by directly mixing the peptide with the polymer before printing. The MEW scaffolds modified using CDI and thiol chemistry with plasma treatment showed improved fibroblast and macrophage penetration and adhesion, as well as increased cell proliferation and superior anti-inflammatory properties, compared to the other groups. When applied to full-thickness excisional wounds in rats, the peptide-modified MEW scaffold significantly enhanced the healing process compared to controls (p < 0.05). This study provides proof of concept for using yeast-derived peptides to functionalize biomaterials for skin wound healing.
Chemical cross-linking methods for cell encapsulation in hydrogels
Mater Today Comm., 2019, 20, 100536. doi: 10.1016/j.mtcomm.2019.05.012
Echalier C, Valot L, Martinez J, Mehdi A and Subra G.
Abstract
Cell-encapsulating hydrogels are of tremendous interest in regenerative medicine. Tissue engineering relies on biomaterials able to act as artificial extracellular matrices to guide cells towards the development of new tissues. Therefore, considerable efforts have been made to design biomaterials which mimic cells’ native environment, thus encouraging natural behavior. The choice of biomaterial in which cells are embedded is crucial for their survival, proliferation and differentiation. Being more stable, chemical hydrogels are preferred over physical hydrogels as cell-laden substrates. When designing chemical hydrogels, scientists must choose not only the nature of the network (synthetic and/or bio-polymers) but also the type of cross-link bridging hydrogel constituents. For that purpose, numerous chemistries have been used (i) to introduce reactive functions on the hydrogel precursors and (ii) to form covalent bonds in the presence of living cells. The review will discuss the advantages and limitations of each strategy.
Self-mineralization and assembly of a bis-silylated Phe–Phe pseudodipeptide to a structured bioorganic–inorganic material
Mater. Horiz., 2019, 6, 2040-2046 doi: 10.1039/C9MH00580C
Jebors S, Valot L, Echalier C, Legrand L, Mikhaleff R,Van Der Lee A, Arenal R, Dumy P, Amblard M, Martinez J, Mehdi A and Subra G.
Abstract
Self-mineralization of a trialkoxysilyl hybrid peptide yields in a single step a nanostructured hybrid material. A bis-silylated pseudodipeptide inspired from the Phe–Phe dipeptide was used to program the assembly by sol–gel polymerization under heterogeneous conditions, in water at pH 1.5 without any structure-directing agent. A mechanism deciphering the hybrid material assembly was proposed thanks to 1H NMR spectroscopy. First, water-insoluble hybrid building blocks were hydrolysed into their soluble silanol counterparts. Then, these transitional species, thanks to hydrogen bonding and π–π stacking, self-assembled in solution. Last, the proximity of the silanol moieties favoured their polycondensation into growing siloxane oligomers, which spontaneously precipitated to produce an ordered hybrid material.
Inorganic polymerization: an attractive route to biocompatible hybrid hydrogels
J. Mater. Chem. B, 2018,6, 3434-3448, doi 10.1039/C8TB00456K
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Abstract
As an intermediate state between liquid and solid materials, hydrogels display unique properties, opening a wide scope of applications, especially in the biomedical field. Organic hydrogels are composed of an organic network cross-linked via chemical or physical reticulation nodes. In contrast, hybrid hydrogels are defined by the coexistence of organic and inorganic moieties in water. Inorganic polymerization, i.e. the sol–gel process, is one of the main techniques leading to hybrid hydrogels. The chemoselectivity of this method proceeds through hydrolysis and condensation reactions of metal oxide moieties. In addition, the mild reaction conditions make this process very promising for the preparation of water-containing materials and their bio-applications.
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
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.
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.
