LPPI

Postdoc (24M) :3D Electrostimulable polymeric scaffolds for drug screening-applications

Publié le 20.05.19

A two-year postdoctoral position is opening at the Institute of Materials (iMat) of the University Paris-Seine (Cergy-Pontoise). The project includes two labs of iMat: LPPI (Polymer chemistry) and ERRMECe (Biology)

Context


In vivo, cells are surrounded by the extracellular matrix (ECM), a 3D-meshwork of macromolecules. A great variety of dynamic biochemical, biophysical, topographical and electrical clues emanates from ECM. They govern cell survival, differentiation and others behaviors, and subsequently physiopathological processes. Especially, the microenvironment modulates cell phenotype and could subsequently orient cells’ response to drug agents and targeted therapies1. To take into account this native 3D-environment in cell-based assays, various supports have been developed. They are classified as scaffold-free (like spheroids) or scaffold-based supports (hydrogels, porous/fibrous scaffold) and are made respectively from natural ECM-derived molecules or synthetic material.2 Among common synthetic commercial scaffolds, there are microfabricated scaffolds and the widely described electrospun fiber mats. Poly(High Internal Phase Emulsion) (polyHIPEs) presenting interconnected porous structures, have been described also as really promising 3D templates3,4 but are, up to now, only available at laboratory scale.


Despite their advantages in terms of robustness, reproducibility and tunability in comparison to natural ECM-derived materials, these synthetic scaffolds rarely incorporate ECM molecules, thus losing the “biochemical component” of cell microenvironment. Moreover, such scaffolds display limited and uncontrolled dynamic and often lack the combined regulatory inputs as porosity, elasticity, topography, or electrical clues from the ECM that all contribute to modulating cell survival and functions.5 In this context, the emergence of electroactive materials is of critical interest to mimic the environment of demanding cells regarding mechanical, morphological or electrical stimulation. Such materials represent a fast growing field and rely on the coatings of 3D porous structures with conducting materials. For instance, graphene coating on silk fibroin fiber mats, providing electrical conduction, improved the differentiation of PC-12 cells into neural phenotypes.6 Coating with a conducting polymer (polyaniline) on similar scaffolds allowed electrical stimulation and enhanced differentiation of myogenic (muscle) C2C12 cells.7 In addition to simple electrical conduction, conducting polymers (CPs), as electroactive polymers, can also provide additional functions rarely described in this field. Indeed, they are also able to change shape/volume and/or mechanical properties when electrochemically oxidized or reduced. Actually, when CPs are stimulated using low potentials (~ 1V), exchanges (insertion/expulsion) of counter-ions with surrounding electrolyte takes place, leading to electrochemically controllable volume changes8 thus, allowing both electrical and mechanical stimulations.


LPPI has described the first rubbery electroactive electrospun scaffolds based on elastomer (Nitrile Butadiene Rubber) and polyethylene oxide (PEO) functionalized by a conducting polymer (poly(3,4-ethylenedioxythiophene) (PEDOT).9,10 Not evaluated yet as electroactive cell culture scaffolds, they presented promising actuation and beating functionalities in the presence of phosphate buffered saline (PBS). Preliminary data suggest their cytocompatibility. More recently conducting polymer coating has been used by Jager et al. to provide mechanical beating functionality to poly(lactic-co-glycolic acid) (PLGA) electrospun fibers and resulted in increased expression of cardiac markers of stem cells.11 Nevertheless this unique example of mechanically active culture scaffolds displayed limited volumevariations due to the high stiffness of PLGA fibers, highlighting the need of soft and rubbery 3D templates for efficient electroactive behavior. It is worth mentioning that polyHIPEs have never been functionalized by any electroactive material contrary to electrospun fiber mats.

Project

In the frame of 3DEStim, we propose:

  • To develop 3D electroactive scaffolds for cell culture combining both electrical and mechanical stimulation. Such materials will be elaborated first from highly porous polyHIPE structures. A conducting polymer will be embedded into this matrix by oxidative chemical vapor phase polymerization of corresponding monomer.
  •  To functionalize these scaffolds with adhesive ECM glycoproteins for displaying controlled

properties and signal dynamic of in vivo cell environments. The cells responses to such ECMcontaining
scaffolds will be then studied.

  • To establish the proof of the concept of using such a device for drug response screening, firstly focusing on anticancer drug response, especially of ovarian cancer metastasis by tuning the scaffold to model their peritoneum implantation site, which displays in vivo dynamic resulting from breathing, digestion, and bodily movements.

Thereafter, capitalizing on the acquired know-how, the 3D electoactive scaffold features as well as its ECM functionalization will be adapted to varied cell types in regard with the desired drug assays

Candidate Profile

Education

  • PhD in Polymer Chemistry or biomaterials

Competencies

  • Relevant research experience and demonstrated competencies in polymer and material synthesis. Experience in biomaterials and cell culture would be an asset
  • Track record of researcher dissemination including peer-reviewed publications
  • Ready to work according to best chemical or biology laboratory practices including lab safety.
  • Excellent project management, analytical, and report writing skills.
  •  Excellent communication skills (oral, written, presentation).
  • Demonstrated ability to generate new ideas, concepts, models and solutions.
  • Collaborative skills, initiative, result oriented, organization, and capacity to work in an interdisciplinary environment.

Language

  •  French and/or English

Requirement

  •  less than 6 months in France since the last 3 years.

Contacts

Cedric.plesse@u-cergy.fr
Cedric.vancaeyzeele@u-cergy.fr
Johanne.leroy-dudal@u-cergy.fr

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1 Jebsen N. L. et al. Biomarker Panels and Contemporary Practice in Clinical Trials of Targeted Therapy. in Biomarkers of the Tumor
Microenvironment. 2017
2 Knight at al. J Anat. (2015), 227(6): 746–756.
3 Moglia R.S. et al. Biomacromolecules (2014), 15, 2870−2878.
4 McGann C.L. et al. Polymer (2017), 126, 408-418
5 Kofron et al. J Physiol (2017), 595(12), 3891-3905.
6 Aznar-Cervantes et al. Materials Science and Engineering: C (2017), 79, 315-325
7 Zhang et al. Macromolecular Bioscience (2017) 17(9), 1700147
8 Otero et al. J. Mater. Chem. B, 2016, 4, 2069--2085
9 Kerr-Phillips et al. J. Mater. Chem. B, 2015,3, 4249-4258
10 Kerr-Phillips et al. Biosensors and Bioelectronics, 2018, 100, 549-555, ISSN 0956-5663

11 Gelmi et al. Adv. Healthcare Mater.2016, 5, 1471–1480

Postdoc (12M) : Development of dielectric elastomeric materials for cardiac assistance

Publiée le 07/11/2018

  • Duration: 12 months
  • Salary: ~ 2990 €/month (gross)
  • Scientific theme (disciplinary field): Materials chemistry
  • Host laboratory: Laboratoire de Physicochimie des Polymères et des Interfaces (LPPI) – Université de Cergy-Pontoise  (France)
  • Background: Thesis in polymer materials.
  • Skills: General knowledge of polymer synthesis methods and their mechanical and electrical characterization.

LPPI (Laboratory of Physicochemistry of Polymer and Interfaces) from University of Cergy Pontoise wants to recruit a postdoctoral fellow for one year starting from January 2019.

 

  • Subject

Electroactive polymers (EAPs) are materials capable of changing shape or volume under the action of electrical stimulation. They therefore have a strong development potential in the field of actuators, precursors of artificial muscles. Among these materials, dielectric elastomers (DEs) are the subject of much research given their high deformation capacity and their high breakdown voltage for producing lightweight actuators with good energy efficiency. The study of their electromechanical properties shows that, for optimal performance, these materials must have high dielectric permittivity and stretching rate, and low dielectric losses and viscoelastic damping.

LAI (Laboratory of Integrated Actuators) of the Ecole Polytechnique Fédérale de Lausanne wishes to use this technology to create an implantable cardiac assist device. However, the specific energy densities of the existing materials are insufficient. In this context, LPPI is seeking to develop new dielectric elastomeric materials. For this purpose the candidate will synthesize new elastomers and / or produce original formulations, then characterize their mechanical properties (stress-strain, viscoelasticity, etc.) and electrical properties (dielectric constant, breakdown voltage, etc.) so as to obtain material meeting a list of specifications. Some of these characterizations can be done at LAI and the adequacy of the envisaged solutions with biocompatibility and integration constraints in the human body will also have to be considered.

 

  • Candidate profile

Doctor in chemistry with a polymer specialty.

Main skills

General knowledge of synthesis methods and characterization of polymer materials, in particular the techniques of mechanical (DMA, traction ...) and electrical (resistivity, breakdown voltage ...) analysis. Experience in the field of dielectric elastomeric materials in general and / or on silicone-based materials would be a plus.

Additional skills

Synthetic, good oral and written communication skills in French and English.

 

  • Contact person to candidate and/or to have informations:

Dr. Philippe Banet - Laboratoire de Physicochimie des Polymères et des Interfaces

philippe.banet @ u-cergy.fr

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