ANR projects

Reactivable photo-polymers for 3D additive fabrication

Coordinator : Jean-Louis Clément

Scientific leader IS2M : Arnaud Spangenberg

01/11/2020-31/10/2023

3D Printing has significantly lowered the barrier-of-entry in terms of cost, time and accessibility to micro-fabricated intricate shapes and sophisticated devices, in various fundamental research domains. 3D printers can manufacture objects with sizes ranging from few microns with two-photon stereolithography (TPS) to centimeter. In the field of microfluidics, the more “user-friendly” implementation and the easiness of 3D printing of complex structures digitally designed (3D CAD) compete the robust but heavy implementation of soft lithography. 3D printing allows direct and rapid fabrication of microfluidic chips. Among all 3D printing technologies, 3D printings based on stereolithography have attracted particular attention since sub-100 µm internal channel diameter has recently been demonstrated.

In this context, polymers are strategic materials. However, the main limitation relies on the fact that the properties of the chosen monomer impose the surface chemistry of the envisioned object. At technological level, substantial efforts have been devoted to improving writing devices (writing resolution and speed). However, little attention has been given to increasing the chemical diversity or surface functionalization of the written scaffolds. Today, it is not yet possible to modify the surface chemistry in a simple way from 3D printers other than robust but heavy and/or cumbersome post physical or chemical treatments. So mechanically compliant and chemically functionalized surfaces (polarity, texturing, biocompatibility, etc…) are still untenable. Moreover, it is a hard puzzle to solve when surface modifications are to be done at located place (patterning).

3D-CustomSurf project aims at developing new photo-initiator with advanced properties and new methodologies in additive manufacturing techniques 3DP-UV (mm to cm scale) and TPS (µm scale). Our strategy is grounded on the use of photoReversible-Deactivation Radical Polymerization (photo-RDRP) techniques adapted to the specific conditions of 3D manufacturing by photo-polymerization applied to microfluidics field where this will be an asset when specific patterning is needed. Indeed, surface modification of internal channels of a microfluidic device is still limited by multi-steps process.

Our strategy is grounded on i) the design and synthesis of unique photo-sensitive alkoxyamines containing specific chromophores for both 3DP-UV and TPS and the initiating moiety ii) a careful examination of their photo-physical and chemical properties iii) a thorough investigations of their efficiencies for first and re-polymerization (living polymerization) under laser writing (3DP-UV, TPS) iv) methodological investigations for first polymerization (3DP-UV) followed by inner surface functionalization (chemical and patterning) by TPS on simple prototypes (tubes) v) the fabrication of a microfluidic device with customized inner surface channels for double emulsion preparation.

Coupling laser writing with RDRP methodologies is a novel approach which has been poorly investigated notably in the field of TPS where no work has been reported with a such combination. Novelty and especially lack of thorough investigations about chemical and physical phenomena involved during the 3D fabrication process explain the absence of such approach in 3D laser printing area. Our strategy is expected to be a breakthrough in this field since .NMP2 coupled with 3D PrintingDLW allow to consider the object on the one hand and its surface modification (chemistry and structuration) on the other hand in a protocol of great simplicity. Our strategy is expected to be a breakthrough in this field.

 

Conception of bioresorbable self-rolled patchs for the local treatment of inflammation induced in the colon after irradiation

Coordinator : Noëlle Mathieu

Scientific leader IS2M : Karine Anselme

01/03/2020-31/08/2023

Pelvic cancers are among the most frequently diagnosed cancers worldwide. Radiotherapy (RT) plays a growing place in the management of malignant pelvic diseases. Even though great advances have been made in RT delivery techniques, radiation exposure of significant volumes of normal bowel persists, impacting on the patient’s quality of life post-treatment. Cancer incidence increases and mortality have been reduced during the past several decades, and the number of cancer survivors has almost tripled during the same period. With an increasing cohort of cancer survivors, efforts to manage the adverse effects of RT have to be intensified. Current therapies are merely palliative. Several drugs have been investigated to prevent the pelvic radiation disease (PRD), amifostine, derivative of 5-aminosalicylic acid (5-ASA), analog of prostaglandin, sucralfate and glucocorticoids but no curative treatment exists. Moreover, these pharmacologic molecules could induce adverse effects especially when they are delivered systemically with a prolonged use. We also demonstrated that cell therapy using mesenchymal stromal cells (MSC) gave encouraging results in animal models (rats and pigs), and could be a new perspective to induce regeneration of the colon.

Today, no medical device exists for the treatment of the colon despite the number of various colonic pathologies as inflammatory diseases. Few studies demonstrated poor results with hydrogel delivered by enema. The objective of OPENN is to develop an innovative medical device dedicated to the colon that could be easily implanted by surgeons using colonoscopy. This new medical device will be designed with self-rolling bilayer polymer films loaded with anti-inflammatory drugs or MSC. In situ, the self-rolled bilayer tube will unfold, selectively attach to the damaged area and release anti-inflammatory drugs or bioactive molecules produced by MSCs by directed diffusion toward the inflamed mucosa. The therapeutic benefit of this new patch will be tested in vivo in rat model developing colonic damages similar to those induced in patients suffering from severe side effects after radiotherapy.

OPENN project will be organized in Workpackages to develop self-rolled tubes with polymers (WP2), load the self-rolled tubes with anti-inflammatory molecules and analyse their release (WP3), develop the cellularized self-rolled tubes and control the cell viability (WP4), and test in rats model relevant to the human pathology induced after RT treatment, the therapeutic benefit of the devices on the structure and the function of the colon (WP5).

The OPENN project will have an impact in development and transfer of knowledge in the field of biomaterials and innovative implantable medical devices to reinforce the French position in this field. The potential of this project for commercialization is significant since systemic anti-inflammatory treatments used for chronic diseases induce numerous adverse effects. Moreover, the use of self-rolled patch loaded with MSCs is very innovative and will provide a new concept in regenerative medicine. The consortium of the OPENN project rallied skills of physicists, chemists and biologists towards a translational research problem dedicated to public health issue.

Mechanical Energy Storage and absorption in microporous materials by high-pressure intrusion of electrolyte solutions

Coordinator : Andrey Ryzhikov

Scientific leader IS2M : Andrey Ryzhikov

01/01/2020-30/12/2022

The project is devoted to development of new highly efficient heterogeneous lyophobic systems for mechanical energy storage and absorption based on high pressure intrusion-extrusion of electrolyte solutions in hydrophobic microporous materials such as pure-silica zeolites (zeosils) and Metal-Organic Frameworks. The understanding of intrusion mechanism at the atomistic and thermodynamic level is the main objective. The project includes the experiments on highly concentrated electrolyte aqueous solutions intrusion-extrusion in the porous solids with varying of cation and anion nature, the study of intrusion process by in situ calorimetry and molecular simulation of the process by Molecular Dynamics and Monte-Carlo methods.

Programmed drug release by rolled-up biopolymer capsules

Coordinator : Valeriy Luchnikov

Scientific leader IS2M : Valeriy Luchnikov

01/12/2017-30/11/2020

The pharmacokinetics of many medicaments : their resorbtion, distribution, methabolism and elimination depends on the hour of administration. As the consequence, these medicaments are more effective and/or better tolerated if taken at appropriate time. Non-uniform distribution of a medicament in a micro/nanoporous matrix media (tablets or capsules) constitutes an advanced approach to programming of diffusion-controlled drug release. However, creation of such media with complex distribution of the drugs is a challenging issue.  We propose a simple and cheap method to create biopolymer cylindrical capsules with complex radial distributions of the drugs, and aim to explore the potential of the method for chronotherapies. The approach consists in rolling up thin biopolymer films functionalized by one drug or several drugs. The drugs pattern will be created on the biopolymer film stripes by inkjet printing. The films will be then rolled up due to internal gradient stress. The kinetics of the drugs release will be studied in physiological media proposed in the 8th European Pharmacopeia, and compared to  numerical simulation models.

Germenene on band gap materials

Coordinator : Carmelo Pirri

Scientifique leader IS2M : Carmelo Pirri

01/10/2017 – 31/03/2021

The project aims at growing germanene, the germanium equivalent of graphene, and study the physics of Dirac fermions in this two-dimensional (2D) material. Indeed, germanene departs from conventional 2D electrons systems and graphene by a buckled atomic structure and a significant spin orbit coupling. It should thus form a rich playground for fundamental studies in low-dimensional physics. Based on the expertise recently gained with the growth of germanene on Al(111) by partners of this project, we want to explore the growth of van der Waals heterostructures, consisting of germanene and 2D layered materials, that allow to minimize the interaction between germanene and these supporting materials. For that purpose, our consortium will rely on state of the art in depth characterization tools at the nanoscale : synchrotron radiation, scanning probe microscopy at low temperature with multiple tips and time-resolved spectroscopy capability. Our analysis based on versatile multi-physical characterization will be compared with calculations performed in the framework of the density functional theory, highlighting the impact of the atomic arrangement on the band structure of germanene and how the nature of the substrate might perturb the structural and electronic properties of this remarkable sheet of Ge atoms. Relevant to this project will be the measurement of the Dirac cone hallmark, the band gap, the carrier mobility and the charge transfer from the underlying layer. Also, we will strive to demonstrate the existence of the quantum spin Hall effect, that is expected due to the substantial spin-orbit coupling in germanene. Of particular interest is the study of defects and lattice deformations, that opens the door to topological transitions, like the Kekulé distortion, causing the attachment of mass to Dirac Fermions. Because of the anticipated poor resistance of germanene to ambient conditions, what would severely limit a deeper characterization and prevent its use in spin/opto-electronic applications, efforts will also be devoted to encapsulate germanene. We want to achieve the growth of germanene on Al(111) ultra-thin films on silicon, followed by the removal of the Si parent substrate and the oxidation of the Al layer, and, to protect the top face of germanene with 2D layered materials transferred in ultra-high vacuum. These schemes will take place along with innovations in instrumentations, in particular Raman spectroscopy in ultra-high vacuum that is the tool of choice for fingerprinting 2D materials. French companies that are involved in the Equipex and Labex investment awards of two of the partner will benefit from transfers of know-how in advanced instrumentations. Progress in the field of the synthesis of germanene, in the understanding of the physics of this material and in the design of dedicated tools will be the key to turn germanene into practical technologies at the end of the project.

3D Photo-structuration of functional magnetic materials

Coordinator : Dominique Berling

Scientific leader IS2M : Dominique Berling

01/01/2017 – 31/01/2021

PHOTOMAGNET proposal proposes to develop new sol-gel matrices incorporating Magnetic Nanoparticles (NPM) homogeneously dispersed and which are photostructurable in 3D structures of sub-micron resolutions by two photon stereolithography (TPS). Last of all, demonstration of the applicative potentialities of these μ-structured functional nanocomposite materials will be achieved through two proofs of concept corresponding to a multifunctional material : photonic crystals and magnetothermal-μ structures.

The realization of 3D CMP seeks a Faraday rotation of exaltation than 1.5 microns by the own slow wave mechanism photonic crystals, while ensuring a good transmittance of micro-structured material. It is the interest of a realization by TPS which guarantees excellent uniformity of the microstructure compared to the self-organizing methods more typically employed to make CMP. Such a demonstration will completely lift the current lock Integration or micro-structuring conventional magneto-optical materials, lock that drastically limits the use of these materials in applications where they are nevertheless highly expected. For the magneto-thermal μ-structures, it is to build a network 2 D micro-pillars which are thermally activatable by application of an external magnetic field, this activation based on the own magnetic hyperthermia of NPM. Adapted for interaction with biological cells, these micro-nanostructured functional surfaces pave the way for the study of cellular events associated with hyperthermia. To characterize the best hyperthermia capacity NPM partners provide a magneto-optical measurement sensitive to internal temperature of these NPM during their thermal activation. Innovative compared with currently available tools, and coupled with the diversity of NPM available in the project, this measurement technique will, in no doubt, valuable information for the community on the mechanisms involved in magnetic hyperthermia.

This project is multidisciplinary and enforce the complementary skills of the three research groups involved in different scientific developments areas :

  1. i) Synthesis of functionalized NPM compatible with the selected matrix and exhibiting controlled magnetic properties will be a key initial step in this project.
  2. ii) The second ambitious challenge lies in the development of host matrices for NPM that will be photostructurable by two photon stereolithography. Several types of matrices are considered, hybrid sol-gel matrices (silane / acrylate) and matrices based on oxo-metallic clusters (Zr and Ti) whose structuration by TPS was recently validated.

iii) The interest will be demonstrated through two applications : resonant magneto-optical 3D structures and 3D microstructures presenting magneto thermic properties. In both cases, the TPS technique associated with these two photostructurable magnetic materials is the only technique to fabricate functional 3D complex microstructures.  Since TPS is a rapid prototyping technology, it enables to modify at will the design of structures in order to achieve their looked-for properties.

 

Photolatent N-Heterocyclic Carbenes for delayed ring-opening polymerizations

Coordinator : Julien Pinaud

Scientific leader IS2M : Abraham Chemtob

01/11/2016 – 20/04/2020

Photopolymerization is a well-established technology showing a growing interest because of significant economical and environmental advantages. Nevertheless, more than 95 % of films and coatings derived wherefrom are based on a radical process strongly inhibited by atmospheric oxygen. There is thus a high demand for novel non-radical photoinitiators. In this respect, N-Heterocyclic Carbenes (NHCs) have emerged as versatile ligands for organometallic catalyst but also as powerful organocatalysts for polymerization reactions (ring-opening, step-growth, anionic) over the past decade. NHCs are usually synthesized by deprotonation of an azolium salt with a strong base, but their generation in situ and “on demand” from thermally labile progenitors has attracted a lot of interests in the past few years. Interestingly, the generation of NHCs by a photochemical process has never been reported and an efficient photolatent NHCs has yet to be fully developed. PHOTON DROP project thus aims at developing a simple synthetic pathway to robust photolatent NHCs. They will be subsequently used as photoligands and photocatalysts in ring-opening metathesis and anionic polymerizations for key applications : film UV-curing and latex production.

 

IS2M

Bâtiment CNRS
15, rue Jean Starcky - BP 2488
68057 Mulhouse cedex

Bâtiment IRJBD
3 bis, rue Alfred Werner
68093 Mulhouse cedex

tel: (+33)3 89 60 87 00
fax: (+33)3 89 60 87 99

Réseaux sociaux

 

  

IS2M

Bâtiment CNRS
15, rue Jean Starcky - BP 2488
68057 Mulhouse cedex

Bâtiment IRJBD
3 bis, rue Alfred Werner
68093 Mulhouse cedex

tel: (+33)3 89 60 87 00
fax: (+33)3 89 60 87 99

Réseaux sociaux

 

  

IS2M

Bâtiment CNRS
15, rue Jean Starcky - BP 2488
68057 Mulhouse cedex

Bâtiment IRJBD
3 bis, rue Alfred Werner
68093 Mulhouse cedex

tel: (+33)3 89 60 87 00
fax: (+33)3 89 60 87 99

Réseaux sociaux