Thèses en cours

Student name : Eve RANDRIANARIDERA
Title : Safe Silicone implants : Towards Zero-migrating, Zero-impact Silicone Products
Thesis director : Karine ANSELME
Co-supervisors : Isabelle BRIGAUD, Hatice MUTLU, Arnaud PONCHE

Summary :  Since the last two decades, use of silicone implants have expanded significantly especially in the field of plastic surgery. Most silicone implants are composed of a solid cross-linked silicone elastomer shell and a liquid gel filling containing a mixture of low-molecular-weight silicone fluids. Regardless of the implant’s location and type, a broad spectrum of chronic inflammatory-related diseases has been observed after implantation. Even without sign of rupture, implant biocompatibility is challenged by the presence of silicone liquid droplets and solid debris diffusing to the periprosthetic tissue, a fibrotic capsule surrounding the implant as a result of the foreign body reaction. Evidence supports the major role played by permeation-driven flow of silicone and platinum (Pt) catalyst species through the shell membrane. The PRCE ANR project SAFE-IMPLANT will achieve a clear understanding of which silicone and Pt species are able to permeate through a silicone elastomer membrane (shell) and their specific immune response. Through this knowledge-based approach, we will develop a new generation gel-filled silicone implant preventing the leaching of toxic species (zero-migration) into the tissue or releasing only products with minimal inflammatory impact (zero-impact). Our inter-disciplinary research consortium consists of the Institut Européen des Membranes (IEM) at Montpellier and the Institut de Science des Matériaux de Mulhouse (IS2M) with recognized expertise in membrane permeation and cellular interactions of silicone material, respectively. They will work in collaboration with the research-intensive SME STATICE at Besançon specialized in the engineering and design of medical silicone devices.

Student name : Nadiia ZUBCHUK
Title : Development of optimal functional surface for intraosseous implants
Thesis director : Karine ANSELME

Summary : The aim of the thesis is to contribute to the development of new endosseous implant surface topographies based on a new concept in surface science : the ‘Multiscale Smart Texturing’.
The first part of the doctoral work consists in defining the topographies to be produced, based on an integrated approach to the literature in the field. By quantitatively considering a considerable body of data found in the bibliography, the concept is to design new functional surfaces with optimal topography using an original methodology based on a new knowledge management tool.
Once these new functional surfaces with controlled topography will be produced using innovative femtolaser-based manufacturing techniques, the in vitro interactions of proteins and cells with these surfaces will be studied to provide a proof of concept for this approach and to determine the most osteoconductive topographies.

Student name : Dorra BEN ELKADHI
Title : Nanoparticles in blood : optimization and control of the protein corona
Thesis director : Lionel MAURIZI
Co-supervisors : Arnaud PONCHE

Summary :  Nanomedicine is a research area that has seen its public interest growing during the last twenty years. The possibility to use and modify physicochemical properties of nanoparticles (NPs) to target and cure any area in the body is becoming more and more encouraging.
However, there are still some problems for the further development of nanoprobes such as the control of their biological behavior. In fact, once in contact with biological fluids, especially in blood, the main access route to the organism, plasma proteins will cover randomly NPs’ surface. This protein corona will then affect the clearance, potential toxicity and targeting efficiency of NPs.
This project aims, first, to innovatively study the physicochemical parameters influencing in vivo biodistribution and blood response of injected model NPs used as medical imaging contrast agent.
The goal is to link biological observations to the formation in vivo on the plasma protein corona on NPs. Thus, nanohybrids bio-functionalized with less interactions and toxicity will be developed for medical imaging or therapy. In depth studies of the behaviors of these new nanohybrids in blood will also be investigated for a global understanding of their optimized biological fates.

Student name : Aurora DE LA O ESPADAS
Title : Development of microfluidic instrumented device to study and optimize interactions between nanoparticles and blood’s proteins
Thesis director : Thérèse LEBLOIS (Femto-ST, Besançon)
Co-supervisors : Franck CHOLLET (Femto-ST, Besançon), Lionel MAURIZI

Summary :  Development of nanomedicine is slow down because of the lack of analyses mimicking living system.
In fact, the vast majority of biological analyses is done in a static way and this approach does not allow a quick transposition of academic results to pharmaceutical industries. Furthermore, blood interactions of NPs irrevocably influence biological behaviors of nanohybrids developed for nanomedicine. Proteins/NPs interactions, called the protein corona, is a crucial parameter to understand and control in order to optimize NPs development.
At the beginning of the project, NPs functionalized with different chemistries will be synthesized. Iron oxide NPs could be chosen as their magnetic properties allowed their use in medical imaging (MRI) and for biological magnetic separation. Surface chemistries with different charges and molecules will be added to the iron oxide NPs. Then, these NPs will be tested in different fluids from the simplest (water) to the most complex (blood).
The goal is to link biological observations to the formation in vivo on the plasma protein corona on NPs. Thus, nanohybrids bio-functionalized with less interactions and toxicity will be developed for medical imaging or therapy. In depth studies of the behaviors of these new nanohybrids in blood will also be investigated for a global understanding of their optimized biological fates.