PhD candidate: Mathilde CHAMPEAU
Date and place of defence: November 4, 2014 - University of Bordeaux, France.
A major area of active research in biopolymers consists in designing materials with appropriate chemical, physical, mechanical and structural properties for use in tissue engineering and regenerative medicine. In order to regenerate a large tissue defect or restore an organ, the standard approach consists in using a highly porous extracellular matrix (or scaffold) as a substrate that will support adequate cellular activity (e. g. attachment, proliferation, differentiation or migration) and optimize tissue regeneration while avoiding any undesirable local or systemic responses in the eventual host. As a further design consideration, bioactive molecules can be incorporated into such devices in order to use them as carriers for controlled delivery. In this context, supercritical fluid (SCF) technology that has already proven to be valuable for many pharmaceutical applications appears to be a promising technique for the preparation of biocompatible three-dimensional structures loaded with bioactive molecules suitable to be used in regenerative medicine.
The objective of the present work is to explore a variety of polymers that could be foamed and loaded with drugs using supercritical fluid technology. The work programme includes a detailed study of the swelling of various polymers by SCF, the solubility of bioactive molecules in SCF as well as the kinetic of the impregnation as a function of the pressure and temperature. Gas foaming experiments will be performed on the selected polymers/drugs systems and the foaming conditions will be investigated in order to control the pore morphology (open porosity) and size (suitable for cells invasion). Foams porosity will be characterized by electron microscopy (see figure) coupled to image analysis and tomography. The influence of the drug loading on the foaming process will also be studied. In vitro drug release studies will be carried out and the most promising materials will be submitted to in vivo biological testing. The properties of the obtained scaffold will be investigated by both in-situ and ex-situ experiments (e. g. AFM, SEM, FTIR, Raman spectroscopy, mechanical testings).
The research will be performed in close collaboration with two academic research groups from UB1 (Bordeaux, France) and ULG (Belgium) having an expertise in the study of the solvation phenomena of low molecular weight compounds and polymers in SCF’s and in the synthesis and foaming of polymers using SCF’s respectively. The industrial partner COVIDIEN (USA), having a plant located in Trévoux (France), is a global healthcare products company that manufactures, distributes and services a diverse range of industry-leading product lines, including medical devices/supplies, pharmaceutical products, diagnostic imaging agents and other healthcare products and services.
Image left: Pieces of a biodegradable polymer before (left) and after (right) foaming in scCO2
Image right: Scanning electron micrograph showing the porous structure of a foam prepared by scCO2
UB1 - ISM (Institute for Molecular Science, Bordeaux) - characterisation, modelling
ULG - CERM (Center for Macromolecular Research, Liege) - polymer processing and synthesis
COVIDIEN, France - in vivo investigation, up-scaling