Abstract :
[en] If the adoption of auto- or xeno- grafts is frequently used in surgery, this approach still raises several concerns, amongst other in terms of risk of rejection, infection, availability, limited amount, weakening of tissue or even pain for the donor. For all these reasons, regenerative medicine becomes more and more attractive, allowing to restore or replace tissues and organs, which have been damaged by diseases or trauma.
According to this new clinical approach, stem cells, specifically mesenchymal cells (MSCs) collected from the umbilical cord or from bone marrow or adipose tissues, are injected locally in order to progressively rebuild the deficient tissue. However, one of the main obstacles to the development of stem cell therapies is the very low number of available stem cells (~40,000 provided by the donor against 500 million needed to achieve efficient therapy). Moreover, upon implantation, MSCs are moving from their injection site and their survival rate is low in situ. In view of these two main bottlenecks to apply stem cell therapy in clinic, the adoption of biocompatible and biodegradable microcarriers could be helpful. Indeed these microparticles combine as main advantages : i) a large surface-to-volume ratio, ii) an easiness for parenteral administration without needs to detach MSCs, a main source for low survival rate iii) biocompatibility and biodegradability leaving place to tissue reconstruction.
To avoid any biocompatibility problems, these microcarriers have to be manufactured from FDA-approved degradable aliphatic polyesters. The degradation rate should be adjusted in order to guarantee the lifetime of the final product while promoting tissue reconstruction after implantation.
Our microcarriers have been designed in two stages. The first step represents the manufacture of the raw microbeads using an emulsion/evaporation process. The size of the resulting microcarriers have been easily adjusted between 180 and 350 microns by playing on the viscosity of the oil phase of the emulsion.
To promote cell adhesion and proliferation, microbeads have been functionalized by physical deposition of polyelectrolytes. The efficacy and stability of different coatings have been demonstrated using fluorescent polyelectrolytes labeled with fluorescein isothiocyanate (FITC) or rhodamine B. In order to adjust the thickness, stability and surface density of this coating, different polymers have been assessed differing in terms of macromolecular characteristics, i.e. molecular weight, charge density and chain mobility. Indeed, all these surface features of biomaterials are well known to influence the cellular behavior, including their mobility, gene expression or their cytoskeleton reorganization. After sterilization, the biocompatibility microbeads have been analyzed in vitro using classical cytotoxicity tests (MTT or Hoechst nuclear labeling).
