Conception d'un revêtement bioactif pour implant cardiovasculaire par la méthode du layer-by-layer

Abstract

The Layer-by-layer (LbL) technique is an interesting approach to modify implant surfaces to improve biocompatibility and clinical performance. The main objective of this project is to conceive an LbL coating that is able to promote vascular smooth muscle cell (VSMC) adhesion, proliferation and migration on and around stent grafts, an implant used to treat abdominal aorta aneurisms (AAA) in a minimally invasive way. For the purpose of this project, several LbL coatings were prepared, including some which contain fibroblast growth factor (bFGF) intended to be released and stimulate VSMC. The developed films were made of chitosan (CHI, chondroitin sulfate (CS), collagen (COL), as well as bFGF, and were built according to the following structures: a) [CS/CHI]; b) [CS/COL] et c) [CS/CHI]-[CS/bFGF]-[CS/COL]. They were characterized by techniques such as quartz crystal microbalance (QCM-D), contact angle, ellipsometry, atomic force microscopy (AFM), enzyme-linked immunosorbent assay (ELISA) and by cell culture tests on VSMC (adhesion, growth and survival). The feasibility of creating such an LbL coating was demonstrated by the QCM-D results that show a mass addition after every polyelectrolyte deposition leading to a linear growth of the film, as confirmed by ellipsometry. The contact angle and AFM results exhibited alternating angles as well as change in roughness between the depositions showing that the coatings are grown in an LbL fashion. The LbL [COL/CS] were more efficient than [CHI/CS] coatings to promote cell adhesion. ELISA results showed that [CS/CHI]-[CS/bFGF]-[CS/COL] films are able to accumulate and release bFGF. The survival tests on VSMC with bFGF in solution showed that a 10ng/ml concentration was sufficient to significantly improve cell survival. However, for the tested conditions, since the amount of released growth factor is much smaller than the one tested in vitro, the effect of the LbL on VSMC survival is uncertain. In conclusion, although additional testing is needed, the LbL coatings are a promising approach to stimulate healing around stent grafts in order to improve fixation to the blood vessel and to limit aneurysm progression.

Date	9 Sept 2014
Original language	French
Awarding Institution	École de technologie supérieure
Supervisor	Sophie Lerouge (Supervisor)