LETOURNEUR ICS 240111

Transcription

LETOURNEUR ICS 240111
3D Scaffolds for Cardiovascular Tissue Engineering
Didier Letourneur
Cardiovascular Bio-engineering - INSERM U 698
X. Bichat Hospital, University Paris 7 - Denis Diderot, 46 rue H. Huchard, 75018 Paris
Institut Galilée, University Paris 13 - Paris Nord, 93430 Villetaneuse
Cardiovascular diseases are the first cause of
mortality in the developed countries. Among these
diseases, those related to the vessel wall thickening
might require heavy surgery techniques such as
multiple bypasses. Current synthetic vascular grafts
used in cardiovascular surgery with less than 6 mm
diameter grafts have a low patency rate, mostly due to
acute thrombus formation and intimal hyperplasia.
We have developed new small-diameter
materials as an alternative for arterial replacement. In
one approach, we have used tubular pulullan/dextranbased grafts of 2 mm internal diameter, prepared and
molded by a cross-linking technique using sodium
trimetaphosphate. Using microsurgical techniques
with Wistar adult rats in infrarenal aortic bypass,
grafts withstood aortic blood pressure and exhibited
physiological blood flow, as evaluated with
ultrasound techniques and angiographies at 4 and 8
weeks post-surgery. Harvested grafts evaluated by
light
microscopy
and
immunohistochemistry
evidenced a neointima formation at 8 weeks with
collagen deposition and smooth muscle-like cells
circumferential growth on the luminal surface without
intimal hyperplasia or aneurysm formation.
In a second approach, polyvinyl alcohol (PVA),
a water-soluble synthetic polymer with excellent film
forming, emulsifying, and adhesive properties, was
cross-link with STMP to form hydrogels and
membranes suitable for biomedical applications. This
procedure requires no organic solvent, nor melting
process to obtain films with high mechanical strength.
The resulting material was successful to be used for
replacement of an arterial vessel in rat during without
mechanical or thrombotic complication. This crosslinking method confers to polyvinyl alcohol particular
mechanical properties such as compliance, elasticity
and resistance to mechanical stress, compatible with
the circulatory blood flow. Lastly, new 3D hydrogels
were prepared by copolymerization of acrylate and
polysaccharides. These polymers coated on surfaces
promoted endothelial cell regeneration.
In conclusion, the ability of these biocompatible
polymer-based grafts to support vascular tissue
synthesis proved to be quite successful. Applications
of these materials also included 3D scaffolds for cell
culture and pharmacotoxicological assays, hybrid
scaffolds to enhance tissue integration, and new
biocompatible materials for drug and gene delivery
by chemical functionalization of the materials.
References
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Didier Letourneur