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Séminaires MSC
"Matière et Systèmes Complexes"

                      
Lundi 31 mai 2010 à 11h30
Bâtiment Condorcet, 4ème étage, salle 454 A.

Didier Letourneur
(Inserm U 698)

Polymeric 3D Scaffolds for Cardiovascular Tissue Engineering

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 membrane devices suitable for biomedical applications. This procedure requires no organic solvent, nor melting process to obtain films with high mechanical strength. The resulting membrane was successful to be used for replacement of an arterial vessel in rat during without mechanical or thrombotic complication. This cross-linking 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 were demonstrated to promote 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, hybrid scaffolds to enhance tissue integration, and new biocompatible materials for drug and gene delivery by chemical functionalization of the materials.

References

Robert, D.; Fayol D.; Le Visage, C.; Frasca, G.; Brulé, S.; Ménager, C.; Gazeau, F.; Letourneur, D.; Wilhelm, C. Magnetic micro-manipulations to probe the local physical properties of porous scaffolds and to confine stem cells. Biomaterials. 2010; 31(7):1586-95.

Poirier-Quinot, M.; Frasca, G.; Wilhelm, C.; Luciani, N.; Ginefri, J. C.; Darrasse, L.; Letourneur, D.; Le Visage, C.; Gazeau, F., High resolution 1.5T magnetic resonance imaging for tissue engineering constructs: a non invasive tool to assess 3D scaffold architecture and cell seeding. Tissue Eng Part C Methods 2010, 16(2) :185-200.

Lavigne, D.; Guerrier, L.; Gueguen, V.; Michel, J.B.; Boschetti, E.; Meilhac, O.; Letourneur, D.; Culture of human cells and synthesis of extracellular matrix on materials compatible with direct analysis by mass spectrometry. Analyst, 2010, 135(3) :503- 511.

San Juan, A.; Bala, M.; Hlawaty, H.; Portes, P.; Vranckx, R.; Feldman, L. J.; Letourneur, D., Development of a functionalized polymer coating in the arterial delivery of small interfering RNA. Biomacromolecules 2009, 10(11): 3074-80.

Hlawaty, H.; San Juan, A.; Jacob, M. P.; Vranckx, R.; Letourneur, D.; Feldman, L. J., Local matrix metalloproteinase 2 gene knockdown in balloon-injured rabbit carotid arteries using nonviral-small interfering RNA transfection. J Gene Med 2009, 11(1): 92-9.

Abed, A.; Deval, B.; Assoul, N.; Bataille, I.; Portes, P.; Louedec, L.; Henin, D.; Letourneur, D.; Meddahi-Pelle, A. A biocompatible polysaccharide hydrogel-embedded polypropylene mesh for enhanced tissue integration in rats. Tissue Eng Part A 2008,14(4), 519-27.

Chaouat, M.; Le Visage, C.; Baille, W. E.; Escoubet, B.; Chaubet, F.; Mateescu, M. A.; Letourneur, D., A novel cross-linked poly(vinyl alcohol) (PVA) for vascular grafts. Advanced Funct Materials 2008, 18, (19), 2855-2861.

C. Le Visage, F. Chaubet, A. Autissier, D. Letourneur. Method for preparing porous scaffold for tissue engineering. PCT WO/2009/047347, 2009.

C. Le Visage, D. Letourneur. Method for preparing porous scaffold for tissue engineering, cell culture and cell delivery. PCT WO/2009/047346, 2009.