Right Ventricular Outflow Tract Regeneration: Last Development of the TEH-Tube Project
david kalfa1, Paul Hommes-Schattmann2, Bilal Ahmad3, Margaux Pontailler4, Axel Neffe2, Marilys Blanchy5, Gareth Williams6, Philippe Menasché7, Andreas Lendlein8, Pierre Pouponneau9.
1TEH-Tube scientific coordinator, Columbia University, NYC, NY, USA, 2Institute of Biomaterial Science and Berlin-Brandenburg Centre for Regenerative Therapies, Helmholtz-Zentrum Geesthacht, berlin, Germany, 3UCL School of Pharmacy, Department of Electrospinning, University College London, London, United Kingdom, 4INSERM U 970, PARCC & Laboratory of Biosurgical Research, Paris, France, 5Rescoll, Bordeaux, France, 6UCL School of Pharmacy, Department of Electrospinning, University College London, london, United Kingdom, 7Department of Cardiovascular Surgery, Hôpital Européen Georges Pompidou; University Paris Descartes, Sorbonne Paris Cité, Paris, France, 8Institute of Biomaterial Science and Berlin-Brandenburg Centre for Regenerative Therapies, Helmholtz-Zentrum Geesthacht, Berlin, Germany, 9Statice SAS, Besacon, France.
OBJECTIVE - Conduits currently used to reconstruct the right ventricular outflow tract (RVOT) have no growth potential and require reoperations. To date, all available materials fail to display the chemical, mechanical and biological features matching the requirements to develop a growing valved tube for children. We present the last result of the TEH-Tube program aiming at developing a tissue engineered heart valve for pulmonary valve replacement METHODS - Polyester-based degradable new-generation polymers were synthetized based on innovative chemical concepts and processed by electrospinning. In vitro fibre morphology, mechanical properties and crystallinity were analysed. Patches of electrospun polymers were implanted in the inferior vena cava of 90 rats: group 1: new-generation non-functionalized polymer (n=30); group 2: new-generation functionalized polymer (n=30); group 3: blends of off-the-shelf polymers (polyurethane/polycaprolactone) serving as controls (n=30). Valved tubes were manufactured by electrospinning and were implanted in a growing lamb model. In vivo results were analyzed by echography, MRI, biological, mechanical and chemical testing. RESULTS - Electrospinning of new-generation polymers led to the formation of highly organized fibres. Mechanical properties were tailorable by fine-tuning electrospinning settings, molecular weight and polymer composition. This new-generation polymer showed a trend towards a better in-situ tissue regeneration (less stenosis, better endothelial function, elastin-enriched extracellular matrix) in the rat model. Mechanical properties tended to replicate those of the native tissue. An advanced design of the valved tube based on computer-assisted designing techniques allowed for the production of second-generation polymeric tubes. Short follow-up of the valve shows a good functionning of the valve in vivo in the large animal model. CONCLUSIONS - The THE-Tube valve offers great promise in the development of scaffolds to match the anisotropic properties of the native RVOT, and paves the way to a future bioresorbable device to replace the RVOT in children.
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