Aujourd hui Didier Letourneur BIOMATERIAUX Conception de systèmes 3D pour l ingénierie tissulaire Futur? BIOMATERIAUX Médecine Régénératrice/réparatrice Problèmes après 60 années de recherche et de développement! Implants intra-occulaires (25% de reinterventions)! Prothèses de hanche (10-15 ans)! Implants dentaires (infections)! Prothèses vasculaires (pas d endothélialisation)! Valves cardiaques (calcifications ou thromboses)! Implants mammaires (contraction capsulaire) Matériaux, Biomatériaux, Ingénierie tissulaire 2000 Nouveau domaine. Biomaterials!!! «Biomaterials» and «Tissue Engineering»! United States National Library of Medicine! 4000! 3500! 3000! 2500! 2000! 1500! 1000! 500! 0! 1984! 1988! 1992! 1996! 2000! Years! 800! 700! 600! 500! 400! 300! 200! 100! 0! Tissue Engineering! 1
Nicolas L Heureux, Cytograft, CA, USA Arteriovenous shunt in humans 1st clinical trial of a tissue-engineering bladder in USA Atala et al, The Lancet, 2006, 367: 1241 Nature Medicine 2006 collagen/ PLGA SMCs Lancet 2009 Urothelial cells Principe thérapeutique général Avec un support (scaffold) Cellules&souches& Cellules Localisation anatomique des cellules souches dans différents tissus. Construction 3D Biocompatible, biodégradable. Trois tissus ont un renouvellement rapide (1-2 mois): Les cellules souches y fonctionnent ainsi en permanence pour renouveler les cellules de la peau (et du système pileux), des villosités intestinales et du système hématopoétique. Biology STEM CELLS Chemistry SCAFFOLD 2
Grellier et al, Trends Biotechnology, 2009, 27:526 Nanoscale Nanoscale (nm) => Nanomedicine Macro-scale (cm) Human-scale (m) Cell-scale (µm) How&to&do&?& A cellularized 3D Scaffold 3
Bea1ng&areas&on&scaffolds& Cellules Souches Embryonnaires Humaines Day 11 Day 18 hes-derived cardiomyocytes Bea1ng&areas&in&3D&scaffolds& Formes et tailles multiples : Matrices 3D 0.3 mm Epaisseur 0.6 mm 0.8 mm 1 mm 2 mm 4 mm 6 mm 8 mm Diamètres*2*et*4mm* Diamètre*20*mm* Diametre Matrices poreuses à base de polysaccharides hes-derived cardiomyocytes retain their contractility in 3D conditions for weeks Hamidi S, Tissue Eng, 2014 Formes*variées* 2 brevets 2010 Composites* MATRICES FOR TISSUE REGENERATION STRUCTURE*OF*A*BLOOD*VESSEL* Bone Regeneration Osteoinduction / osteoconduction Animal models : mice, rat, goat Skin Regeneration Burns, irradiations (rat) and healing (pig) empty Adven@ce* Fibroblasts* Media* External*Elas@c*Lamina* Smooth*Muscle*Cells* Funding ANR Emergence 2011-2014 ANR Tecsan 2012-2015 Matrix Funding Jour 4 Jour Fondation de l Avenir 2011-2012 25 Collaboration Collaboration Inserm U1026 (Bordeaux) CRSSA (Grenoble) IMMATIS, SAS Fricain JC, Biomaterials, 2013 In@ma* Internal*Elas@c*Lamina* Endothelial*Cells* Blood* 4
3D&VASCULAR&ENGINEERING&& STRUCTURE*OF*A*BLOOD*VESSEL* Volume 22, Number 11 ISSN 0963-6897 E-ISSN: 1555-3892 CELL TRANSPLANTATION The Regenerative Medicine Journal CoIculture:*progenitors*endothelial*cells*+*mesenchymal*stem*cells* Collabora@on*:*F*Gazeau,*C*Wilhelm,*CNRSIUniv*Paris*7* Fayol et al, Cell Transplant 2013 Fayol et al, Nov 2013. Cover Cell Transplantation Nano/micro porous systems SubIcutaneous*injec@on*in*mice& Morphology of freeze-dried microspheres analyzed by scanning electron microscopy Fluorescent hydrated microspheres prepared with FITC-dextran observed with a confocal microscope 24*hours* cells* cells* Beads* After hydratation Patent, 31/08/2011 Hydratation with cells Ø&200I300*µm,*beadsIFITC,*SC* Histology,&SC* Tissue&engineering& From%preclinical%models%to%clinical%applica0ons% Materials Tissue** Engineering* Di*Maggio*N*et*al.,*Biomaterials*2011,*32:321* Preclinical evaluation From small to large animals 5
Tissue&engineering& Preclinical%models,%industrializa0on%and%clinical%applica0ons% Preclinical evaluation From small to large animals? Clinical evaluation M A R K E T Research Polymer Chemistry Characterizations 3D Matrices & Cell assemblies Chemistry Engineering Polymer Chemistry Engineering Biology In vitro In vivo Medical imaging for tissue engineering Medicine Engineering Biology Cell Biology Molecular Biology Medicine In vivo Experiments Medical imaging Aujourd hui Merci de votre attention Quand? didier.letourneur@inserm.fr http://www.u1148.fr 6