Fabien Guillemot. BioTis INSERM U1026 Group Tissue Engineering Assisted by Laser (TEAL)

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1 La reconstruction d organes par Impression 3D Fabien Guillemot BioTis INSERM U1026 Group Tissue Engineering Assisted by Laser (TEAL) fabien.guillemot@inserm.fr Phone: Fax: XMP-Biotech,

2 Context: Tissue Engineering Challenges: C Blitterswijk, Book Tissue Engineering (2008) Tissue Engineering needs process engineering D. Williams, Nature Biotechnology (2005) Tissue Complexity Vascularization Cost-effectiveness Skin graft Customization Safety Regulation XMP-Biotech,

3 Tissue Complexity Dynamic interactions between: (stem)-cells, morphogens and extracellular matrix cell fate tissue formation Homeostasis Griffith et al. Nature Rev. Mol. CellBiol, 2009 Lecuit& Le Goff, Nature (2007) At cell level: - nanotopography -stiffness - ligand density - growth factors - cell neighbors - gradients, patterns At tissue level: - cell migration - collective behavior - cell sorting - XMP-Biotech,

4 Our approach: dealing with tissue complexity using Bioprinting kick-off 1 st bioprinter 3B'09 3D bioprinter cell printing in vivo 3D controlling3d distribution of cellsand cues using Laser-Assisted Bioprinting drivingtissue self-organization(4 th D) to produce functional tissues B. Guillotin & F. Guillemot, Trends in Biotechnology(2011) XMP-Biotech,

5 3D Printing + Biology = Bioprinting Transformational technology Gartner Institute, 2012 Duality digital -biology Robotized fabrication of complex, personalized tissues XMP-Biotech,

6 Bioprinting: an old story inkjet graphics plotter First 3D assembly : 2 layers of collagen XMP-Biotech,

7 Bioprinting technologies Inkjet (thermal, piezo) Bioplotting (extrusion through syringe) Laser Acoustic Droplet Ejection Laser - Assisted Bioprinting XMP-Biotech,

8 Laser-Assisted Bioprinting (principle) XMP-Biotech,

9 Numerical modeling of jet formation Hydrocode CHIC (CELIA) High pressure in the apex area (singular point) Mezel et al. Phys. Plasma (2009) 2 jets are created: bubble collapsing droplet ejection Interaction of the bubble with the free surface: by analogy to studies on cavitation dimensionless coefficient: Γ = h / R max - h film thickness - R max E, viscosity (Pearson, Engineering Analysis with Boundary Elements, 2004) XMP-Biotech,

10 Development of Laser-Assisted Bioprinters 1st bioprinter: delivered in 2007 (a collaboration with NovaLase S.A. (Canéjan, France)) 2 nd bioprinter: delivered end-2013 (a collaboration with Alphanov (Talence, France) XMP-Biotech,

11 Cell printing: main focus Cell function Viability Resolution Multicolor printing Speed / high throughput XMP-Biotech,

12 Critical parameters for controlling cell viability Cell injuries may be associated with: i) bioinkcomposition (e.g.: glycerol), ii) interactions of cellular components withlight (UV DNA), iii) thermal effect iv) pressure generatedduringbubblegrowth, v) shear stress within the jet (viscosity, jet speed) vi) landing conditions (hydrogel thickness + ink viscosity) Day 0 Day 2 Day 15 Viability of Human Osteoprogenitors(HOP) after printing (Live/dead assay) XMP-Biotech,

13 Current project: 3D bioprinting of human cornea Bioprinting human keratocytes XMP-Biotech,

14 4D Bioprinting: 4 th Dimension isself-organisation.. to create objects that can change after they are printed, making them self-adapting. Theactofprintingisnolongertheendofthecreativeprocessbutmerelyawaypoint. S. Tibbits(MIT) G. Villar et al., Science (2013) Mesenchymal stem cells onto collagen XMP-Biotech,

15 Bioprinting in vivo, in situ Aim: demonstrating feasibility of bioprinting in vivo Bioprinting mesenchymal stem cells into mouse critical size bone calvaria defect XMP-Biotech,

16 Start-up Emergence, 2012 On demand fabrication of human tissues for: - research(pharma and cosmetic industry) - Personnalizedmedicine - grafting(regenerative medicine) XMP-Biotech,

17 La reconstruction d organes par impression 3D Fabien Guillemot Tissue BioEngineering Lab(BioTis U1026) Group Tissue Engineering Assisted by Laser (TEAL) fabien.guillemot@inserm.fr Phone: Fax: XMP-Biotech,

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