??? Bioparc Bordeaux Métropole F Pessac CNRS. Poietis

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1 ??? Bioparc Bordeaux Métropole F Pessac 1 / 23

2 Company Profile Business: Provide patients and clinicians with Regenerative Medicine Therapies based on Laser-Assisted Bioprinting Overview Founded in Sept Key Milestones INSERM spin-off Seed Capital Funding ( 1,3m) Located in Bordeaux, France 100 m² clean room lab I-LAB 2014 World Innovation Challenge 2016 (Phase I) 22 FTE (incl. 18 researchers) Partnerships with world-class leaders: BASF, L'Oréal IP: 7 patent families 2 / 23

3 Company Background Spun-out from pioneer lab. at INSERM, one of the largest government-funded life sciences Institute in EU Cell printing 1st Bioprinter 1st Bioprinting in vivo Modeling Project Bone Printing 3D Bioprinter 1st Laser Bioprinting company International Conference Bioprinting and Biofabrication 3 in Bordeaux (3B 09) 3 / 23

4 Interdisciplinary team Arthur Douillet, Data Modeling Aude Clapies, Bioengineering Bertrand Viellerobe PhD, CTO Bruno Brisson, CBO Caroline Sion, Cell Biology Claire Poiron, Cell Biology Delphine Fayol PhD, CPO Etienne Pagin, Tissue production Evarzeg Le Bouffant, Opto-mechanics Fabien Guillemot PhD, CEO & CSO Guillaume Simon, Software Guillaume Vandeneeckhoutte, Software Jennifer Garnier, Quality Management Jérôme Bouter, Laser Process Laurent van Steenkiste, Marketing Dir. Lydie Pilorget, Business Intelligence Marc Nicodeme PhD, Image Analysis Marie Lassalle, Admin & Finances Marine Salducci, Cell Biology Mikael Garcia PhD, Cell Biology Romain Vaucelle, Image Processing 4 4 / 23

5 Bioprinting Market Market: 8bn in 2025 (CAGR >16 % / Y from 2015) Source: Research&Markets Tissue product issues: Tissue Complexity The translation of scaffold-based tissue engineering therapies to clinical used remains a failure Vascularization S. Hollister, Tissue Eng. Part B Reviews (2011) Personalization Safety Regulatory compliance Cost-effectiveness 5 Few products into the EU market: - ChondroCelect - MACI - Holoclar 5 / 23

6 Tissue complexity Dynamic interactions between: (stem)-cells, morphogens and extracellular matrix Tissue formation Cell fate Griffith et al, Nature Rev. Mol. Cell Biol (2009) Lecuit & Le Goff, Nature (2007) cell level: nanotopography stiffness ligand density growth factors cell neighbors Homeostasis tissue level: 6 migration, polarization, sorting, gradients patterns 6 / 23

7 Relation between form and function McBeath et al. Dev. Cell (2004) Peerani et al. EMBO J, (2007) Creating adequate geometries of cells, cues, ECM (or even drugs) defined at the cellular scale. Engineering complex7and functional tissues Winer and Janmey, PlosOne (2009) 7 / 23

8 htp:// Bioprinting = 3D Printing + Biology the use of computer-aided transfer processes for patterning and assembling living and non-living materials with a prescribed 2D or 3D organization in order 8 to produce bio-engineered structures serving in regenerative medicine, pharmacology and basic cell biology studies. F. Guillemot, V. Mironov & M. Nakamura, Biofabrication (2010) 8 / 23

9 Competitive Landscape Laser Cell concentration (millions / ml) Bioextrusion Microvalve Ink-jet Resolution (µm) 9 / 23

10 Why resolution matters? Standardization Bioextrusion Laser-Assisted Bioprinting Safety Morphogenesis Control Complexity Functionality Patient-specific / 23

11 4D Bioprinting Platform To design and bioprint tissues at Single-Cell Resolution New standard in tissue manufacturing / 23

12 Cytocentric CAD / 23

13 Cytocentric CAD / 23

14 NGBNGB bioprinter Sterile Multi-modal 8-axis translation stage Control of T, hygrometry In line imaging control of cell deposition User-friendly interface / 23

15 Bioprinting of skin models Laser assisted bioprinting (LAB) 10 µm Poietis Bioprinter Microvalve printing ECM µm µm 15 / 23

16 Control of dermis bioprinting sequence F1 - Fibroblasts C2 - Collagen F2 - Fibroblasts 500 µm 500 µm 500 µm 500 µm 500 µm 500 µm 16 Cell pattern is maintained Precise positioning 16 / 23

17 What do we learn from time-lapse imaging? / 23

18 Self-assembly depends on cell type 1h 24h 48h 72h Human Corneal fibroblasts hadscs Human melanoma cells 18 Human Skin fibroblats 18 / 23

19 4D bioprinting paradigm Programming self-organisation from 1D to 4D Design appropriate 3D micropatterns of tissue components (cells, ECM ) to drive self-organisation so that specific tissue function emerges with time 1 Precision 2 Resolution 3 Layering 4 Self-organisation 19 / 23

20 Bioprinting in vivo, in situ Bioprinting mesenchymal stem cells into mouse critical size bone calvaria defect / 23

21 Effect of cell patterns on bone healing Day 0 Day 5 Day 0 Day 5 21 control control 21 / 23

22 4D bioprinting paradigm Programming self-organisation from 1D to 4D Design appropriate 3D micropatterns of tissue components (cells, ECM ) to drive self-organisation so that specific tissue function emerges with time 1 Precision 2 Resolution 3 Layering 4 Self-organisation + considering interactions with host (external) 22 / 23

23 Bioprinting vs. 3D cell culture? Specificities : Similarities - Cell sourcing / preparation / characterization - Printable ECM - Appropriate culture media - Bioprinter parameters - Computer Design of 3D tissues - Guiding self-organization: more than a robotic pipette! Benefits (on going) - Precise control of initial cell locations in 3D (by design + in line controls) Non planar DEJ - Reproductibility - Reduction of fabrication time - Customization and complexification µm 23 / 23