April 2018 Bioprinting Landscape: Technology and Trends Report BROWN UNIVERSITY – SENIOR THESIS INQUIRY THOMSON, ANDREW Table of Contents Executive Summary ............................................................................................................... 4 Introduction .......................................................................................................................... 7 Value Proposition ..........................................................................................................................7 Research Approach ........................................................................................................................8 Secondary Research: Multiple Search Sources ................................................................................................... 9 Primary Research: Expert Interviews .................................................................................................................. 9 Section 1: Fundamental Bioprinting Information .................................................................. 11 Bioprinting Technology Overview ................................................................................................. 11 Bioprinting History ....................................................................................................................... 13 Terminology Clarification: Biofabrication, Bioprinting and Bioassembly ......................................... 17 Why Bioprinting? ......................................................................................................................... 17 Microtissue Construction Processes: Biomimicry, Self-assembly and Bioassembly ......................... 22 Short- and Long-Term Goals ......................................................................................................... 24 Short-Term Goals ............................................................................................................................................... 24 Long-Term Goals ................................................................................................................................................ 25 Section 2: Vascularized Tissues ............................................................................................. 26 The Vasculature Issue .................................................................................................................. 26 Human Vascular Anatomy Overview............................................................................................. 27 Arteries, Capillaries and Veins ...................................................................................................... 29 Lymphatic System ........................................................................................................................ 30 Micro-network Processes: Vasculogenesis and Angiogenesis ......................................................... 31 Vasculogenesis ................................................................................................................................................... 31 Angiogenesis ...................................................................................................................................................... 32 Section 3: Bioprinting Approaches and Modalities ................................................................ 34 Macro-network Definition ............................................................................................................ 34 Micro-network Definition ............................................................................................................. 35 Macro-network Approaches ......................................................................................................... 36 Scaffold-Based (SB) ............................................................................................................................................ 36 Droplet and Inkjet (DBB) ................................................................................................................................... 38 Microextrusion (MBB) ....................................................................................................................................... 42 Laser (LBB) .......................................................................................................................................................... 47 Stereolithography (SBB) .................................................................................................................................... 50 Scaffold-Free (SFB) ............................................................................................................................................. 51 Micro-Network Approaches ......................................................................................................... 55 Guided Organization .......................................................................................................................................... 55 In vivo Integration .............................................................................................................................................. 57 Section 4: The Bioprinting Industry ....................................................................................... 61 Andrew Thomson, April 2018 Not for public disclosure or reproduction without written consent 1 Market Overview and Macro-Trends ............................................................................................ 62 Industry Player Archetypes: Producers, End-Users and Watchers .................................................. 63 Industry Archetype: Producers .......................................................................................................................... 63 Industry Archetype: End-Users .......................................................................................................................... 64 Industry Archetype: Watchers .......................................................................................................................... 64 The Bioprinting Pathway .............................................................................................................. 65 Industry-Wide Technical Limitations ................................................................................................................ 65 Technical Limitation – Vascularization Issue .................................................................................................... 67 Technical Limitation – Characterization Issue .................................................................................................. 67 Value Chain and Administrative Considerations .............................................................................................. 69 Bioinks ................................................................................................................................................................ 70 Bioprinters .......................................................................................................................................................... 71 Tissue Producer Companies............................................................................................................................... 74 Bioprinted Tissue Products ................................................................................................................................ 77 Product Commercialization Timeline ................................................................................................................ 80 Funding and Workforce Development .............................................................................................................. 81 Collaborations .................................................................................................................................................... 83 Regulatory and Intellectual Property Concerns................................................................................................ 85 Potential Opportunity Areas......................................................................................................... 87 Potential Opportunity Area: Large-Diameter Vascular Grafts ......................................................................... 88 Potential Opportunity Area: Small-Diameter Vascular Grafts ......................................................................... 90 Conclusion and Future Directions ......................................................................................... 92 Section 1: Key Findings and Takeaways ......................................................................................... 93 Section 2: Key Findings and Takeaways ......................................................................................... 93 Section 3: Key Findings and Takeaways ......................................................................................... 94 Section 4: Key Findings and Takeaways ......................................................................................... 94 Bioprinting Pathway Conclusions .................................................................................................. 90 Characterization Issue Guideline ........................................................................................................................ 96 Bioink Developmental