3D Bioprinting: Strategies and Applications
Transcript of 3D Bioprinting: Strategies and Applications
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3D Bioprinting: Strategies and ApplicationsProf Yeong Wai Yee
Singapore Centre for 3D Printing
HP-NTU Digital Manufacturing Corp Lab
School of Mechanical & Aerospace Engineering
Nanyang Technological University
www.yeongresearch.com
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#1World’s Best Young
University 2014 – 2021
QS Top 50 Under 50
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Flagship 3D Printing research centres @ NTU
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Realize new applications for different industries.
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Design of tissue for Bioprinting
Oil and gas applications
Aerospace industry construction design
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3D Bioprinting: The inevitable
5Increasing shape and bioactivity complexity
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3D Bioprinting
6Murphy & Atala, Nature Biotechnology 32(8), 2014
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3D Bioprinting • Are we there yet?
https://www.biogelx.com/bioprinting-wth-ihydrogels/ https://3dprint.com/235208/bioprinting-101-part-2-hydrogels/
https://www.brinter.com/press-and-news/what-is-3d-bioprinting-part-1-of-6-history-and-significance/
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• Conflicting requirements on materials
• Soft and porous hydrogel -friendly to cells but not friendly to process
• High printability material -Good shape fidelity but challenging to host cells inside the material
Material-process relationship
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Systems Thinking in 3D Bioprinting
9Murphy & Atala, Nature Biotechnology 32(8), 2014
It’s an overall strategies !
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3D Bioprinting Current Strategies in Materials and Processes
https://www.advancedsciencenews.com/3d-printed-heart-with-patients-own-cells/
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Strategizing printing processes: Extrusion Bioprinting
• Jia Min Lee; Wai Yee Yeong. (2016). Design and Printing Strategies in 3D Bioprinting of Cell-Hydrogels: A Review. Advanced Healthcare Materials, 5(22), 2856-2865.
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Current Strategies in Materials: Material-design
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Optimizing viscosity of bio-ink
Semi-crosslinked, additive of thickening agent
[1] W. Schuurman, P. A. Levett, M. W. Pot, P. R. van Weeren, W. J. A. Dhert, D. W. Hutmacher, et al., "Gelatin-Methacrylamide Hydrogels as Potential Biomaterials for Fabrication of Tissue-Engineered Cartilage Constructs," Macromolecular Bioscience, vol. 13, pp. 551-561, 2013.
[1]
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Hydrogel with high Printability Small batch production
Suntornnond, R., Tan, E.Y.S., An, J. et al. A highly printable and biocompatible hydrogel composite for direct printing of soft and perfusable vasculature-like structures. Sci Rep 7, 16902 (2017). https://doi.org/10.1038/s41598-017-17198-0
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Current Strategies in Materials : Tool-design
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Co-extrusion of bio-ink and crosslinker
Crosslinker
Bio-ink
Q. Gao, Y. He, J.-z. Fu, A. Liu, and L. Ma, "Coaxial nozzle-assisted 3D bioprinting with built-in microchannels for nutrients delivery," Biomaterials, vol. 61, pp. 203-215, 8// 2015.
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Current Strategies in Materials : Time-design
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Sequential deposition of precursor and crosslinker
Hydrogel with rapid crosslink mechanism
C. Li, A. Faulkner-Jones, A. R. Dun, J. Jin, P. Chen, Y. Xing, et al., "Rapid Formation of a SupramolecularPolypeptide–DNA Hydrogel for In Situ Three-Dimensional Multilayer Bioprinting," Angewandte ChemieInternational Edition, vol. 54, pp. 3957-3961, 2015.
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Current Strategies in Materials: Process-design
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Deposition of bio-ink into crosslinker Science Advances 23 Oct 2015: Vol.
1, no. 9, e1500758DOI: 10.1126/sciadv.1500758 Three-dimensional printing of complex biological structures by freeform reversible embedding of suspended hydrogels
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Strategies in Process : Indirect Bioprinting to achieve high resolution using low viscosity hydrogels
• Improved line resolution
Printing of high-resolution 3D construct
Edgar Y.S. Tan1, Ratima Suntornnond1,*, Wai Yee Yeong1,2 “High resolution novel indirect bioprinting of low viscosity cell-laden hydrogels via model-support bioinksinteraction”, 3D PRINTING AND ADDITIVE MANUFACTURING ( accepted paper)
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Resolution of cells : Droplet-based bioprinting process
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Wei Long Ng*, Jia Min Lee*, Wai Yee Yeong, May Win Naing (2017) Microvalve-based bioprinting - process, bio-inks and applications. Biomaterials Science DOI:10.1039/C6BM00861E 5, 632 - 647
Advantages: high resolution can be achieve
Disadvantage:Cells consolidation inside the catridge
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Resolution of cells ( consistency and control)
Wei Long Ng, Jia Min Lee, Wai Yee Yeong, and May Win Naing. "Microvalve-based bioprinting–process, bio-inks and applications." Biomaterials Science (2017). DOI: 10.1039/C6BM00861EWei Long Ng, Wai Yee Yeong, and May Win Naing. "Polyvinylpyrrolidone-based bio-ink improves cell viability and homogeneity during drop-on-demand printing." Materials 10, no. 2 (2017): 190.
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To investigate the droplet profile with and without cells, using high speed imaging , on-going work with HP-NTU digital manufacturing corp lab
Droplet impact
Increasing resolution using micro or nanodroplet
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• Resolution of print
• Shapes • Control on
Cells Location ( resolution of cells)
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Bioprinting is LIVE
Beyond just shape and cell deposition.
The function of the cells is also critical
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Bioink with tunable stiffness for Directed Cell Response
Shi P, Laude A, Yeong WY. 2017. Investigation of cell viability and morphology in 3D bio-printed alginate constructs with tunable stiffness. J Biomed Mater Res Part A105A:1009–1018.
Day 7 culture , L929
Cell has more space to accommodate & reproduce
Cell is moderately restrained , may migrate in blebbing shapes
Cells formed spheroids
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Functional Extrusion Bioprinting with Cell Alignment
Directing Cell Alignment for Cardiac Patch
Jia Min Lee, and Wai Yee Yeong. "Engineering macroscale cell alignment through coordinated toolpath design using support-assisted 3D bioprinting." Journal of the Royal Society Interface 17, no. 168 (2020): 20200294
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Cell patterning
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Bilayer photoreceptor-retinal tissue model: cell distribution
Shi, Pujiang, Yong Sheng Edgar Tan, Wai Yee Yeong, Hoi Yeung Li, and Augustinus Laude. "A bilayer photoreceptor-retinal tissue model with gradient cell density design: A study of microvalve-based bioprinting." Journal of Tissue Engineering and Regenerative Medicine 12, no. 5 (2018): 1297-1306.
F-actin ZO-1 Claudin-1
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Interdisciplinary nature of 3D Bioprinting
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Interface of Biology: Bioprinted In Vitro Models
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Many organs can be bioprinted, and these physiologically relevant bioprinted in vitromodels could substitute the a combination of animal and in vitro data to supportdecision making.A M Holmes et al, Biofabrication 9 ( 2017 ) 033001
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3D Printed Microfluidics Chip
• Jia Min LEE, Meng ZHANG, Wai Yee YEONG. (2016). Characterization and evaluation of 3D printed microfluidic chip for cell processing. Microfluidics and Nanofluidics, 20(1), 1-15
• 3D printing provides design freedom in micro-to-macro fluidics chip designs.
Enable new capabilities in cells processing, and cell-encapsulated droplets production.
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Biology +
Electronics
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Flexible 3D Printed Electronics (aerosol jet printing)
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Low cost and flexible carbon nanotube pH sensor for live cell applications
Wearable Bandage based Strain Sensor for Home Healthcare
A Low Cost and Flexible Carbon Nanotube pH Sensor fabricated using Aerosol Jet Technology for Live Cell Applications, Sensors and Actuators B: Chemical, 260, 227-235.
Wearable Bandage-Based Strain Sensor for Home Healthcare: Combining 3D Aerosol Jet Printing and Laser Sintering, ACS Sensors, 4(1), 218-22 DOI: 10.1021/acssensors.8b01293
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3D bioprinted flexible and biocompatible hydrogel bioelectronic platform
Biosensors and Bioelectronics,102, 365-371
Living cells inside hydrogel
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Bioprinting: Beyond Biology
• Advanced Simulation for 3D printing • Digital nature of 3D Printing enabled data-
driven approaches and machine learning • AI for Bioprinting
Goh, G.D., Sing, S.L. & Yeong, W.Y. A review on machine learning in 3D printing: applications, potential, and challenges. Artif Intell Rev (2020) https://doi.org/10.1007/s10462-020-09876-9Joel Heang Kuan Tan, Swee Leong Sing & Wai Yee Yeong (2020) Microstructure modelling for
metallic additive manufacturing: a review, Virtual and Physical Prototyping, 15:1, 87-105, DOI: 10.1080/17452759.2019.1677345
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Shape Fidelity - Free Form Bioprinting (BioCADapproach) using support-build material + robotics
2) Generating appropriate support structure
GelMA
Pluronic
Ventricle Wall Printed1) Selection of left ventricle
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Expanding Processes of Bioprinting
35Biofabrication 2016Biofabrication: reappraising the definition of an evolving field
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Summary • Bioprinting is still at emerging stage • 3D Bioprinting evolves fast and
dynamically; researchers must innovate with systems thinking
• Bioprinting is Beyond Biology ( lab on chip, bioelectronics, AI and ML)
• New strategies are expected for optimal cells responses.
• Knowledge and knowhow in material, process and biology will continue to expand.
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3D printing & Bioprinting
Scaffold for tissue
engineering
Bioprinting
Micro-tissue ,Organ chip
Biomodel Metal Implant Smart wearable
3D printing of polymer, metal and electronics
Personalized drug platform, bioelectronics
3D printing of implants and tissues
3D printed microfluidic chip
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Thank you
www.yeongresearch.com
https://sc3dp.ntu.edu.sg/Pages/Home.aspx
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