Post on 15-May-2022
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
#1World’s Best Young
University 2014 – 2021
QS Top 50 Under 50
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
3D Bioprinting: The inevitable
5Increasing shape and bioactivity complexity
3D Bioprinting
6Murphy & Atala, Nature Biotechnology 32(8), 2014
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/
• 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
Systems Thinking in 3D Bioprinting
9Murphy & Atala, Nature Biotechnology 32(8), 2014
It’s an overall strategies !
3D Bioprinting Current Strategies in Materials and Processes
https://www.advancedsciencenews.com/3d-printed-heart-with-patients-own-cells/
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.
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]
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
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.
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.
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
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)
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
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.
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)
Bioprinting is LIVE
Beyond just shape and cell deposition.
The function of the cells is also critical
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
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
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
Interdisciplinary nature of 3D Bioprinting
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
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
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
3D bioprinted flexible and biocompatible hydrogel bioelectronic platform
Biosensors and Bioelectronics,102, 365-371
Living cells inside hydrogel
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
Expanding Processes of Bioprinting
35Biofabrication 2016Biofabrication: reappraising the definition of an evolving field
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.
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
Thank you
www.yeongresearch.com
https://sc3dp.ntu.edu.sg/Pages/Home.aspx
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