SlideShare a Scribd company logo
Trends in Biotechnology, 34(9), 689-99.
wyyeong@ntu.edu.sg
Assistant Professor
School of Mechanical & Aerospace Engineering
College of Engineering
Wai Yee Yeong - Google Scholar Citations
scholar.google.com.sg/citations?user=CgowDcwAAAAJ&hl=en
Skin bioprinting:
Impending reality or fantasy?
Trends in Biotechnology, 34(9), 689-99.
3
Bioprinting
Gartner's 2015 Hype Cycle for Emerging Technologies
In Bioprinting
http://www.rapidtoday.com/future.html
source: Google, Youtube
In Skin Bioprinting….
In Situ printing
F. Rengier, A. Mehndiratta, H. von Tengg-Kobligk, C. M. Zechmann, R. Unterhinninghofen, H.-U. Kauczor, et al., "3D printing based on imaging data: review of medical
applications," International journal of computer assisted radiology and surgery, vol. 5, pp. 335-341, 2010.
Rúben F Pereira; Cristina C Barrias; Pedro L Granja; Paulo J Bartolo Advanced Biofabrication Strategies for Skin Regeneration and Repair
Nanomedicine. 2013;8(4):603-621.
Wake Forest School of Medicine
Bioprinting: Process Flow
3D bioprinting of tissues and organs, NATURE BIOTECHNOLOGY(2014), Sean V Murphy & Anthony Atala
Bioprinting Techniques
Print Format
Cell spheroidsCells-laden gelCell suspension
Multi-layered culture of human skin
fibroblasts and keratinocytes through 3-D
freeform fabrication
• Materials & cells:
• Materials: Collagen type I (rat tail), 2.05 mg/mL
• Cells: Primary adult human dermal FB and KC (1mil/mL for both)
W. Lee, J. C. Debasitis, V. K. Lee, J.-H. Lee, K. Fischer, K. Edminster, et al., "Multi-layered culture of human skin
fibroblasts and keratinocytes through three-dimensional freeform fabrication," Biomaterials, vol. 30, pp. 1587-1595, 3//
2009.
Valved-based
Skin Tissue Generation by Laser Cell Printing
• Materials & cells:
• Technology: laser-based
• Materials: Collagen Type I
(3mg/mL), Matriderm
• Cells: NIH-3T3 mouse
fibroblasts, HaCaT human
keratinocytes
L. Koch, A. Deiwick, S. Schlie, S. Michael, M. Gruene, V. Coger, et al., "Skin tissue generation by laser cell
printing," Biotechnology and bioengineering, vol. 109, pp. 1855-1863, 2012.
Laser-based
Tissue Engineered Skin Substitutes created by Laser-
assisted bioprinting form skin-like structures in the
dorsal skin fold chamber in mice
• Materials & cells:
• Materials: Collagen Type I
(3mg/mL), Matriderm
• Cells: NIH-3T3 mouse
fibroblasts, HaCaT human
keratinocytes
S. Michael, H. Sorg, C.-T. Peck, L. Koch, A. Deiwick, B.
Chichkov, et al., "Tissue Engineered Skin Substitutes Created by
Laser-Assisted Bioprinting Form Skin-Like Structures in the
Dorsal Skin Fold Chamber in Mice," PloS one, vol. 8, p. e57741,
2013.
Laser-based
Bioprinted Amniotic Fluid-Derived Stem Cells
Accelerate Healing of Large Skin Wounds
• Materials & cells:
• Collagen Type I (2.2mg/mL) and
fibrinogen in 1:1 ratio, with
Amniotic fluid-derived stem cells
A. Skardal, D. Mack, E. Kapetanovic, A. Atala, J. D. Jackson, J. Yoo,
et al., "Bioprinted Amniotic Fluid-Derived Stem Cells Accelerate
Healing of Large Skin Wounds," Stem cells translational medicine,
vol. 1, p. 792, 2012
Valved-based
• Challenges:
• No cell migration into the underlying
tissue
• Potential:
• Bioprinted amniotic fluid-derived stem
cells demonstrated effective closure of
large skin wounds
Challenges and Potential
2D vs 3D microenvironment
Material vs cellular approach
Process-dependent vs design dependent
The Outlook of Skin Bioprinting
Single vs multiple cell types
Designing the microenvironment
Multi-material multi-cellular printing
Potential in skin model
Applications: Development of bioprinted skin models (May
2015)
Concept: Bioprinting of tissue spheroids to fabricate
bioprinted tissue (based on Organovo’s exVive3D liver model)
Potential in Digital Pre-
Processing
• Developing natural-looking, 3D-printed skin
• 3D camera technology, image processing and and
skin modelling techniques that can almost exactly
match an individual's skin tone and skin texture
under varying light sources
Ref: http://phys.org/news/2013-11-natural-looking-
3d-printed-skin.html#jCp
Fantasy or Reality: Cost
• No for now
• High cost
• More likely to be an enabler in medicine, or creating
microtissues for testing
• Depends on definition of organ
• Functional organs are more complex -> require better nutrient
transport
Fantasy or Reality: Organ Complexity
SKIN
3D bioprinting of tissues and organs, NATURE BIOTECHNOLOGY(2014), Sean V Murphy & Anthony Atala
Summary
• Bioprinting field is currently still in its stage of infancy
• More work has to be conducted
• Material
• Printing process
• Maturation process
• Proof of concept that skin cells can be printed and cultured
• Missing functionality as implant
• Lack of skin pigmentation
• Lack of vascularization
• Immediate use of bioprinting as an enabler or study tool
References:
• Skin Bioprinting: Impending Reality or Fantasy?
• Wei Long Ng · Shuai Wang · Wai Yee Yeong · May
Win Naing
• Article · Sep 2016 · Trends in Biotechnology
• Development of Polyelectrolyte Chitosan-gelatin
Hydrogels for Skin Bioprinting
• Wei Long Ng · Wai Yee Yeong · May Win Naing
• Full-text Article · Dec 2016
• Polyelectrolyte gelatin-chitosan hydrogel
optimized for 3D bioprinting in skin tissue
engineering
• Wei Long Ng · Wai Yee Yeong · May Win Naing
• Full-text Article · Jan 2016
• Potential of Bioprinted Films for Skin Tissue
Engineering
• Wei Long Ng · Wai Yee Yeong · May Win Naing
• Conference Paper · Jan 2014
• Bioprinting in cardiovascular tissue engineering: a
review
• Jia Min Lee · Swee Leong Sing · Edgar Yong Sheng
Tan · Wai Yee Yeong
• Full-text Article · Jan 2016
• Smart hydrogels for 3D bioprinting
• Shuai Wang · Jia Min Lee · Wai Yee Yeong
• Full-text Article · Jul 2015
• A preliminary model of time-pressure dispensing
system for bioprinting based on printing and
material parameters
• Lee · Yeong
• Article · Jan 2015 · Virtual and Physical Prototyping
Thank you

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Skin bioprinting: fantasy or reality?

  • 1. Trends in Biotechnology, 34(9), 689-99. wyyeong@ntu.edu.sg Assistant Professor School of Mechanical & Aerospace Engineering College of Engineering Wai Yee Yeong - Google Scholar Citations scholar.google.com.sg/citations?user=CgowDcwAAAAJ&hl=en Skin bioprinting: Impending reality or fantasy?
  • 2. Trends in Biotechnology, 34(9), 689-99.
  • 3. 3 Bioprinting Gartner's 2015 Hype Cycle for Emerging Technologies
  • 5. In Skin Bioprinting…. In Situ printing F. Rengier, A. Mehndiratta, H. von Tengg-Kobligk, C. M. Zechmann, R. Unterhinninghofen, H.-U. Kauczor, et al., "3D printing based on imaging data: review of medical applications," International journal of computer assisted radiology and surgery, vol. 5, pp. 335-341, 2010. Rúben F Pereira; Cristina C Barrias; Pedro L Granja; Paulo J Bartolo Advanced Biofabrication Strategies for Skin Regeneration and Repair Nanomedicine. 2013;8(4):603-621. Wake Forest School of Medicine
  • 6. Bioprinting: Process Flow 3D bioprinting of tissues and organs, NATURE BIOTECHNOLOGY(2014), Sean V Murphy & Anthony Atala
  • 9. Multi-layered culture of human skin fibroblasts and keratinocytes through 3-D freeform fabrication • Materials & cells: • Materials: Collagen type I (rat tail), 2.05 mg/mL • Cells: Primary adult human dermal FB and KC (1mil/mL for both) W. Lee, J. C. Debasitis, V. K. Lee, J.-H. Lee, K. Fischer, K. Edminster, et al., "Multi-layered culture of human skin fibroblasts and keratinocytes through three-dimensional freeform fabrication," Biomaterials, vol. 30, pp. 1587-1595, 3// 2009. Valved-based
  • 10. Skin Tissue Generation by Laser Cell Printing • Materials & cells: • Technology: laser-based • Materials: Collagen Type I (3mg/mL), Matriderm • Cells: NIH-3T3 mouse fibroblasts, HaCaT human keratinocytes L. Koch, A. Deiwick, S. Schlie, S. Michael, M. Gruene, V. Coger, et al., "Skin tissue generation by laser cell printing," Biotechnology and bioengineering, vol. 109, pp. 1855-1863, 2012. Laser-based
  • 11. Tissue Engineered Skin Substitutes created by Laser- assisted bioprinting form skin-like structures in the dorsal skin fold chamber in mice • Materials & cells: • Materials: Collagen Type I (3mg/mL), Matriderm • Cells: NIH-3T3 mouse fibroblasts, HaCaT human keratinocytes S. Michael, H. Sorg, C.-T. Peck, L. Koch, A. Deiwick, B. Chichkov, et al., "Tissue Engineered Skin Substitutes Created by Laser-Assisted Bioprinting Form Skin-Like Structures in the Dorsal Skin Fold Chamber in Mice," PloS one, vol. 8, p. e57741, 2013. Laser-based
  • 12. Bioprinted Amniotic Fluid-Derived Stem Cells Accelerate Healing of Large Skin Wounds • Materials & cells: • Collagen Type I (2.2mg/mL) and fibrinogen in 1:1 ratio, with Amniotic fluid-derived stem cells A. Skardal, D. Mack, E. Kapetanovic, A. Atala, J. D. Jackson, J. Yoo, et al., "Bioprinted Amniotic Fluid-Derived Stem Cells Accelerate Healing of Large Skin Wounds," Stem cells translational medicine, vol. 1, p. 792, 2012 Valved-based • Challenges: • No cell migration into the underlying tissue • Potential: • Bioprinted amniotic fluid-derived stem cells demonstrated effective closure of large skin wounds
  • 13. Challenges and Potential 2D vs 3D microenvironment Material vs cellular approach Process-dependent vs design dependent The Outlook of Skin Bioprinting Single vs multiple cell types Designing the microenvironment Multi-material multi-cellular printing
  • 14. Potential in skin model Applications: Development of bioprinted skin models (May 2015) Concept: Bioprinting of tissue spheroids to fabricate bioprinted tissue (based on Organovo’s exVive3D liver model)
  • 15. Potential in Digital Pre- Processing • Developing natural-looking, 3D-printed skin • 3D camera technology, image processing and and skin modelling techniques that can almost exactly match an individual's skin tone and skin texture under varying light sources Ref: http://phys.org/news/2013-11-natural-looking- 3d-printed-skin.html#jCp
  • 16. Fantasy or Reality: Cost • No for now • High cost • More likely to be an enabler in medicine, or creating microtissues for testing
  • 17. • Depends on definition of organ • Functional organs are more complex -> require better nutrient transport Fantasy or Reality: Organ Complexity SKIN 3D bioprinting of tissues and organs, NATURE BIOTECHNOLOGY(2014), Sean V Murphy & Anthony Atala
  • 18. Summary • Bioprinting field is currently still in its stage of infancy • More work has to be conducted • Material • Printing process • Maturation process • Proof of concept that skin cells can be printed and cultured • Missing functionality as implant • Lack of skin pigmentation • Lack of vascularization • Immediate use of bioprinting as an enabler or study tool
  • 19. References: • Skin Bioprinting: Impending Reality or Fantasy? • Wei Long Ng · Shuai Wang · Wai Yee Yeong · May Win Naing • Article · Sep 2016 · Trends in Biotechnology
  • 20. • Development of Polyelectrolyte Chitosan-gelatin Hydrogels for Skin Bioprinting • Wei Long Ng · Wai Yee Yeong · May Win Naing • Full-text Article · Dec 2016
  • 21. • Polyelectrolyte gelatin-chitosan hydrogel optimized for 3D bioprinting in skin tissue engineering • Wei Long Ng · Wai Yee Yeong · May Win Naing • Full-text Article · Jan 2016
  • 22. • Potential of Bioprinted Films for Skin Tissue Engineering • Wei Long Ng · Wai Yee Yeong · May Win Naing • Conference Paper · Jan 2014
  • 23. • Bioprinting in cardiovascular tissue engineering: a review • Jia Min Lee · Swee Leong Sing · Edgar Yong Sheng Tan · Wai Yee Yeong • Full-text Article · Jan 2016
  • 24. • Smart hydrogels for 3D bioprinting • Shuai Wang · Jia Min Lee · Wai Yee Yeong • Full-text Article · Jul 2015
  • 25. • A preliminary model of time-pressure dispensing system for bioprinting based on printing and material parameters • Lee · Yeong • Article · Jan 2015 · Virtual and Physical Prototyping