Trends in Biotechnology, 34(9), 689-99.

wyyeong@ntu.edu.sgAssistant 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 spheroids Cells-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 mousefibroblasts, HaCaT humankeratinocytes

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 mousefibroblasts, HaCaT humankeratinocytes

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, withAmniotic 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 oflarge 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 (May2015)

Concept: Bioprinting of tissue spheroids to fabricatebioprinted 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