Nathaniel Hwang, Ph.D.
Seoul National University,
School of Chemical and Biological Engineering
Nanobiomaterials for Cell and Tissue Engineering
Topics Nanomaterials for Direct Conversion
Nanopatterned Substrates for Stem Cells
Injectable Hydrogels for Cartilage Tissue Engineering
Origami Tissue Engineering
Cell Surface Engineering for Stem Cell-based Therapy
Synthetic Inorganic Nanoparticles of in situ
bone regeneration
Tissue Engineering
http://www.tissueeng.net /
Biological “living” replacements
http://bmsce.snu.ac.kr
Selected Publications (April. 2015)
1. Advanced Healthcare Materials 2015 10.1002/adhm.201400835 2. Drug Delivery and Translational Research 2015, March 26 3. J. Controlled Release 2015 Feb 28;200:212-21.
4. Biotechnology Journal 2014 10.1002/biot.201400020 5. Journal of Biomedical Materials Research 2014 6. Acta Biomaterials 2014 Jul;10(7):3007-17 7. PNAS 2014 Jan 21;111(3):990-5
8. Biomaterials 2013;34(28):6607-6614. (2013 IF=8.312) 9. Tissue Engineering 2014
10. Advanced Functional Materials 2012 Jul 24;22(14):2949-2955.
11. Adv. Drug Deliv. Rev. 2013 Apr;65(4):536-58
Stem cell engineering via nonviral
delivery of reprogramming factors Bioactive substrates for stem cell differentiation and epigenetic regulations
Cell surface engineering for stem cell based therapies
Injectable hydrogels for orthopaedics applications
Fabrication of customizable scaffolds for tissue engineering Synthetic Biominerals for in situ
Bone Formation
Yamanaka factor delivering
nanoparticle Bioactive substrates and
photopolymerizing hydrogels
Controlling Stem Cells for Musculoskeletal Tissues
Regeneration
O
O O O O O O O OH
O O
O
O O
O O
O O
O O
O O
O O
O O 7
O O
O
O O
O O
O OH
O O
O
2 3 2
O O
O OH
O O
O O
O H
O O
O
O O
O O O
O
O
O OH
3
O O
O O
O O
3 CH2 O
O O
O O
O O
O O
O
2
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O O
O O O
O O
O
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F F F F F F O
O
O
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O O O
O 1
2 3 4
5
6 7
8
9
10 11 12 13 14
15
16
A
B
C
D
E
F O
O O
O O
O
a
b
100% 1 90% 1 10% A 85% 1 15% A 80% 1 20 % A 75% 1 25% A 70% 1 30 % A
100% 1 90% 1 10% B 85% 1 15% B 80% 1 20 % B 75% 1 25% B 70% 1 30 % B
100% 1 90% 1 10% C 85% 1 15% C 80% 1 20 % C 75% 1 25% C 70% 1 30 % C
100% 1 90% 1 10% D 85% 1 15% D 80% 1 20 % D 75% 1 25% D 70% 1 30 % D
100% 1 90% 1 10% E 85% 1 15% E 80% 1 20 % E 75% 1 25% E 70% 1 30 % E
100% 1 90% 1 10% F 85% 1 15% F 80% 1 20 % F 75% 1 25% F 70% 1 30 % F O
O
O
O O O O O O O OH
O O
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O O
O O
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O O 7
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3 CH2 O
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F F F F F F O
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2 3 4
5
6 7
8
9
10 11 12 13 14
15
16
A
B
C
D
E
F O
O O
O O
O
a
b
100% 1 90% 1 10% A 85% 1 15% A 80% 1 20 % A 75% 1 25% A 70% 1 30 % A
100% 1 90% 1 10% B 85% 1 15% B 80% 1 20 % B 75% 1 25% B 70% 1 30 % B
100% 1 90% 1 10% C 85% 1 15% C 80% 1 20 % C 75% 1 25% C 70% 1 30 % C
100% 1 90% 1 10% D 85% 1 15% D 80% 1 20 % D 75% 1 25% D 70% 1 30 % D
100% 1 90% 1 10% E 85% 1 15% E 80% 1 20 % E 75% 1 25% E 70% 1 30 % E
100% 1 90% 1 10% F 85% 1 15% F 80% 1 20 % F 75% 1 25% F 70% 1 30 % F
O
O O O O O O O OH
O O
O
O O
O O
O O
O O
O O
O O
O O 7
O O
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O O
O OH
O O
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O O
O O
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3
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O O
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3 CH2 O
O O
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O O O
O O
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F F F F F F O
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2 3 4
5
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8
9
10 11 12 13 14
15
16
A
B
C
D
E
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O O
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3
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3 CH2 O
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2
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O O O
O O
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F F F F F F O
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2 3 4
5
6 7
8
9
10 11 12 13 14
15
16
A
B
C
D
E
F O
O O
O O
O O
O O
O O
O O
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O O
O O
O O
O O 7
O O
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O O
O O
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O O
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O OH
O O
O O
O H
O O
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O
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3
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3 CH2 O
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2
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O O O
O O
O
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F F F F F F O
O
O
O N
O O O
O 1
2 3 4
5
6 7
8
9
10 11 12 13 14
15
16
A
B
C
D
E
F O
O O
O O
O
a
b
100% 1 90% 1 10% A 85% 1 15% A 80% 1 20 % A 75% 1 25% A 70% 1 30 % A
100% 1 90% 1 10% B 85% 1 15% B 80% 1 20 % B 75% 1 25% B 70% 1 30 % B
100% 1 90% 1 10% C 85% 1 15% C 80% 1 20 % C 75% 1 25% C 70% 1 30 % C
100% 1 90% 1 10% D 85% 1 15% D 80% 1 20 % D 75% 1 25% D 70% 1 30 % D
100% 1 90% 1 10% E 85% 1 15% E 80% 1 20 % E 75% 1 25% E 70% 1 30 % E
100% 1 90% 1 10% F 85% 1 15% F 80% 1 20 % F 75% 1 25% F 70% 1 30 % F O
O O O
Basic Strategy
Establishment of iPSCs Establishment of
Differentiation Protocols Application in TE and
Cell Therapy
Implantation of Carticel® :
Autologous Chondrocyte Transplantation
Periosteal flap
Defect
Biopsy
GMP Cell Processing
Carticel
J. Wenz, MD
Cell Number Issues
Cell Number Required to Engineer Cartilage: ~40 million cells/ml
3 ml = ~120 million cells
T150 = 150 cm 2 ,
Typically holds ~3 million cells
Loss of phenotype with expansion
Chondrocytes
Part I: Stem Cells
Induced pluripotent stem cells-the science and technology
(2012 Nobel Prize Physiology and Medicine)
Totipotent
(zygote)
Pluripotent
(ES, iPSCs)
Multipotent
(adult stem cells)
Unipotent
(differentiated)
Stem Cells and Reprogramming
Hochedlinger and Platch. Developmnent. 2009 (136); 509-23
24 candidate factors:
Ecat1, Dpp5(Esg1), Fbx015, Nanog, ERas, Dnmt3l, Ecat8, Gdf3, Sox15, Dppa4, Dppa2, Fthl17, Sall4, Oct4, Sox2, Rex1, Utf1, Tcl1, Dppa3, Klf4, b-cat, cMyc, Stat3, Grb2
Transcription factors are delivered by retroviral vectors and the colonies became visible by day 16
The generation of induced pluripotent stem cells –
the Takahashi and Yamanaka paper, Cell, 2006
Gene Carrier/Gene Vector
Retrovirus Herpes Simplex V
Adenovirus AAV Lipos ome
DNA Polymer
Integration Yes Non Non Yes Non
Expression Stable Transient Transient Stable Transient Transfection Efficient Efficient Efficient Low Low
Immune Response
No Yes High No Yes Yes or
No
No
Generally, viral vector system show higher gene transfer efficiency than
non-viral gene carrier system, but viral systems have potential risk of
wild type virus regeneration, immunogenecity and cancer formation.
Derivation of iPSCs using non-viral delivery strategy
Safety issues related to the current strategy to make iPSCs: Yamanaka Factors
(Oct3/4, Sox2, Nanog, Lin28)
Totipotent
(zygote)
Pluripotent
(ES, iPSCs)
Multipotent
(adult stem cells)
Unipotent
(differentiated)
Transdifferentiation
Hochedlinger and Platch. Developmnent. 2009 (136); 509-23
Cartilage vs. Muscle
Chondrocytes Muscle Fibres
Myogenic Conversion from Reprogrammed Chondrocytes
iPSCs Plastic states
Chondrocytes
Two-three weeks process
Myogenic Induction (myogenic cells from chondrocytes?)
Cell morphology change during reprogramming
+ + + +
+ + ++
++
+ Nucleofection
PBAE transfection
Plastic cells
TGF-b inhibitor SB-431542
Human chondrocytes Myoblasts
Reprogramming
factor delivery Myogenic
differentiation
Complex Formation of a Polymer and a Plasmid DNA
-
- -
- +++++
DNA Ligand Polycation DNA Complex
+
Gene Delivery Pathways
1. Electro static interaction between carrier/DNA complex and anionic plasma membrane 2. Receptor mediate
endocytosis, pinocytosis, or phagocytosis (depending on the size of the
carrier/DNA complex
3. Endosomal release in the cytoplasm- leading to the release of the DNA
All gene therapy strategies depend on getting the gene or genetic materials into the targeted cells = TRANSDUCTION
Three barriers of gene delivery: Cell membrane, endosomal membrane, nuclear membrane
Combinatorial Polymer Library for DNA Delivery
Poly (b-amino ester)-based nanocarriers for iPSC generations
O O
O
O
O O N O O
O
O O
O OH
n OH
NH 2
C
+
32 C 32 - Ac
a
O O N O O
O
O O
O OH
n
C32-Ac
H 2 N NH 2
H 2 N NH 2
NH 2
O O O H 2 N
H 2 N N H
O O N O
O N
H
NH 2
H 2 N N H
O O N O
O N
H
NH 2
H 2 N O
O O
N H
O O N O
O N
H
O O O
NH 2 O
O n
OH
O
O
O O
O O n
OH
O
O O n
OH
O
C32-103
C32-117
C32-122
b
Chondrocyte Reprogramming
C A B
7.5 mg/ 1M cells 18.75 mg/ 1M cells 37.5 mg/ 1M cells
Human chondrocyte
Reprogramming factor delivery Nucleofection
MCDNA
MCDNA- MCDNA+
Col II
CS-4S Col III
18s
J.E. Hong et al., JCR 2015
A
Plastic cells
TGF-b inhibitor SB-431542
Myoblasts
SB- SB+
Myog MyoD 18S
C
D
B
Myogenic Commitment of Reprogrammed Human Chondrocytes
J.E. Hong et al., JCR 2015
Conclusion I: Stem Cells Reprogramming of human chondrocytes via non-viral minicircle DNA delivery
Conversion of partially reprogrammed chondrocytes into myogenic cells
Feasibility in various cell-based therapeutic
application
Yamanaka factor delivering
nanoparticle Bioactive substrates and
photopolymerizing hydrogels
Controlling Stem Cells for Musculoskeletal Tissues
Regeneration
O
O O O O O O O OH
O O
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O O
O O
O O
O O
O O
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O O
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O O
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2
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O O O
O O
O
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F F F F F F O
O
O
O N
O O O
O 1
2 3 4
5
6 7
8
9
10 11 12 13 14
15
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A
B
C
D
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F O
O O
O O
O
a
b
100% 1 90% 1 10% A 85% 1 15% A 80% 1 20 % A 75% 1 25% A 70% 1 30 % A
100% 1 90% 1 10% B 85% 1 15% B 80% 1 20 % B 75% 1 25% B 70% 1 30 % B
100% 1 90% 1 10% C 85% 1 15% C 80% 1 20 % C 75% 1 25% C 70% 1 30 % C
100% 1 90% 1 10% D 85% 1 15% D 80% 1 20 % D 75% 1 25% D 70% 1 30 % D
100% 1 90% 1 10% E 85% 1 15% E 80% 1 20 % E 75% 1 25% E 70% 1 30 % E
100% 1 90% 1 10% F 85% 1 15% F 80% 1 20 % F 75% 1 25% F 70% 1 30 % F O
O
O
O O O O O O O OH
O O
O
O O
O O
O O
O O
O O
O O
O O 7
O O
O
O O
O O
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O O
O
2 3 2
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O OH
O O
O O
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O O
O
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O O O
O
O
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3
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3 CH2 O
O O
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O O
O O
O
2
O O
O O
O O O
O O
O
O O
F F F F F F O
O
O
O N
O O O
O 1
2 3 4
5
6 7
8
9
10 11 12 13 14
15
16
A
B
C
D
E
F O
O O
O O
O
a
b
100% 1 90% 1 10% A 85% 1 15% A 80% 1 20 % A 75% 1 25% A 70% 1 30 % A
100% 1 90% 1 10% B 85% 1 15% B 80% 1 20 % B 75% 1 25% B 70% 1 30 % B
100% 1 90% 1 10% C 85% 1 15% C 80% 1 20 % C 75% 1 25% C 70% 1 30 % C
100% 1 90% 1 10% D 85% 1 15% D 80% 1 20 % D 75% 1 25% D 70% 1 30 % D
100% 1 90% 1 10% E 85% 1 15% E 80% 1 20 % E 75% 1 25% E 70% 1 30 % E
100% 1 90% 1 10% F 85% 1 15% F 80% 1 20 % F 75% 1 25% F 70% 1 30 % F
O
O O O O O O O OH
O O
O
O O
O O
O O
O O
O O
O O
O O 7
O O
O
O O
O O
O OH
O O
O
2 3 2
O O
O OH
O O
O O
O H
O O
O
O O
O O O
O
O
O OH
3
O O
O O
O O
3 CH2 O
O O
O O
O O
O O
O
2
O O
O O
O O O
O O
O
O O
F F F F F F O
O
O
O N
O O O
O 1
2 3 4
5
6 7
8
9
10 11 12 13 14
15
16
A
B
C
D
E
F O
O O
O O
O
O
O O O O O O O OH
O O
O
O O
O O
O O
O O
O O
O O
O O 7
O O
O
O O
O O
O OH
O O
O
2 3 2
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O OH
O O
O O
O H
O O
O
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O O O
O
O
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3
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O O
3 CH2 O
O O
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O O
O O
O
2
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O O
O O O
O O
O
O O
F F F F F F O
O
O
O N
O O O
O 1
2 3 4
5
6 7
8
9
10 11 12 13 14
15
16
A
B
C
D
E
F O
O O
O O
O O
O O
O O
O O
O O
O O
O O
O O
O O 7
O O
O
O O
O O
O OH
O O
O
2 3 2
O O
O OH
O O
O O
O H
O O
O
O O
O O O
O
O
O OH
3
O O
O O
O O
3 CH2 O
O O
O O
O O
O O
O
2
O O
O O
O O O
O O
O
O O
F F F F F F O
O
O
O N
O O O
O 1
2 3 4
5
6 7
8
9
10 11 12 13 14
15
16
A
B
C
D
E
F O
O O
O O
O
a
b
100% 1 90% 1 10% A 85% 1 15% A 80% 1 20 % A 75% 1 25% A 70% 1 30 % A
100% 1 90% 1 10% B 85% 1 15% B 80% 1 20 % B 75% 1 25% B 70% 1 30 % B
100% 1 90% 1 10% C 85% 1 15% C 80% 1 20 % C 75% 1 25% C 70% 1 30 % C
100% 1 90% 1 10% D 85% 1 15% D 80% 1 20 % D 75% 1 25% D 70% 1 30 % D
100% 1 90% 1 10% E 85% 1 15% E 80% 1 20 % E 75% 1 25% E 70% 1 30 % E
100% 1 90% 1 10% F 85% 1 15% F 80% 1 20 % F 75% 1 25% F 70% 1 30 % F O
O O O
Basic Strategy
Establishment of iPSCs Establishment of
Differentiation Protocols Application in TE and
Cell Therapy
Substrate-dependent differentiation
Nanoscale surfaces for the long-term maintenance of mesenchymal stem cell phenotype and multipotency
The control of human mesenchymal cell differentiation using nanoscale symmetry
and disorder
Dalby et al., Nature Materials 2007
McBurray et al., Nature Materials 2011
Signaling Between the Cyotoskeleton and Nucleus
Cells are inherently sensitive to local mesoscale, microscale,
and nanoscale topographic and molecular patterns in
the cellular microenvironment
Substrate/Nanotopography Induce
Epigenetic Regulation of Stem Cells?
Molecular Mechanisms that Mediate Epigenetic Phenomena
Harp, J.M., et al., Asymmetries in the nucleosome core particle at 2.5 A resolution. Acta crystallographica. Section D, Biological crystallography,
2000. 56(Pt 12): p. 1513-34.
H2A H2B H3 H4
Histone Modification DNA methylation
5’ ApTpGp me Cp GpApTpG 3
3’ TpApCp Gp me CpTpApC 5’
Structure & Epigenetics of
Euchromatin versus Heterochromatin
The Dynamic Nucleosome: An Epigenetic Signaling Module
Euchr omatin He ter och ro matin
Bivalent Mark: H3K4me3 & H3K27me3
Bivalent Histone Modification in Stem Cell Differentiation
Bivalent Mark: H3K4me3 & H3K27me3
Fabrication of ECM Substrates with Nanotopography
PUA + acrylated-carboxylate mononer (10:1)
UV
EDC/NHS
300 nm 5 mm Flat
E. A. Kim, JBMR B
Immobilized vs. Adsorbed ECM Proteins
Immobilized Adsorbed
Post Seeding Pre Seeding
E. A. Kim, JBMR B
Nano-Patterned/FN-immobilized Substrates
1 2 3 4
5 6 7 8
9 1 0 1 1 1 2
1 3 1
4 1
5 1
6
1 w: 500
p: 1000
2 w: 450
P: 900
3 w: 400
p: 800
4 w: 350
p: 700
5 w: 800
p: 1600
6 w: 750
p: 1500
7 w: 700
p: 1400
8 w: 600
P: 1200
9 w: 1250
p: 2500 10 w: 1200 p: 2400 11 w: 1000 p: 2000
12 w: 900
p: 1800 13 w: 2000 p: 4000 14 w: 1800 p: 3600 15 w: 1600 p: 3200 16 w: 1500 P: 3000
w (width), p (period) in nm 16 different line patterned PUA on PS slide
J. Kim et al., In Review, Nature Methods
hMSC Staining for H3K3me3/H3K27me3
1 2 3 4
5 6 7
8
9 10 11
12
13 14 15
16
J. Kim et al., In Review, Nature Methods
Pattern-Specific Histone Modification and Nuclear Signatures
1 2 3 4
5 6 7
8
9 10 11
12
13 14 15
16
-25 -20
-15 -10
-5 0
5 10
15 20
-15 -10 -5 0 5 10 15 -20 -10 0 10
PC 2 PC 1
P C 3
P4 P7 P10 P13
Greater levels of H3K27me3 expression as the line widths/spacing increases
Cells cultured on different patterns exhibited nuclear signatures that
appear responsive to line/space width
J. Kim et al., In Review, Nature Methods
Topographical and ECM Effect on Myogenic Commitment
R e lat ive Fold In du ct io n
0 0.2 0.4 0.6 0.8 1 1.2
0 0.5 1 1.5 2 2.5 3
0 0.5 1 1.5 2
MHCd 2.5 MHCa MYOG
300 nm 5 mm 300 nm 5 mm 300 nm 5 mm 0 0.5 1 1.5 2 2.5
0 0.5 1 1.5 2
0 0.5 1 1.5 2 2.5
MHCd MHCa 3 MYOG
300 nm 5 mm 300 nm 5 mm 300 nm 5 mm
Scale bar: 100 mm
FN-immobilized Substrates
300 nm 5 mm
Laminin-immobilized Substrates
300 nm 5 mm
E. A. Kim, G. Y, Jung et al., JBMR B
Application is Tissue Engineering?
FN-Immobilized Nanofibers for MI
Myocardiac Infarction Model
Fibronectin Iimmobilization
Aligned PCL Nanofiber pGMA Coated Nanofiber Fibronectin Immobilized Nanofiber
A
Coating by iCVD pGMA
Fibronectin Immobilized Nanofiber Cardiac Patch Fibronectin Immobilized
Nanofiber Mesh
B
UCB Cells Seeding Transplantation
Cell adhesions and viability on pGMA-FN coated PCL Nanofibers
Increased cell adhesion and proliferation on pGMA-FN coated nanofibers
PCR arrays showed increased growth factor genes (i.e., VEGF, IGF, FGF) on pGM-FN coated nanofibers
B. J. Kang, et al., Acta Biomat.
Evaluation of cardiac function after MI
Evaluation of cardiac function by echocardiography
B. J. Kang, et al., Acta Biomat.
Conclusion II: Substrate-dependent differentiation
Materials containing the topography with nanoscale
features can induce histone modification and modulate cell behavior
Cells cultured on different patterns exhibited nuclear signatures that appear responsive to line/space width
Greater levels of H3K27me3 expression as the line widths/spacing increases
Toward the myogenic commitment, immobilization of proteins to PUA nano-patterned substrates significantly enhanced the myogenic gene expressions.
Immobilized nanofibers for efficient delivery of stem cells
in to MI model
Injectable Hydrogels for Tissue Engineering
Hydrogel Integration into Defected Tissue
catehcol-methacrylated hyaluronic acid Aldehyde-methacrylated hyaluronic acid Thiolated HA + PEGDA
Catehcol-methacrylated chitosan Aldehyde-methacrylated chitosan Catechol-methacrylated CS Aldehyde-mathacrylated CS
Meniscus
Hydrogel
D.A. Wang et al., Nature Materials 2007
Bioactive hydrogels: providing physical signals
PEGDA PEGDA-HA
• Extracellular microenvironment plays a significant role in controlling cellular behavior
N.S. Hwang et al., Cell and Tissue Res 2011
Fabrication of ECM-based hydrogels for functional cartilage tissue engineering
Glycidyl Methacrylate Chondroitin Sulfate
Hyalruronic Acid
Methacrylated Chondroitin Sulfate
Methacrylated Hyalruronic Acid
PEG-RGD MeCS/HA PEGDA
RGD
Hydrogel Construct
PEG CS HA
RGD RDG
Kim H et al., Tissue Engineering 2014
PEG-RGD PEG-RDG CS-RGD CS-RDG HA-RGD HA-RDG
DA Y 1 DA Y 3 DA Y 7
Morphological analysis and biochemical analysis of chondrocytes in RGD/RDG-modified ECM hydrogels
Kim H et al., Tissue Engineering 2014
Cartilage Tissue Formation (3weeks in vitro)
H& E Staining Safranin-O Staining
Kim H et al., Tissue Engineering 2014
ECM-mediated Cell Behavior in Hydrogels
Kim H et al., Tissue Engineering 2014
Cartilage Specific Gene Expression Analysis
* * *
* *
Kim H et al., Tissue Engineering 2014
Alternative Biocompatible PI: Riboflavin-collagen gel
Riboflavin enables collagen crosslinking at visible light range
Collagen is a widely utilized biomaterials but portrays weak mechanical properties
Riboflavin(vitamin B2) as photoinitiator
Collagen gel 37℃
(90min)
Collagen+0.006% riboflavin UV (10 min)
J.S. Heo et al., Drug Delivery and Trans. Med. 2015
Injectable Hydrogels for Cartilage Tissue Engineering
Bioactive photopolymerizing hydrogels for tissue engineering
CS-RGD microenvironment for enhanced SZP gene expression
Vitamin B for visible range photoactivation
Yamanaka factor delivering
nanoparticle Bioactive substrates and
photopolymerizing hydrogels
Controlling Stem Cells for Musculoskeletal Tissues
Regeneration
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100% 1 90% 1 10% C 85% 1 15% C 80% 1 20 % C 75% 1 25% C 70% 1 30 % C
100% 1 90% 1 10% D 85% 1 15% D 80% 1 20 % D 75% 1 25% D 70% 1 30 % D
100% 1 90% 1 10% E 85% 1 15% E 80% 1 20 % E 75% 1 25% E 70% 1 30 % E
100% 1 90% 1 10% F 85% 1 15% F 80% 1 20 % F 75% 1 25% F 70% 1 30 % F O
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100% 1 90% 1 10% A 85% 1 15% A 80% 1 20 % A 75% 1 25% A 70% 1 30 % A
100% 1 90% 1 10% B 85% 1 15% B 80% 1 20 % B 75% 1 25% B 70% 1 30 % B
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100% 1 90% 1 10% E 85% 1 15% E 80% 1 20 % E 75% 1 25% E 70% 1 30 % E
100% 1 90% 1 10% F 85% 1 15% F 80% 1 20 % F 75% 1 25% F 70% 1 30 % F
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100% 1 90% 1 10% A 85% 1 15% A 80% 1 20 % A 75% 1 25% A 70% 1 30 % A
100% 1 90% 1 10% B 85% 1 15% B 80% 1 20 % B 75% 1 25% B 70% 1 30 % B
100% 1 90% 1 10% C 85% 1 15% C 80% 1 20 % C 75% 1 25% C 70% 1 30 % C
100% 1 90% 1 10% D 85% 1 15% D 80% 1 20 % D 75% 1 25% D 70% 1 30 % D
100% 1 90% 1 10% E 85% 1 15% E 80% 1 20 % E 75% 1 25% E 70% 1 30 % E
100% 1 90% 1 10% F 85% 1 15% F 80% 1 20 % F 75% 1 25% F 70% 1 30 % F O
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Basic Strategy: Biomimetic Materials and Stem Cell Engineering Lab (BMSCE)
Establishment of iPSCs Establishment of
Differentiation Protocols Application in TE and
Cell Therapy
Customized Scaffolds for Tissue Engineering
Paper Origami
Suhwan Kim, B.S.
Origami-based Approach for Trachea Tissue Engineering
Bare paper
PSMa coated paper
PSMa-PLL/CaCl 2 coated paper
Hydrogel-cell-laden Paper scaffold
3D paper tissue scaffold
<Front view>
<Upper view>
Key
Scaffold implantation
Paper scaffold
P ap er ori ga mi
SH Kim et al., PNAS 2015
Initiated Chemical Vapor Deposition (iCVD) of PSMA
Sung Gap Im (KAIST)
SH Kim et al., PNAS 2015
Poly –l-Lysine Conjugation to PSMA coated Paper Substrate
600 400 200
C o u n ts /s ( a .u )
Binding energy (eV) N1s
O1s C1s
PSMa -PLL
PSMa
450 400 350
