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Biomaterials Res. Center, KIST
Bioengineering on arterial system
2006. 3. 4
생체재료 연구센터
김 수 현
Biomaterials Res. Center, KIST
Cell-sheet Engineering
Beating cardiac patch
Biomaterials Res. Center, KIST
Regenerative cornea
cell sheet
Biomaterials Res. Center, KIST
Biomaterials Res. Center, KIST
대구경 ( >6mm)
인공혈관 : Dacron, ePTFE 시판, 상용화/반영구적
성장기 환자에 적용불가
연구개발 목적-심혈관
소구경(
Biomaterials Res. Center, KIST
Key Elements in Tissue Engineering
Cells
Scaffold
Tissue
Signal
Materials,Structure,
Porosity, Function
Mechanically active cellsAutologous cells
Stem cell technology
Growth factorsAdhesion moleculesMechanical signals
Differentiation factor
Biomaterials Res. Center, KIST
Elasticity of polymers
Mechanical stimuli
Tissue engineered bio-organ regeneration having good
performance
In-vitro/vivo experiments for tissue
engineering
High elasticityBiodegradabilityHigh cell affinity
Mechano-active biomaterials
Mechanical stimuliHigh kinetic rate
High mass transfer
Mechano-active bioreactors
Mechano-active Tissue engineering
Strategy
Biomaterials Res. Center, KIST
Elastic and flexible behaviors of PLCL scaffold
Stretching RecoveryOriginal
Twistable FoldablePLGA (7:3)Broken at 20% strain
Biomaterials Res. Center, KIST
PLCL in CHCl3
Salt (NaCl),
Various sizes of 50-200 um
Various porosity of 60-95 %
Fabrication of tubular PLCL scaffolds
ID = 4 mm,
t = 1 mm
Biomaterials Res. Center, KIST
SMC & EC
Culture (3)
SMC & EC isolation
Rabbit artery
Subculture
SMCs seeded on PLCLcoated w. collagen
Static culture
No mechanical stimulation
(Medium: M199, 2 passage)
( 2.0 x 106 cells)
Smooth muscle cell Endothelial cell
In vitro SMCs static cultured stabilized for 1-7 days
In vitro ECs culture on a bioreactor, 1 w
SMCs culture on a bioreactor, 5-8 wMechanical stimulation
Biomaterials Res. Center, KIST
In vitro Cells culture in a bioreactor ; 8 weeks
Cells seeded on
the scaffold
Bioreactor (Pulsatile flow for 8w)
Regenerated vascular tissue
Biomaterials Res. Center, KIST
ECM analysis
1 2 3 4 5
0.10
0.15
0.20
0.25
0.30
0.35
0.40
Ab
so
rb
an
ce
(5
40
nm
)
weeks
Static condition
Pulsatile condition
1 2 3 4 50.10
0.15
0.20
0.25
0.30
0.35
0.40
0.45
0.50
0.55
Ab
so
rb
an
ce
(4
05
nm
)
weeks
Static condition
Pulsatile condition
Collagen contents Elastin contents
Biomaterials Res. Center, KIST
M-T staining of collagen network in regenerated vessels
Biomaterials Res. Center, KIST
Van-Giesen staining of elastin network in regenerated vessels
Biomaterials Res. Center, KIST
[Smooth Muscle -Actin]
1 3 5 8w 1 3 5
8w43 kDa
[Smooth Muscle Myosin Heavy Chain]
1 3 5 8w 1 3 5
8w204 kDa
Western blotting
static dynamicdynamic static
Biomaterials Res. Center, KIST
Morphology of fibrous scaffolds
5% 7.5% 10%
A B C
D E F
G H I
Controllable diameter size
A-C: surface morphology, D-E: magnification of A-C
G-I: cross-sectional morphology
Fibrous PLCL scaffolds are open-pore structures and well-interconnected
between pores.
Individual fibers are found either fused or forked together with neighboring
fibers
SEM images of fibrous scaffolds
Biomaterials Res. Center, KIST
In vivo
Dog
Dog
Bone marrow
mononuclear cell
Press seeding
Bone marrow
http://images.google.co.kr/imgres?imgurl=http://www.arts.monash.edu.au/korean/klec/Clipart02/KLEC2003_C117.gif&imgrefurl=http://www.arts.monash.edu.au/korean/klec/Clipart/index.php%3FRollID%3DClipart02%26FrameID%3DKLEC2003_C117&h=266&w=400&sz=7&tbnid=n6O6JyzmqIei5M:&tbnh=79&tbnw=120&hl=ko&start=6&prev=/images%3Fq%3D%25EA%25B0%259C%26svnum%3D10%26hl%3Dko%26lr%3D%26newwindow%3D1%26sa%3DGhttp://images.google.co.kr/imgres?imgurl=http://www.arts.monash.edu.au/korean/klec/Clipart02/KLEC2003_C117.gif&imgrefurl=http://www.arts.monash.edu.au/korean/klec/Clipart/index.php%3FRollID%3DClipart02%26FrameID%3DKLEC2003_C117&h=266&w=400&sz=7&tbnid=n6O6JyzmqIei5M:&tbnh=79&tbnw=120&hl=ko&start=6&prev=/images%3Fq%3D%25EA%25B0%259C%26svnum%3D10%26hl%3Dko%26lr%3D%26newwindow%3D1%26sa%3DG
Biomaterials Res. Center, KIST
▶ patch type : IVC 8 wks
Inner Outer
Implantation Harvest
Biomaterials Res. Center, KIST
▶ Tube type : abdominal aorta, 4 wks
Scaffold Seeding
Implantation Harvest
Biomaterials Res. Center, KIST
J. of Polymer Sci., Polymer Chem., 39, 7, 973 ( 2001)
J. Biomaterials Sci., Polymer Ed, 12, 10, 1147 (2001)
J. of Polymer Sci., Polymer Chem., 40, 544 (2002)
J. Polymer Sci., Polymer Chem., 40, 15, 2545 (2002)
Macromolecules, 36, 5585 (2003)
J. Biomed. Mat. Res.,66A, 1, 29 (2003).
Biomaterials, 24, 5049 (2003)
Biomaterials, 25, 2979 (2004)
J. of Biomat. Sci., Polymer ed., 15, 5, 645 (2004)
Biomaterials, 25, 5939 (2004)
Macromolecular Bioscience, 4, 802 (2004)
Biomacromolecules, 5, 1303 (2004)
Biomaterials, 26, 1405 (2005)
Biomaterials, 26, 1915 (2005)
Cover Page : J. Biomed. Mat. Res., July (2003)
Tissue Engineering : Mechano-active Tissue Engineering