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Transcript of Biomaterial Carbon
E-Learning CardioBioMat
Jürgen M. Lackner / JR-Materials / 2010-11 1
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Biomaterial
CARBON
Biomaterial
CARBONJ.M. Lackner, W. Waldhauser
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Preamble – Biomaterial research
INTE
RD
ISC
IPLI
NA
RIT
Y
E-Learning CardioBioMat
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Contents
1.1. BiocompatibilityBiocompatibility –– AspectsAspects of of biomaterialbiomaterial--tissuetissue interactioninteraction
2.2. BulkBulk biomaterial biomaterial „„carboncarbon““
3.3. SurfaceSurface coatingcoating biomaterial biomaterial „„carboncarbon““
4.4. ConclusionsConclusions
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Contents
1.1. BiocompatibilityBiocompatibility –– AspectsAspects of of biomaterialbiomaterial--tissuetissue interactioninteraction
2.2. BulkBulk biomaterial biomaterial „„carboncarbon““
3.3. SurfaceSurface coatingcoating biomaterial biomaterial „„carboncarbon““
4.4. ConclusionsConclusions
E-Learning CardioBioMat
Jürgen M. Lackner / JR-Materials / 2010-11 3
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Biocomptibility – Aspects
• Primary aspects and definitions
• Biofunctionality – Implant design
• Biomaterial – tissue interaction
• Host response
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Biomaterials
= artificial / synthetic materials withbiocompatibility for the contact duration to thebiosystem (tissue, body fluids)
≠ materials of biological origin
=> Medical equipment and devices (syringes, catheters, etc.), Implants
E-Learning CardioBioMat
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Biocompatibility= compatibility between a technical and biological system
(1)(1) StructuralStructural compatibilitycompatibility::Adapting the implant structure to the (geometrical, mechanical, etc.) behavior of the donee tissue
(2)(2) SurfaceSurface compatibilitycompatibility::Adapting chemical, physical, biological and morphologicalsurface properties to the donee tissue
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Development in Biomaterials
Scaffolds withcultivated cells
Cell-materialcompounds (vital-avital)4
Triggering of naturaltissue growth
Bioactive and metabolicinductive3
No reactionInert materials2
Distinct foreign bodyreaction (inflammation)Industrial materials1
Body reactionMaterialsGeneration
E-Learning CardioBioMat
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Biocompatible materials features
1. Absence of carcinogenicitycarcinogenicity (the ability or tendency to produce cancer)
2. Absence of immunogenicityimmunogenicity (absence of a recognition of an external factor which could create rejection
3. Absence of teratogenicityteratogenicity (ability to cause birth defects)
4. Absence of toxicitytoxicity
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Implants – Overview
E-Learning CardioBioMat
Jürgen M. Lackner / JR-Materials / 2010-11 6
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Biofunctionality - Aspects
- Load transmission (e.g. bone healing – screws, nails, etc.)
- Joint replacement (tribology, friction – lubrication – wear, hip, knee, ellbow, shoulder, finger)
- Fluid transport (catheders, bypasses, stents, etc.)
- Optical and acoustic transmission (lenses, cochlea implants, etc.)
- Control of drug-delivery (drug-eluting stents, wound care, etc.)
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Biomaterial – tissue interaction
Proteins, cells and tissue sense:
- Surface physical properties (roughness, porosity, etc.)- Surface chemistry (hydrophilicity, dissolution – corrosion, etc.)- Bulk mechanical properties (elasticity, compliance, etc.)- Bulk geometry (edges, etc.)
E-Learning CardioBioMat
Jürgen M. Lackner / JR-Materials / 2010-11 7
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Where’s interaction in/on the cell?
1. Nukleolus2. Zellkern (Nukleus)3. Ribosomen4. Vesikel5. Raues Endoplasmatisches Reticulum (ER)6. Golgi-Apparat7. Mikrotubuli
8. Glattes ER9. Mitochondrien10. Lysosom11. Zytoplasma12. Mikrobodies13. Zentriolen
binding site
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Cell adhesion to their surrounding
Extracellular matrix(collagen and fibronectin)
E-Learning CardioBioMat
Jürgen M. Lackner / JR-Materials / 2010-11 8
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Steps in cell adhesion
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Scale of Interactions
Macro-/M
icro-Structure
Nano-Structure
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Jürgen M. Lackner / JR-Materials / 2010-11 9
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Scale of interaction
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Implantation – Host respone
Cell indicators for host response: => Biomolecules (proteins, etc.)
„Body“ recognices and eradicates any foreign substanceentering the body (implant, drugs, organ transplant, etc.)
„body“ = tissue (lymphoid), cells (leucocytes) and biomolecules (antibodies)
Any substance, not seen to have body origin, = potential threat
=> eliminated („walled off“) to preventinteraction with normal tissue function
E-Learning CardioBioMat
Jürgen M. Lackner / JR-Materials / 2010-11 10
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Host response – Micron scale
0
1 min
1-24hrs.
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Host response – macro scale
0 1 min 1-24 hrs. 1-5 days 5-14 days 21 days
E-Learning CardioBioMat
Jürgen M. Lackner / JR-Materials / 2010-11 11
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Host response - regenerationRegenerative capacity of cells following injury:
Heart musclecells, nerves
No replication, replacement by
scarnoneStatic /
permanent
Endothelium, fibroblasts, liver
cells
Marked increaselowExpanding /
stable
Skin, intestinalmucosa, bonemarrow, bone
Modest increasehighRenewing /
labile
ExamplesResponse to stimulus / injury
Normal rate of replicationCategory
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Host response - effects
• Acute inflammation
• Chronic inflammation
• Scarring
E-Learning CardioBioMat
Jürgen M. Lackner / JR-Materials / 2010-11 12
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Host response – Bone
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Host response - blood
Integrated hemostatic reactions between a foreign surface and platelets, coagulation factors, the vessel endothelium and the fibrinolytic system
Thrombus
E-Learning CardioBioMat
Jürgen M. Lackner / JR-Materials / 2010-11 13
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Contents
1.1. BiocompatibilityBiocompatibility –– AspectsAspects of of biomaterialbiomaterial--tissuetissue interactioninteraction
2.2. BulkBulk biomaterial biomaterial „„carboncarbon““
3.3. SurfaceSurface coatingcoating biomaterial biomaterial „„carboncarbon““
4.4. ConclusionsConclusions
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Bulk carbon biomaterials
• Pyrolytic carbon
• Carbon fibres (composite materials)
E-Learning CardioBioMat
Jürgen M. Lackner / JR-Materials / 2010-11 14
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Pyrolytic Carbon (PyC)
TEM image of unalloyed PyCwith turbostratic carbon crystals
ManufacturingManufacturing::High temperature pyrolysis / thermal decomposition of hydrocarbons and subsequent recrystallization of elemental carbon
=> High mechanical strength (fatigue) and chemical resistance
ApplicationsApplications::Artificial joints (rarely used)Heart valves (main use)
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PyC - Biocompatibility
BiocompatibilityBiocompatibility problemsproblems
Pitting
Cavitation
Generally high:
E-Learning CardioBioMat
Jürgen M. Lackner / JR-Materials / 2010-11 15
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Carbon fibre composites (CFC)CarbonCarbon fibrefibre manufacturingmanufacturing::Carbonizing or graphitizing of poly(acrylnitrile) fibres under tension at high temperatures and pressures
ApplicationsApplications::Carbon fibre embedded in polymeric matrix(e.g. epoxy based)
=> Joint replacement (hip)
Carbon fibre embedded in bone cement=> fracture healing
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Contents
1.1. BiocompatibilityBiocompatibility –– AspectsAspects of of biomaterialbiomaterial--tissuetissue interactioninteraction
2.2. BulkBulk biomaterial biomaterial „„carboncarbon““
3.3. SurfaceSurface coatingcoating biomaterial biomaterial „„carboncarbon““
4.4. ConclusionsConclusions
E-Learning CardioBioMat
Jürgen M. Lackner / JR-Materials / 2010-11 16
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Surface coating biomaterial carbon
• ThreeThree--dimensionaldimensional surfacesurface structuresstructures– Carbon nanotubes
• TwoTwo--dimensionaldimensional surfacesurface structuresstructures– Plasma polymers and DLC coatings
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Manufacturing:Manufacturing:e.g. PVD / CVD growth
Applications:Applications:• Cell tracking and labeling• Sensing cellular behavior --> • Cytotoxicity
neuron bridging an array of carbon nanotubes thereby creating neural networks.
Biomaterials Volume 28, Issue 2, January 2007, Pages 344‐353
Carbon nanotubes
Cell chips
E-Learning CardioBioMat
Jürgen M. Lackner / JR-Materials / 2010-11 17
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Surface coatings
Film Film thicknessthickness:: as thick as necessary – as thin as possible
StabilityStability:: no delamination, no cracking(otherwise: irreversible change of surface chemistry)
DemandsDemands
CarbonCarbon--basedbased coatingscoatings
• Plasma polymers• „DLC“
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Plasma depositionEffects of plasma on surfaces:
Ablation:Removing surface layers
Implantation:Sub-surface burying of atoms(O, N, metal atoms etc.)
Radical / peroxide formation
Deposition(plasmapolymerization,metal / ceramic PVD & CVD)
E-Learning CardioBioMat
Jürgen M. Lackner / JR-Materials / 2010-11 18
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Plasma polymers
DepositionDeposition of of polymerizablepolymerizablegasesgases in in glowglow dischargedischarge plasmaplasma::
e.g.: methane – ethylene - acetylene
PropertiesProperties::+: homogenous films
high variety of polymers, even fromone monomer
-: complex mechanisms (control?)mixture of structures
ApplicationsApplications::- stents- contact lenses
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Bone contact – Artificial joints
Polyethylene wear debris is the main factor limiting the lifetime of the implants
Aseptic loosening, wear debris initiates inflammatory response
=> osteoclast cells activation => bone resorption
V. Saikko et al., Biomaterials 22 (2001) 1507
Polyethylene wear debris
E-Learning CardioBioMat
Jürgen M. Lackner / JR-Materials / 2010-11 19
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DLC – Improvements & Problems
Pin on Disk
DLC/UHMWPE (literature overview)
Hip joint simulator (Lappalainen, Finnland)
Pin on DiskLubrication:- air- dest. water - 1wt% NaCl in water
reduction of UHMWPE wear
Hip joint simulator
Lubrication:- diluted calf serum- synovial fluid
no change in UHMWPE wear
To be clinically relevant, tribological investigations on DLC/UHMWPE require:- Adequate tribological setup- Adequate lubricant (phospholipids, adsorbed on surfaces, strongly influences tribology)
√G. Taeger et al., Mat.-wiss. u. Werkstofftech. 34 (2003) 1094
Wear problems with DLC
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DLC – Problems
Shoulder-joint, the Ti-alloy ball coated with DLC (carbioceram™)
ankle-joint, AISI Z5 CNMD 21 steelcoated with DLC (carbioceram™)
knee-joints coated with DLC (carbioceram™)=> USE NOW FORBIDDEN
No medical follow-up on these products found
E-Learning CardioBioMat
Jürgen M. Lackner / JR-Materials / 2010-11 20
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DLC in Blood contact
Surface has to prevent thrombus formation and restenosis
Adsorption of proteins
Increased platelet adhesion
Platelet activation and aggregation
Formation of a thrombusThrombus on a mechanical heart valve
(courtesy of RWTH-Aachen)
albumin/fibrinogen ratio
Steps for Thrombus formation
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DLC – Improvements high ratio of albumin/fibrinogen
low number of adhering platelets
low tendency of thrombus formation
0
0.2
0.4
0.6
0.8
1
1.2
1.4
Ti TiN TiC DLC silicone elastomer
PMMA CN
Alb
umin
/ Fi
brin
ogen
Rat
io Jones et al.Dion et al.Cui et al.
Albumin/fibrinogen ratio for different surfaces.
PC c
oate
d ac
cele
rato
r
DLC
coa
ted
acce
lera
tor
E-Learning CardioBioMat
Jürgen M. Lackner / JR-Materials / 2010-11 21
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DLC - Improvements
184 kD
115 kD
86.3 kD61.5 kD
50.8 kD
37.6 kD
25.4 kD
Plasma Glas Ti 23 13 7 0 a-C:H, at% Ti
Molecular weight Tunable protein adsorption
between Ti and DLC by Ti concentration in Ti-DLC.
Adsorption of human plasma proteins on a-C:H/Ti Chromatographic analysis of the proteins. Molecular weight marker is indicated on the left side.
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Diamond-like Carbon Coatings
aa--C:HC:Haa--C:H/3% VC:H/3% V
aa--C:H/7.4% VC:H/7.4% V aa--C:H/15% VC:H/15% V
after 10 days in vitroafter 10 days in vitro
Tunable poisoning:Poisoning of the BMC cells due to vanadium dissolution out of the V-DLC film
300 µm
E-Learning CardioBioMat
Jürgen M. Lackner / JR-Materials / 2010-11 22
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Diamond-like Carbon Coatings
CARBOFILM™ made by PVD using a pyrolytic turbostraticcarbon target. Probably it is a-C.
Chrome-cobalt alloy cage, coated with CARBOFILM™
Problems: Wear in hinges, Hemocompatibility
Titanium alloy coated with DLC Products under development by Cardio Carbon Company Ltd.
CarbofilmTM by Sorin Biomedica, Inc.Catheter
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DLC – Problems
0.00 0.02 0.04 0.06 0.08 0.10 0.120
100
200
300
400
500
Forc
e (N
)
ΔL/L
(a) (b) (c) (d)
(a)
(b)(c) (d)
Problem – Evolution of Coating Failure
Stents
E-Learning CardioBioMat
Jürgen M. Lackner / JR-Materials / 2010-11 23
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Example
Own research –
Coatings for blood contact
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Coatings for Artificial Hearts
Optimization of polyurethane human implant surfaces (artificial heart) bybiocompatible coatingsGoal: prevention of thrombus formation
Medical implants – artificial hearts:
POLVAD
E-Learning CardioBioMat
Jürgen M. Lackner / JR-Materials / 2010-11 24
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Cell adhesion
0 10 20 30 40 500
2
4
6
8
Ti
TiN
TiCNl
TiCNh
DLC
Det
achm
ent r
ate
[min
-1]
Hydrodynamic stress [Pa]
σ(r) = 3 D η / (π r e²)Flow rate
Dynamic viscosity (Sörensen buffer)
Radius from centre hole
Disc spacing
σ(r) = 3 D η / (π r e²)Flow rate
Dynamic viscosity (Sörensen buffer)
Radius from centre hole
Disc spacing
Good binding of cells on Ti and DLC, decreasing with lower C content in films.
DLC static
DLC dynamic
No damage of adhering cells by
hydrodynamic shear stress (no
change in size and morphology)
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Cell adhesion – Critical shear flow(for 50 % cell detachment)
Higher carbon content=> Higher cell adhesion
Comparable threshold
shear stress for films on
both Si wafer & medical Tisubstrates.
E-Learning CardioBioMat
Jürgen M. Lackner / JR-Materials / 2010-11 25
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Thrombogeneity
0 20 40 60 80 100
PU
a-C:H
Si:a-C:H
Ti:a-C:H
Ti:a-C:H:N
ADP
Content [%]
PLT-PLTPLT-MPLT-N
0 20 40 60 80 100
PU
a-C:H
Si:a-C:H
Ti:a-C:H
Ti:a-C:H:N
ADP
Content [%]
GP IIb/IIIaP Selectin
ImpactImpact--RR Test:Test:Activation and Aggregation of Platelets, measured by flow cytometry
Activation
Aggregation
Reversible bindingof aggregates
Degree of activation
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Contents
1.1. BiocompatibilityBiocompatibility –– AspectsAspects of of biomaterialbiomaterial--tissuetissue interactioninteraction
2.2. BulkBulk biomaterial biomaterial „„carboncarbon““
3.3. SurfaceSurface coatingcoating biomaterial biomaterial „„carboncarbon““
4.4. ConclusionsConclusions
E-Learning CardioBioMat
Jürgen M. Lackner / JR-Materials / 2010-11 26
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Conclusions
CARBON = applied BIOMATERIAL
Artificial heart valvesStent surfaces
PROBLEMS of CARBON
Adhesion of coatingsHemocompatibility (?)