nanotechnology in bionic research - engineers australia · bionic eye bionic ear: cochlear implant...
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Nanotechnology in Bionic Research
Dr. Simon MoultonQEII Fellow
ARC Centre of Excellence for Electromaterials Science (ACES)
Intelligent Polymer Research Institute
University of Wollongong
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1 mm
1 m
100 nm
What Defines Nanotechnology?
Any thing that has one dimension less than 100 nm
Synthetic Natural
Civil StructuresManufactured Products
Raw Materials
Silicon Transistors
Colloid Particles
Single MoleculesAtoms
Animals
Insects
NervesCells
BacteriaProteins
Human Hair!
1 mMACRO
MICRO
NANO
MOLECULAR
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Fantasy and Fact
www.uml.edu/.../media/nanotechnology-kd-001.jpg
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Pros and Cons• Entertainment
– IPOD Nano
• Medicine/Health
– Cancer therapy
– Sun screens
• Unknown technology (similar to GM foods –fear of the unknown)
• Health
– asbestos (CNTs)
– Cell membranes (nanoparticles)
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Biology ElectronicsBio nics
1791
• Metals as Electrodes • Organic Materials
2009
Platinum Electrodes
LUIGI GALVANI’SANIMAL ELECTRICITY
HN
NH
HN
NH
HN
NH x
A-
A-
Fibers
PPy
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Bionics?The University of Melbourne
Bionic Ear 1978The Bionic Man
Col. Steve Austin 1973
GCLARK FOUNDATION/NLA
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Bionic Eye Bionic Ear:Cochlear Implant
The Argus II bionic eye is currently undergoing trials
in 50-75 patients in the US. The system uses a
spectacle mounted camera that feeds visual
information to 60 electrodes implanted in the retina.
Cochlear implants are
one of the oldest pieces
of the bionic man.
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Enhanced Performance Implantables
Wearables for Prosthetics and Monitoring
Bionics
MAYBE THEBIONIC GAMES?
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Oscar Pitorius - the “blade runner”
Oscar Pistorius - also known as ‘Blade Runner’ -is a double leg amputee who is using speciallydeveloped artificial legs to compete in races. Aworld record holder in the 100, 200 and 400meters Paralympic events, Pistorius was deniedby the International Association of AthleticsFederations (IAAF) his application to participatein the 2008 Summer Olympics. The IAAF arguedthat his prosthetic racing legs give him a clearcompetitive advantage. On May 16, the IAAF’sdecision was overturned by the Court ofArbitration for Sport, allowing Pistorius toparticipate in the Olympics if he could make theminimum qualifying time.
BIONICS IN SPORT
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http://blog.800hightech.com/bionic-hand-iraq-war-veteran/782/
U.S. Department of Defense UsesFuturistic Robotic Technology for a NewBionic Hand for Sgt. Juan Arredondo anIraq War Veteran who Lost His Hand onPatrol.
BIONICS FOR DEFENSE
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Not just Ordinary Electromaterials….
Mechanical Level SwitchingSwitching Surface Interactions Controlled Release of Active Molecules
NH
oxidation
A-
NH n
n
+A-
N
N
N
N
H
H
H
H
A-
++
A-
N
N
N
N
H
H
H
H
2A-++ e-
- e-
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Novel Materials – Novel Structures –
Unforeseen Opportunities!!
Conducting Polymer (micro) Grid A Novel Fluid Transfer System
Videos courtesy of Shannon Little
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1 m
1 mm
1 m
100 nm
MACRO
MICRO
NANO
MOLECULAR
HumanHair
NanostructuredElectro -Materials
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External stimulation
Response to the biological environment
e.g. biodegradation
swelling (phase change)
Galvanic coupling
(Functional batteries)
Can we achieve temporal distribution of function?
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Control at the Nano Level
e-e-
N
N
N
N
H
H
H
H
A-
++
A-
N
N
N
N
H
H
H
H
2A-++ e-
- e-
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Advanced Cochlear Electrodes
(with an Eye on the Eye)
Nerve Regeneration
(Peripheral and Spinal Cord)
Muscle Regeneration
Epilepsy Detection and Control
Bionic Stents (Boston Scientific)
ACES - BIONICS
Infection Control
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Bionic Implants - Advanced Cochlear Implant Electrode
Safety studiescommenced
Electrochemicaldata obtained
Carbon nanotube structures as implant electrodes
Electrode-Cellular Interface, G.G. Wallace, S.E. Moulton, G.M.Clark, Science 2009, 324, 185-186.
Nerve cell body
Nerve fibres
Spiral Ganglion Neurite
ExplantNerve cell body
Nerve fibres
Spiral Ganglion Neurite
Explant
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Nanobionics – Advanced cochlear implants
GCLARK FOUNDATION/NLA
Organ of
Corti
Basal(High frequency)
Auditory Nerve
Fluid canals
Apical(Low frequency)
Mastoid
BrainMiddle
Ear
Cochlea(Inner Ear)
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Organ of Corti
Basilarmembrane
Peripheral auditorynerve fibres
Brain
Innerhair cell
Outerhair cell
Nanobionics – Advanced cochlear implants
GCLARK FOUNDATION/NLA
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Cochlea and Auditory Nerves
ElectrodeBrain
Nanobionics – Advanced cochlear implants
GCLARK FOUNDATION/NLA
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PPy/pTS PPy/pTS/NT3 PPy/pTS/NT3/BDNF
No
n-s
tim
ula
ted
Ele
ctro
-sti
mu
late
dIntroducing an Additional Growth Factor (BDNF)
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Dual Neurotrophins: Synergy at Work
Electrical stimulation
No Electrical stimulation
BDNF
NT-3 Cochlear explant
PPy/pTS/NT-3/BDNF
NT-3/BDNF
BrainBrain
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SIBS
PEDOT
MWNT
forest
Ppy/pTS/NT-3
SIBS
PEDOT
MWNT
forest
Ppy/pTS/NT-3
SIBS = poly(styrene-b-isobutylene-b-styrene)
non-conducting, very stretchy polymer used in
several tissue engineering applications recently
FDA-approved as coronary stent coating
PEDOT = Polyethylenedioxythiophene
conducting polymer which has been used for
several cell culturing application, but not widely
explored as a biomaterial
MWNT= multi-walled carbon nanotubes
there is lots of controversy about the
toxicity/biocompatibility of nanotubes, so the
compatibility of tissues with this component is
one matter that needs to be addressed
A Nanostructured Platform(Patent Pending)
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PPy deposited
on tips of CNTs
Comparison of CNT Array to Flat Film
Nanostructured PPys for Controlled Release
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Conductive polymer materials for controlled release
Wet fibre spinning to produce microdimensionalstructure
Spinal Cord Regeneration
Injured Spinal Cord Repair of Lesion
Biodegradable Fibre Constructs
Hydrogels and
Fibres
Injured Spinal Cord Repair of Lesion
Biodegradable Fibre Constructs
Hydrogels and
Fibres
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spoollinear controller
coagulation baths
syringe and pump
PLGA:PLA fibers
(a)
(c)(b)
(a)
spoollinear controller
coagulation baths
syringe and pump
PLGA:PLA fibers
(a)
(c)(b)
(a)
Schematic Representation of Wet-spinning Fibers
Scale bars are 100 m
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Vapour phase PPy/pTS on glass –oxidant printed with 10pL cartridge
Ink Jet Printing Fibre Spinning
75:25 PLA/PLGA fibers
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Nanofabricated Platforms
C
E
G
PPPPyy MMyyllaarr
PPPPyy MMyyllaarr
AAxxoonnaall
ggrroowwtthh
ffrroonntt
SScchhwwaannnn cceellll
mmiiggrraattiioonn
ffrroonntt
DRG
DRG
PPLLAA//PPLLGGAA ffiibbrreess
PPLLAA//PPLLGGAA ffiibbrreess
Scale bar = 50 m
Scale bar = 500 m
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MUSCLE REGENERATION
Muscular Diseases
Damage Due toTrauma
Grow / ReplaceMuscle Tissue
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1. Wet-spun PLA:PLGA fibers on
gold-coated mylar substrate
2. PPy polymerization of the
exposed gold surface
1. Myoblast proliferation (2 days) 2. Myotube differentiation (4 days)
(a)
(b)
1. Wet-spun PLA:PLGA fibers on
gold-coated mylar substrate
2. PPy polymerization of the
exposed gold surface
1. Myoblast proliferation (2 days) 2. Myotube differentiation (4 days)
(a)
(b)Formation of the linear cell-seeded bio-synthetic fiber constructs. (a)
The two-step fabrication of the hybrid platform involves: (1) wet-
spinning of PLA:PLGA fibers onto a gold-coated mylar substrate to
create an aligned micro-fiber array pattern, and (2) exclusive
electrochemical modification of the exposed gold surface of the
substrate with the conducting polymer polypyrrole (PPy). (b) The
compatibility of the hybrid platform towards skeletal muscle was
assessed by: (1) allowing the cells to proliferate and adhere for 2 days,
and (2) inducing their differentiation for 4 days.
The Bio-Synthetic Cell Culture Platform
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(a)
(c)
(b)
(d)
(a)
(c)
(b)
(d)
Fluorescence images of
differentiated, multinucleated
desmin (green) expressing
myotubes on PPy/pTS
substrate (a-b) with and (c-d)
without the presence of
PLA:PLGA fiber array. Cell
nuclei are shown in blue.
Scale bars are 200 m.
Fluorescence Images of Differentiated, Multinucleated Desmin (Green) Expressing Myotubes
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• Myotubes on fibres were most prominent on
composites with narrow gaps between fibres.
• Confirming prior results, myotubes tend to align
along the fibre axis.
• Presence of fibres also constricts the
directionality of the myotubes on Ppy.
Novel Ex Vivo Platform for Muscle Cell Growth
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A C
A
C
B
B
Multinucleate myofibres were observed to align on the PLGA:PLA fibres, and
some on PPy surface, forming linear cell-seeded “bio-synthetic” muscle fiber
Novel Ex Vivo Platform for Muscle Cell Growth
Ppy surface
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The Implantable Conduit
Aligned
Fiber
Structure
In-built
Power
Supply
Spatial
Distribution
of Growth
Factor
Molecules
in 3-D
Distribution
of Stem
Cells
Biodegradable
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Epilepsy is commonest serious
neurological illness after stroke.
About 1% of the population
affected by recurrent seizures.
5% will have seizures during
their life.
Epilepsy Detection and Control
Prof. Mark Cook, St Vincent’s Hospital and University of Melbourne.
Anti Convulsant Drugs
Electrical Stimulation
Current Treatments
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Warning
Some of the next slides contain medical images
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Detection
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Electrode Design
More electrodes = more dataMore electrode = connection issues
SEM courtesy of Dr Jun Chen
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Targeted Drug Delivery
• Current therapeutic interventions for epilepsy, control seizures in only around 60% of affected individuals with the remaining people un-responsive to current therapeutic interventions.
• Side effects of systemic anti-convulsant medications administration include;
– Nausea
– Rashes
– Weight changes
– Dizziness
• Importantly, these side effects are a major factor limiting these drugs’ effectiveness in controlling epileptic seizures by preventing use of larger doses.
• In addition, use of some of the stronger anti-convulsant drugs (eg Leviteracetam and phenytoin) is severely restricted due to the need for their systemic administration.
• The local delivery of anti-convulsant drugs only to the brain regions involved in the epileptic seizure activity could prevent the severe side effects caused by systemic delivery.
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in vivo degradable polymer based drug delivery
3 mm
3 mm
3 mm
3 mm
Data and images courtesy of Dr Toni Campbell and Miss Amy Halliday.
PLA-PLGA + Leviteracetam
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Other Materials
• Wet-spinning– Incorporation of AEDs in fibres– AED loaded fibres woven into sheets
– Vary pore size
• Microparticles (Spray Drying)• Nanoparticle (Electrospray)
•Layer-by-Layer
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Seizure Initiated Release
Epilepsy Research 39 (2000) 103–114: An automated drug delivery system for focal epilepsy, Alan G. Stein et al
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Parameters for drug release
V = ~130 mV
Polypyrrole + dexamethasone [1] Polypyrrole + neurtrophin-3 [2]
1 Galvanic coupling conducting polymers to biodegradable Mg initiates autonomously powered drug release. S.E Moulton, et al, J. Mater. Chem.18, 3608-13, 2008.2 Optimizing the Incorporation and Release of a Neurotrophic Factor using Conducting Polypyrrole. B. C. Thompson, et al, Journal of Controlled Release, 116, 285-294 2006.
Effect of Frequency
General trend is that more
release is observed at slow
frequencies.
Speed of Delivery
Require the drug to be released
within the same time frame as
seizure onset.
Voltage (mV)
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• take multifunctional materials from
fundamental research to proof of concept
$52 million from the Federal Government
EXISTING
IC CENTRAL
EXISTING
A.I.I.M BUILDING
A.I.I.M: PROCESSING
AND DEVICES
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Shorter Term
Medium Term
Longer Term
Targeted End Users: Projects
Collaborator Initiated Projects
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In current projects
In new collaborative ventures
An invitation to engage ….
From Basic R&D to Processing and Prototype Development
Become a Foundation Partner …
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Fitting out of workshop/engineering design area
Scale up of organic/materials synthesis
(100 L capacity)
Fabrication equipment including:
Ink-jet printing
3D printing
Reel to reel printing
Wet-spinning
Electrospinning
Dry spinning capabilities
Knitting and weaving
Excimer laser capabilities
Bio fabrication facilities will be housed in
PCl environment
Major Equipment
Direct-Print Scaffolds
Produced by nscrytp
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Thankyou
AcknowledgmentsARC
NHMRCACES staff and students