Nanotechnology in Bionic Research
Dr. Simon Moulton QEII Fellow
ARC Centre of Excellence for Electromaterials Science (ACES) Intelligent Polymer Research Institute University of Wollongong 1
What Defines Nanotechnology? Any thing that has one dimension less than 100 nm
1 mm MICRO
Civil Structures Manufactured Products
Colloid Particles Single Molecules Atoms
Pros and Cons • Entertainment – IPOD Nano
• Unknown technology (similar to GM foods – fear of the unknown)
• Medicine/Health – Cancer therapy – Sun screens
• Health – asbestos (CNTs) – Cell membranes (nanoparticles) 4
nics Electronics LUIGI GALVANI’S ANIMAL ELECTRICITY
• Metals as Electrodes
• Organic Materials
H N N H
H N N H
Bionics? The University of Melbourne Bionic Ear 1978
The Bionic Man Col. Steve Austin 1973
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.
Bionics Enhanced Performance Implantables Wearables for Prosthetics and Monitoring
MAYBE THE BIONIC GAMES?
BIONICS IN SPORT Oscar Pistorius - also known as ‘Blade Runner’ is a double leg amputee who is using specially developed artificial legs to compete in races. A world record holder in the 100, 200 and 400 meters Paralympic events, Pistorius was denied by the International Association of Athletics Federations (IAAF) his application to participate in the 2008 Summer Olympics. The IAAF argued that his prosthetic racing legs give him a clear competitive advantage. On May 16, the IAAF’s decision was overturned by the Court of Arbitration for Sport, allowing Pistorius to participate in the Olympics if he could make the minimum qualifying time.
Oscar Pitorius - the “blade runner”
BIONICS FOR DEFENSE
U.S. Department of Defense Uses Futuristic Robotic Technology for a New Bionic Hand for Sgt. Juan Arredondo an Iraq War Veteran who Lost His Hand on Patrol.
Not just Ordinary Electromaterials…. + A
Switching Surface Interactions
+ A- N
Controlled Release of Active Molecules
H N A-
Mechanical Level Switching
Novel Materials – Novel Structures – Unforeseen Opportunities!! Conducting Polymer (micro) Grid
A Novel Fluid Transfer System
Videos courtesy of Shannon Little
Nanostructured Electro Materials MACRO Human Hair MICRO NANO
1 mm 1 m
Can we achieve temporal distribution of function? External stimulation Response to the biological environment e.g. biodegradation swelling (phase change)
Galvanic coupling (Functional batteries)
Control at the Nano Level
+ A- N
H N A-
ACES - BIONICS 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)
Infection Control 16
Bionic Implants - Advanced Cochlear Implant Electrode Spiral Ganglion Neurite Explant Nerve cell body Nerve fibres
Electrode-Cellular Interface, G.G. Wallace, S.E. Moulton, G.M. Clark, Science 2009, 324, 185-186.
Safety studies commenced
Electrochemical data obtained
Carbon nanotube structures as implant electrodes 17
Nanobionics – Advanced cochlear implants
Apical (Low frequency)
Cochlea (Inner Ear)
Organ of Corti Basal (High frequency)
Fluid canals GCLARK FOUNDATION/NLA 18
Nanobionics – Advanced cochlear implants
Organ of Corti Outer hair cell
Inner hair cell
Peripheral auditory nerve fibres 19
Brain GCLARK FOUNDATION/NLA
Nanobionics – Advanced cochlear implants
Cochlea and Auditory Nerves
Electrode GCLARK FOUNDATION/NLA
Introducing an Additional Growth Factor (BDNF) PPy/pTS/NT3
Dual Neurotrophins: Synergy at Work BDNF
PPy/pTS/NT-3/BDNF Cochlear explant
No Electrical stimulation
A Nanostructured Platform (Patent Pending) Ppy/pTS/NT-3
MWNT forest PEDOT SIBS
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
Nanostructured PPys for Controlled Release PPy deposited on tips of CNTs
Comparison of CNT Array to Flat Film 24
Spinal Cord Regeneration Injured Spinal Cord
Repair of Lesion
Hydrogels and Fibres
Biodegradable Fibre Constructs
Conductive polymer materials for controlled release Wet fibre spinning to produce microdimensional structure 25
Schematic Representation of Wet-spinning Fibers
syringe and pump
coagulation baths linear controller
Scale bars are 100 m
Ink Jet Printing
Vapour phase PPy/pTS on glass – oxidant printed with 10pL cartridge
75:25 PLA/PLGA fibers
E Schwann cell migration front
Axonal growth front PLA/PLGA fibres
Scale bar = 50 m
Scale bar = 500 m
Muscular Diseases Damage Due to Trauma Grow / Replace Muscle Tissue 29
The Bio-Synthetic Cell Culture Platform
(a) 1. Wet-spun PLA:PLGA fibers on gold-coated mylar substrate
2. PPy polymerization of the exposed gold surface
Formation of the linear cell-seeded bio-synthetic fiber constructs. (a) The two-step (b) fabrication of the hybrid platform involves: (1) wetspinning 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(2 days) exposed gold 2.surface of the (4 days) 1. Myoblast proliferation Myotube differentiation 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.
Fluorescence Images of Differentiated, Multinucleated Desmin (Green) Expressing Myotubes
(b) 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.
Novel Ex Vivo Platform for Muscle Cell Growth
• 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 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 33
The Implantable Conduit Spatial Distribution of Growth Factor Molecules in 3-D
Aligned Fiber Structure
In-built Power Supply
Distribution of Stem Cells
Epilepsy Detection and Control Epilepsy is commonest serious neurological illness after stroke.
Current Treatments About 1% of the population affected by recurrent seizures.
Anti Convulsant Drugs Electrical Stimulation
5% will have seizures during their life.
Prof. Mark Cook, St Vincent’s Hospital and University of Melbourne. 35
Warning Some of the next slides contain medical images
SEM courtesy of Dr Jun Chen
More electrodes = more data More electrode = connection issues 38
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.
in vivo degradable polymer based drug delivery PLA-PLGA + Leviteracetam
3 mm 3 mm
Data and images courtesy of Dr Toni Campbell and Miss Amy Halliday.
Other Materials • Wet-spinning – Incorporation of AEDs in fibres – AED loaded fibres woven into sheets – Vary pore size
• Microparticles (Spray Drying) • Nanoparticle (Electrospray)
Seizure Initiated Release Epilepsy Research 39 (2000) 103–114: An automated drug delivery system for focal epilepsy, Alan G. Stein et al
Parameters for drug release V = ~130 mV
Polypyrrole + neurtrophin-3 
Polypyrrole + dexamethasone  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.
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.
• take multifunctional materials from fundamental research to proof of concept $52 million from the Federal Government A.I.I.M: PROCESSING AND DEVICES
EXISTING A.I.I.M BUILDING EXISTING IC CENTRAL
Targeted End Users: Projects Shorter Term Medium Term Longer Term
Collaborator Initiated Projects
An invitation to engage …. In current projects In new collaborative ventures From Basic R&D to Processing and Prototype Development
Become a Foundation Partner …
Major Equipment 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
Direct-Print Scaffolds Produced by nscrytp
Acknowledgments ARC NHMRC ACES staff and students