1

Nanotechnology in Bionic Research

Dr. Simon MoultonQEII Fellow

ARC Centre of Excellence for Electromaterials Science (ACES)

Intelligent Polymer Research Institute

University of Wollongong

2

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

3

Fantasy and Fact

www.uml.edu/.../media/nanotechnology-kd-001.jpg

4

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)

5

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

6

Bionics?The University of Melbourne

Bionic Ear 1978The Bionic Man

Col. Steve Austin 1973

GCLARK FOUNDATION/NLA

7

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.

8

Enhanced Performance Implantables

Wearables for Prosthetics and Monitoring

Bionics

MAYBE THEBIONIC GAMES?

9

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

10

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

11

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-

12

Novel Materials – Novel Structures –

Unforeseen Opportunities!!

Conducting Polymer (micro) Grid A Novel Fluid Transfer System

Videos courtesy of Shannon Little

13

1 m

1 mm

1 m

100 nm

MACRO

MICRO

NANO

MOLECULAR

HumanHair

NanostructuredElectro -Materials

14

External stimulation

Response to the biological environment

e.g. biodegradation

swelling (phase change)

Galvanic coupling

(Functional batteries)

Can we achieve temporal distribution of function?

15

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-

16

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

17

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

18

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)

19

Organ of Corti

Basilarmembrane

Peripheral auditorynerve fibres

Brain

Innerhair cell

Outerhair cell

Nanobionics – Advanced cochlear implants

GCLARK FOUNDATION/NLA

20

Cochlea and Auditory Nerves

ElectrodeBrain

Nanobionics – Advanced cochlear implants

GCLARK FOUNDATION/NLA

21

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)

22

Dual Neurotrophins: Synergy at Work

Electrical stimulation

No Electrical stimulation

BDNF

NT-3 Cochlear explant

PPy/pTS/NT-3/BDNF

NT-3/BDNF

BrainBrain

23

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)

24

PPy deposited

on tips of CNTs

Comparison of CNT Array to Flat Film

Nanostructured PPys for Controlled Release

25

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

26

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

27

Vapour phase PPy/pTS on glass –oxidant printed with 10pL cartridge

Ink Jet Printing Fibre Spinning

75:25 PLA/PLGA fibers

28

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

29

MUSCLE REGENERATION

Muscular Diseases

Damage Due toTrauma

Grow / ReplaceMuscle Tissue

30

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

31

(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

32

• 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

33

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

34

The Implantable Conduit

Aligned

Fiber

Structure

In-built

Power

Supply

Spatial

Distribution

of Growth

Factor

Molecules

in 3-D

Distribution

of Stem

Cells

Biodegradable

35

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

36

Warning

Some of the next slides contain medical images

37

Detection

38

Electrode Design

More electrodes = more dataMore electrode = connection issues

SEM courtesy of Dr Jun Chen

39

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.

40

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

41

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

42

Seizure Initiated Release

Epilepsy Research 39 (2000) 103–114: An automated drug delivery system for focal epilepsy, Alan G. Stein et al

43

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)

44

• 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

45

Shorter Term

Medium Term

Longer Term

Targeted End Users: Projects

Collaborator Initiated Projects

46

In current projects

In new collaborative ventures

An invitation to engage ….

From Basic R&D to Processing and Prototype Development

Become a Foundation Partner …

47

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

48

Thankyou

AcknowledgmentsARC

NHMRCACES staff and students