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Medical Bionics‐ from the ear to the brain

Mark Cook

University of Melbourne

St. Vincent’s Hospital 

Bionics – what is it?

• Bionics means the replacement or enhancement of organs or other body parts by mechanical versions. 

• Bionic implants are more than just• Bionic implants are more than just prostheses – they mimic or improve the original function

Why Now?

• Advances in materials sciences

• Advances in computing technologies

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Bionic EyeMedical Bionics

Inner ear(cochlea)

Middleear

Receiver‐stimulatorTransmitting

coil

Behind‐the‐earSpeech processor

Brain

Electrodearray

Auditorynerve

Receiver‐stimulatorCoils

Behind‐the‐earSpeech processor

Electrodearray

Spinal Cord Repair

Medical Bionics

Neural Repair

University of Wollongong

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Control of epileptic seizures

•Prediction modelling•Control via drug delivery& electrical stimulation

Medical Bionics

DL

Biomaterials

• Materials intended to interface with biological systems to evaluate, treat, augment or replace any tissue, organ or function of the body. 

• A biomaterial is different from a biological• A biomaterial is different from a biological material such as bone that is produced by a biological system. 

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PPy-DBS NaNO3

NH

+

n

A-

m

+e

-e NH

0

n+ A-

m

Dynamic Properties of Conducting PolymersDynamic Properties of Conducting Polymers

Δ Resistance Δ Ion Flux (Ionic/Non Ionic)Δ Capacitance Δ Hydrophobicity / Surface Energy

For Small MobileDopant A-

Mechanical Level SwitchingMolecular Level Switching Controlled Release

Ink Jet Printing

Novel Structures for Controlled Release

Ink Jet Printing Fibre Spinning

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

75:25 PLA/PLGA fibers

“Intelligent” Polymer Nerve Growth Factor

Medical Bionics

Neural Repair

Scaffolds for Nerve & Spinal cord repair

University of Wollongong

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NERVE REPAIR SCAFFOLDS

Neural Repair Polymer Scaffold 

Development85:15 50:50 1.05IVBiodegradable Polymers

Sheaths

Cells

Biofactors/Gel

Materials

75 25

Fibres

Prototype

Animals:‐ April 14, 2008 (Second Iteration)

75:25

85:15

PU

85:15 PLA:PLGA

DRG

DRGDorsal Root Ganglia: Sensory Nerves of the

Peripheral Nervous System

Dorsal Root Ganglia and Anterior Horn

Dorsal Root Ganglia: Sensory Nerves of the Peripheral Nervous System

Dorsal Root Ganglia and Anterior Horn

Nerve Repair Polymer Scaffold

Second Iteration NeRPS Conduits(April 14, 2008)

– Sheath:• PLA knit• TP4 e‐spun

– Fibres:• 75:25/85:15 • 30μm (50:50 mix)• 30μm (50:50 mix)

• 300 fibres (300‐600)

– Neurogel:• BDNF, SMDF, LIF, IGF‐1 Peptide (x5)• NT3, SMDF, LIF, IGF‐1 Peptide (x5)• Alginate Hydrogel

Animals:‐ April 14, 2008 (Second Iteration)

Animals: June 2, 2008: Second Iteration Conduits Removed (4 weeks)

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BDNF‐NeRPS Conduit(4 weeks)

1. Sciatic Nerve: Proximal to the Conduit

‐ Growth of Axons

‐ Schwann Cells Migration

‐ Through the NeRPS

‐ Distal Nerve Protected

2. Conduit Entry 3. Mid Conduit 4. Conduit Exit

Nerve NeRPS Nerve

1       2        3       4

Sampling Map:

Proximal                                                                     Distal

TREATING FOCAL EPILEPSY

Current Complications in Epilepsy Treatment

• Systemic delivery

• Boom-bust cycle

• Refractory to polydrug therapy

• Intolerable side effects

• Electrical Stimulation

• Surgical intervention required

• Low-medium success rate

• Surgical resection

• Risk to eloquent areas

• Possible multi-focus seizure initiation

• <5% of partial epilepsy patients suitable

New Approaches to Epilepsy Treatment

• Polymer based targeted delivery

• poly-lactide:poly-lactide-co-glycolide (PLA:PLGA)

• biocompatible and bioresorbable

• currently used in other biomedical applications

• versatile degradation kinetics based on ratios of PLA to PLGA

PLA:PLGA Configurations

• One Polymer – Infinite Constructions

Microspheres Sheets Wet spun fibres  (showing LEV crystals on surface)

LEV Loaded PLA:PLGA Sheets

• Targeted Delivery for Focal Neocortical Epilepsies

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PLA:PLGA 85:15 / Lev polymers

Lev 40 mg/ml  Lev 20 mg/ml

Lev 50 mg/ml 

Continuous release sheets

• POLYMER: biodegradable

• METHOD: solvent casting

Surface Deep

PO

LYME

R TYP

E

ContinuousContinuous release sheets

Continuous release spheres

On-demand

Stimulated release sheets

LEV Loaded PLA:PLGA Sheets

• Targeted Delivery for Focal Neocortical Epilepsies

LEV Loaded PLA:PLGA Sheets

• Biocompatibility – coronal section through rat MCx

Previous polymer sheet location Mechanical damage from surgery

Underlying cortical layer organisation unaffected

LEV Loaded PLA:PLGA Sheets

• Biocompatibility – FluoroJade C histological analysis 

Background fluorescence level

Positive Neural Degeneration Control

Efficacy

• Tetanus toxin model

• Inject tetanus toxin into hippocampus

• Spontaneous seizures @  1 week

• ~ 1 2 hourly•  1‐2 hourly,Last several months

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Where to next?• Continue to implant sheets in seizing rats

• Similar studies using injectable polymer

– Biocompatibility

– Efficacy

• Further development of stimulated release polymer– Incorporate epilepsy drugsIncorporate epilepsy drugs

– Detect release in seconds, not minutes

• Issues to consider– Titration onto drugs necessary/possible with implants?

– If person becomes unresponsive to drug while implant still present?

– Development of degradable conductive polymer

Continuous release spheres

• POLYMER: biodegradable

• METHOD: emulsion 

Surface Deep

PO

LYME

R TYP

E

ContinuousContinuous release sheets

Continuous release spheres

On-demand

Stimulated release sheets

g

y = 0.0101x + 0.0747R2 = 0.9879

00.10.20.30.4

0.50.6

0.70.8

0 20 40 60 80Time (days)

leve

tirac

etam

rel

ease

d ug

/ mg

sphe

res

Microspheres A3

Stimulated release

e‐

• POLYMER: organic conductive

• METHOD: growing the polymer

Surface Deep

PO

LYME

R TYP

E

ContinuousContinuous release sheets

Continuous release spheres

On-demand

Stimulated release sheets

‐

‐

‐‐‐ ‐

‐‐

++

++

++

+

e

Stimulated release

e‐

• POLYMER: organic conductive

• METHOD: growing the polymerSurface Deep

PO

LYME

R TYP

E

ContinuousContinuous release sheets

Continuous release spheres

On-demand

Stimulated release sheets

‐

‐

‐

‐‐

‐‐

‐

++

++

++

+

e

Stimulated release

TEXT TEXT

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ELECTRICAL THERAPY FOR SEIZURES

Electrical Therapy for Epilepsy

• Counter‐stimulation known to be effective –sometimes

50

History of Electrical Stimulation1970s – Jose Delgado Electrical therapy for Epilepsy

• Counter‐stimulation known to be effective –sometimes

• Well established in Parkinson’s Disease

52

Current Technology

Deep Brain Stimulation for Parkinson’s disease

Deep Brain Stimulation for Parkinson’s disease

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Electrical therapy for Epilepsy

• Counter‐stimulation known to be effective –sometimes

• Already one type of electrical therapy available vagal nerve stimulationavailable – vagal nerve stimulation

• Low efficacy of VNS a problem

• Need new systems to detect then counter‐stimulate to abort seizures 

55

1624

101826

34425057

3240485664

12345678

Epileptiform Afterdischarge Duration

Non-stimulated case

EAD duration

Parameter Space

Failed stimulation case

Parameter Space

Successful stimulation case

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Parameter Space Parameter Space

Improving Available Technologies

• Combination of electrical stimulation and intelligent polymers

• Improve integration of materials with tissues.

Nerve cell body

Nerve fibres

Spiral Ganglion NeuriteExplant

Primary Neuron Interaction: PPy.pTS.NT3Primary Neuron Interaction: PPy.pTS.NT3

Effect of Growth Factor NT3

Effect of Electrical Stimulation

Cells

Cell Culture Media

Conducting polymer containing growth factor

Cells

Cell Culture Media

Conducting polymer containing growth factor

Spiral Ganglion Neurite (SGN) ExplantsSpiral Ganglion Neurite (SGN) Explants

SGN Outgrowth is Affected by Surface Chemistry

Richardson et alBiomaterials2007, 28, 513

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Conclusions

• Advances in materials sciences and computer technologies are driving the very rapid development of medical bionics.

• Many technologies already in use• Many technologies already in use.

• Significant issues to be addressed still around problems of material and tissue interfaces

• Safety of nanotechnologies still uncertain

• Ethics of artificial enhancement?