Capadona Lecture 7 10-9-2012 Final

7/28/2019 Capadona Lecture 7 10-9-2012 Final

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EBME201:

Finishingthe

eye,

visual

prosthetics,

andneuroinflammationinresponse

toneural

prosthetics

JeffCapadona

10/9/2012


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Peripheralarea

foveal area

light

Transmission


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5/23

Howdoweseemorethat3colors?


6/23

Whydoesthiswork???


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VisualprosthesisTheProblem:Iftherodsandconesdie

off,lightcannolongerbeconverted

intoelectricalsignalsandtransferredto

theopticnerve. Therefore,thepatient

becomesblind.

Historyofthedevice:1929

electricalstimulationofthevisual

cortexledtoperceptionoflight;1968

contactlens

electrode

=blind

can

senseelectricallyexcited

PopulationAffected:Nearly1M

legallyblindinUSA,Australiaand

Europe

Researchworldwide:onlyabout20

groupsandcompaniesworldwide

workingonthesetypesofdevices


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Visualprosthesis:BionicEye

Itsas

if

youre

throwing

atelevision

into

the

ocean

and

expecting

it

to

work


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Biomaterials and Devices for the Nervous System

http://neuroanimations.com/Hydrocephalus/Shunts/Complications

http://www.ima.umn.edu/industrial/97_98/hamlen/Image3.jpg

10 mm

5 mm

5 mm

5 mm

2 mm

200 um

10 mm

10 mm2 mm

2 mm

2 mm

5 mm

200 um

a)

f)

g)

h)

b) c)d)

e)

k) j)i)

Ordonez, J . et al. (2012) MRS Bulletin37:6;590-598Zhong, Y. et al. (2011) J Roy Soc Inter5:957Hamann M.C. et al. (2003) Exper Neuro 182:2; 300-309

Deguchi et a l. (2006) Cere Blood Flow 26:10; 1263-1273


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BrainMachineInterfacesRequireProximitytoNeuronalCellBodies

http://news.brown.edu/pressreleases/2009/06/braingate2; Buzski,G,NatNeurosci2004;Normann etal.JNeuroscienceMethods 1998


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Cortical Neuroprostheses implantation causes insult:

Cut through soft

tissue & expose

skull

Drill through

skull to expose

cortical tissue

Insert

electrodes into

the cortical tissue

InfectionHemorrhage

Damaged brain

barriers

Inflammation

AbbotNat. Rev. Neurosci, 2006


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He,W.W.Reichert,CRCPress, 2008;Potter,KA.JournalofNeuroscienceMethods 2012;Winslow,B.D.andP.A.Tresco (2010).Biomaterials

2010;McConnell,G.C.,etal.JournalofNeuralEngineering 2009

Microglia

Healthy

Neuron

Dying

Neuron

ActivatedMicroglia

Astrocyte

Soluble

Factors

Blood

ChronicInflammatoryResponseleadstoNeurodegeneration

Scalebar=100m


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Trescoetal2005;StensaasandStensaas,1976;Reieretal.,1983;Turneretal.,1999;Edelletal.,1992

Variability

from

two

shanks

on

one

device

one

shows

no

scaring,

and

theothershowsdenseglialscar

Resultsarejustasvariableforpreventativemeasures


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GlialScarStab/removevs.chronicimplanthealing

Stab Chronic Stab Chronic

4wk

s

2wks

Microglia Astrocytes

Stab

=

Heals

in

weeks,

with

no

residual

activated

microglia

orastrocytes

Chronic=Scargetsmoredensewithtime,stayaslongas

probeisimplanted

Biranetal.ExpNeurol2005


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GlialScarStab/removevs.chronicimplanthealing

NeuralFilament

4wks

2wks

Stab Chronic

Stab=Nolongtermeffectson

neurons

Chronic=Neuronalfilamentdoes

notregenerate,

and

neuronal

cell

bodiesdonotsurviveinclose

proximitytotheinterface.

Biranetal.ExpNeurol2005

Stab

Chronic

NeuronalCellBodies

2wks 4wks

Deadzone

=>100

m (4weeks);

Recording

site

must

be


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Microglia

Healthy

Neuron

Dying

Neuron

Activated

Microglia

Astrocyte

Soluble

Factors

Blood

ChronicInflammatoryResponseleadstoNeurodegeneration

MorphologyShape,Size,Roughness

Porosity

Chemistry

Modulus


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1030m =pressurechanges,respiration

24m =vascularpulsatility

1060m=administrationofanesthesia

Kipke etal.JNeuralEng 2005.

1 GPa 1MPa100 GPa

CompliantMaterials

Reduce

Strain

Micromotion CausesContinualStrainandTissueDamage

Highmodulus

enables

insertion

Lowmodulusreducesstrain


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Relaxed Soft Threatened Stiff

Capadonaet al. NatureNanotech.2007;Capadonaetal.Science 2008;Capadonaetal.Biomacromolecules 2009,2010;Capadonaetal.

MaterialsResearchBulletin 2012

Matrix:Lowmodulus

biomatrix

SeaCucumberDermis

SeaCucumberInspiredMechanicallyAdaptiveNanocomposite

FillerInteractions:

Glycoprotein

Nanofiller:Collagen

Matrix:Lowmodulus

polymer(PVAc)

Nanofiller:Cellulosewhiskers

FillerInteractions:Hydrogen

bonds

AdaptivePolymerNanocomposite


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MajorPlayers:CellTypesGlialScar

Microglia inthenormalbrainareinaquiescent state,withshort

branchedprocesses.(510%glialpopulation,nomacrophagelike

receptors.

Followinginjurytheyexhibitvariousbehaviors,includingactivation,

celldivision,andmigration totheinjury.Also,upregulateenzymes,

receptors,andreleaseinflammatoryfactors MHCI,II(leakyBBB=

macrophagerecruitment).Activationpersistininjurysitesformany

weeks until

healed.

Macrophages=Wherethereisvasculardamage,therewillalsobe

massive

macrophage

recruitment

from

the

blood.

Elevated

numbers

ofmicroglial/macrophagecellspersistuntilinjuryisphagocytosed.

Foreignobjectsneedtoberemoved phagocytosis


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RestingAstrocytes =

810

nm

in

diameter

GFAP

filaments,

round

neucleus,maintainnueronalenvironment,gapjunctionswithother

astrocytes,3065%ofglialpopulation

ReactiveAstrocyte =largeincreaseinGFAPfilaments,irregular

nucleus,proliferates,phagocytosis,migration,secretionofECM

proteins,producesneurotrophicandinflammatorycues

Whatcantberemoved,mustbewalledoff


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MeningealCells =Anyinjurythatpenetratesthemeningealsurfaceofthe

brainorspinalcordisrapidlyinvadedby migratingmeningealcells,whichre

createthecontinuouslayerofcellsthatcoverstheCNS.Thesecellsalsoplay

apart

through

their

interactions

with

astrocytes

in

the

re

formation

of

the

glialimitansthatsurroundstheCNS.

Sources??? TheextenttowhichtheyparticipateinCNSinjuriesisnotclear,

sincethereisatpresentnoreliablemarkerthatallowsthesecellstobe

identified.

Myelindebrisisslowlyremovedbymicroglia.Someofthe

oligodendrocytesdie,butsomesurviveandglialscarstherefore

generallycontainsome oligodendrocytesandforsometimecontain

myelindebris.

Whether

these

oligodendrocyes

can

regenerate

their

processestomakenewmyeliniscontroversial.

Noninflammatory,

resident

cells

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Capadona Lecture 7 10-9-2012 Final