Natural Materials for Dural Replacement and Neuroprotection

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    Vanessa AguilarProject PlanOctober 27, 2010

    Natural Materials for DuralReplacement and Neuroprotection

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    Dural Replacement Therapy Needs

    Dura lesioncomplications:

    Meningitis Cerebral spinal fui

    lea! Pseuomeningocele Arac"noiitis #piural abscess

    Current uralreplacementmar!et

    $ore%&e' (eP&)#* +europatc" (polesteruret"ane*

    Duragen (Collagen* Dura-eal (P#$%basespra*

    &isseel ()ibrin.trombinsolutions*

    Preclue (P&)#.elastomericfuoiropolmer*

    /istor o uralreplacement 13 4rst ural

    replacement1

    Mi 05s 'enograp"an allograp" 6ereuse

    -ince 705s biosnt"eticgrat 6ere inestigate

    189 o spinal surgeriesreuires a uralreplacementtec"nolog2

    "ttp:..666;nlm;ni";go.melineplus.enc.imagepages.1718

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    Anatomical Dural Overview

    "ttp:..members;co';net.injections.images.esi?images.roots;jpg

    +arotam P; et al, -pine 2008

    -tenel > et al;= +eurosurg 200,

    >un@a et al, Anest" Analg, 1

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    Dural >eplacement . Cranial A"esion arriersarrier Deice Dura$en

    (Bntegra ie -ciences*-nt"ecel Dura

    (-nt"es*Dura-eal(Coiien*

    A"erus(/perranc"*

    Moel

    Description Dura$en.Dura$enPlus is an innoatiematri' esigne topreent periural4brosis an a"esions

    Cellulose Emicrobiall gro6ncellulose

    P#$ "rogel -nt"etic surgicalsealant E P#$"rogel blen

    Properties Collagen baseAe cellulose laeror suturable

    perormance

    &"ic!, er strongs"eets o cellulose

    1009 snt"eticFater%tig"t sealantto be applie uring

    cranial or spinalsurgeries or urarepair

    C# approe orspinal applications

    Aantages )DA approe orneural applications+atural%basematerialioresorbable but

    egraation resistant

    )DA approe orural replacementan 6oun ressingP"ase BBB clinicaltrials

    )DA approe orcranial an spinalsurgeries;Bnjectable an easto use

    -pra%use, eas touse

    Disaantages

    +ot eas to "anle+ot an a"esionbarrierAttracts a"esions

    Ver e'pensie&imel to gro6Cannot be gro6nmass%scale

    -et up reuire-nt"eticCan beprocoagulant+ere compressionma ocur1

    -et up reuire-nt"eticCan beprocoagulant

    1; -potnit@, F an ur!s, -; &ransusion;200

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    Plan of WorkGOA! To develop composite" dual#functionin$ materials that wouldserve to encoura$e healthy cell $rowth" wound healin$ and inhi%its

    post#sur$ical scar tissue formation for neural applications& We aim todevelop an all#in#one product to replace dural tissue as well assupport healthy healin$&

    A'M (! Develop andcharacteri)e sutura%leanti#adhesion *lm +

    foam

    ,iocompati%le Non#immuno$enic Non cell#adhesive +

    cytoto-ic

    'nhi%its proteina%sorption Mechanically ro%ust Waterti$ht + sealin$ Anti#*%rotic

    A'M .! Dru$ releasestudies

    ,iocompati%le /0ective at reducin$

    adhesions /ncapsulate aspirin

    or i%uprofen

    Tuna%le releaserates

    A'M 1! Develop %ilayer%iofunctionali)ed 2A#%ased *lm

    ,iocompati%le ,ioa%sor%a%le Non#immuno$enic Dual functionin$

    Re$enerative

    Anti#adhesive Mechanically ro%ust 3ost e0ective 3linically si)ed Repositiona%le

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    GOA! To develop composite" dual#functionin$ materials that wouldserve to encoura$e healthy cell $rowth" wound healin$ and inhi%its

    post#sur$ical scarred tissue formation for neural applications& Weaim to develop an all#in#one product to replace dural tissue as well assupport healty heallin$&

    A'M (! Develop andcharacteri)e sutura%leanti#adhesion *lm +

    foam

    ,iocompati%le Non#immuno$enic Non cell#adhesive +

    cytoto-ic

    'nhi%its proteina%sorption Mechanically ro%ust Waterti$ht + sealin$ Anti#*%rotic

    A'M .! Dru$ releasestudies

    ,iocompati%le /0ective at reducin$

    adhesions /ncapsulate aspirin

    or i%uprofen

    Tuna%le releaserates

    A'M 1! Develop %ilayer%iofunctionali)ed 2A#%ased *lm

    ,iocompati%le ,ioa%sor%a%le Non#immuno$enic Dual functionin$

    Re$enerative

    Anti#adhesive Mechanically ro%ust 3ost e0ective 3linically si)ed Repositiona%le

    Plan of Work

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    Material Properties

    "ttp:..666;masci;org.posts.arc"ies.apr2001.

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    Anti 3ell#Adhesion Properties

    2; Culture 4broblast cells

    G; 1;3 "ours in culture

    8; )i' an stain or DAPB;

    3; Valiate cell%a"esion . noncell%a"esions

    666;biomecentral;com

    1; Fell an 4lm

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    Results

    Alginate Alginate .$M/A

    Alginate .$M/A ./A Control&"ere is signi4cant iHerencebet6een control an 4lms (p J

    0;003*

    0

    23

    3073

    100

    123

    3ell Adhesion 4tudies

    5 3ell Adhesion

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    3ytoto-icity1; Culture 4broblastcells

    2; -ee cells in P coate &Ccoerslips

    8; -tain coerslips 6it"calcein . et"iium to label lie .ea cells;

    3; #aluatectoto'icit

    8; Fait 28"ours

    666;biomecentral;com

    3; Place Alginate . /A4lm supernatant on topo cells

    G; Place Alginate . /A4lm on cell meium

    8; Fait 28"ours

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    Results

    Alginate Alginate .$M/A

    Control

    &"ere is no statistical iHerencebet6een control an 4lms in lie an

    ea assa

    ie Dea0

    10

    20

    G0

    8030

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    Anti*%rotic studies6usin$ laminectomy model7

    1; Collect t"e tissue

    2; De"rate in et"anol

    G; Aci ecalci

    8; Fait or G as

    3; -lice eer 30 um

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    Waterti$ht 4tudies

    L; /ia et al; -urgical +eurolog

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    Protein Adsorption 4tudies

    2; >inse 6it" P-

    /uang an ang, Polmers aance tec"nologies, 200

    )ilm

    1; -"a!e or 28 "ours at G7NC

    /uman serum albumen an"uman plasma 4bronectin

    G; Aition o soium oeclsulate (-D-*

    3; Measure absorbance at 3

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    Ac!no6legments

    P'! Dr& 3hristine 4chmidt"Graduate 4tudents! 4arah Mayes

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    3urrent Technolo$ies

    Autologous grats Pericranium or temporal ascia

    enograts an allograts Menengitis an Creut@elt%=acobs Disease

    +atural an sntet"ic materials $ore%&e' (eP&)#*

    +europatc" (polester uret"ane* Duragen (Collagen* Dura-eal (P#$%base spra* &isseel ()ibrin.trombin solutions* Preclue ( P&)#. elastomeric fuoiropolmer*

    "ttp:..megaget;com.arc"ies.2003.08.uraseal;"tml

    "ttp:..666;mecompare;com.etails.1

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    Results

    Alginate Alginate .$M/A

    Alginate .$M/A./AControl

    &"ere is no statistical iHerencebet6een control an 4lms in lie an

    ea

    ie Dea0

    10

    20

    G0

    8030