Research Article Feasibility of Crosslinked Acrylic Shape Memory Polymer for a Thrombectomy ...

13 Pages·2015·5.13 MB·English

Hindawi Publishing Corporation
Smart Materials Research
Volume 2014, Article ID 971087, 12 pages
http://dx.doi.org/10.1155/2014/971087
Research Article
Feasibility of Crosslinked Acrylic Shape Memory
Polymer for a Thrombectomy Device
AndreaD.Muschenborn,KeithHearon,BrentL.Volk,
JordanW.Conway,andDuncanJ.Maitland
BiomedicalEngineeringDepartment,TexasA&MUniversity,3120TAMU,CollegeStation,TX77843,USA
CorrespondenceshouldbeaddressedtoDuncanJ.Maitland;[email protected]
Received29August2013;Revised25December2013;Accepted16January2014;Published25February2014
AcademicEditor:HidekiHosoda
Copyright©2014AndreaD.Muschenbornetal. This is an open access article distributed under the Creative Commons
AttributionLicense,whichpermitsunrestricteduse,distribution,andreproductioninanymedium,providedtheoriginalworkis
properlycited.
Purpose.ToevaluatethefeasibilityofutilizingasystemofSMPacrylatesforathrombectomydevicebydetermininganoptimal
crosslink density that provides both adequate recovery stress for blood clot removal and sufficient strain capacity to enable
catheterdelivery.Methods.Fourthermosetacryliccopolymerscontainingbenzylmethacrylate(BzMA)andbisphenolAethoxylate
diacrylate(Mn∼512,BPA)weredesignedwithdifferingthermomechanicalproperties.Finiteelementanalysis(FEA)wasperformed
toensurethatthematerialswereabletoundergothestrainsimposedbycrimping,andfabricateddevicesweresubjectedtoforce-
monitoredcrimping,constrainedrecovery,andbench-topthrombectomy.Results.Deviceswith25and35mole%BPAexhibitedthe
highestrecoverystressandthehighestbrittleresponseastheybrokeuponconstrainedrecovery.Onthecontrary,the15mole%BPA
devicesenduredalltestingandtheirrecoverystress(5kPa)enabledsuccessfulbench-topthrombectomyin2/3times,comparedto
0/3forthedeviceswiththelowestBPAcontent.Conclusion.Whilethe15mole%BPAdevicesprovidedthebesttrade-offbetween
deviceintegrityandperformance,otherSMPsystemsthatofferrecoverystressesabove5kPawithoutincreasingbrittlenesstothe
pointofcausingdevicefailurewouldbemoresuitableforthisapplication.
1.Introduction remain significantly limited. Only 2-3% of ischemic stroke
patients are eligible to receive tPA because of its narrow
Thrombectomydevicesareutilizedendovascularlytoremove treatment time window and other exclusion criteria [6, 7].
bloodclotsandreestablishbloodflowinanoccludedartery. Consequently,tPA-ineligiblepatientsareusuallytreatedwith
When the occluded artery is part of the neurovasculature, oneoftheapprovedthrombectomydevices,whichareoften
failure to reestablish blood flow in a timely manner results associated with other complications, including blood clot
inasignificantreductionintheoxygenationofbraintissue. dislodgement and distal migration, limited device maneu-
Such an event is called acute ischemic stroke and occurs verability,andarterialperforation[2,8–10].Thereremainsa
approximately every minute to someone in the US [1–3]. needtoevaluatealternativematerialsanddevicedesignsthat
Of all ischemic stroke cases, 8–12% are fatal, and the 6- canenablerapidandsuccessfulreestablishmentofbloodflow
month poststroke period for survivors renders this disease inischemicstrokepatients.
the leading cause of adult long-term disability [1, 2, 4, 5]. The emergence of smart materials has given rise to the
To date, there is one drug, tissue plasminogen activator investigative development of numerous minimally invasive
(tPA),andfourdevices,MerciRetriever(Stryker,California), endovasculardevicesthatexploitnovelmaterialcapabilities.
Penumbra System (Penumbra Inc., California), Solitaire FR One such capability is shape memory, which is a material’s
(ev3, California), and Trevo Retriever (Stryker, California), ability to store temporary shape(s) and then actuate to a
thathavebeenapprovedbytheUSFoodandDrugAdmin- primary geometry when exposed to stimuli such as heat or
istration(FDA)forthetreatmentofacuteischemicstroke[2, moisture[11–13].Shapememoryalloys(SMAs),particularly
3,6].However,thesuccessratesoftheseclinicaltreatments nickel titanium (nitinol), have been used in the biomedical
2 SmartMaterialsResearch
field for over 20 years [14]. Three out of the four FDA-
0.50
approved devices for the treatment of ischemic stroke are
made with nitinol. For example, the Merci Retriever is a
nitinolwirethathasbeenpreshapedwithacorkscrewgeom-
etry. The other two nitinol-based thrombectomy devices
are self-expanding stents, Solitaire FR and Trevo. However, 6
one major drawback of these devices is their length, which
0.80
limitstheirplacementandmaneuverabilityduringtreatment
[15].
Shapememorypolymers(SMPs)arebeinginvestigatedas
alternativecandidatematerialsforendovascularapplications
such as thrombectomy, primarily because SMPs exhibit
recoverabledeformationsupto100timesgreaterthanthose
reported for SMAs [13, 16, 17]. Consequently, many SMP-
based endovascular devices are capable of undergoing the ∅0.60
significantshapechangesnecessaryforcatheterdelivery[11, 1.05
18–22].Thispropertyenablestheexplorationofnoveldevice
designs that have the potential to address the issues with
commerciallyavailablethrombectomydevices,forexample,
Figure1:Flower-shapedthrombectomydevicedesignedinSolid-
difficult maneuverability. For example, Buckley et al. [23] Workswithdimensionsinmm.Thisdesignwasadaptedfroman
proposedadesignthatiscrimpedtoacylinderforcatheter originalthrombectomydeviceproposedbyBuckleyetal.[23].
delivery and is actuated to a flower shape distal to the
occlusionsuchthatonlytheedgeofthe“petals”isincontact
with the vessel during treatment minimizing device-vessel
2.1.DeviceDesign. Flower-shapeddevicesweredesignedin
contactpoints.
SolidWorks based on the geometry proposed by Buckley et
While SMPs generally exhibit maximum recoverable
al.[23].Modificationstothedesignwerenecessarytoprevent
forces less than 1/100 times the recovery force of SMAs,
portionsofthedevicefoldingoverthemselvesduringcrimp-
another advantage is tunability of thermomechanical prop-
ing and to reduce potential areas of stress concentrations.
ertiesincludingrecoveryforce,modulus,actuationtemper-
In order to better visualize the devices during testing, we
ature (for thermally actuated SMPs), and recoverable strain
designed them to be 4 times larger than they would be for
to meet the material demands of various applications. One
in vivo testing. The design used in this study is depicted in
effective,demonstratedmethodoftailoringthermomechan-
Figure1.
ical properties of SMPs is controlling crosslink density [24,
25]. Increasing crosslink density of SMP systems has been
generally shown to increase recovery stress [11, 26, 27]. At 2.2. Finite Element Analysis Simulations. The device design
the same time, however, increasing crosslink density can was imported from the SolidWorks file created to fabricate
alsohaveundesiredeffectssuchasincreasedbrittlenessand the device (see Figure1), and the crimping funnel (small
decreasedstraincapacity[28]. inner diameter = 3.5mm, large inner diameter = 12.5mm)
The objective of this study is to evaluate the feasibil- andball(outerdiameter=2mm)werecreatedinAbaqusas
ity of fabricating SMP-based thrombectomy devices from analytical rigid parts. The device was modeled using 1/14th
crosslinkedSMPacrylatesby(1)findingthecrosslinkdensity symmetryinacylindricalcoordinatesystem.Thedevicewas
thatresultsinincreasedrecoverystresswithoutcompromis- meshed using approximately 12000 linear, 3D, hybrid brick
ingthestraincapacitynecessaryforcrimpingandactuation elements(C3D8H)andwasmodeledasanisotropicMooney-
and (2) determining whether the resulting thermomechan- Rivlin material with coefficients of C10 = 3.06865MPa and
ical properties would be suitable for thrombectomy in a C01 = −0.94798MPa. These coefficients were obtained by
bench-topmodel. analyzing,usingthematerialevaluatorfunctioninAbaqus,
thetensiletestdataforeachofthepolymercompositionsand
averagingtheresultingMooney-Rivlincoefficients.Because
2.MaterialsandMethods the strain—which is dictated by the geometry change in
passing through the funnel—of the thrombectomy device
After finalizing the device design, the deformation of the was the primary quantity of interest, efforts were not made
device was modeled via finite element analysis (FEA) to to further optimize the constitutive response to the tensile
estimate maximum strains. Then, a system of crosslinked test data. The nonlinear geometry feature was enabled for
acrylic SMPs was designed with varying crosslink densities the simulation, and “hard” contact (i.e., no penetration)
andwithstraincapacitiesgreaterthanthemaximumstrains was assumed between the funnel and the device, the ball
predicted by FEA. Devices were subsequently machined and the device, and the analytical planes and the device
andsubjectedtoforce-monitoredcrimpingandconstrained (tomodelself-contactintheloopsduringthecrimping).A
recovery, and finally blood clot removal experiments were coefficientoffrictionof0.04wasassignedbetweenthefunnel
performedinabench-topthromboticmodel. and the device based on a bench-top friction test between
SmartMaterialsResearch 3
blocks of polytetrafluoroethylene (PTFE) and poly(methyl
50N load cell
methacrylate) (PMMA). A value of 0.8 was assigned as the
Manual screw
coefficient of friction between the device and the analytical
action grip
planes(forself-contact)andbetweentheballandthedevice
(toaccountforroughnessoftheball)basedonpublisheddata
Alignment Wire
ofthenominalcoefficientoffrictioninacrylic[29].Theball,
hole
device, and funnel were initially concentrically positioned, PMMA fixture
andthentheballwasheldspatiallyfixedwhilethefunnelwas
PTFE insert
movedtoencompassthedevice.
with funnel
2.3. Polymer Synthesis. The monomer benzyl methacrylate
(BzMA), the crosslinker bisphenol A ethoxylate diacrylate Pneumatic
(Mn∼512, BPA), and the photoinitiator 2,2-dimethoxy-2- grip
phenylacetophenone (DMPA) were purchased from Sigma
Aldrich and used as received without further purification.
This monomer and difunctional crosslinker combination,
whichissimilartothatreportedbySafranskiandGall[24],
was selected because it enables the synthesis of a series of
SMPswithtailorablecrosslinkdensitiesandglasstransitions Figure2:Sketchofcustom-madeapparatusforthecrimpingofthe
above body temperature in the range of 65 to 75∘C. Benzyl thrombectomydevices.Theapparatuswasdesignedsothatitwas
compatiblewiththeInstrontensiletester.Eachdevicewasinserted
methacrylate was also selected because Safranski and Gall
in the PTFE funnel, and after thermal equilibrium was achieved
[24]demonstratedthatpoly(benzylmethacrylate)thermoset
after1hour,thedevicewasslidupwardsbythemovementofthe
SMPshavehighertoughnessthannumerousotherthermoset
crossheadconnectedtothemanualscrewactiongrip.Thedevice
acrylics. Four thermoset acrylic BzMA-BPA copolymers
wasallowedtocooldowninthenarrowcylindricalfeatureofthe
containing 5, 15, 25, and 35 mole% BPA and 0.5 weight%
PTFEinsert,abovethefunnel.
DMPA were prepared in 51 × 76 × 0.4mm sheets by bulk
UV curing. After massing, the monomer, crosslinker, and
photoinitiator mixtures were injected between 51 × 76mm
glassslidescoatedwithRain-Xseparatedby0.4mmspacers 40W Gravograph LS100 CO2 laser machining device with
andcuredfor99minutesusing365nmUVirradiationinside thesameinstrumentparametersusedtocuttherectangular
aUVPCL-1000crosslinkingchamber.Thecuredthermoset DMA specimens. Specimens were cleaned with a methanol
filmswerethenpostcuredat130∘Cwithvacuumat1torrfor damp Kimwipe, dried at 90∘C under vacuum at 1Torr, and
12hoursandsubsequentlystoredunderdesiccation. subsequentlystoredunderdesiccationpriortobeingtested.
Specimen deformation was measured optically using an
Instron Advanced Video Extensometer with a 60mm field-
2.4. Dynamic Mechanical Analysis. Dynamic mechanical
of-view lens. Specimens were heated to target temperatures
analysis (DMA) experiments were carried out in tension
under zero loads (unclamped bottom grip) and were held
usingaTAInstrumentsQ800dynamicmechanicalanalyzer
isothermally for 30 minutes to allow thermal equilibrium
and 4 × 30 × 0.4mm rectangular specimens (𝑛 = 5). The
to be reached. The bottom grip was then clamped, and the
rectangular specimens were machined with a 40W Gravo-
strain-to-failureexperimentsweresubsequentlybegunusing
graph LS100 CO2 laser machining device using a 38.1mm adeformationrateof10mm/min.Datawererecordedusing
lens, a speed setting of 5, a power setting of 10, and a laser
InstronBluehill3software.
resolution of 1200 dots per inch. Specimens were cleaned
∘
withamethanoldampKimwipe,driedat90 Cundervacuum
at 1Torr, and subsequently stored under desiccation prior 2.6. Device Fabrication. The postcured 51 × 76 × 0.4mm
to being tested. DMA experiments were carried out from sheets of the four different copolymers were cut with the
−20to140∘CintheDMAmultifrequency/straininstrument design pattern shown in Figure1 utilizing the 40W Gravo-
mode using a frequency of 1Hz, a strain of 0.1%, a preload graph LS100 CO2 laser machining device. The same instru-
force of 0.01N, a force track of 150%, and a heating rate mentparameterswereimplementedastheonesusedtocut
of 2∘C/min. Data were recorded using TA Instruments Q- the DMA and dog bone specimens. Devices were carefully
∘
seriessoftwareandanalyzedusingTAInstrumentsUniversal cleaned with a methanol damp Kimwipe, dried at 90 C
Analysissoftware. undervacuumat1Torrprior,andsubsequentlystoredunder
desiccationpriortobeingtested.
2.5.TensileTesting. Uniaxialtensiletestingexperimentswere
conductedtofailureonASTMtypeVdogbonesamples(𝑛= 2.7. Device Crimping. A custom fixture compatible with
5)usingadual-columnInstronmodel5965tensiletesterwith Instrontensiletestersystemswasfabricatedwithaminicom-
a500Nloadcell,1000Nhightemperaturepneumaticgrips, puter numerically controlled (CNC) milling machine (see
and a temperature chamber thermally controlled by forced Figure2).ItconsistedofaremovableportionmadeofPTFE
convectionheating.Thedogbonesampleswerecutusinga with a funnel-like geometry on the inside and a stationary
4 SmartMaterialsResearch
50N load cell
TT
PP
Catheter WB
Q
TB VM
CD
HW
Blockwise radial tester TP DC
TB DV
Figure 4: Bench-top thrombotic stroke model. WB: water bath
∘
(37C); PP: peristaltic pump; TT: tensile tester (extension rate =
75mm/min);Q:experimentalflowrate(=57mL/min);TB:Touhy
Figure 3: Sketch of Blockwise radial tester utilized in the con-
Borst valve; CD: crimped device location; VM: vessel model; TP:
strainedrecoveryexperiments(notdrawntoscale).Thediameter
thermocoupleprobe;HW:hotwatersyringe;DV:dischargevalve;
enclosed by the blades was set with a high accuracy gage pin,
DC:dischargecontainer.
and each device was inserted in its crimped configuration. The
∘
temperatureofthebladeswasrampedfrom30to55C,whilethe
diameteroftheradialtesterwaskeptconstant.Asthethrombectomy
devicerecovereditsshape,itexertedaloadontotheblades,which thecrimpeddevices(seeFigure3).Theradialtestertemper-
wassensedbytheloadcell. ∘ ∘
aturewasrampedfrom30 Cto55 Candtherecoverystress
ofthedevicesthatwerepreviouslycrimpedatlossmodulus
peaktemperaturewasmeasuredat1HzusingInstronBluehill
portion made of PMMA that was attached to the tensile 3software.Athermocouplewasinstalledincloseproximity
tester’s bottom pneumatic grip. The maximum diameter of of each device, and temperature was also recorded at 1Hz
thefunnelwas12.5mmanditcontractedgraduallyto3.5mm usingLabView.Thediameterofthetesterwaskeptconstant
(the portion with the smallest diameter was 1cm long and at3.75mmaftersettingitwithahighaccuracygagepin.The
it served to fit the length of the crimped device and allow blade heating effects of the radial tester were accounted for
it to cool down). The stationary portion had a cap with a bysubtractingdatameasuredwiththeemptytesterfromthe
0.3mm hole machined with an excimer laser that helped dataofallmeasureddevicesforthesametemperaturerange.
centerthewirethatheldthedevicesthroughoutthecrimping
process.Thiswirehad∼2mmdiameterballof96.5Sn3.5Ag 2.9.Bench-TopBloodClotRemoval. Abench-topthrombotic
solder purchased from Indium Corporation at the tip to strokemodelshowninFigure4wasconstructedtotest the
hold the devices as they were pulled during crimping. By feasibility of the SMP flower-shaped devices for blood clot
insertingathermocoupleinsidethefunneloftheassembled hold during removal. The blood clots were prepared with
crimpingfixture,itwasdeterminedthatinordertoachieve bovine blood (10mL), which was acquired from Vet Med
the target temperature inside the funnel within 45 minutes Park,CollegeStation,Texas.Bariumsulphate(1g)andbovine
∘
thetemperaturechamberwasrequiredtobeset4 Chigher. thrombin(25IU),bothpurchasedfromVWRInternational,
Thus, devices were allowed to thermally equilibrate inside wereaddedtothebovineblood,andthemixturewasinjected
the funnel for a minimum of 1 hour prior to testing. The intoasiliconetubewith10mminnerdiameter.Themixture
tensile tester had a 50N load cell, rated with a resolution was gently agitated for about 5 minutes and was incubated
of 0.00025N, and was set to extension mode at a strain atroomtemperatureforatleast1hourpriortotesting[30].
rateof5mm/min.DatawererecordedusingInstronBluehill Bloodclotsofroughly2cminlengthwerecutwithascalpel.
3 software. The crimping experiments were performed at
Eachcrimpeddevicewasinsertedintothesiliconebifur-
temperatures corresponding to the mechanical transition
catedvesselmodel(purchasedfromShelleyMedicalImaging
temperatures,DMAlossmoduluspeak,andtandeltapeak,
Technologies, Ontario, Canada) followed by a blood clot.
ofeachcopolymer’scomposition(𝑛=5). ∘
Water at 37 C was pumped into the main vessel segment
(lumendiameter=8mm)ataflowrateof57mL/minviaa
2.8. DeviceConstrainedRecovery. Acommerciallyavailable peristaltic pump. The in vivo dynamically similar flow rate
BlockwiseEngineeringRJA62radialstresstestercompatible via the matching of the Reynolds number that corresponds
withInstrontensiletestersystemswitha50Nloadcellwas to the experimental flow rate is within the range of flow
utilized to perform constrained recovery measurements of ratesrecordedinthemiddlecerebralartery,acommonsite
SmartMaterialsResearch 5
LE, maximum. principal
(avg:75%)
0.83
0.40
0.37
Device in funnel 0.33
0.30
0.27
0.23
0.20
0.17
0.13
0.10
0.07
0.03
0.00
Top view Side view Bottom view
Figure5:Estimatesinthethrombectomydevicefortheprincipallogarithmicstrainsduringthecrimpingprocedure.Themaximumprincipal
strainsareapproximately40%andarelocatedonthestrutsofthebottomloopsofthedeviceaswellasnearthecentercircle.
forthromboembolicocclusionintheneurovasculature[31]. Table1:Rubberymodulusandmechanicaltransitiontemperature
Each device was actuated by injecting water near boiling values.
temperature with a syringe while shutting the valve that
Rubbery Lossmoduluspeak Tandeltapeak
connects one of the bifurcations of the vessel model to the Composition modulus temperature temperature
dischargecontainer.Thedevicewasattachedtoaguidewire, (MPa) (∘C) (∘C)
whichwasconnectedtoaSynergyMTStensiletesterthrough 5%BPA 1.67±0.18 62.3±0.16 72.3±0.16
a catheter. To ensure the repeatability of device testing,
15%BPA 5.92±0.08 53.6±0.17 66.9±0.16
the crosshead of the tensile tester pulled each device at an
25%BPA 11.0±0.32 50.8±0.25 62.8±0.24
extension rate of75mm/min to removetheblood clot. The
temperaturebeforeandduringactuationwasrecordedat1Hz 35%BPA 15.6±1.02 50.8±0.11 61.5±0.12
byplacingathermocouplenearthelocationofthedevice.
near the center hole of the device were a result of the large
3.Results
deformation necessary to bend the petals upward, and the
concentrations on the struts were a result of the twisting
3.1. FEA Simulations. Finite element simulations were per-
necessarytoalignportionsofthepetalsforinsertionintothe
formed using Abaqus 6.12-1 finite element software to esti-
funnel.
matethestrainsimposedonthethrombectomydeviceduring
thecrimpingprocedure.Thegeometryofthethrombectomy
device, adapted from Buckley et al. [23], was imported 3.2.MaterialPropertiesofCopolymers. Plotsofstoragemod-
fromSolidWorks,andtheadditionalpartsnecessaryforthe ulus, loss modulus, and tan delta for acrylic SMP samples
crimping—specifically, a funnel with a final inner diameter containing 5, 15, 25, and 35 mole% BPA are provided
of 3.5mm and a rigid sphere with a diameter of 2mm— in Figures 6(a)–6(c), and numerical values for rubbery
were created as analytical rigid parts in Abaqus. The ball modulus, loss modulus peak temperatures, and tan delta
wasplacedincontactwiththethrombectomydeviceandthe peaktemperaturesareprovidedinTable1.Rubberymoduli
funnelwasmovedsoastocrimpthedevicearoundtherigid were defined as the lowest value in the rubbery storage
ball.Thismotionmimickedthatofpullingthedevicethrough moduluscurvesforallfourchemicalcompositions.AsBPA
thefunnelusingawirethatwasterminatedbya2mmball. crosslinker was increased from 5 to 35 mole%, rubbery
Figure5showsthestraincontoursonthedevicewhenitwas modulusincreasedfrom1.6to15.6MPa.Lossmoduluspeak
∘
inthefinalcrimpedstateinsidethefunnel.Inthisfigure,the temperatures were in the range of 50.8 to 62.3 C, tan delta
∘
device,whichwasmodeledusing1/14thsymmetryaboutthe peak temperatures were in the range of 61.5 to 72.3 C,
longitudinalaxis,wasmirroredandthenpatterned7timesto and both loss modulus peak temperatures and tan delta
be displayed in its entirety. The maximum principal strains peaktemperaturesdecreasedwithincreasingBPAcrosslinker
were approximately 0.35–0.4mm/mm and were located at composition. Although increasing crosslink density often
thebaseofthedevicenearthecircularcutoutaswellason resultsinincreasedglasstransitiontemperatureinthermoset
thestrutsoftheinnermostloops.Thestrainconcentrations polymers, the decrease in glass transition with increasing
6 SmartMaterialsResearch
104 300
250
1000 5% BPA
MPa) Pa) 200 15% BPA
M
dulus ( 100 ulus ( 150 25% BPA
o d
m o
orage 35% BPA Loss m 100 35% BPA
St 25% BPA
10
15% BPA 50
5% BPA
0
1
0 20 40 60 80 100 120 140 0 20 40 60 80 100 120 140
Temperature (∘C) Temperature (∘C)
(a) (b)
2.5
2
5% BPA
1.5 15% BPA
a
elt
d
n 25% BPA
Ta 1
35% BPA
0.5
0
0 20 40 60 80 100 120 140
Temperature (∘C)
(c)
Figure6:Dynamicmechanicalresponseofthefourcopolymers,storagemodulus(a),lossmodulus(b),andtandelta(c).Inpanel(a),
thelowestpointofthecurve(i.e.,therubberymodulus)increasedasafunctionofincreasingcrosslinker.Additionally,anincreaseinthe
temperaturethatcorrespondstolossmoduluspeakandtandeltapeakinpanels(b)and(c),respectively,wasobservedasaresultofincreasing
crosslinker.
BPA composition in this study was expected because the Figures7(a)and7(b),andaveragestress-at-failure,strain-to-
BPA crosslinker contains flexible polyethylene oxide repeat failure, and toughness (area under the stress/strain curves)
units,whichhaveacompetingeffectwithcrosslinkdensityon data is listed in Table2. For strain-to-failure experiments
glasstransition.Itwasthiscompetingeffectthatwasusedto conducted at loss modulus peak temperatures, increasing
enablethesynthesisoffourSMPswithsignificantlydifferent the BPA crosslinker from 5 to 35 mole% resulted in an
crosslinkdensitiesandsimilarglasstransitiontemperatures. averagestress-at-failureincreasefrom11.9to23.0MPaandan
Strain-to-failureexperimentswereperformedonallfour averagestrain-to-failuredecreasefrom1.43to0.48mm/mm.
BPAcompositionsamplesatbothlossmoduluspeakandtan Forstrain-to-failureexperimentsconductedattandeltapeak
deltapeaktemperatures.Allstress/strainresultsareshownin temperatures, increasing BPA composition resulted in an
SmartMaterialsResearch 7
Table2:Rubberymodulusandmechanicaltransitiontemperaturevalues.
Strain-to-failure Stress-at-failure Toughness
Composition
(mm/mm) (MPa) (MJ/m3)
5%BPA 1.43±0.0985 11.9±2.14 8.99±1.72
𝑇=temperatureatlossmoduluspeak 15%BPA 0.773±0.0906 14.2±1.51 6.21±0.992
25%BPA 0.609±0.119 13.2±1.07 3.96±0.747
35%BPA 0.475±0.0957 23.0±4.15 6.38±1.79
5%BPA 1.41±0.254 2.75±0.338 1.49±0.296
𝑇=temperatureattandeltapeak 15%BPA 0.590±0.182 2.87±0.254 0.697±0.169
25%BPA 0.357±0.0354 4.09±0.251 0.647±0.0723
35%BPA 0.376±0.0879 7.73±1.56 1.24±0.316
T= loss modulus peak temperature T= tan delta peak temperature
30 30
35% BPA
25 25
25% BPA
20 20
15% BPA a) 35% BPA
Pa) MP
Stress (M 15 5% BPA Stress ( 15 25% BPA15% BPA
10 10
5% BPA
5 5
0 0
0 0.5 1 1.5 0 0.5 1 1.5
Strain (mm/mm) Strain (mm/mm)
(a) (b)
Figure7:Tensilepropertiesofthefourcopolymersmeasuredateachcopolymer’slossmoduluspeak(a)andtandeltapeak(b)temperatures.
Inbothtemperatures,thestraincapacityofthecopolymersdecreasedasaresultofincreasingcrosslinker;however,amorebrittleresponse
wasobservedattandeltapeaktemperatures.
averagestress-atfailureincreasefrom2.8to7.7MPaandan showplotsofforceversusextensionduringcrimpingatloss
averagestrain-to-failuredecreasefrom1.41to0.37mm/mm. moduluspeaktemperaturesandtandeltapeaktemperatures,
For both the loss modulus peak temperature and tan respectively. Figures 8(b) and 9(b) show images of the top,
delta peak temperature strain-to-failure series, toughness side, and bottom views of crimped 35 mole% BPA devices
decreased as BPA composition was increased from 5 to 15 at the two respective crimping temperatures. The crimping
to 25 mole% and then increased for the 35% BPA samples. temperature had a significant effect on both the magnitude
One possible explanation for this increase in toughness for oftheforcerequiredforcrimpingandonthepropensityfor
the most highly crosslinked samples is that bisphenol A device failure during crimping. For devices crimped at loss
groups have been shown to be capable of undergoing 𝜋- moduluspeaktemperature,themaximumaveragecrimping
𝜋 stacking, which increases toughness in materials such force increased from 0.41 to 1.05N as BPA composition
as poly(bisphenol A carbonate) [32]. It is possible that, at increased from 5 to 35 mole%. For devices crimped at tan
high enough BPA compositions, 𝜋-𝜋 stacking can become deltapeaktemperature,themaximumaveragecrimpingforce
predominantenoughtoimprovetoughness. increasedfrom0.10to0.58NasBPAcompositionincreased
from 5 to 35 mole%. None of the devices crimped at loss
3.3. Device Crimping. A total of five devices were crimped modulus peak temperature failed upon crimping. On the
foreachofthefourBPAcompositions.Figures8(a)and9(a) contrary,thedevicescrimpedattandeltapeaktemperature
8 SmartMaterialsResearch
T= loss modulus peak temperature Top view
1.4
35% BPA
1.2
1 Side view
25% BPA
N)
e ( 0.8
c
or
ng f 0.6 15% BPA
pi
m
Cri 0.4 5% BPA
Bottom view
0.2
0 No sample
−0.2
0 50 100
Extension (%)
(a) (b)
Figure8:Forcemeasurementsofdevicescrimpedatlossmoduluspeaktemperature(a).Exampleofonedevicewith35mole%BPAcrimped
atlossmoduluspeaktemperature(scalebar=1mm)(b).Imagesweretakenat2.5xmagnification.
T= tan delta peak temperature Top view
1.4
35% BPA
1.2
1 25% BPA Side view
N)
e ( 0.8 15% BPA
c
or
ng f 0.6 5% BPA
pi
m
Cri 0.4
Bottom view
0.2
0 No sample
−0.2
0 50 100
Extension (%)
(a) (b)
Figure9:Forcemeasurementsofdevicescrimpedattandeltapeaktemperature(a).Exampleofonedevicewith35mole%BPAcrimpedat
tandeltapeaktemperature(scalebar=1mm)(b).Imagesweretakenat2.5xmagnification.Whitearrowpointsatacommonsiteforfailure.
weremuchmoresusceptibletofailureduringcrimping:for 3.4.DeviceConstrainedRecovery. Becauseofthesignificant
the 5, 15, 25, and 35 mole% BPA samples, the number of device failures that occurred during crimping at tan delta
devicesthatfailedwas1,2,3,and5,respectively.Mostfailure peak temperatures, only devices crimped at loss modulus
locationsconsistentlyoccurredatthebasesofthedevicesand peak temperatures were subjected to constrained recovery
appearedtoinitiateattheedgesofthecenterholes,asshown tests.FivedevicesweretestedforeachBPAcomposition.In
inFigure9(b). Figure10,aplotofaveragerecoverystressversustemperature
SmartMaterialsResearch 9
20
35% BPA
15
25% BPA
a)
P
ess (k 10 15% BPA
y str
er
v
o 5
c
e
R 5% BPA
0
−5
30 35 40 45 50 55 60
Temperature (∘C)
Figure10:Recoverystressofthrombectomydevicesduringconstrainedrecovery.Increasingthecrosslinkeramountresultedinanincrease
inrecoverystressmeasuredunderconstrainedconditions.However,forthetwohighestcrosslinkedcompositions,therecoverystresswas
notsignificantlydifferent,becausefailureswereobservedinbothcompositionsbutweremoreprevalentindeviceswith35mole%BPA.
T=33∘C T=37∘C T=43∘C T=46∘C T=49∘C T=54∘C T=55∘C
A
P
B
%
5
2
A
P
B
%
5
3
T=31∘C T=38∘C T=43∘C T=47∘C T=50∘C T=53∘C T=55∘C
Figure 11: Crack development in devices of each composition (i.e., 25 and 35 mole% BPA) during constrained recovery test at various
temperaturepointsasthedevicewasrecoveringitsprimaryshape.
isshownfordeviceswithvaryingBPAcomposition.AsBPA flowratesrecordedinthemiddlecerebralartery,acommon
composition was increased from 5 to 35 mole%, average site for thromboembolic occlusion in the neurovasculature
recoverystressincreasedfrom0.526to12.2kPa.Itisnotable [31]. Because the 25 and 35 mole% BPA devices developed
thatduringtheconstrainedrecoverytests,twooutofthefive cracks during recovery under constrained conditions, they
25mole%BPAdevicesandfouroutofthefive35mole%BPA werenotconsideredforthebloodclotremovalexperiments.
devices developed cracks and subsequently broke. Images Imagesofthethrombectomyexperimentsfora15mole%BPA
ofcrackdevelopmentatdifferenttemperaturepointsduring deviceandadiagramofthesiliconevascularmodelusedin
constrained recovery of 25 and 35 mole% BPA samples are the experiments are provided in Figure12. To demonstrate
showninFigure11. that the crimped devices could maintain their crimped
geometries under physiological conditions, they were first
∘
3.5.BloodClotRemovalExperiments. Three5and15mole% immersedin37 Cwaterandpositionedpastthebovineblood
BPA devices were subjected to blood clot removal experi- clotinthesiliconevesselmodel,aspicturedinFigure12(a).
∘
mentswithflow.Inordertobettersimulateinvivoconditions, After holding at 37 C to demonstrate shape fixity for 4-
anexperimentalflowrateof57mL/minwaschosen.Thisflow 5min, the water temperature was elevated to ∼T𝑔 + 15 ∘C
∘
rateisequivalentto113mL/minafterdynamicsimilarityvia (maximum recorded temperature: 77 C) over the course of
matchingtheReynoldsnumber,whichiswithintherangeof 45sbyinjectingwaternearboilingtemperaturetotheflow
10 SmartMaterialsResearch
Catheter Blood clot
(e) (d) (c)
Q=57mL/min
(e)
(d) (c)
Extension rate =75mm/min (b)
(a)
(b)
Actuation:
t=0s t=42s t=44s
T=Tg−40∘C T=Tg+10∘C T=Tg+15∘C
(a)
Figure12:Actuationandclotremovalwith15mole%BPAdevice.Q:experimentalflowrate(=57mL/min).Panel(a)showsthedevice
duringactuationasthehotwaterwasinjected.Panels(b)–(e)depicttheactuatedthrombectomydeviceasitiswithdrawnbythetensiletester
successfullymovingthebloodclotfromtheoccludedvessel(panel(b))tothelocationofthecatheter(panel(e)).
system.Thebenefitofincreasingcrosslinkdensityondevice Given the geometry of the device, recovery stress plays
blood clot removal was demonstrated: 0/3 of the 5 mole% an important role in achieving blood clot entrapment and
BPAdevicesresultedinasuccessfulextraction,while2/3of successful removal. The devices tested in the bench-top
the15mole%BPAdevicesresultedinasuccessfulbloodclot thromboticstrokemodelinthisstudyconsistedof5and15
extraction(i.e.,thedeviceswereabletomovethebloodclot mole% BPA. The average recovery stress of the 15 mole%
fromitsoriginatthebifurcationpicturedinFigure12(b)to BPAdeviceswasroughlyoneorderofmagnitudehigherthan
thecathetertipattheendofthevasculaturemodel,pictured that of the 5 mole% BPA devices. This positive correlation
inFigure12(e)). between crosslink density and recovery stress in SMPs has
been reported in numerous previous studies [11, 26, 27]. In
anidealrubber,elasticmodulusisinverselyproportionalto
4.Discussion
theaveragemolecularweightbetweencrosslinks,soamore
The motivation for this study is the need for a SMP-based highlycrosslinkedrubberwillhaveahigherstiffnessthana
thrombectomy device that can exhibit sufficient recovery morelightlycrosslinkedrubber.Consequently,moreenergy
stress to reduce the likelihood of blood clot dislodgement isrequiredtoachieveaspecificdeformationinamorehighly
during thrombectomy, while also being able to undergo crosslinkedrubberthaninamorelightlycrosslinkedrubber.
sufficient deformation for catheter delivery. Thrombectomy Since the energy required to achieve these deformations is
isapromisingtreatmenttechniqueforthe∼97%ofischemic metastablystoredwhenthermallyactuatedSMPsarestrained
stroke patients who are not eligible to receive tPA, the only andthencooledbelowtheirthermaltransitionregions,the
FDA-approved drug for the treatment of ischemic stroke force exerted by an SMP during recovery is consequently
[2,6]. higher for a more highly crosslinked SMP [11, 25–27, 30].