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Medical 3D Prin.ng: Opportuni.es and Challenges Ahead

Prof Paul McMenamin The Centre for Human Anatomy Education Department of Anatomy & Developmental Biology

Monash University, Melbourne, Australia

STRUCTUREOFTALK

•  3Dprin9ngtechnologyinMedicine

•  Gatheringdata–prin9ng

•  Describethe‘Monash3DPrintedAnatomySeries”–anopportunityrealised

•  Aproblemwithasolu9on-3Dprintsformedicalschoolslackingcadavers

•  Aproblemwithoutasolu9on-3Dprintswitharealis9c‘feel’

•  Mul9materialmul9colourprin9ng

•  Thinkingoutsidethe3DBOX

•  ModelsforSimula9ontraining

•  TheBIGchallenges

•  Conclusions

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3D Printing in MEDICINE •  Addi$vemanufacturing(3Dprin$ng-inventedin1984byCharlesW.(Chuck)Hullin1989.

“OhlookwhatI3Dprinted”…….Unlessit’sacomplexshape–whybotherUsedinindustryasameanstoprototype

3D Printing in MEDICINE

Not all media-launched advances are commercially available/viable …negotiating the space as a novice can be challenging (47M HITS ON GOOGLE) (3M -“3D PRINTING MEDICINE)

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Applications: Anatomy and Medicine

Generating 3D Content For Printing: Photogrammetry

Considerations •  Variable resolution •  Variable cost (Labor)

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Generating 3D Content For Printing: Surface Scanning •  Generation of a 3D point cloud from an object •  Non-contact method employing lasers or light sources

Considerations •  High geometric resolution •  Variable texture capability •  Variable cost ($2K- $30k) •  Variable labor and post-

processing

Generating 3D Content For Printing: Medical Imaging •  Computerized tomography (CT) and CT Angio

•  Magnetic resonance imaging (MRI)

Considerations

•  Variable geometric resolution

•  Variable accessibility

•  Variable labor and post-processing

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The Process (not a secret)

CTscanning

3Dmodelling

3Dcolouring

3Dprin9ng

Digitalsegmenta9on

McMenaminetal,2014(mostcitedpaperinhistoryofthejournal)

The Process Crea9ngandcolouringthe3Dmodel

Constantreferencingbacktooriginalprosec9ontoensurecorrectanatomicaliden9fica9on

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Meshdeformallowsustoremoveoralterpersonalcharacteris9cs(maintaindonorconfiden$ality)

7oftheSeriesof57specimens

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We can also print real anatomy that is impossible to dissect - CT angiography data

CHALLENGE–9metosegmentthis–weeks/months

EbolaCrisis(2014-2015)Guinea,SierraLeone,Liberia11,500peopledied(500healthworkers)Disrup9ontoalreadylimitedhealthcaresystemMedicalSchoolinMonroviawaspartlyclosedin2014

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OPPORTUNITY–TOHELPDEVELOPINGCOUNTRIES(Liberia)

Other Outreach Programs being planned : Fiji Sierra Leone CHALLENGE – finding $ support

Otheropportuni9esineduca9on

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Applications: Anatomy Education

3Dprin9ngisbeingusedinpre-opera9veplanning–manyexamplesfromDrMorrisandothersCraniofacial-(Rose,A.S.,etal.Interna9onalJournalofPediatricOtorhinolaryngology,2015;Arvier,J.Bri9shJournalofOralandMaxillofacialSurgery,1994;Scawn,R.L,Orbit,2015)

Knee.(Huang,AustralasianPhysical&EngineeringSciencesinMedicine,2015;Krishnan,S.,.JBoneJointSurgBr,2012.

Foot(Giovinco,N.A.,TheJournalofFootandAnkleSurgery,2012)

Heart-(Jacobs,S.Interac9vecardiovascularandthoracicsurgery,2008)……….Andmanyothers

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Types of 3D Prin.ng TheAmericanSocietyforTes9ngandMaterials(ASTM)createdasetofstandardsthatclassify3Dprin9ngprocessesintosevencategoriesaccordingtostandardterminology:1)VatPhotopolymerisa9on2)Powderbedfusion3)Materialextrusion4)MaterialJelng5)Binderjelng6)Sheetlamina9on

7)Directedenergydeposi9on.

CHALLENGE–findingonethatcanprintmaterialwith9ssuebiomechanicalproper9es

Material Jetting

Considerations •  High resolution (0.014mm) •  Price range: $200k - $500k •  Material properties •  Build area

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• MaterialproducedbyourgroupusingMul9materialmul9colour3DmaterialjetprinterfromStratasys(J750–cost~$500,000(Aust$)

• Weweredissapointed

SOARETHEREANYALTERNATIVES–THINKOUTSIDETHE‘3D’BOX!!

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SYNDAVER • Hydrogelsimulatedcadaver• Soqmouldedmaterial,builtaroundaplas9cskeleton,musclessownbyhandto‘bones’

• Storedunderfluid-detergentmix

• Verybasicanatomybutmaybeadequateforsimula9onofprocedures(thoracotomy,PICClines,….)

THINKOUTSIDETHE3DBOX Use 3D prin.ng to make the moulds to make the devices ….. May allow us to create novel realis.c surgical simulators based on real anatomy

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OUR EXPERIENCE Paediatric anaesthesia simulator

Externalventriculardrain(EVD)orVentriculostomy(HonsProject:SophieFranklin)

•  HELPreduceintra-cranialpressureintheeventof↑cerebrospinalfluid(CSF)pressure

•  Catheterinsertedthroughthefrontalboneandcortexintotheventricles

Muralidharanetal.,SurgicalNeurologyInterna$onal,2015.VincentandHall.,Encyclopediaofintensivecaremedicine,2011.

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HumanVentricularSystem(HVS)•  Fourinterconnectedcavi9es

•  Twolateralventricles,a3rdventricle,a4thventricle

•  Siteofcerebrospinalfluid(CSF)produc9on

Howdenetal.,ComputerMethodsinBiomechanicsandBiomedicalEngineering,2008.Muralidharanetal.,SurgicalNeurologyInterna$onal,2015.Speakeetal.,MicroscopyResearchandTechnique,2000.

Hydrocephalus

Surgicalsimula9on

Liveanimalsurgery VirtualrealitybasedCadavereduca$on

• Currentsimula9onmethodshaveissues•  Ethicalimplica9ons•  Anatomicaldifferences•  Costrelatedproblems

• Can3Dprintedmodelsbeusedtosolvethese?

Badashetal.,AnnalsofTransla$onalMedicine,2016.

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Wearehopingtobuildatrainingsimulatorthatismodular

•  Scalp• Bone• Dura•  SubarachnoidspacecontainingCSF• Brain• VentricleswithmockCSF

Challenges• Accuratelyreplicatethebiomechanicalproper9esofhuman9ssuemayneedtoreplicateextracellular/intracellularfluidcompartmentsinsomeway

•  The3Dprin9ngtechniqueusedmayalsoneedtoallowforintegra9onofmul9plematerialswhenreplica9ngpar9cularanatomicalstructurese.g.amuscleanditsassociatedtendon.

•  Tissueplanes–howdowecreatethese?

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Challenges

• Tissueresponsetosurgicalinsultseg.vasospasmofarterieswhentransected,contrac9onofmuscles-diathermy,

• Allowdiathermyandnotreleasetoxicfumes

The Final Innova.on !

Virtual Reality

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What is Virtual Reality (VR)

• VRhasbeendefinedas"...arealis$candimmersivesimula$onofathree-dimensionalenvironment,createdusinginterac$vesoMwareandhardware,andexperiencedorcontrolledbymovementofthebody”orasan"immersive,interac$veexperiencegeneratedbyacomputer”.

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THANKYOUAcknowledgments:

CHAETeam–oppositeStaff:DrJus9nAdams,ProfJohnBertram,MsMichelleQuayleandHonoursstudents,PhDstudentsinCHAECollaborators:ProfJRosenfeldACCEL–supportinLiberiaInfantmannekin-AndrewWeatherall,St.Vincent’sHospital,NSWFunding:MonashUniversity,FacultyofMedicine,NursingandHealthSciences

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Applications: Palaeontological Research

Adams JW, Olah A, McCurry MR, and Potze S. 2015. Surface model and tomographic archive of fossil primate and other mammal holotype and paratype specimens of the Ditsong National Museum of Natural History, Pretoria, South Africa. PLoS ONE 10(10): e0139800.

Future 3D Printing Applications Palaeontological Education and Research

•  Expansion of anatomical and palaeontological archiving

•  Development of field and museum toolkits

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Future 3D Printing Applications

Creation of realistic simulators

•  Assessment of student outcomes

•  Post-graduate and

professional training replicas

Additive Manufacturing: SLA

Considerations •  High resolution (0.025mm) •  Price range: $4k+ •  Material color and properties •  Build volume

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Additive Manufacturing: Binder Jetting • 1990s: MIT patented method of depositing liquid binders

into ceramic powder • 1996: ‘Z Corp’ launches Z402 printer (starch/plaster)

Printers – deposi.on type printers chosen – single material but mul.colour

•  ZCorp650–Gypsumpowderbasedprinter(3DSystems)

•  Projet4500plas9cpowderprinter(3DSystems)

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Additive Manufacturing: Binder Jetting

Considerations •  Price range: $80k+ •  Material properties •  Build volume •  Projet 4500 – plastic

powder – declared ‘End-of-life’

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Additive Manufacturing: Fused Deposition Modelling • 1991: Originally developed by Stratasys using

thermoplastic material (in filament form) • 2009: Patent expiration and open-source FDM systems

Additive Manufacturing: Fused Deposition Modelling

EgMakerbot($3-4000)

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Considerations •  Resolution (0.2 -<0.1mm) •  Price range: $2k+ •  Material colors •  Material properties

Additive Manufacturing: Current FDM Printers

Additive Manufacturing: Material Jetting Printers • Method of depositing jetted photopolymers and UV light • 2000: Objet Geometries develops the Quadra • 2007: Stratasys - Connex 500 first multi-material printer

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HYDROGELS

• Many9ssue-engineeringtechniquesdependonu9lizingmaterialscaffolds,whichserveasasynthe9cextracellularmatrix[87].Poly(lac9de-co-glycolide)(PLG)isanexampleofahydrogelthatismechanicallystrongandapprovedbytheFDAforuseortransplanta9onwithinhumans.Duetotheirabilitytoabsorbalargevolumeofwater,hydrogelsarebe}erabletomimicsoq9ssueandcanretainasignificantfrac9on(>20%)ofwaterwithinitsstructurewithoutdissolvinginthewater[88].

• Noprinterprintshydrogels,biodegradable

Challenges – bone

•  Thechallengethatwouldariseinreplica9ngboneasa3Dprint,forsurgicalteachingpurposes,wouldbemimickingthetrabecularorcancellousbonegiventhatthespaceswithinthecancellousbonewouldpossiblyhavetobefilledwithliquidmaterial.Integra9ngafluidcomponentintominisculecompartmentsina3Dprint,tomimicthestructureofeitherredoryellowmarrow,isachallengeyettobeovercomebycurrent3Dprin9ngtechnology.Mimickingthemechanicalproper9esofbonewouldmeantryingtoreplicatethehierarchicalorganisa9onandthusnotprin9ngasauniformdensity,whichisalsodifficultinpresentprinters.Alsothefactthatmechanicalproper9esimpartedtoeachbonedifferaccordingtoitsloca9onissomethingthatneedstobeconsiderediftheanatomicalprintistobeusedfororthopaedictrainingpurposes

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Challenges - car.lage

•  Thedifficultyinreplica9ngcar9lageasa3Dprintwouldbecrea9ngamaterialthatwillA)imitatethelubrica9ngproper9esofcar9lageB)adherefirmlytothesurfaceofthe3DprintedbonewithoutshearingandC)possessthesameviscoelas9cproper9esofcar9lage.Thischallengecouldprobablybetackledbynotonlycrea9nga3Dprintedmaterialwithahighamountofwaterincorporatedintoit,toreplicatetheviscoelas9cproper9esofcar9lage,butalsocrea9ngaprintwithalowenoughsta9candkine9cfric9onalcomponenttoallowthesameeaseofmovementofjointsina3Dprint.Thecurrentresolu9onofhigh-endprinterssuchastheStratasysConnex3seriesprintersand3DsystemsProjetseriesprinterswhichcanbothprintataresolu9onof16micrometersallowsforthecrea9onofsmoothsurfaces.Thiswouldmostlikelyrequireacompositematerialtobeused;onewherebythesurfacematerialprovidesthelowfric9oncoefficientandthedeepercomponentprovidestheshockabsorbingquali9es.Interfacingwithadjacentprintedmaterialreplica9ngbonewillrequirecarefulconsidera9onifsepara9onatinterfacesaretobeavoided.

Challenges – muscle

•  Givenmuscle’sanisotropicquality,thefibre-orientedstructureorfascicularpa}ernofmuscleanditssuppor9vecollagenousmatrixwouldneedtobeincorporatedonsomelevelina3Dprintinordertoreplicatethischaracteris9c.Muscletensilestrengthismarkedlyhigherparalleltomusclesfibres.Muscle9ssuealsocontractswhensubjectedtoacurrent/diathermy,whichiscommonlyusedinsurgery.Replica9ngthisqualityinaprintedmaterialcouldbeachievedviaprin9ngwiths9muli-responsivehydrogels.S9muli-responsivehydrogelscanshowquali9essimilartonaturalmuscleandareac9vematerialscapableofchangingtheirproper9essuchasvolumereversiblyinresponsetochangesintheenergy-basedcondi9onsoftheliquid[92].3Dprintsareinherentlyanisotropicduetotheirlayer-by-layerforma9on[93].TheDuruswhiteplusVerowhiteplusorRigurplusTangopluscombina9onsfromStratasysmayserveasgoodstar9ngmaterialsformuscleduetotheirhightensilestrengthandelonga9onatbreak(Table1).

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Challenges in replica.ng tendons, ligaments and aponeuroses •  Ofallthe9ssues,humantendon,eventhoughitpossessesviscoelas9citywouldprobablybetheleastchallengingtoreplicategivenitslowvalueofresidualstrainandnormalisedhysteresisloop.Thedifficultywouldcomeinreplica9ngdifferenttendonssinceasseenabovetheshapeofatendongreatlyimpactsitsmodulusofelas9cityandfailureload.Ligamentsontheotherhandwouldbemoredifficulttoreplicateina3Dprintgiventheirtri-phasicbehaviourinresponsetostressandhowtheirproper9esarehighlygovernedbythenatureoftheira}achments(somemoveable,somenot).Replica9nginter-fibrillarslippageanddefibrilla9onoffibrilsina3Dprintcouldprobablyonlyhappenatamacroscopiclevelbyincorpora9ngfibrilsintothe3Dprin9ngprocess,whichiscurrentlynotavailable.Aponeuroseswouldbechallengingtoreplicatein3Dprintsgiventheirveryhightensilestrengthandmodulusofelas9city.

Challenges in replica.ng skin and fat

•  Themostdifficultchallengeinreplica9ngskincomesnotonlyinmimickingitsanisotropiccharacteris9csbutinrecognisingthelinesoftension(Langer’slines)thatarepresentinthecollagenousdermisofthehumanbody.Thispre-exis9ngtensioninskinwouldbedifficulttoincorporateintoa3Dprint,as3Dprintmaterialsarenotundertensionwhenprinted.Thischallengewouldmostlikelybeaddressedbyaddingtensionintotheprintinthepost-prin9ngphasebycrea9ngstretchintheskinlayeroftheprintandpossiblyapplyingthistotheprintlaterinamoreconven9onalmanner.

•  Fatshouldbeeasier

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Challenges - neurovascular

3D Prin.ng aids pre-surgical planning

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Cerebral Aneurysms •  Abnormal focal dilation of a cerebral

artery due to an area of weakening in the

vascular wall

•  Amidst the highly sensitive, specialised

areas of the brain

•  Aneurysmal subarachnoid haemorrhage

•  Aneurysm growth may cause compression

of adjacent nerves

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BrismanJL,Song,JK&Newel,lDW2006,‘Cerebralaneurysms’,NEnglJMed,vol.355,pp.928-939.

Surgical Clipping

•  Craniotomy

•  A small metal clip is applied to the base of the aneurysm

•  Exclude the lesion from cerebral circulation

Endovascular Coiling

• Visualisation through fluoroscopy

• Coils are deployed into the aneurysm

• The coiled aneurysm resists the entry of blood

Treatment

Krings,T.,Mandell,D.,Kiehl,T.,Geibprasert,S.,Tymianski,M.,Alvarez,H.,terBrugge,K.andHans,F.(2011).Intracranialaneurysms:fromvesselwallpathologytotherapeu9capproach.NatureReviewsNeurology,7(10),pp.547-559.

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Current simulators •  Animal models •  3D imaging •  Virtual reality •  Medical manikins

RehderRetal.2016.TheRoleofsimula9oninneurosurgery.ChildsNervousSystem32:43-54

Intraoperative challenges

ENDOVASCULARCOILING

•  Difficulttomaintainthestabilityofmicro-catheters

•  Highriskofincompletepacking

SURGICALCLIPPING•  Riskofadjacent9ssuedamage-proximityofaneurysmtohighlydelicateorcomplexstructures

•  Riskofintra-opera9verupture•  Broadbase,wideneckofaneurysm•  Complexityofaneurysmshape

COMMONCHALLENGES

Cheng,Xetal.2016,.JournalofClinicalNeuroscience,26,pp.50-56.

Mor9mer,A.etal.2015JournalofNeuroInterven9onalSurgery,8(3),pp.256-264.

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Cerebral Aneurysm Clipping Surgery Simulation

Justin Ryan et al. 2016

•  RyanJR,AlmeqyKK,NakajiP,FrakesDH2016,‘Cerebralaneurysmclippingsurgerysimula9onusingpa9ent-specific3Dprin9ngandsiliconecas9ng.WorldNeurosurgery,88;175-181.

Aneurysm ‘sleeve’ Solid Circle of Willis Hard skull Hollow, flexible aneurysm