組織工程TissueEngineering教學(xué)課件

LowwearbearingcouplesConservative,minimallyorlessinvasiveHipJointReplacement&TissueEngineeringCells,TissuesandOrgansBiologicaltissues:Cells:Extracellularmatrix(ECM):AcomplexofcellsecretionsimmobilisedinspacescontinuouswithcellsExampleofbone:Cells:osteoblasts,osteoclasts,osteocytesECM:acompositefibrousnetworkofcollagenencasedwithinahardmatrixofcalcium/phosphorousSymbioticrelationship:cellscreatingECMfirst,thenremodellingitandinturnbeingregulatedbyit.

Cells,TissuesandOrgansCellbiology:CellsFundamentalunitandsimplestformoflife75trillioncells200differenttypesofcellsinahuman10-30mCells,TissuesandOrgansCellanatomySmallmembrane(cellmembrane)boundcompartmentNucleus(geneticinf.)Mitochondria(energy)Lysosomes(proteolyticenzymes)Endoplasmicreticulum(proteinsynthesisandcellulartransport)Golgiapparatus(assembly)Cytoplasm,containingcytoskeleton(cellmovement,shape)J.Bevan,APictorialHandbookofAnatomyandPhysiology,2019Cells,TissuesandOrgansCellanatomyCellmembraneAdoublelayerofphospholipidsProteins:“Floating”proteinsIntegrins

SpecificreceptorsitesBiomaterialsScience,edsBDRatnerCells,TissuesandOrgansCellfunctionsMetabolism:producingenergy,proteins,lipids,...Adhesion:causingattachmentamongcells,andbetweencells/ECMforstructuralintegrityProliferation:cellsreplacingthemselvesMigration:fromplacetoplaceMechanicalcontraction:likethebeatingheartSignalling:communicationwithinandamongcellsDifferentiation:developmentofcellswithspecializedstructureandfunctionfromunspecializedprecursorcells.Cells,TissuesandOrgansCellmechanics:CellactionsandresponsesMechanicalChemicalElectrical …...Cell-cellandcell-matrixInitialrecognitionPhysicaladhesionElectrical/chemicalcommunicationCytoskeletalreorganizationMigration

Cells,TissuesandOrgansExtracellularmatrix:MechanicalsupportforcellanchorageDeterminationofcellorientationControlofcellgrowthMaintenanceofcelldifferentiationScaffoldingfororderlytissuerenewalEstablishmentoftissuemicroenvironmentSequestration,storage,andpresentationofsolubleregulatorymoleculesCells,TissuesandOrgansBasictissues:Epithelium:CoversinternalandexternalsurfacesAprotectivebarrier(skinepidermis)Anabsorptivesurface(gutlining)Amoist,mucousmembrane,lubricatedbyglandularsecretions(digestiveandrespiratorytracts)Amoist,serousmembrane,lubricatedbyserousfluidthatderivesfrombloodplasma(peritoneum,pleura,pericardium),linedbymesotheliumTheinnerliningofthecirculatorysystem,lubricatedbybloodorlymph,calledendotheliumCells,TissuesandOrgansBasictissues:ConnectivetissueSkindermisPericardium,tendonBonemarrow,bloodcellsCartilage,boneMuscletissueArterialorgutsmoothmuscleHeartNervetissueBraincells,peripheralnerve

Cells,TissuesandOrgansOrgans:tissuelayersinthedigestivetract

ConnectivetissueEpitheliumInnerlayer(mucosa)Outerlayer(serosa)EpitheliumConnectivetissueMiddlelayermuscleconnectivemuscleLumenOrganFailureandTreatmentsOrganfailure:Infection:DrainageofpusUseofantibiotictherapy,andsteriletechniqueDisease:Injury:Treatments:Repair(reconstructivesurgery,…):Replace(orthopaedicsurgery,transplantation,…):

OrganFailureandTreatmentsTreatments:Repair:(maintenanceoflife)RemovaloftumoursBypassofthebowelinthecaseofintestinalobstructionReplace:(restorationoflostfunction)Limbs,teeth,……

OrganFailureandTreatmentsTransplantation:Auto-grafting: fromonelocationtoanother (samepatient)Iso-grafting: geneticallyidenticalindividualsAllo-grafting: fromadonortoapatientXeno-grafting: fromanimaltohumanOrthotopic: sameanatomicpositionHeterotopic: differentanatomicpositionImplants:Man-madematerialsandmedicaldevices

OrganFailureandTreatmentsAuto-grafting:Advantages:NorejectionissuesExamples:BloodvesselgraftsforcoronarybypassSpinalfusionSkingraftsforburnsNervegraftsforfacialandhandreconstructionProblems:AdditionalsurgicalcostsInfectionandpain

OrganFailureandTreatmentsAllo-grafting:Advantages:Off-the-shelfavailabilityExamples:Dieddonors:heart;kidney;liver;bone;pancreas,...Livingdonors:lungsandkidney

Problems:ProblemswithimmunesystemShortagesindonoravailability(about1in10)

OrganFailureandTreatmentsXeno-graft:Advantages:Off-the-shelfavailabilitySupplyExamples:TissueheartvalveProblems:ProblemswithimmunesystemVirustransmission

OrganFailureandTreatmentsTraditionalimplants:Advantages:Replicate,augmentorextendfunctionsperformedbybiologicalsystemsExamples:ArtificialheartandvalveArtificialjointreplacementsProblems:Non-physiologicalBio-compatibility

OrganFailureandTreatmentsArtificialwoodenbigtoe:Egypt:1550and700BCOrganFailureandTreatmentsTakecartilagefromthepatient'sribcage,andshapethiscartilageintoanear-likestructure.

/~schmidt/overview/resurg.htmlOrganFailureandTreatmentsBovine,pericardialPorcinesulzermedica/mainpage.htmOrganFailureandTreatmentsTendons,Nerves,Veins,andArteriesmustbeattached.Beforetheskinisclosed,thearteriesarereattached.handtransplant/procedure/3d.htmlOrganFailureandTreatmentsArtificiallimbsorthoprodnews.co.uk/TissueEngineeringIntroduction:ScientificAmerican“GrowingNewOrgans”“HeadTransplants”

sciam/specialissues/0999bionic/0999quicksummary.htmlTissueEngineeringIntroduction:BBCHumanbonegrownoutsidebodyHeartvalvesgrownintesttubeGonetoday,hairtomorrowHeartinaboxThumbsupfororgans'growntoorder'

Organ'farming'movesnearer

TissueEngineeringIntroduction:BBC

TransplantsofpigheartswillhappeninafewyearsandclonedheartslaterPigheartssoon,clonedheartslater

SixbeaglesreceivedbladderscreatedinincubatorsfromtheirowncellsDoctorsheraldgrow-your-ownorgans

TissueEngineeringIntroduction:BBCDoctorstrytore-growseveredthumb

Themouseearsparkedprotest“Theearwasmadeofcartilagewhichhadgrownoverascaffoldingmadeoffibres.Ithadbeenplacedundertheskinofthemouseforafewweeks…….“DrVacanti,UniversityofMassachusettsTissueEngineeringIntroduction:BBCCloning:clonedsheepDolly(2019)andBonnythelamb(2019)

TissueEngineeringIntroduction:BBCArthritis:clonedsheepDolly(2019)developedarthritis

TissueEngineeringDefinition:”...istheapplicationoftheprinciplesandmethodsofengineeringandthelifesciencestowardthefundamentalunderstandingofstructure-functionrelationshipsinnormalandpathologicalmammaliantissuesandthedevelopmentofbiologicalsubstitutestorestore,maintainorimprovefunctions.”

SkalakandFox(eds.),TissueEngineering,AlanLiss,1988

TissueEngineeringDefinition:"Tissueengineeringisaninterdisciplinaryfieldthatappliestheprinciplesofengineeringandthelifesciencestowardthedevelopmentofbiologicalsubstitutesthatrestore,maintainorimprovetissuefunction."

LangerandVacanti,Science260,920,1993

TissueEngineeringDefinition:"Theageof'Tissueengineering'isuponus.Aswearethrusttowardanewmillenniumsotooareourbeliefsthattheamalgamationofengineeringandmedicinewillresultinanexplosionofknowledgethatwillenhanceourunderstandingofdevelopmentalbiologyandculminateinaneweraofmedicineenablingustorestorelosttissuefunction."

MikosandVacanti,TissueEngineering1,1,2019

TissueEngineeringDefinition:Developmentandmanipulationoflaboratory-grownmolecules,cells,tissues,ororganstoreplaceorsupportthefunctionofdefectiveorinjuredbodyparts.Betweentraditionaltransplantation/implantsandbiotechnology(genetherapies):

moreeffectiveandlessinvasiveReparativemedicine;RegenerativeorReparativebiologyImitatingnatureTissueEngineeringDefinition:Closecollaborationsbetweenbasicbiologicalscientists,bioengineersandclinicalresearchers:Cellbiologists;Molecularbiologists;Biomaterialengineers;Computer-assisteddesigners,Microscopicimagingspecialists;Manufacturingengineers;suchasdesignofbioreactors,wheretissuesaregrownandnurturedTissueEngineeringSomegoalsoftissueengineering:Providereplacementpartsorcellularprostheses.Providevehiclestodeliverengineeredcellstotheorganism.Providetissuemodelswithcellstostudythestatesofdiseasesusingaberrantcells.Providenon-biologicalscaffoldsfortissuegrowth.Provideacellularpartscapableofregenerating.TissueEngineeringGeneralcompositionalconsideration:ProsthesisScaffoldsCellsSignalingnaturalman-madecompositesourcingmanipulationTGF,FGFHomeoboxHedgehogWNTTissueEngineeringGeneraltechnologicalconsideration:Celltechnology:CellsourcingManipulationofcellfunctionsConstructtechnology:DesignandengineeringoftissuelikeconstructsManufacturingforclinicaluseIntegrationtechnology:Engineeringofimmuneacceptance

TissueEngineeringCelltechnology:Cellsourcing:AutologousAllogeneic:skinsubstitutesXenogeneic:Cellfunctionandgeneticengineering:Manipulatingacell’sextracellularenvironment(mechanical,chemical,electrical,……)Manipulatingacell’sgeneticprogramme(alternationofmatrixsynthesis,inhibitionoftheimmuneresponse,……)TissueEngineeringCelltechnology:Stemcell(“mother”cells):Embryonic:embryoorfetaltissue/alltypesHematopoietic:bonemarrow/bloodcells,brains(?)Neuronal:fetalbrain/neurons,glia,blood(?)Mesenchymal:bonemarrow/muscle,bone,cartilage,tendonTissueEngineeringCelltechnology:Stemcell(“mother”cells):embryonicnewssearch.bbc.co.uk/hi/english/sci/tech/newsid_208000/208497.stmTissueEngineeringConstructtechnologies:Constructdesignandengineering:Acellularmatrix:requirestherecruitmentofhostcellsCell-seededcollagengels:skinsubstituteCell-seededpolymericscaffolds:skinsubstitutesCellself-assembly:cellssynthesizingtheirownmatrixAcellularapproach:constructswithoutcells+recruitingcellsfromthehostManufacturingtechnology(bioreactortechnology)Cost-effective,scale-up,deliveryandpreservation,...

TissueEngineeringIntegrationintothelivingsystem:Thelivingsystem:Animalstrials/clinicaltrials:Functionalcharacterisation:EngineeringimmuneacceptanceTransplantimmunologyBiocompatibilityInflammatoryresponseThrombosis:forbloodvesselTissueEngineeringTechniques(1):Designandgrowhumantissuesoutsidethebodyforlaterimplantationtorepairorreplacediseasedtissues

skingraftreplacements

pittsburgh-tissue/TissueEngineeringTechniques(2):Implantationofcell-containingorcell-freedevicesthatinducetheregenerationoffunctionalhumantissues.

biomaterialmatrixusedtopromotebonere-growthforperiodontaldisease.

pittsburgh-tissue/TissueEngineeringTechniques(3):Thedevelopmentofexternalorinternaldevicescontaininghumantissuesdesignedtoreplacethefunctionofdiseasedinternaltissues.

repairofbone,muscle,tendon,andcartilage,aswellascell-linedvasculargraftsandartificialliver

pittsburgh-tissue/TissueEngineeringEngineeringchallengesProductionoftherapeuticdoesofprimarycells.Manufacturing,qualityassuranceandqualitycontrolHarvestingandsafetytestingFunction,choice,manufacturingandtreatmentofbiomaterials(biocompatibleandbiodegradable)forcellgrowthanddeviceconstruction.Fluidmechanics;masstransfer;systemsanalysisofcell-cellandtissueinteractions.

TissueEngineeringExamples:nose

TheSundayTimesMagazine:25July2019TissueEngineering

businessweek/2019/30/covstory.htmTissue