整形修复 组织工程中英对照辅导阅读材料.docx

整形修复 组织工程中英对照辅导阅读材料.docx

《整形修复 组织工程中英对照辅导阅读材料.docx》由会员分享，可在线阅读，更多相关《整形修复 组织工程中英对照辅导阅读材料.docx（13页珍藏版）》请在冰豆网上搜索。

整形修复组织工程中英对照辅导阅读材料

Chapter15Basicprincipleoftissueengineeringanditsapplications

上海交通大学医学院附属第九人民医院

刘伟，曹谊林

Treatmentoftissueinjuryanddefectremainsamajorchallengetoreconstructivesurgery,partlybecausethereislimitedsourceavailableforautologoustissuegrafts.Currently，manyofthesurgicalproceduresinreconstructivesurgerytrytorepairtissuedefectwiththepriceofcreatinganotherdefectsomewhere,whichisnotfunctionallyasimportantasthesitetoberepaired.Thedevelopmentoftissueengineeringtechniqueprovidesapromisingapproachforregenerativerepairoftissuedefect.Asanexample,thegenerationofhumanearshapecartilageonthebackofmousevividlyillustratesthepotentialofusingengineeredearcartilagetorepairhumaneardefect[1].

Definitionoftissueengineering

Thebasicconceptoftissueengineeringincludesascaffoldthatprovidesanarchitectureonwhichseededcellscanorganizeanddevelopintothedesiredorganortissuepriortoimplantation.Thescaffoldprovidesaninitialbiomechanicalprofileforthereplacementtissueuntilthecellsproduceanadequateextracellularmatrix.Duringtheformation,deposition,andorganizationofthenewlygeneratedmatrix,thescaffoldiseitherdegradedormetabolized,eventuallyleavingavitalorganortissuethatrestores,maintains,orimprovestissuefunction（Figure1）[2].

Figure1

Threekeycomponentsoftissueengineeringandtheirroles

（1）Seedcells:

thecomponentformatrixproduction,depositionandtissueformation.

（2）Scaffold:

thesubstancethatprovidesathree-dimensionalplaceforcellstoreside,proliferateandproducematrix.

（3）Tissueformationenvironment:

afterseedingonthescaffold,cellsstarttogrow,produceanddepositextracellularmatricesonthescaffold.Inaproperenvironment,withgradualdegradationofthescaffoldandgradualcellproliferationandmatrixproductionandpropertissueremodeling,anengineeredtissuegraduallyformandbecomemature.

Scaffoldmaterialtypesandthegeneralrequirements

Basedonthesourceofmaterials,thescaffoldscanbedividedintotwogroups:

naturalscaffoldsandsyntheticpolymerscaffolds.Naturalscaffoldsaregenerallyderivedfromplantandanimalsourcesandarecomposedofproteinorcarbohydrates,includingcollagen,gelatin,glygosaminoglycans,hyaluronicacid,fibrinandchitosan,etc.Theadvantageofnaturalscaffoldsistheirexcellentbiocompatibility.

Syntheticpolymersarethepolymerizationofdifferentmonomerssuchashydroxylacidandester.Themostcommonlyusedpolymersarepoly（-hydroxyacids）,includingpolyglycolicacid（PGA）,polylacticacid（PLA）andtheirco-polymerpoly（lacticacid-co-glycolicacid）orPLGA.ThesepolymerscanbehydrolyzedbywatertoreducetheirmolecularweightandeventuallybemetabolizedintowaterandCO2.Theadvantageofthesescaffoldsisthatsyntheticpolymerscanbedesignedandmanufacturedfortheirexactdegradabilityanddegradationtimeaswellastheirporesizeandporosityandotherphysicalandchemicalproperties.Thusthequalityofsyntheticscaffoldscanbebettercontrolledcomparingwithnaturalscaffolds.Thisallowsforreproductioninlargequantitieswithsimilarcharacters.

Thegeneralrequirementsforscaffoldsinclude:

（1）Goodbiocompatibility:

thiswillmakesurethatcellsarehappytostayinthescaffoldandareabletoproliferateandmakeextracellularmatrix.

（2）Suitablebiodegradability:

scaffoldshouldbecompletelydegradedaftertissueformation.Inaddition,thedegradationrateshouldmatchtherateofcellgrowthandtissueformation.Furthermore,thedegradationrateshouldbeabletocontrolaccordingtotherequirementsofdifferenttypesoftissues.

（3）Three-dimensionalporousstructure:

thisisimportanttoprovidecellsaproperspacetoattach,growandproducematrix.Italsoallowsfornutritionandwastetransportationandtheaccessofneovascularization.

（4）Goodplasticityandmechanicalproperty:

thisistomakesuretogenerateascaffoldwithadesiredshapeandthescaffoldwillhaveenoughstrengthtosupportthefunctionsoftheengineeredtissues.

（5）Appropriatesurfacepropertiesforcell-scaffoldinteraction:

thisisparticularlyimportantformaintainingnormalcellphenotype,orpromotingcelldifferentiationinadditiontocellattachmentandgrowth.

（6）Easytomanufacture:

lowcostandeaseformanufactureisgenerallyrequiredinordertofabricatescaffoldinlargescaleforthepracticalapplications.

（7）Easeforsterilization:

thisistomakesuresterilizationwillnotaffectthebasiccharactersofthescaffold.

Applicationsofengineeredtissuestotissuerepair

Plasticsurgeryisaspecializedbranchofsurgeryconcernedwiththerepairofdeformitiesandthecorrectionoffunctionaldeficits.However,itisanoticeablefactthatdonorsitemorbidityisthepricethatpatientsmustpayformanyreconstructiveplasticsurgeriesinordertoachievethegoalsofdeformityrepairandfunctionaldeficitcorrection.Ithasbeenalongingaimforplasticsurgeonstogainsatisfactoryresultofrepairingprimarydefectbytissuestransferwithoutcausingsecondarydefect.Thedevelopmentoftissueengineeringtechnologyprovidessuchafeasibleapproach.Thefollowingsaretheexamplesofengineeredtissuerepairforbone,cartilageandtendon.

Boneengineeringandrepairinimmunocompetentanimals

Thefirstexampleistissueengineeredbonerepairforcraniofacialdefect[9].Inasheepmodel,bilateralcranialdefectswithadiameterof20mmwerecreatedandtheexperimentalsidedefectwasrepairedwithabonegraftconstitutedwithinvitroinducedautologousbonemarrowstromalcells（BMSCs）andcalciumalginate.Histologydemonstratedthatnewbonetissuewasformedat6weekspost-repairattheexperimentaldefect,whichbecamemorematuredandcontainedabundantcollagenmatrixat18weeks.Three-dimensionalCTscanningdemonstratedthatthebonedefectsinexperimentalgroupwerealmostcompletelyrepairedbytheengineeredbonetissueat18weeks.Incontrast,thecontroldefects,intowhichcalciumalginatealonewastransplanted,remainedunrepaired（Figure2）.Furthermore,chemicalanalysisshowedthattheengineeredbonetissuescontainedahighlevelofcalcium（71.6%ofnormalbonetissue）,suggestingthatengineeredbonecanreachahighlevelofmineralization.

Anotherexampleisengineeredbonerepairofweightbearingbonedefect[10].First,abonedefectatthediaphysisofthefemurwascreatedbyremovinga2.5cmlongbonesegment.Afterinternalfixationwithinterlockingnails,thedefectwasthenrepairedbyinsertingasimilarsizedcoralconstructthathasbeenseededwithinducedBMSCsandco-culturedfor3days.Asacontrol,thedefectwasrepairedbyacoralconstructalone.Radiographydemonstratedthatbonedefectwasmostlyrepairedbythenewlyformedbonetissueat3monthspost-repair.Thedefectswerecompletelyrepairedat6monthswitharadiodensitysimilartothatofadjacentnormalbone（Figure3）.Thisresultwasalsoconfirmedbygrossobservationandhistologyoftherepairedbonetissueharvestedat8monthspost-repair.Thegoatswereabletostandandwalkfreelywithrepairedfemurwheninternalfixationwasremovedat8monthspost-repair.Incontrast,thecoralscaffoldincontrolgroupwascompletelyabsorbedatthesecondmonthwhenevaluatedradiologicallyandanon-osseousunionwasobservedat6months（Figure3）.Theresultsofthesestudiesindicatethatbothflatandweight-bearinglongbonecanbegeneratedwithtissueengineeringapproaches.

Invitroengineeringofhumanearshapecartilage

Microtiadeformityisacommondiseaseinplasticsurgery,whichneedstobetreatedwithearreconstructionusingautologousribcartilage.Thefollowingisanexampletoshowthepotentialofusingengineeredcartilageforpatient’searreconstruction[11].

First,patientwholosthis/herearorwithadeformedearshouldbescannedwithlasertocollectgeometricdataapatient’snormalear,theinformationwasthenprocessedbyaCAD（computeraideddesign）systemtogeneratebothpositiveandnegativeimagedataofthenormalear,theresultantdataweretheninputintoaCAM（computeraidedmanufacture）systemtoprintamoldwith3Dstructureofanormalearinhalfsize.Then,polyglycolicacidunwovenfiberswereinsertedintothemoldandcoatedwith0.3%polylacticacidsolutionandthustogeneratearelativelysolidearshapescaffoldmaterial.Theresultingscaffoldwaslaserscannedtogeneratea3Dimage,whichcouldbedigitallycomparedwiththeoriginalear3Dimagetoanalyzethesimilarityin3Dstructure.AsrevealedinFigure4,theresultingear-shapedscaffoldachievedasimilaritylevelofabove97%comparedtothepositivemoldoforiginalearshape,indicatingthatthemoldfabricatedbyCAD/CAMisallowedtoaccuratelyfabricateascaffoldintoanear-shapemirror-symmetricaltothenormalear.

Afterwards,total50106cellsin1mlvolumewereevenlyseededontotheear-shapedscaffoldandinvitroculturedwithmediumchangeatregulartimeintervals.Interestingly,ahumanearcartilagecouldbegeneratedinvitroafter12weeksofculturewithgoodelasticity（Figure5）.TheengineeredcartilagealsorevealedrelativelymaturehistologicalstructureofcartilagewithlacunastructureformationandstrongstainingforSafranin-OandcollagenIIasshowninFigure6.Moreimportantly,theinvitroformedhumanearshapedcartilagecouldreachamorphologicalsimilarityof82.6%tothepositiveearmold,indicatingthatthistechniquecannotonlygeneratecartilagetissueinvitrobutisalsoabletomaintainadesigned3Dtissuestructure.Curren