生物增材制造进展――清华大学

孙伟-WeiSun清华大学–TsinghuaUniversityDrexelUniversity–德雷塞尔大学，USADecember13-16,2012Wuhan,ChinaRecentDevelopmentonBio-AdditiveManufacturing生物增材制造进展TsinghuaUniversity/DrexelUniversity:GraduateAssistantsandColleaguesCollaboratorsFundingSupport:NSF,DARPA,NASANSFC(国家基金委),MST(科技部-863)Acknowledgements3Bio-AdditiveManufacturing生物增材制造Bio-AdditiveManufacturingusesbiomaterials,cells/proteinsetcasbasicbuildingblockstofabricate3DstructuresorinvitrobiologicalmodelsthroughAdditiveManufacturingtechniques.将生物材料和/或生物单元（细胞/蛋白质等）按仿生形态学，生物体功能，细胞特定微环境等要求用增材制造的方法制造出具有复杂结构，功能和个性化的生物材料三维结构或体外三维生物功能体。4生物增材制造是制造学从使用单一结构材料，功能材料，到使用生物材料和生命体材料学科的拓展延伸。也是工程，材料，信息和生命科学等多学科的交叉融合。生命科学工程制造生物增材制造生物材料Bio-AdditiveManufacturing生物增材制造CT/MRIImageBio-ManufacturingofTissueScaffoldsandConstructsDesignRepresentationofScaffoldComplexityVirtualandPhysicalBiomodelingScaffoldInformatics&RepresentationBiomimeticModelingandDesignMulti-scaleModelingofBio-SystemBioCADforTissue&AnatomyModelingBio-RPModelsandCustomizedProsthesesBiomodelingforSurgicalPlanningSFFbasedBiomaterialFabricationforTissueScaffoldsDirectCellWritingforCell-embeddedTissueConstructsCell/OrganPrintingforPhysio-logical&PharmacokineticModel外科整形模型手术方案模型个性化假肢Bio-AdditiveManufacturing生物增材制造技术的应用范围组织工程支架细胞/器官打印再生医学、病/药理学模型仿生设计/模拟仿生建模多尺度生物系统模型生物增材制造应用的四个层次依据材料的发展和其生物学性能，生物增材制造技术的应用可分为如下四个层次：第一层次：医疗模型和体外医疗器械的制造(medicalmodelsandmedicaldevices)无生物相容的材料:non-biocompatiblematerials第二层次：永久植入物的制造(medicalimplants)生物相容，但非降解的材料:biocompatiblebutnotbiodegradable第三层次:组织工程支架的制造(tissuescaffolds)生物相容且可降解的材料:biocompatibleandbiodegradable第四层次:体外生物结构体的制造(invitrobiologicalmodels)细胞,蛋白及其它细胞外基质:cellasmaterialsBiomodelingforsurgicalplanning生物增材制造技术应用-医疗模型的制造8BiomodelingofCleftPalateDeformities-Dr.HDNah(CHOP)defectedskullcleftpalatereplacementCorrectedmandible生物增材制造技术应用-医疗模型的制造9BiomodelingofEpilepticRegionsofBrainwithElectrodes-Dr.Sperling(TJU)生物增材制造技术应用-医疗模型的制造Custom-madekeenreplacementCustom-madehipreplacement生物增材制造技术应用-个性化永久植入物的制造11CustomizedTitaniumProsthesesProfessors李涤尘等西安交通大学，第四军医大学MedicalImagesofoperativeday(L)and6Months(R)生物增材制造技术应用-个性化永久植入物的制造PrincipleSelectiveLaserMelting(SLM)Discretizationof3DmodelBuildmetalpartlayerbylayerSelectivemeltingpowders生物增材制造技术应用-个性化永久植入物和医疗器械的制造杨永强教授华南理工骨植入体外科手术模板SLM:SelectLaserMeltingStainlesssteel杨永强教授华南理工生物增材制造技术应用-个性化永久植入物和医疗器械的制造Acetabularcupandhipstems(hipjoint)producedbyDiMetal-100Prof.YangYongqiang杨永强，SouthChinaUniversityofTechnology生物增材制造技术应用-个性化永久植入物和医疗器械的制造发明专利ZL200810026491.1，PCT/CN2008/000965Customizedlingualbrackets生物增材制造技术应用-个性化永久植入物和医疗器械的制造Prof.YangYongqiang杨永强，SouthChinaUniversityofTechnology生物增材制造应用的四个层次依据材料的发展和其生物学性能，生物增材制造技术的应用可分为如下四个层次：第一层次：医疗模型和体外医疗器械的制造(medicalmodelsandmedicaldevices)无生物相容的材料:non-biocompatiblematerials第二层次：永久植入物的制造(medicalimplants)生物相容，但非降解的材料:biocompatiblebutnotbiodegradable第三层次:组织工程支架的制造(tissuescaffolds)生物相容且可降解的材料:biocompatibleandbiodegradable第四层次:体外生物结构体的制造(invitrobiologicalmodels)细胞,蛋白及其它细胞外基质:cellasmaterialsNEEDstructural,mechanical,andchemicalcues-toguidecellmorphology,migration,andproliferation-toregulatecelldifferentiation-tomodulatecellularprocesstogrowfunctionaltissues.Wecannotjustharvestcells,layouttheminthedesignedpatterns,andexpectthemtogrowandformatissue,Why?ChallengesinTissueEngineering18ECM/ScaffoldTissuespecificgeneexpressionAlterphonotypeTumorizationGrowthApoptosisAhierarchyofECM-mediatedsignalingregulatestissue-specificgeneexpressionCalvinD.etal,CurrentopinioninCellBiology,1995,7:736-747ChallengesinScaffoldTissueEngineering-MicroenvironmentInducedCellularResponses1919191)Biophysicalrequirements:scaffoldstructuralintegrity,strengthstability,anddegradation;cell-specificpore,shape,size,porosity,andinter-architecture2)Biologicalrequirements:cellloadingandspatialdistributions;cellattachment,growthandnewtissueformation;3)Transportporetopologyandinter-connectivity4)Anatomicalrequirements:anatomicalcompatibility;geometricfitting5)Manufacturabilityrequirements:processability(biomaterialavailability,printingfeasibilityetc.)processeffect(wrapping,distortion,structuralintegrity,etc.)Itisamulti-constrainedSystemDesignProblemChallengesinScaffoldGuidedTissueEngineering-asystemapproachformultipledesignconstrains(NSF-0219176&NSF-0427216)20CT/MRI–CAD–SFF:FDM/SLA/SLS3DPPEDAdvantages:NorestrictiononshapeHighcontrolcapabilityConsistent–reproducibleDisadvantages:LimitedresolutionNotacell-friendlyenvironmentHarshHeatToxicSolventsNon-SterileAdditiveManufacturingBio-AdditiveManufacturingforTissueScaffoldFabrication-DirectMethodsScaffoldMRICT-ScanCADImagingDataScaffoldScaffoldsbyMicro-SLASLAbuildsconcept-verificationmodelsofitstensegritystructures70mmindiameter.MolecularGeodesics,Inc.Innovationthroughbiologicalmimicry,(POSTECH,Korea),Miro-SLAforTissueScaffolds,Biofabrication,2009生物增材制造技术应用-组织工程支架的制造ScaffoldsbyFDMD.HutchmachergroupatNUS&QUT,Australia生物增材制造技术应用-组织工程支架的制造SLSPCLMechanicalTestScaffold(A)OriginalCondyle,(B)SLSFabricatedPCLScaffoldAB(Das&HollisterGroup,UM)Scaf