MassMassachachuusesettstts InInssttiittuutte of Technole of TechnoloogygyHaHarvarvarrd Md Meedicadicall SScchohoololBrBrigighaham am annddWWoomemenn’’s Hs HoossppitalitalVA BVA Boossttonon HeHealalthcthcaare Sre Syysstteemm2.782J/3.961J/BEH.451J/HST524J2.782J/3.961J/BEH.451J/HST524JBONE SBONE SUUBSTITUTE MATERIALS ANDBSTITUTE MATERIALS AND TISSUE ENGINEERINGTISSUE ENGINEERINGM. Spector, Ph.D.M. Spector, Ph.D.Many slides have been removed due to copyright restrictions.INCUBATION OF TISSUE ENGINEERINGINCUBATION OF TISSUE ENGINEERING CONSTRUCTS IN ECTOPIC SITESCONSTRUCTS IN ECTOPIC SITES••AllowsAllows ffoor addir addititionalonal development for thedevelopment for theconstruct in anconstruct in an in vivoin vivo((aauutoltologousogous))environenvironmmentent––Exposed to host cells and regulatory moleculesExposed to host cells and regulatory molecules ––Not exposed to mechanical loading duringNot exposed to mechanical loading duringdevelopmentdevelopment––Development can be monitoredDevelopment can be monitored––At the appropriate stage of development theAt the appropriate stage of development theconstruct can be transpconstruct can be transplanted to the targetlanted to the targetdefectdefectINCUBATION OF TISSUE ENGINEERINGINCUBATION OF TISSUE ENGINEERING CONSTRUCTS IN ECTOPIC SITESCONSTRUCTS IN ECTOPIC SITES••Nude (Immune Deficient) MouseNude (Immune Deficient) Mouse Experimental ModelExperimental Model––Subcutaneous site used as theSubcutaneous site used as the in vivoin vivoenvironment to investigate the development ofenvironment to investigate the development of tissue induced bytissue induced by xenogeneicxenogeneic(human) cells(human) cellsCONSIDERATIONS IN TISSUECONSIDERATIONS IN TISSUE ENGINEERINGENGINEERING••••••Clearly define thClearly define the specie specifific clinicalc clinical problprobleemm to be solved.to be solved.Implement thImplement the simplest pe simplest prrocedure forocedure for treatintreatingg the probthe problem to achieve alem to achieve a meaningful clinical benefit.meaningful clinical benefit.––BenefitBenefit--Risk Ratio (e.g., risRisk Ratio (e.g., riskkss of using cells:of using cells:cell transformation, morbidity of a 2ndcell transformation, morbidity of a 2ndsurgical procedure)surgical procedure)––CostCostNeed to evaluate tissue enNeed to evaluate tissue engineeringineeringgproducts in animal models that relate toproducts in animal models that relate tohuman phuman prroblems to be treatedoblems to be treated..CLINICAL PROBLEMS REQUIRINGCLINICAL PROBLEMS REQUIRING BONE TISSUE ENGINEERINGBONE TISSUE ENGINEERING••FusionFusion––Spine fusionSpine fusion••Defects resulting fromDefects resulting from ththe excisione excision ofoftumors or cysts.tumors or cysts.••IncomplIncompleete fractte fractuure healire healinngg••Bone lBone loosss associs associated wiated with prosthth prostheseseses––ParticleParticle--induced osteolysisinduced osteolysis––Stress shieldingStress shieldingELEMENTS OF TISSUE ENGINEERING/ELEMENTS OF TISSUE ENGINEERING/ REGENERATIVE MEDICINEREGENERATIVE MEDICINE••MATRIMATRIXX (SCAFFOLD)(SCAFFOLD)––Porous, absorbablePorous, absorbable synthetic and naturalsynthetic and natural biomaterialsbiomaterials••CELLSCELLS(Autologous or Allogeneic)(Autologous or Allogeneic)––Differentiated cells of same type as tissueDifferentiated cells of same type as tissue––Stem cells (Stem cells (e.ge.g., bon., bonee marromarroww--derived)derived) ––Other cellOther cell typestypes••REGULATORSREGULATORS––GrowGrowth factors orth factors or their genestheir genes••ENVIRONMENTAL FACTORSENVIRONMENTAL FACTORS––Mechanical loadingMechanical loading––Static versus dynamic (Static versus dynamic (““bioreactorbioreactor””))TISSUE ENGINEERING ENDPOINTSTISSUE ENGINEERING ENDPOINTS••••••Morphological/Histological/BMorphological/Histological/Biochemicaliochemical––Match the cMatch the composition and architeomposition and architeccture oture off thethe tissue.tissue.––ProbleProblem: A complete am: A complete annalysisalysis is difficult and no cleais difficult and no clearr relationships yet wrelationships yet wiith functith functional and clinical endpoints.onal and clinical endpoints.Functional (Functional TissueFunctional (Functional Tissue Engineering)Engineering)––Achieve certain functions; dispAchieve certain functions; display certain propertieslay certain properties((e.ge.g., mechanical properties).., mechanical properties).––ProbleProblem: Difficult to measm: Difficult to measure aure all pll prroperties; Whichoperties; Whichmechanical properties are the most important?mechanical properties are the most important?ClinicalClinical––Pain relief.Pain relief.––Problems:Problems: Can only be evalCan only be evaluated in human subjects anduated in human subjects andthe methe mechanisms (incchanisms (including theluding the placebo effect) and kineticsplacebo effect) and kineticsof pain relief (of pain relief (e.ge.g., how., how long it wlong it wiill last) are unknoll last) are unknown.wn.SCAFFOLDSSCAFFOLDS••••••••••••••••••Chemical CompositionChemical CompositionCollagenCollagen--GAG (Yannas)GAG (Yannas)PolyglycPolyglycololic/polic/polylactic acid (Langer and Freed)ylactic acid (Langer and Freed)SelfSelf--asseassemblyingmblyingproteins (Zhang)proteins (Zhang)NanoNano--Ap/CollagenAp/CollagenCompositeComposite--self asseself assembly (Cui)mbly (Cui)Chitin/chitosan (Chitin/chitosan (XuXuand others)and others)Structure/ArchitectureStructure/ArchitectureFiber mesFiber meshh, li, like noke noododles (Langer and Freed)les (Langer and Freed)Free Form FabricationFree Form Fabrication--33--D printing (D printing (YanYan))SpongeSponge--like (Yannas and Cui)like (Yannas and Cui)Fine filament mesh (Zhang)Fine filament mesh (Zhang)Fiber mesh, like noodlesScaffold StructuresPhotos removed due to copyright restrictions.PRINCIPLES AND PRACTICEPRINCIPLES AND PRACTICEOF TISSUEOF TISSUE ENGINEERINGENGINEERINGPrinciplPrincipleses••ScafScafffooldlds cans can regulatregulatee cellcell functionfunction by theiby theirr chemicalchemical makemake--upup••ScafScafffooldlds cans can regulatregulatee cellcell functionfunction by theiby theirr structustructurre/architecturee/architecturePracticePractice••MethodsMethods for prodfor producing sucing sccafaffoldsfolds withwith