103 Advances in Biochemical Engineering/Biotechnology SeriesEditor:T.Scheper EditorialBoard: W.Babel·I.Endo·S.-O.Enfors·A.Fiechter·M.Hoare·W.-S.Hu B.Mattiasson·J.Nielsen·H.Sahm·K.Schügerl·G.Stephanopoulos U.vonStockar·G.T.Tsao·C.Wandrey·J.-J.Zhong AdvancesinBiochemicalEngineering/Biotechnology SeriesEditor:T.Scheper RecentlyPublishedandForthcoming Volumes WhiteBiotechnology MicroscopyTechniques VolumeEditors:Ulber,R.,Sell,D. VolumeEditor:Rietdorf,J. Vol.105,2007 Vol.95,2005 AnalyticsofProtein-DNAInteractions RegenerativeMedicineII VolumeEditor:Seitz,H. ClinicalandPreclinicalApplications Vol.104,2007 VolumeEditor:Yannas,I.V. Vol.94,2005 TissueEngineeringII BasicsofTissueEngineeringandTissue RegenerativeMedicineI Applications Theories,ModelsandMethods VolumeEditors:Lee,K.,Kaplan,D. VolumeEditor:Yannas,I.V. Vol.103,2007 Vol.93,2005 TissueEngineeringI TechnologyTransferinBiotechnology ScaffoldSystemsforTissueEngineering VolumeEditor:Kragl,U. VolumeEditors:Lee,K.,Kaplan,D. Vol.92,2005 Vol.102,2006 RecentProgressofBiochemicalandBiomedical CellCultureEngineering EngineeringinJapanII VolumeEditor:Hu,W.-S. VolumeEditor:Kobayashi,T. Vol.101,2006 Vol.91,2004 BiotechnologyfortheFuture RecentProgressofBiochemicalandBiomedical VolumeEditor:Nielsen,J. EngineeringinJapanI Vol.100,2005 VolumeEditor:Kobayashi,T. Vol.90,2004 GeneTherapyandGeneDeliverySystems VolumeEditors:Schaffer,D.V.,Zhou,W. PhysiologicalStressResponsesinBioprocesses Vol.99,2005 VolumeEditor:Enfors,S.-O. Vol.89,2004 SterileFiltration VolumeEditor:Jornitz,M.W. MolecularBiotechnologyofFungalβ-Lactam Vol.98,2006 AntibioticsandRelatedPeptideSynthetases VolumeEditor:Brakhage,A. MarineBiotechnologyII Vol.88,2004 VolumeEditors:LeGal,Y.,Ulber,R. Vol.97,2005 Biomanufacturing VolumeEditor:Zhong,J.-J. MarineBiotechnologyI Vol.87,2004 VolumeEditors:LeGal,Y.,Ulber,R. Vol.96,2005 NewTrendsandDevelopmentsinBiochemical Engineering Vol.86,2004 Tissue Engineering II BasicsofTissueEngineeringandTissueApplications Volume Editors: Kyongbum Lee · David Kaplan Withcontributionsby J.P.Acker·E.S.Ahn·S.T.Andreadis·F.Berthiaume·S.N.Bhatia R.J.Fisher·J.A.Garlick·Y.Nahmias·R.A.Peattie·V.L.Tsang T.J.Webster·M.L.Yarmush 123 AdvancesinBiochemicalEngineering/Biotechnologyreviewsactualtrendsinmodernbiotechnology. Itsaim isto coverallaspects ofthisinterdisciplinary technologywhereknowledge, methodsand expertisearerequiredforchemistry,biochemistry,micro-biology,genetics,chemicalengineeringand computerscience.Specialvolumesarededicatedtoselectedtopicswhichfocusonnewbiotechnological productsandnew processes for their synthesis and purification.They give the state-of-the-art of atopicinacomprehensivewaythusbeingavaluablesourceforthenext3–5years.Italsodiscusses newdiscoveriesandapplications.Specialvolumesareeditedbywellknownguesteditorswhoinvite reputedauthorsforthereviewarticlesintheirvolumes. In references Advances in Biochemical Engineering/Biotechnologyis abbeviated Adv Biochem En- gin/Biotechnolandiscitedasajournal. SpringerWWWhomepage:springer.com VisittheABEcontentatspringerlink.com LibraryofCongressControlNumber:2006929797 ISSN0724-6145 ISBN-103-540-36185-5SpringerBerlinHeidelbergNewYork ISBN-13978-3-540-36185-5SpringerBerlinHeidelbergNewYork DOI10.1007/11749219 Thisworkissubjecttocopyright.Allrightsarereserved,whetherthewholeorpartofthematerial isconcerned,specificallytherightsoftranslation,reprinting,reuseofillustrations,recitation,broad- casting,reproductiononmicrofilmorinanyotherway,andstorageindatabanks.Duplicationof thispublicationorpartsthereofispermittedonlyundertheprovisionsoftheGermanCopyrightLaw ofSeptember9,1965,initscurrentversion,andpermissionforusemustalwaysbeobtainedfrom Springer.ViolationsareliableforprosecutionundertheGermanCopyrightLaw. SpringerisapartofSpringerScience+BusinessMedia springer.com (cid:1)c Springer-VerlagBerlinHeidelberg2007 Theuseofregisterednames,trademarks,etc.inthispublicationdoesnotimply,evenintheabsence ofaspecificstatement,thatsuchnamesareexemptfromtherelevantprotectivelawsandregulations andthereforefreeforgeneraluse. Coverdesign:WMXDesignGmbH,Heidelberg TypesettingandProduction:LE-TEXJelonek,Schmidt&VöcklerGbR,Leipzig Printedonacid-freepaper 02/3141YL–543210 SeriesEditor Prof.Dr.T.Scheper InstituteofTechnicalChemistry UniversityofHannover Callinstraße3 30167Hannover,Germany [email protected] VolumeEditors Prof.Dr.KyongbumLee Prof.Dr.DavidKaplan AssistantProfesssor ProfessorandChair ChemicalandBiologicalEngineering DepartmentofBiomedicalEngineering TuftsUniversity ScienceandTechnologyCenter 4ColbyStreet,Room142 Medford,MA02155,USA Medford,MA02155,USA [email protected] [email protected] EditorialBoard Prof.Dr.W.Babel Prof.Dr.M.Hoare SectionofEnvironmentalMicrobiology DepartmentofBiochemicalEngineering Leipzig-HalleGmbH UniversityCollegeLondon Permoserstraße15 TorringtonPlace 04318Leipzig,Germany London,WC1E7JE,UK [email protected] [email protected] Prof.Dr.S.-O.Enfors Prof.Dr.I.Endo DepartmentofBiochemistryand SaitamaIndustrialTechnologyCenter Biotechnology 3-12-18,KamiaokiKawaguchi-shi RoyalInstituteofTechnology Saitama,333-0844,Japan Teknikringen34, [email protected] 10044Stockholm,Sweden [email protected] Prof.Dr.A.Fiechter InstituteofBiotechnology EidgenössischeTechnischeHochschule ETH-Hönggerberg 8093Zürich,Switzerland ae.fi[email protected] VI EditorialBoard Prof.Dr.W.-S.Hu Prof.Dr.J.Nielsen ChemicalEngineering CenterforProcessBiotechnology andMaterialsScience TechnicalUniversityofDenmark UniversityofMinnesota Building223 421WashingtonAvenueSE 2800Lyngby,Denmark Minneapolis,MN55455-0132,USA [email protected] [email protected] Prof.Dr.K.Schügerl Prof.Dr.B.Mattiasson InstituteofTechnicalChemistry DepartmentofBiotechnology UniversityofHannover,Callinstraße3 ChemicalCenter,LundUniversity 30167Hannover,Germany P.O.Box124,22100Lund,Sweden [email protected] [email protected] Prof.Dr.U.vonStockar Prof.Dr.H.Sahm LaboratoiredeGénieChimiqueet InstituteofBiotechnolgy Biologique(LGCB),DépartmentdeChimie ForschungszentrumJülichGmbH SwissFederalInstitute 52425Jülich,Germany ofTechnologyLausanne [email protected] 1015Lausanne,Switzerland urs.vonstockar@epfl.ch Prof.Dr.G.Stephanopoulos DepartmentofChemicalEngineering Prof.Dr.C.Wandrey MassachusettsInstituteofTechnology InstituteofBiotechnology Cambridge,MA02139-4307,USA ForschungszentrumJülichGmbH [email protected] 52425Jülich,Germany [email protected] Prof.Dr.G.T.Tsao ProfessorEmeritus PurdueUniversity WestLafayette,IN47907,USA [email protected] [email protected] Prof.Dr.J.-J.Zhong CollegeofLifeScience&Biotechnology ShanghaiJiaoTongUniversity 800Dong-ChuanRoad Minhang,Shanghai200240,China [email protected] AdvancesinBiochemicalEngineering/Biotechnology AlsoAvailableElectronically For all customers who have a standing order to Advances in Biochemical Engineering/Biotechnology, we offerthe electronic version via SpringerLink freeofcharge.Pleasecontactyourlibrarianwhocanreceiveapasswordorfree accesstothefullarticlesbyregisteringat: springerlink.com Ifyoudonothaveasubscription,youcanstillviewthetablesofcontentsofthe volumesandtheabstractofeacharticlebygoingtotheSpringerLinkHome- page,clickingon“BrowsebyOnlineLibraries”,then“ChemicalSciences”,and finallychooseAdvancesinBiochemicalEngineering/Biotechnology. Youwillfindinformationaboutthe – EditorialBoard – AimsandScope – InstructionsforAuthors – SampleContribution atspringer.comusingthesearchfunction. AttentionallUsers ofthe“SpringerHandbookofEnzymes” Informationonthishandbookcanbefoundontheinternetat springeronline.com AcompletelistofallenzymeentrieseitherasanalphabeticalNameIndexor as the EC-Number Index is available at the above mentioned URL. You can downloadandprintthemfreeofcharge. Acompletelistofallsynonyms(morethan25,000entries)usedfortheenzymes isavailableinprintform(ISBN3-540-41830-X). Save 15% We recommend a standing order for the series to ensure you automatically receiveallvolumesandallsupplementsandsave15%onthelistprice. Preface It is our pleasure to present thisspecial volume ontissue engineering in the series Advances in Biochemical Engineering and Biotechnology. This volume reflects the emergence of tissue engineering as a core discipline of modern biomedical engineering, and recognizes the growing synergies between the technological developments in biotechnology and biomedicine. Along this vein,thefocusofthisvolumeistoprovideabiotechnologydrivenperspective oncellengineeringfundamentalswhilehighlightingtheirsignificanceinpro- ducingfunctionaltissues.Ouraimistopresentanoverviewofthestateofthe artofaselectionofthesetechnologies,punctuatedwithcurrentapplications intheresearchanddevelopmentofcell-basedtherapiesforhumandisease. To prepare this volume, we have solicited contributions fromleaders and experts in their respective fields, ranging from biomaterials and bioreactors to gene delivery and metabolic engineering. Particular emphasis was placed on including reviews that discuss various aspects of the biochemical pro- cessesunderlyingcellfunction,suchassignaling,growth,differentiation,and communication. The reviews of research topics cover two main areas: cellu- larand non-cellularcomponents andassembly; evaluation andoptimization oftissuefunction;andintegratedreactororimplantsystemdevelopment for researchandclinicalapplications.Manyofthereviewsillustratehowbiochemi- calengineeringmethodsareusedtoproduceandcharacterizenovelmaterials (e.g. genetically engineered natural polymers, synthetic scaffolds with cell- typespecific attachment sitesorinductive factors),whose unique properties enable increased levels of control over tissue development and architecture. Otherreviewsdiscusstheroleofdynamicandsteady-statemodelsandother informatics tools in designing, evaluating, and optimizing the biochemical functionsofengineeredtissues.Reviewsthatillustratetheintegrationofthese methodsandmodelsinconstructingmodel,implant(e.g.skin,cartilage),or ex-vivosystems(e.g.bio-artificialliver)arealsoincluded. It is our expectation that the mutual relevance of tissue engineering and biotechnologywillonlyincreaseinthecomingyears,asourneedsforadvanced healthcareproductscontinuetogrow.Already,tissuederived cellsconstitute important production systems for therapeutically and otherwise useful bio- moleculesthatrequirespecializedpost-translationalprocessingfortheirsafety andefficacy.Biochemicalengineeringproducts,rangingfromgrowthfactorsto X Preface polymerscaffolds,areusedasbuildingblocksorsignalmoleculesatvirtually every stage of engineered tissue formation. Importantly, the realization of engineered tissuesas clinicallyuseful andcommercially viableproductswill at least in part depend on overcoming the same efficiency challenges that thebiotechnologyindustryhasbeenfacing.Inthislight,weseetheinterface betweentissueengineeringandvariousotherfieldsofbiochemicalengineering asaveryexcitingareaforresearchanddevelopmentwithenormouspotential for cross-disciplinary education. In this regard, we anticipate that this and othersimilarvolumeswillalsobeusefulassupplementarytextforstudents. We extend our special thanks to all of the contributing authors as well as Springer for embarking on this project. We are especially grateful to Dr. Thomas Scheper and Ulrike Kreusel for their incredible patience and hard workasourproductioneditors. Medford,August2006 KyongbumLee,DavidKaplan