PolycaprolactoneCollagen Tubes as Scaffolds for Ne

Materials2010,3,3714-3728;doi:10.3390/ma3063714materialsISSN1996-1944*,ThucNhiT.Dang1,EveC.Tsai3andXudongCao41OttawaHospitalResearchInstitute,501SmythRoad,Ottawa,Ontario,K1H8L6,Canada;E-Mail:[e-mail](T.T.D.)2DepartmentofClinicalandExperimentalMedicine,LinköpingUniversity,58185Linköping,Sweden3OttawaHospitalResearchInstitute,725ParkdaleAvenue,Ottawa,Ontario,K1Y4E9,Canada;E-Mail:[e-mail](E.C.T.)4DepartmentofChemicalandBiologicalEngineering,UniversityofOttawa,161Louis-Pasteur,Ottawa,Ontario,K1N6N5,Canada;E-Mail:[e-mail](X.C.)*Authortowhomcorrespondenceshouldbeaddressed;E-Mail:[e-mail];Tel.:[phone];Fax:[phone].Received:4May2010/Accepted:17June2010/Published:19June2010Abstract:Studiesusingcellulartherapies,scaffolds,andtubularstructuredimplantshavebeencarriedoutwiththegoaltorestorefunctionalrecoveryafterspinalcordinjury(SCI).Noneofthesetherapeuticstrategies,bythemselves,havebeenshowntobesufficienttoachievecompleterestorationoffunction.ToreversethedevastatingeffectsofSCI,aninterdisciplinaryapproachthatcombinesmaterialsscienceandengineering,stemcellbiology,andneurosurgeryisbeingcarriedout.Wearecurrentlyinvestigatingascaffoldthathastheabilitytodelivergrowthfactorsfortheproliferationanddifferentiationofendogenousstemcells.Neuralstemcells(NSCs)derivedfrommicearebeingusedtoassesstheefficacyofthereleaseofgrowthfactorsfromthescaffoldinvitro.Thefabricationofthetubularimplantallowsaporousscaffoldtobeformed,whichaidsinthereleaseofgrowthfactorsaddedtothescaffold.Keywords:neurospheres;nervetissueengineering;electrospunnanofibers;differentiationOPENACCESSMaterials2010,337151.IntroductionIrreversibledamagetothecentralnervoussystem(CNS)aftertraumatic,ischemic,orinflammatoryinjuryresultsinpermanentfunctionalimpairment.Asthereisnocurativetherapy,theinterdisciplinaryfieldofneuraltissueengineeringhasemergedasapossiblesolutionforfabricatingabiologicalsubstitutethatcanmaintain,restore,orimproveneuraltissuefunction.Multipotentneuralstemcells(NSCs)isolatedfromfetaloradultrodentsourceshavenowbeenshowntodifferentiateintoneuralcellswithappropriatephenotypes.ThesecanpossiblyestablishconnectivitywithinspecificCNSregionsaftertransplantation[1,2].However,theappropriateenvironmentalcuesareneeded.Theinteractionbetweencellsandtheextracellularmatrix(ECM)playsanimportantroleinregulatingprogenitorcelldifferentiation,aswellasreparativeandregenerativefunctions.Forexample,Schwanncells,usedtoimprovespinalcordrepair,havebeenshowntoproduceaxonsproutingECMmolecules,suchaslaminin,fibronectin,andcollagen[3].Hence,inthetreatmentoftraumaticspinalcordinjury(SCI),thereisparticularinterestindevelopingtissueengineeringscaffoldsusingbiomaterialsthatmimicthefunctionalityoftheECM.Thesescaffolds,inturn,wouldaidincontrollingtheappropriatedifferentiationofNSCstransplantedintoinjuredspinalcordstoaffectregeneration.In1981,CNSaxonregenerationwasdemonstratedutilizingthepermissiveenvironmentoftheperipheralnervoussystem(PNS)toconstructabridgethatwouldfacilitateaxonregenerationacrossaspinalcordinjurysite[4,5].WhileCNSaxonregenerationwasdemonstrated,theabilityoftheregeneratingaxonstoreenterthespinalcord,findsuitabletargets,formconnections,andrestorefunctionhasbeenlimited[6-8].Theseexperimentsdemonstratedboththepossibilitiesandtheproblemsofthebridgingconcept—axonsfromnearbyneuronsregeneratedintothegrafts,butrarelyleftthePNSgrafttore-entertheCNStissue.Sincethen,therehavebeenmanymodificationstothiscellulartotissuegraftstrategy,manyofwhichhaveemployedbiomimeticmaterials[9-12].ItisnowestablishedthatanidealSCIneuronalbridgemustintegrateseamlesslyintospinalcordtissue,notstimulateaglialscar,andpromoteaxongrowthandencouragere-entryintothetargettissue.Electrospinningproducesnanofibrousscaffoldswithhighsurfaceareatovolumeratios,andfiberdiametersdowntothenanometerrangewithsufficientporesforthecellgrowth,proliferation,anddifferentiation[13-15].Variousdegradablebiomaterialsareavailableandabroadspectrumofnanofiber-basedscaffoldswithdifferentmechanicalandbiochemicalpropertiesarebeingusedfortissueengineeringapplications.Thesebiomimeticscaffoldscanbereconstructedtoprovidephysicalandchemicalcuesthatmatchthesurroundingtissues,andprovidesupporttotheparticularcelltyperequiredforspecifictissueengineeringapplications[16].Inparticular,poly(ε-caprolactone)(PCL)isasynthetic,biodegradableandbiocompatiblepolymer,whichhasbeeninvestigatedasabiomaterialforsurgeryanddrugdeliverysystems[17,18],astherearenotoxiceffectsfromdegradationproducts[19,20].Furthermore,PCListhemostwidelyinvestigatedsyntheticpolymerandhasFDAapprovalinvariousdevicesformedicalapplications[21].Collagen,incontrast,isanaturalECMwithexcellentcelladhesionproperties.Therefore,themixturesynthesizedbyblendingcollagenwithPCLusingelectrospinningwilllikelyproduceabiocompositescaffoldthatwillimprovethebiocompatibilityofPCLwhilepreservi