Biomaterials26(2005)3131–3140MicrogroovedfibrillarcollagenmembranesasscaffoldsforcellsupportandalignmentRobertB.Vernona,�,MichelD.Goodena,StephanieL.Larab,ThomasN.Wighta,baHopeHeartProgram,BenaroyaResearchInstituteatVirginiaMason,1201NinthAvenue,Seattle,WA98101-2795,USAbDepartmentofPathology,UniversityofWashington,Seattle,WA98195,USAReceived17May2004;accepted17August2004Availableonline1October2004AbstractForseveralyears,microgroovedsubstrateshavebeenevaluatedasameanstoorientcellsinengineeredtissues.Recently,wefabricatedthin(0.1–5.3mm)planarandtubularcollagenmembranes(CMs)fromair-driedhydrogelsofnative,fibrillartypeIcollagen(Vernonetal.,Biomaterials2004;26:1109–17).TheCMswerestrong,stable,andpermeableand,hence,ofpotentialuseasscaffoldsfortissueengineering.Inthepresentstudy,planarCMssupportedarobustattachment,spreading,andproliferationofhumandermalfibroblasts(HDFs)andhumanumbilicalarterysmoothmusclecells(HUASMCs).Collagenhydrogelswereair-driedontomicrogroovedtemplatesandsubsequentlyremovedintheformofgroovedCMswiththepotentialtoaligncells.ThegroovedCMswerehighlyeffectiveatinducingHDFsandHUASMCstoelongateandalign,asrevealedbyscanningelectronmicroscopyandbyassaysoff-actinandnuclearorientation.Alignmentofcellswasmaintainedathighcelldensities.CMswithgroovesofsubstantiallydifferentwidthsanddepthsweresimilarlyeffectiveincausingcellalignment;however,cellsalignedpoorlyonCMsthathadgrooveslessthan1mmindepth.GroovedCMswiththecapabilitytoaligncellsmightbeofconsiderableuseinthefabricationoftissuesubstitutes.r2004ElsevierLtd.Allrightsreserved.Keywords:Cellculture;Collagen;Fibroblast;Hydrogel;Membrane;Microgroove;Micropatterning;Scaffold;Smoothmusclecell;Surfacetopography1.IntroductionAprimarygoalofregenerativemedicineisthecreationofmaterialconstructstofacilitatehealingortosupplementorreplacemalfunctionaltissuesandorgans.Typically,engineeredtissuesubstitutesconsistofanon-cellular,supportive‘‘scaffold’’thatiseitherinoculatedwithculturedcellsinvitroorcellularizedafterimplant...