Endothelial Cell Capture of Heparin-Binding Growth Factors under Flow 英文参考文献.docVIP

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Endothelial Cell Capture of Heparin-Binding Growth Factors under Flow 英文参考文献.doc

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Endothelial Cell Capture of Heparin-Binding Growth Factors under Flow 英文参考文献

EndothelialCellCaptureofHeparin-BindingGrowth FactorsunderFlow BingZhao1.,ChangjiangZhang3.,KimberlyForsten-Williams2,JunZhang3,MichaelFannon1* 1Department of Ophthalmology and Visual Sciences, University of Kentucky, Lexington, Kentucky, United States of America, 2Department of Chemical Engineering, VirginiaPolytechnicInstituteandStateUniversity,Blacksburg,Virginia,UnitedStatesofAmerica,3DepartmentofComputerScience,LaboratoryforHighPerformance ComputingandComputerSimulation,UniversityofKentucky,Lexington,Kentucky,UnitedStatesofAmerica Abstract Circulationisanimportantdeliverymethodforbothnaturalandsyntheticmolecules,butmicroenvironmentinteractions, regulatedbyendothelialcellsandcriticaltothemolecule’sfate,aredifficulttointerpretusingtraditionalapproaches.Inthis work, we analyzed and predicted growth factor capture under flow using computer modeling and a three-dimensional experimental approach that includes pertinent circulation characteristics such as pulsatile flow, competing binding interactions, and limited bioavailability. An understanding of the controlling features of this process was desired. The experimental module consisted of a bioreactor with synthetic endothelial-lined hollow fibers under flow. The physical designofthesystemwasincorporatedintothemodelparameters.Theheparin-bindinggrowthfactorfibroblastgrowth factor-2 (FGF-2) was used for both the experiments and simulations. Our computational model was composed of three parts:(1)mediaflowequations,(2)masstransportequationsand(3)cellsurfacereactionequations.Themodelisbasedon theflowandreactionswithinasinglehollowfiberandwasscaledlinearlybythetotalnumberoffibersforcomparisonwith experimental results. Our model predicted, and experiments confirmed, that removal of heparan sulfate (HS) from the systemwouldresultinadramaticlossofbindingbyheparin-bindingproteins,butnotbyproteinsthatdonotbindheparin. Themodelfurtherpredictedasignificantlossofboundproteinatflowratesonlyslightlyhigherthanaveragecapillaryflow r