Calcium-Based Nanoparticles Accelerate Skin Wound Healing 英文参考文献.docVIP

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Calcium-Based Nanoparticles Accelerate Skin Wound Healing 英文参考文献.doc

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Calcium-Based Nanoparticles Accelerate Skin Wound Healing 英文参考文献

Calcium-BasedNanoparticlesAccelerateSkinWound Healing KenichiroKawai1,2.,BarrettJ.Larson1.,HisakoIshise2,AntoineLyonelCarre1,SohNishimoto2 ,Michael Longaker1,H.PeterLorenz1* 1HageyLaboratoryforPediatricRegenerativeMedicine,StanfordUniversitySchoolofMedicine,Stanford,California,UnitedStatesofAmerica,2DepartmentofPlastic andReconstructiveSurgery,HyogoCollegeofMedicine,Hyogo,Japan Abstract Introduction:Nanoparticles(NPs)aresmallentitiesthatconsistofahydroxyapatitecore,whichcanbindions,proteins,and other organic molecules from the surrounding environment. These small conglomerations can influence environmental calciumlevelsandhavethepotentialtomodulatecalciumhomeostasisinvivo.Nanoparticleshavebeenassociatedwith various calcium-mediated disease processes, such as atherosclerosis and kidney stone formation. We hypothesized that nanoparticlescouldhaveaneffectonothercalcium-regulatedprocesses,suchaswoundhealing.Inthepresentstudy,we synthesizedpH-sensitivecalcium-basednanoparticlesandinvestigatedtheirabilitytoenhancecutaneouswoundrepair. Methods: Different populations of nanoparticles were synthesized on collagen-coated plates under various growth conditions.Bilateraldorsalcutaneouswoundsweremadeon8-week-oldfemaleBalb/cmice.Nanoparticlesweretheneither administeredintravenouslyorappliedtopicallytothewoundbed.Therateofwoundclosurewasquantified.Intravenously injectednanoparticlesweretrackedusingaFLAGdetectionsystem.Theeffectofnanoparticlesonfibroblastcontraction andproliferationwasassessed. Results:ApopulationofpH-sensitivecalcium-basednanoparticleswasidentified.Whenintravenouslyadministered,these nanoparticlesacutelyincreasedtherateofwoundhealing.Intravenouslyadministerednanoparticleswerelocalizedtothe wound site, as evidenced by FLAG staining. Nanoparticles increased fibroblast calcium uptake in vitro and caused contractureofafibroblastpopulatedcollagenlatticeinadose-dependentmanner.Nanoparticlesalsoincreasedtherateof fibroblastproliferation. Conclusion: Intravenously admin