Injectable myocardial matrix-grapheme composite hydrogels for functional cardiac tissue engineering
Injectable myocardial matrix-grapheme composite hydrogels for functional cardiac tissue engineering
批准号:
9034827
负责人:
Deok-Ho Kim
金额:
$22.75万
依托单位:
依托单位国家:
美国
项目类别:
财政年份:
2016
资助国家:
美国
项目状态:
已结题
起止时间:
2016-09-30 至 2018-07-31
关键词:
ATP2A2Action PotentialsAreaAttentionBiochemicalBiocompatibleBiocompatible MaterialsCalciumCardiacCardiac MyocytesCause of DeathCell DeathCell TherapyCellsCessation of lifeCharacteristicsChemicalsChronicCollagenCommunicationConnexin 43CountryCuesCultured CellsDevelopmentEffectivenessElectric ConductivityElectrophysiology (science)EngineeringExtracellular MatrixFibronectinsGap JunctionsGenetic EngineeringGoalsHeartHeart DiseasesHumanHydrogelsIn VitroInfarctionInjectableInjection of therapeutic agentKnowledgeLeadLifeMapsMeasurementMechanicsMediatingMethodsMorbidity - disease rateMusMyocardialMyocardial InfarctionMyocardial dysfunctionMyocardiumNatural regenerationNatureOpticsOxidesPhenotypePhysiologicalPopulationPropertyProteinsProteoglycanPuromycinResearchScanning Electron MicroscopyScienceSignal TransductionStaining methodStainsStem cellsStructureSurfaceSystemTestingTherapeuticThickTimeTissue EngineeringTissuesUnited StatesWestern Blottingbasebiomaterial compatibilitycardiac repaircombatelectric impedanceimmunogenicimprovedin vivoinduced pluripotent stem cellinnovationinsightnanomaterialsnovelpublic health relevancerepairedresponsescaffoldtreatment strategy
中文摘要
英文摘要
DESCRIPTION: Heart disease is the leading cause of death and morbidity in many countries in the developed world, including the United States. Due to the terminally differentiated and non-proliferative nature of cardiomyocytes, the heart is unable to regenerate and repair itself after infarction, and the resulting chronic cardiac dysfunction often leads to death within 5 years. Stem cell-based therapies involving the direct injection of cells into infarcted tissue have garnered much attention recently. However, while these therapies hold tremendous potential, the overwhelming cell death and limited ability of graft cells to integrate with the surrounding host tissue limit their effectiveness at restoring cardiac function. The goal of the proposed research is to develop injectable, three- dimensional myocardial matrix-graphene composite scaffolds that mimic the electrical, mechanical and biochemical environmental cues seen in healthy myocardium, and then to test their ability to generate functional tissues. The central hypothesis is that the high conductivity of graphene will enhance action potential propagation through direct and indirect (e.g. increased gap junction formation) mechanisms, thereby improving the functionality of the incorporated human induced pluripotent stem cell-derived cardiomyocytes. By combining the unique characteristics of graphene and native myocardial matrices synergistically, we aim to create a new class of three-dimensional scaffolds for the engineering of cardiac tissues for therapeutic purposes. Towards this end, we will first develop biocompatible and injectable myocardial matrix-graphene 3D composite scaffolds with tunable electrical and mechanical properties. Then we will evaluate the capability of conductive 3D composite scaffolds in enhancing cardiomyocyte electrophysiological function in vitro.
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