A Hydrogel-Based Cellular Model of the Human Vocal Fold
基于水凝胶的人类声带细胞模型
基本信息
- 批准号:10604269
- 负责人:
- 金额:$ 49.67万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2015
- 资助国家:美国
- 起止时间:2015-12-01 至 2026-03-31
- 项目状态:未结题
- 来源:
- 关键词:AcousticsAdoptedAffectAgingAirAir MovementsAmericanAnimal ModelApoptosisArchitectureBasement membraneBiochemicalBiologyBiomechanicsBiophysicsCalibrationCell modelCellsCellular MorphologyChemical ExposureChemicalsCicatrixClinicalCommunitiesConnective TissueConsensusCuesCustomDataDecision MakingDepositionDevelopmentDiseaseElasticityEngineeringEpithelial CellsEpitheliumExtracellular MatrixFGF2 geneFUS-1 ProteinFibroblastsFibrosisFunctional disorderFutureGene ExpressionGrowth FactorHealthHumanHydrogelsIn SituIn VitroInterventionLamina PropriaLarynxLigationLungMechanical StressMechanicsMesenchymalMesenchymal Stem CellsMethodologyMethodsMicrofluidic MicrochipsMicrofluidicsModelingMolecularMonitorMotionMultipotent Stem CellsMuscleMyofibroblastOperative Surgical ProceduresOrganParentsPathologicPermeabilityPharmaceutical PreparationsPharmacotherapyPhenotypePhonationPhysiologicalPhysiologyPliabilityPredispositionProcessProliferatingPropertyProtein KinaseResearchSideSignal TransductionStratified EpitheliumStratified Squamous EpitheliumStreamStructureTGFB1 geneTestingTherapeuticTissue EngineeringTissue MicroarrayTissue ModelTissuesTracheaTreatment EfficacyVoicecytokinedesignefficacious treatmentepithelial injuryfasudilfibrogenesisfundamental researchgraphenehealinghuman tissueimprovedinduced pluripotent stem cellinhibitorinterfacialinterstitialmechanical propertiesmimeticsminiaturizepharmacologicpreventreal time monitoringrepairedrhosensorsoundspatiotemporaltissue injuryvocal cordvocalis musclewound healing
项目摘要
Project Summary
Voice is produced when the vocal folds are driven into a wave-like motion by the airstream from the trachea,
converting aerodynamic energy and airflow into acoustic energy in the form of sound. Each vocal fold consists
of a pliable vibratory layer of connective tissue, known as the lamina propria (LP), sandwiched between a muscle
and a stratified squamous epithelium (EP). Numerous environmental, mechanical and pathological factors can
damage this delicate tissue, resulting in vocal fold scarring that affects millions of Americans with limited
treatment options. Although there is a general consensus on the pathophysiology of vocal fold scarring, the
molecular and cellular mechanisms that control unremitting fibrosis remain poorly understood. Studies on other
fibrotic diseases suggest that fibroblasts, epithelial cells and the interstitial matrix are active players in
fibrogenesis. This project aims to engineer a reliable, physiologically relevant in vitro tissue model that can be
used to investigate vocal fold development, health, and disease, and more importantly, to facilitate the
development and testing of new treatment options. We propose to develop a microengineered organ chip that
integrates the epithelial and mesenchymal cells in a tissue-mimetic configuration with built-in airflow to stimulate
phonation. Using the microfluidic model, we will investigate how damage to the epithelium initiates fibrosis, how
the fibrotic extracellular matrix (ECM) sustains fibrosis and how myofibroblast proliferation and matrix deposition
continue unabated. Finally, we will calibrate our model with an antifibrotic growth factor that has shown efficacy
in treating vocal fold scarring, and test a promising pharmacological inhibitor that has not been previously tested
in the context of vocal fold scarring. Highly efficient bioorthogonal tetrazine ligation will be used to establish the
initial LP matrix surrounding healthy fibroblasts and to introduce compositional and mechanical alterations that
promote fibroblast activation. Pluripotent and multipotent stem cells will be guided to differentiate into vocal fold-
like epithelial cells and fibroblasts by adopting a development paradigm and through systematic manipulation of
the engineered microenvironment. Piezoresistive strain sensors embedded in the sidewalls of the microfluidic
channels will be used to monitor tissue stiffness and EP permeability in situ. The microengineered tissue model
will be characterized in terms of cell phenotype, microstructure, mechanical properties and physiological function.
For comparison purposes, a stand-alone, human-sized vocal fold model will be developed and characterized
employing methodologies established in the laryngology field. Data generated from this project should
significantly impact fundamental research related to vocal fold scarring and provide critical information on
therapeutic decision-making in the near future.
项目总结
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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{{ truncateString('Xinqiao Jia', 18)}}的其他基金
Bottom-Up Assembly of Functional Salivary Gland Tissues
功能性唾液腺组织的自下而上组装
- 批准号:
10400243 - 财政年份:2021
- 资助金额:
$ 49.67万 - 项目类别:
Bottom-Up Assembly of Functional Salivary Gland Tissues
功能性唾液腺组织的自下而上组装
- 批准号:
10546502 - 财政年份:2021
- 资助金额:
$ 49.67万 - 项目类别:
A Hydrogel-Based Cellular Model of the Human Vocal Fold
基于水凝胶的人类声带细胞模型
- 批准号:
9028226 - 财政年份:2015
- 资助金额:
$ 49.67万 - 项目类别:
A Hydrogel-Based Cellular Model of the Human Vocal Fold
基于水凝胶的人类声带细胞模型
- 批准号:
10209183 - 财政年份:2015
- 资助金额:
$ 49.67万 - 项目类别:
A Hydrogel-Based Cellular Model of the Human Vocal Fold
基于水凝胶的人类声带细胞模型
- 批准号:
10394924 - 财政年份:2015
- 资助金额:
$ 49.67万 - 项目类别:
A Hydrogel-Based Cellular Model of the Human Vocal Fold
基于水凝胶的人类声带细胞模型
- 批准号:
9193072 - 财政年份:2015
- 资助金额:
$ 49.67万 - 项目类别:
ELASTOMERIC POLYMERS & TUNABLE BIOLOGICAL FUNCTIONS FOR VOCAL FOLD TISSUE ENG
弹性聚合物
- 批准号:
8360585 - 财政年份:2011
- 资助金额:
$ 49.67万 - 项目类别:
ELASTOMERIC POLYMERS & TUNABLE BIOLOGICAL FUNCTIONS FOR VOCAL FOLD TISSUE ENG
弹性聚合物
- 批准号:
8168491 - 财政年份:2010
- 资助金额:
$ 49.67万 - 项目类别:
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