Engineered Developmental Microenvironments: Cartilage Formation and Maturation
Engineered Developmental Microenvironments: Cartilage Formation and Maturation
批准号:
10611977
负责人:
Jason A Burdick
金额:
$49.86万
依托单位国家:
美国
项目类别:
财政年份:
2009
资助国家:
美国
项目状态:
未结题
起止时间:
2009-05-01 至 2025-04-30
关键词:
3-DimensionalActivities of Daily LivingAcuteAddressAdhesionsAnimal ModelAnimalsAutologousBiochemicalBiomedical EngineeringBiophysicsBone MarrowCartilageCartilage MatrixCartilage injuryCell CommunicationCell DensityCell Differentiation processCellsChondrocytesChondrogenesisChronicClinicalCoculture TechniquesCollaborationsCommunicationCuesCustomDefectDevelopmentDiseaseDoseEncapsulatedEngineeringEnvironmentExtracellular MatrixFamily suidaeFormulationFosteringFundingGoalsGrowth FactorHarvestHistologyHyaluronic AcidHydrogelsHypertrophyImageImaging TechniquesIn VitroInflammation MediatorsInjectableInjectionsJointsLigandsManuscriptsMechanicsMediatingMentorsMesenchymal DifferentiationModelingMolecularMonitorN-CadherinOperative Surgical ProceduresOrthopedic SurgeryOsteogenesisOutcomePain FreeParacrine CommunicationPatientsPeptidesPhenotypeProductionProgress ReportsPropertyProteomicsResearchResourcesSignal TransductionSports MedicineSurfaceSurgeonSystemTechniquesTimeTissuesTraumatic injuryVesicleVisualizationWeight-Bearing stateWorkarticular cartilagecartilage developmentcartilage regenerationcartilage repairclinical translationclinically relevantcombinatorialcrosslinkdesignefficacy evaluationextracellular vesicleshealingimaging biomarkerimprovedin vivoinnovationintercellular communicationinterdisciplinary approachmechanical loadmesenchymal stromal cellminimally invasivenovelnovel therapeutic interventionnovel therapeuticsparacrinepre-clinicalregenerativerepairedscale upscreeningtissue regenerationtraffickingtransmission process
中文摘要
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英文摘要
Abstract
Articular cartilage lines the surfaces of joints and transmits the forces generated with loading; however, cartilage
can be damaged due to traumatic injury and disease and has a limited natural healing capacity. Although there
have been many advances in the development of cartilage therapies with autologous mesenchymal stromal cells
(MSCs), there is still much work to be done in order to identify the appropriate cell carriers and culture
environments that best promote the formation of functional cartilage. Our general approach for MSC-based
cartilage repair has been to engineer environments that recapitulate key developmental signals. Towards this,
in early funding cycles, we engineered hydrogel environments based on the biomolecule hyaluronic acid (HA),
including controlled degradation, growth factor presentation, and mechanical loading. During the most recent
funding cycle, we tethered and controlled the temporal presentation of a bioactive peptide (HAV) found in N-
cadherin, which is abundant in the developing microenvironment and mediates direct cell-cell communication. In
this renewal, we continue to address developmentally relevant cell-cell signaling, focusing now on indirect
communication mechanisms. Specifically, we recently found that a small fraction of differentiated chondrocytes
improves the amount and quality of matrix formation by MSCs and promotes their phenotypic stability. We further
showed that this phenomenon was the consequence of paracrine vesicle-mediated cell-to-cell signaling from
‘broadcasting’ chondrocytes to ‘receiver’ MSCs. Here, we hypothesize that both the production and reception of
these signals is regulated by the microenvironment (matrix stiffness, interaction with developmental ligands, and
molecular diffusivity of the embedding material). To address this novel hypothesis, the first Aim will utilize our
recently developed microenvironmental screening platform to determine the hydrogel formulation that optimally
supports MSC chondrogenesis in co-cultures of MSCs and chondrocytes. This will be achieved by spatially
varying peptide and encapsulating material properties and imaging early markers of chondrogenesis and
cartilage matrix formation to identify optimal environments. In the second Aim, hydrogel formulations that
optimize MSC chondrogenesis in co-cultures will be scaled up and evaluated over longer time courses and when
implemented in an injectable format that is compatible with current clinical workflows. In the third Aim, these
optimized formulations will be arthroscopically administered in clinically-relevant load-bearing porcine focal
cartilage defects to assess the efficacy of this cell delivery system to promote functional repair. Successful
completion of these Aims will identify new translational options for patients suffering from cartilage injuries.
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DOI:
10.1038/s41467-018-03021-5
发表时间:
2018-02-09
期刊:
Nature communications
影响因子:
16.6
作者:
[Vega SL, Kwon MY, Song KH, Wang C, Mauck RL, Han L, Burdick JA]
通讯作者:
Burdick JA
DOI:
10.3791/1590
发表时间:
2009-10-26
期刊:
Journal of visualized experiments : JoVE
影响因子:
--
作者:
[Khetan, Sudhir, Burdick, Jason]
通讯作者:
Burdick, Jason
DOI:
10.1007/s10439-016-1622-6
发表时间:
2016-06
期刊:
Annals of biomedical engineering
影响因子:
3.8
作者:
[Vega SL, Kwon M, Mauck RL, Burdick JA]
通讯作者:
Burdick JA
DOI:
10.1038/srep38852
发表时间:
2016-12-12
期刊:
Scientific reports
影响因子:
4.6
作者:
[McLeod CM, Mauck RL]
通讯作者:
Mauck RL
DOI:
10.22203/ecm.v019a08
发表时间:
2010-02-26
期刊:
European cells & materials
影响因子:
3.1
作者:
[Huang AH, Farrell MJ, Kim M, Mauck RL]
通讯作者:
Mauck RL
共 35 条
Engineered Granular Hydrogels for Endogenous Tissue Repair
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批准号:10629201
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Image Guided Delivery of Bioresponsive Hydrogels
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Localized Targeting of Matrix Proteases Following Myocardial Infarction
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资助金额:$4.03万
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Localized Targeting of Matrix Proteases Following Myocardial Infarction
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资助金额:$45.59万
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Localized Targeting of Matrix Proteases Following Myocardial Infarction
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POLYMER/NANOROD COMPOSITES FOR CONTROLLED DRUG DELIVERY
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Dynamic Fibrous Scaffolds for Repairing Dense Connective Tissues
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资助金额:$52.7万
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Dynamic Fibrous Scaffolds for Engineering Dense Connective Tissues
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批准号:7626527
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资助金额:$34.14万
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负责人:Jason A Burdick
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Engineering Developmental Microenvironments: Cartilage Formation and Maturation
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批准号:7653444
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资助金额:$34.4万
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Dynamic Fibrous Scaffolds for Engineering Dense Connective Tissues
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Dynamic Fibrous Scaffolds for Engineering Dense Connective Tissues
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依托单位:
海外基金