A microphysiological system of tendon inflammation and fibrosis for drug screening and efficacy testing: MPS Database Engagement
用于药物筛选和功效测试的肌腱炎症和纤维化的微生理系统:MPS 数据库参与
基本信息
- 批准号:10430792
- 负责人:
- 金额:$ 7.54万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2020
- 资助国家:美国
- 起止时间:2020-08-15 至 2022-07-31
- 项目状态:已结题
- 来源:
- 关键词:AddressAnimal ModelAwardBiological ModelsBlood VesselsBlood coagulationCell Culture TechniquesCellsCharacteristicsCicatrixClinicalClinical TrialsCollagenCommunitiesCompanionsConnective TissueConsensusDatabase Management SystemsDatabasesDevelopmentDevicesDiseaseDrug ScreeningEnzyme-Linked Immunosorbent AssayEvaluationFDA approvedFRAP1 geneFeedbackFibrosisFundingGelGene ExpressionGenerationsGeneticHumanImmuneIn SituInfiltrationInflammationInflammatoryInterventionMeasurableMeasurementModelingMorphologyMusMyofibroblastOperative Surgical ProceduresParentsPathologyPatientsPhenotypePlayProceduresProcessProtocols documentationReproducibilityResearch DesignRoleSafetySystemTendon InjuriesTendon structureTimeTissuesUniversitiesVascular Endothelial Cellbasecytokinedesigndrug efficacyefficacy evaluationefficacy testingfollow-uphealinghuman diseasehuman modelinduced pluripotent stem cellinjury and repairmTOR Inhibitormicrophysiology systemmonocyteneovascularizationnovelphotonicspre-clinicalpre-clinical researchrepairedresponsesenescencesensorsimulationsuccesstemporal measurementtissue injurytoolvirtual clinical trial
项目摘要
Abstract
The continued advancement of microphysiological systems (MPS) as pre-clinical research tools is vital to
overcome the low throughput and inaccuracies inherent in animal models of human disease. The limitations of
pre-clinical animal models, most commonly mice, are particularly apparent in inflammatory diseases which are
known to have distinct genetic and cytokine responses to inflammation. The establishment of MPS alternatives,
however, will require scientific consensus on the protocols and systems best suited to address particular
diseases. As the current MPS era is characterized by a proliferation of approaches, the Microphysiological
System Data Base (MPS-db) created by the University of Pittsburgh is a valuable tool to hasten the
development of MPS standards. Because the success of the MPS-db requires the active participation by MPS
developers and users, we seek supplemental funding to contribute the designs, protocols and results for an
MPS system that models the interplay between inflammation and fibrosis in tendon healing (UG3TR00287).
Importantly, the injury and repair of connective tissue injury is not represented in the current MPS-db but
accounts for more than 8.5 million clinical procedures annually, including 2 million major surgeries. Our human
tendon-on-a-chip (hToC) model focuses on the early inflammatory stages of tendon repair, where timely
interventions may promote scarless healing. The hToC features vascular and collagen compartments which
exchange soluble and cellular factors in a simulation of the neovascularized microenvironment established
shortly after blood clotting. Monocyte infiltration is hypothesized to play an essential role in the generation of
contractile myofibroblasts which progress to senescence and release monocyte activating factors in a positive
feedback loop that causes scar tissue. The model uses iPSCs derived from primary human tenocytes to create
vascular endothelial cells and monocytes in an isogenic, patient-centric triculture. With supplemental funding we
will share: 1) descriptions of the mechanisms of the tendon injury and fibroinflammatory repair process; 2)
design details for the hToC including device components and modules for both flow and integrated photonic-
based sensing; 3) cell culture and device protocols including phenotypic characteristics and operational
parameters such as flow rates for priming of ECs and the introduction of immune cells; 4) The design and
rationale for studies under baseline and inflammation/repair conditions; and 5) Results including an analysis of
intra-study reproducibility.
摘要
项目成果
期刊论文数量(11)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Preclinical tendon and ligament models: Beyond the 3Rs (replacement, reduction, and refinement) to 5W1H (why, who, what, where, when, how).
临床前肌腱和韧带模型:超越 3R(替换、减少和细化)到 5W1H(为什么、谁、什么、何地、何时、如何)。
- DOI:10.1002/jor.25678
- 发表时间:2023
- 期刊:
- 影响因子:0
- 作者:Little,Dianne;Amadio,PeterC;Awad,HaniA;Cone,StephanieG;Dyment,NathanielA;Fisher,MatthewB;Huang,AliceH;Koch,DrewW;Kuntz,AndrewF;Madi,Rashad;McGilvray,Kirk;Schnabel,LaurenV;Shetye,SnehalS;Thomopoulos,Stavros;Zhao,Chunf
- 通讯作者:Zhao,Chunf
The Modular µSiM: A Mass Produced, Rapidly Assembled, and Reconfigurable Platform for the Study of Barrier Tissue Models In Vitro.
- DOI:10.1002/adhm.202200804
- 发表时间:2022-09
- 期刊:
- 影响因子:10
- 作者:McCloskey, Molly C.;Kasap, Pelin;Ahmad, S. Danial;Su, Shiuan-Haur;Chen, Kaihua;Mansouri, Mehran;Ramesh, Natalie;Nishihara, Hideaki;Belyaev, Yury;Abhyankar, Vinay V.;Begolo, Stefano;Singer, Benjamin H.;Webb, Kevin F.;Kurabayashi, Katsuo;Flax, Jonathan;Waugh, Richard E.;Engelhardt, Britta;McGrath, James L.
- 通讯作者:McGrath, James L.
A computer vision approach for analyzing label free leukocyte trafficking dynamics on a microvascular mimetic.
- DOI:10.3389/fimmu.2023.1140395
- 发表时间:2023
- 期刊:
- 影响因子:7.3
- 作者:Ahmad SD;Cetin M;Waugh RE;McGrath JL
- 通讯作者:McGrath JL
NF-κB activation persists into the remodeling phase of tendon healing and promotes myofibroblast survival.
- DOI:10.1126/scisignal.abb7209
- 发表时间:2020-11-17
- 期刊:
- 影响因子:7.3
- 作者:Best KT;Nichols AEC;Knapp E;Hammert WC;Ketonis C;Jonason JH;Awad HA;Loiselle AE
- 通讯作者:Loiselle AE
In vitro Studies of Transendothelial Migration for Biological and Drug Discovery.
- DOI:10.3389/fmedt.2020.600616
- 发表时间:2020
- 期刊:
- 影响因子:0
- 作者:Salminen AT;Allahyari Z;Gholizadeh S;McCloskey MC;Ajalik R;Cottle RN;Gaborski TR;McGrath JL
- 通讯作者:McGrath JL
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Hani A Awad其他文献
Hani A Awad的其他文献
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{{ truncateString('Hani A Awad', 18)}}的其他基金
Training in Musculoskeletal Science: Comprehensive Training in Pain Studies
肌肉骨骼科学培训:疼痛研究综合培训
- 批准号:
10853550 - 财政年份:2023
- 资助金额:
$ 7.54万 - 项目类别:
Biomechanics, Biomaterials and Multimodal Tissue Imaging Core (BBMTI Core)
生物力学、生物材料和多模态组织成像核心(BBMTI 核心)
- 批准号:
10232836 - 财政年份:2022
- 资助金额:
$ 7.54万 - 项目类别:
A microphysiological system of tendon inflammation and fibrosis for drug screening and efficacy testing
用于药物筛选和疗效测试的肌腱炎症和纤维化的微生理系统
- 批准号:
10515790 - 财政年份:2020
- 资助金额:
$ 7.54万 - 项目类别:
A microphysiological system of tendon inflammation and fibrosis for drug screening and efficacy testing
用于药物筛选和疗效测试的肌腱炎症和纤维化的微生理系统
- 批准号:
10239102 - 财政年份:2020
- 资助金额:
$ 7.54万 - 项目类别:
A microphysiological system of tendon inflammation and fibrosis for drug screening and efficacy testing
用于药物筛选和疗效测试的肌腱炎症和纤维化的微生理系统
- 批准号:
10674534 - 财政年份:2020
- 资助金额:
$ 7.54万 - 项目类别:
A microphysiological system of tendon inflammation and fibrosis for drug screening and efficacy testing
用于药物筛选和疗效测试的肌腱炎症和纤维化的微生理系统
- 批准号:
10037991 - 财政年份:2020
- 资助金额:
$ 7.54万 - 项目类别:
Project 1: Elucidating the Mechanisms of S. aureus Motility in Bone and Developing Interventions
项目 1:阐明金黄色葡萄球菌在骨中的运动机制并制定干预措施
- 批准号:
10247795 - 财政年份:2017
- 资助金额:
$ 7.54万 - 项目类别:
Elucidating the Mechanisms of S. aureus Motility in Bone and Developing Interventions
阐明金黄色葡萄球菌在骨中的运动机制并制定干预措施
- 批准号:
10402966 - 财政年份:2017
- 资助金额:
$ 7.54万 - 项目类别:
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