"Clinical Trials" on a Premature Vascular Aging-on-a-Chip Model
血管过早老化芯片模型的“临床试验”
基本信息
- 批准号:10225588
- 负责人:
- 金额:$ 54.11万
- 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:2020-08-01 至 2022-07-31
- 项目状态:已结题
- 来源:
- 关键词:AdsorptionAgingAortaAortic Valve StenosisArteriesAtherosclerosisAutopsyBehaviorBiochemicalBiologicalBiological MarkersBiomimeticsBiophysicsBiosensorBlood VesselsCAV1 geneCardiovascular systemCarotid ArteriesCellsClinical ResearchClinical TrialsClinical Trials DesignCollagenCombined Modality TherapyCongestive Heart FailureCultured CellsDevicesDoseElastinEncapsulatedEndothelial CellsExtracellular MatrixFibroblastsGenetic DiseasesGenetic TranscriptionGoalsHumanHuman bodyHydrogelsHypertensionIL6 geneLeadLiquid substanceLonafarnibMaintenanceMeasurementMechanical StressMechanicsMedialMembraneMethodologyMicrofluidic MicrochipsMicrofluidicsModelingMonitorMorphologyMyocardial InfarctionOpticsOutcomePathologicPatientsPeriodicityPeripheralPharmaceutical PreparationsPhasePhenotypePhysiologicalPolyurethanesProgeriaPublishingRare DiseasesReportingResistanceSchemeSeedsSmooth Muscle MyocytesStretchingStructureSymptomsSyndromeSystemTechnologyThickThinnessTissue BanksTissuesTranslationsTunica AdventitiaUltrasonographyVascular Smooth Muscleabsorptionbasecalcificationcell bankclinically relevantcohortdosagedrug candidateexperienceimprovedin vitro Modelin vivoinduced pluripotent stem cellinflammatory markerjun Oncogenemonolayermortalitynon-invasive imagingpolydimethylsiloxaneprematurepreventresponseresponse to injuryscreeningshear stress
项目摘要
Abstract
Hutchinson-Gilford progeria syndrome (HGPS) is a genetic disorder that results in premature and accelerated
aging, while accumulation of progerin also occurs during physiological aging. Notably, one of the major targets
of HGPS is the cardiovascular system, which are mechanically active tissues. Typical symptoms include
hypertension, myocardial infarction, congestive heart failure, calcific aortic stenosis, and peripheral
atherosclerosis. For example, autopsy findings have illustrated profound loss of vascular smooth muscle cells
(SMCs) in the medial layer of large arteries, such as the aorta and carotid arteries, with replacement by
collagen and extracellular matrix. Vascular wall echodensity is also increased in HGPS patients associated
with exaggerated fibrotic adventitia formation. The overarching goal of this proposal is to optimize a biomimetic
HGPS-on-a-chip system generated with patient-derived fibroblasts (FBs), SMCs, and endothelial cells (ECs)
that allow application of relevant cyclic stretch for performing ‘clinical trials’ or informing clinical trial designs for
HGPS patients. In particular, we will generate a whole-thermoplastic microfluidic system with a dual-layer
blood vessel-mimicking structure. Based on our preliminary device previously already reported, the proposed
system will be whole-thermoplastic consisting of two channels separated by a thin thermoplastic polyurethane
(TPU) membrane. On top, layers will include a collagen hydrogel encapsulating FBs (adventitia) and an elastin
hydrogel embedded with SMCs (media), post-seeded again with a monolayer of ECs. This methodology
recreates the in vivo microenvironment of blood vessels to faithfully model pathological changes in HGPS.
抽象的
哈钦森-吉尔福德早衰综合症 (HGPS) 是一种遗传性疾病,会导致早衰和加速
值得注意的是,早老素的积累也发生在生理衰老过程中。
HGPS 的核心是心血管系统,它是机械活动组织,典型症状包括。
高血压、心肌梗死、充血性心力衰竭、钙化性主动脉瓣狭窄、外周血管疾病
例如,尸检结果表明血管平滑肌细胞严重丧失。
(SMC)位于大动脉的内侧层,例如主动脉和颈动脉,替换为
HGPS 患者的胶原蛋白和细胞外基质也增加。
该提案的首要目标是优化仿生结构。
由患者来源的成纤维细胞 (FB)、SMC 和内皮细胞 (EC) 生成的 HGPS 芯片系统
允许应用相关的循环拉伸来执行“临床试验”或为临床试验设计提供信息
特别是,我们将生成具有双层的全热塑性微流体系统。
根据我们之前报道的初步装置,提出了模拟血管的结构。
系统将是全热塑性的,由两个由薄热塑性聚氨酯隔开的通道组成
(TPU) 膜的顶部包括封装 FB(外膜)的胶原蛋白水凝胶和弹性蛋白。
嵌入 SMC(介质)的水凝胶,再次接种单层 EC。
重建体内血管微环境,忠实地模拟 HGPS 的病理变化。
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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Yu Shrike Zhang其他文献
Plasmonic Nanoprobe of (Gold Triangular Nanoprism Core)/ (Polyaniline Shell) for Real-Time Three-Dimensional pH Imaging of Anterior Chamber
用于前房实时三维 pH 成像的(金三角纳米棱柱核)/(聚苯胺壳)等离子体纳米探针
- DOI:
10.1021/acs.analchem.7b01623 - 发表时间:
2017 - 期刊:
- 影响因子:7.4
- 作者:
Peijun Tang;Xueqin Jiang;Yangyang Wang;Huanjun Chen;Yu Shrike Zhang;Panpan Gao;Hao Wang;Xuemeng Li;Jianhua Zhou - 通讯作者:
Jianhua Zhou
Preparation of Ag@CNT Nanohybrids and Investigations on Their Antibacterial and Cytotoxicological Effects
Ag@CNT纳米杂化物的制备及其抗菌和细胞毒作用研究
- DOI:
10.1166/nnl.2018.2844 - 发表时间:
2018-12 - 期刊:
- 影响因子:0
- 作者:
Meng Yin;Di Huang;Xiumei Zhang;Yuan Peng;Jingjing Du;YanWei;Xiaojie Lian;Yinchun Hu;Weiyi Chen;Yu Shrike Zhang - 通讯作者:
Yu Shrike Zhang
Special Magnetic Catalyst with Lignin-Reduced Au–Pd Nanoalloy
木质素还原金钯纳米合金特种磁性催化剂
- DOI:
10.1021/acsomega.7b00830 - 发表时间:
2017-08 - 期刊:
- 影响因子:4.1
- 作者:
Guocheng Han;Xiaoyun Li;Jiaming Li;Xiaoying Wang;Yu Shrike Zhang;Runcang Sun - 通讯作者:
Runcang Sun
Injectable Decellularized Dental Pulp Matrix-Functionalized Hydrogel Microspheres for Endodontic Regeneration
用于牙髓再生的可注射脱细胞牙髓基质功能化水凝胶微球
- DOI:
10.1016/j.actbio.2022.11.047 - 发表时间:
2022 - 期刊:
- 影响因子:9.7
- 作者:
Liwen Zheng;Yaxian Liu;Lin Jiang;Xiaoping Wang;Yuqin Chen;Lan Li;Mingyu Song;Hongmei Zhang;Yu Shrike Zhang;Ximu Zhang - 通讯作者:
Ximu Zhang
Gold Nanoprobe-Enabled Three-Dimensional Ozone Imaging by Optical Coherence Tomography
金纳米探针通过光学相干断层扫描进行三维臭氧成像
- DOI:
10.1021/acs.analchem.6b04785 - 发表时间:
2017 - 期刊:
- 影响因子:7.4
- 作者:
Xueqin Jiang;Peijun Tang;Panpan Gao;Yu Shrike Zhang;Changqing Yi;Jianhua Zhou - 通讯作者:
Jianhua Zhou
Yu Shrike Zhang的其他文献
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{{ truncateString('Yu Shrike Zhang', 18)}}的其他基金
Cryobioprinting for Shelf-Ready Tissue Fabrication and Storage
用于货架组织制造和储存的冷冻生物打印
- 批准号:
10927669 - 财政年份:2023
- 资助金额:
$ 54.11万 - 项目类别:
"Clinical Trials" on a Premature Vascular Aging-on-a-Chip Model
血管过早老化芯片模型的“临床试验”
- 批准号:
10691727 - 财政年份:2022
- 资助金额:
$ 54.11万 - 项目类别:
"Clinical Trials" on a Premature Vascular Aging-on-a-Chip Model
血管过早老化芯片模型的“临床试验”
- 批准号:
10432667 - 财政年份:2021
- 资助金额:
$ 54.11万 - 项目类别:
"Clinical Trials" on a Premature Vascular Aging-on-a-Chip Model
血管过早老化芯片模型的“临床试验”
- 批准号:
10515795 - 财政年份:2020
- 资助金额:
$ 54.11万 - 项目类别:
"Clinical Trials" on a Premature Vascular Aging-on-a-Chip Model
血管过早老化芯片模型的“临床试验”
- 批准号:
10038138 - 财政年份:2020
- 资助金额:
$ 54.11万 - 项目类别:
"Clinical Trials" on a Premature Vascular Aging-on-a-Chip Model
血管过早老化芯片模型的“临床试验”
- 批准号:
10687068 - 财政年份:2020
- 资助金额:
$ 54.11万 - 项目类别:
Recapitulating Ductal Carcinoma on a Chip for Personalized Breast Cancer Therapy
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- 批准号:
9109971 - 财政年份:2016
- 资助金额:
$ 54.11万 - 项目类别:
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