Improving fibrin-based bioartificial arteries by prolonging ERK activation
通过延长 ERK 激活来改善基于纤维蛋白的生物人工动脉
基本信息
- 批准号:8058406
- 负责人:
- 金额:$ 5.58万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2010
- 资助国家:美国
- 起止时间:2010-12-10 至 2012-12-09
- 项目状态:已结题
- 来源:
- 关键词:AmericanAmerican Heart AssociationArteriesAutologousBalloon AngioplastyBehaviorBiochemicalBiologicalBiological AssayBiomechanicsBioreactorsBlood PressureBypassCellsCellularityChemicalsCollagenCollagen Type ICoronary ArteriosclerosisCoronary heart diseaseDermalDevelopmentDiseaseEngraftmentEventFeedbackFellowshipFibrinFibroblastsGelGenetic TranscriptionGoalsHarvestHealthcareImmuneIn VitroIncubatedInfectionLeadLuciferasesMAPK14 geneMechanical StimulationMechanicsMinnesotaMitogen-Activated Protein KinasesMonitorMorbidity - disease rateOutcomePathway interactionsPatientsPhosphoric Monoester HydrolasesPhysiologic pulsePhysiologicalPolymersPolytetrafluoroethyleneProcessProductionPropertyQuality of lifeReporterReportingResearchRiskSamplingSaphenous VeinSignal PathwaySignal TransductionStentsStimulusSystemTensile StrengthTestingThrombosisTimeTissue EngineeringTissuesTrainingTransplantationTubular formationTunica MediaUniversitiesVascular GraftWorkWound Infectionbasecare burdenconditioninghemodynamicsimplantationimprovedinhibitor/antagonistinternal thoracic arteryneonatal humanpressurepreventresearch and developmentresponserestenosistype I collagen alpha 1
项目摘要
DESCRIPTION (provided by applicant): Nationally, coronary artery disease is a tremendous health care burden. Current therapies for coronary artery disease suffer from multiple risks to the patient including restenosis, thrombosis, infection, and other graft disease. A completely biological bioartificial artery graft would circumvent these issues and improve the outcome for sufferers of coronary artery disease. Fibrin-based tissue engineering has already shown significant progress but as yet has not produced a bioartificial artery with sufficient mechanical strength for implantation without risk. A new strategy is needed to exploit signaling pathways for cellular stimulation. The hypothesis for the proposed work is that: Prolonged ERK signaling during in vitro culture will improve the mechanical strength of fibrin-based bioartificial arteries, via stimulation of type I collagen transcription and increased collagen content. By manipulating extracellular signal-regulated kinase (ERK) signaling by the cells seeded in tubular fibrin- based constructs, this project will improve the collagen content of bioartificial arteries and ultimately their mechanical strength. The specific aims of the proposed work are as follows: #1. Establish that ERK activity is necessary for the production of mechanically strong bioartificial arteries. #2. Promote prolonged ERK activation in bioartificial arteries by inhibiting negative feedback pathways. #3. Promote prolonged ERK activation in bioartificial arteries by mechanical stimulation. The primary readouts for the response to ERK signal manipulation will be type I collagen transcription, using a luciferase reporter, collagen content, using a biochemical assay, and mechanical strength, using mechanical testing systems. Significant training in tissue engineering and biomechanics from experts at the University of Minnesota will be a key goal for this fellowship. It is expected that this project will produce bioartificial arteries that can withstand physiological blood pressure.
PUBLIC HEALTH RELEVANCE: The proposed research will accelerate the production of a completely biological implantable bioartificial artery, which is a current need for proper treatment of coronary artery disease. By manipulating cellular signaling during artery development, collagen content will be increased, leading to enhanced mechanical strength.
描述(由申请人提供):在全国范围内,冠状动脉疾病是一个巨大的医疗保健负担。目前冠状动脉疾病的治疗方法给患者带来多种风险,包括再狭窄、血栓形成、感染和其他移植物疾病。完全生物化的生物人工动脉移植物将规避这些问题并改善冠状动脉疾病患者的预后。基于纤维蛋白的组织工程已经取得了重大进展,但迄今为止尚未生产出具有足够机械强度的生物人工动脉,可以无风险地进行植入。需要一种新的策略来利用信号通路进行细胞刺激。这项工作的假设是:体外培养期间延长 ERK 信号传导将通过刺激 I 型胶原蛋白转录和增加胶原蛋白含量来提高基于纤维蛋白的生物人工动脉的机械强度。通过在基于管状纤维蛋白的结构中接种的细胞来操纵细胞外信号调节激酶(ERK)信号传导,该项目将提高生物人工动脉的胶原蛋白含量,并最终提高其机械强度。拟议工作的具体目标如下:#1。确定 ERK 活性对于产生机械强度高的生物人工动脉是必需的。 #2.通过抑制负反馈途径,促进生物人工动脉中 ERK 的延长激活。 #3。通过机械刺激促进生物人工动脉中 ERK 的延长激活。对 ERK 信号操作响应的主要读数将是使用荧光素酶报告基因的 I 型胶原蛋白转录、使用生化测定的胶原蛋白含量以及使用机械测试系统的机械强度。明尼苏达大学专家在组织工程和生物力学方面的重要培训将是该奖学金的一个关键目标。预计该项目将生产出能够承受生理血压的生物人工动脉。
公共健康相关性:拟议的研究将加速完全生物植入的生物人工动脉的生产,这是当前正确治疗冠状动脉疾病的需要。通过在动脉发育过程中操纵细胞信号传导,胶原蛋白含量将增加,从而增强机械强度。
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)
数据更新时间:{{ journalArticles.updateTime }}
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
JUSTIN Sol WEINBAUM其他文献
JUSTIN Sol WEINBAUM的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
{{ truncateString('JUSTIN Sol WEINBAUM', 18)}}的其他基金
Improving fibrin-based bioartificial arteries by prolonging ERK activation
通过延长 ERK 激活来改善基于纤维蛋白的生物人工动脉
- 批准号:
8207809 - 财政年份:2010
- 资助金额:
$ 5.58万 - 项目类别:
Improving fibrin-based bioartificial arteries by prolonging ERK activation
通过延长 ERK 激活来改善基于纤维蛋白的生物人工动脉
- 批准号:
8597625 - 财政年份:2010
- 资助金额:
$ 5.58万 - 项目类别:
相似海外基金
American Heart Association Tobacco Regulation and Addiction Center (A-TRAC)
美国心脏协会烟草管制和成瘾中心 (A-TRAC)
- 批准号:
8585218 - 财政年份:2013
- 资助金额:
$ 5.58万 - 项目类别:
American Heart Association Tobacco Regulation and Addiction Center (A-TRAC)
美国心脏协会烟草管制和成瘾中心 (A-TRAC)
- 批准号:
9328116 - 财政年份:2013
- 资助金额:
$ 5.58万 - 项目类别:
American Heart Association Tobacco Center for Regulatory Science (A-TRAC) 2.0
美国心脏协会烟草监管科学中心 (A-TRAC) 2.0
- 批准号:
10017285 - 财政年份:2013
- 资助金额:
$ 5.58万 - 项目类别:
American Heart Association Tobacco Center for Regulatory Science (A-TRAC) 2.0
美国心脏协会烟草监管科学中心 (A-TRAC) 2.0
- 批准号:
10246435 - 财政年份:2013
- 资助金额:
$ 5.58万 - 项目类别:
American Heart Association Tobacco Regulation and Addiction Center (A-TRAC)
美国心脏协会烟草管制和成瘾中心 (A-TRAC)
- 批准号:
9133442 - 财政年份:2013
- 资助金额:
$ 5.58万 - 项目类别:
American Heart Association Tobacco Center for Regulatory Science (A-TRAC) 2.0
美国心脏协会烟草监管科学中心 (A-TRAC) 2.0
- 批准号:
10219710 - 财政年份:2013
- 资助金额:
$ 5.58万 - 项目类别:
American Heart Association Tobacco Regulation and Addiction Center (A-TRAC)
美国心脏协会烟草管制和成瘾中心 (A-TRAC)
- 批准号:
8737954 - 财政年份:2013
- 资助金额:
$ 5.58万 - 项目类别:
American Heart Association Tobacco Regulation and Addiction Center (A-TRAC)
美国心脏协会烟草管制和成瘾中心 (A-TRAC)
- 批准号:
8906919 - 财政年份:2013
- 资助金额:
$ 5.58万 - 项目类别:
American Heart Association Tobacco Center for Regulatory Science (A-TRAC) 2.0
美国心脏协会烟草监管科学中心 (A-TRAC) 2.0
- 批准号:
10474438 - 财政年份:2013
- 资助金额:
$ 5.58万 - 项目类别: