Preclinical Assessment of a Compliance Matched Biopolymer Vascular Graft
顺应性匹配的生物聚合物血管移植物的临床前评估
基本信息
- 批准号:10540762
- 负责人:
- 金额:$ 63.64万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2021
- 资助国家:美国
- 起止时间:2021-12-15 至 2025-11-30
- 项目状态:未结题
- 来源:
- 关键词:AcuteAdultAnimal ModelAnimalsAnti-Inflammatory AgentsAortaAutologousBilateralBiopolymersBlood VesselsBypassCd68CellsCessation of lifeCharacteristicsClinicalClinical TreatmentCollagenComputer SimulationCoronary Artery BypassCoronary heart diseaseDepositionDevelopmentDiameterDiseaseElementsEndotheliumEnvironmentExhibitsExtracellular MatrixFailureGelatinHeart DiseasesHyperplasiaImplantIn VitroIndividualInfiltrationLegal patentMacrophageMaintenanceMechanicsModelingMyosin Heavy ChainsOrgan TransplantationPerformancePhenotypePlayProcessProductionRattusReportingResearchResearch Project GrantsRoleSaphenous VeinSheepSiteSmooth Muscle MyocytesSprague-Dawley RatsTestingThrombosisTissue EngineeringTransforming Growth Factor Beta 2TropoelastinUnited StatesVascular DiseasesVascular GraftVascular Smooth MuscleWomanWorkcalponincomputerized toolscontrolled releasecost efficientdesigngraft failurehemodynamicsimplantationimprovedin vivoin vivo Modelmechanical propertiesmennovelpre-clinicalpre-clinical assessmentpreimplantationrecruitresponsethrombogenesistranslational potentialvascular tissue engineering
项目摘要
Project Summary
There are approximately 250,000 coronary artery bypass graft (CABG) procedures performed annually to treat
coronary heart disease (CHD) with graft failure rates reported to be as high as 42.8%. A major cause of graft
failure in CABG has been attributed to graft compliance mismatch leading to subsequent intimal hyperplasia
and graft thrombosis. The development of a compliance matched functional small diameter vascular graft will
therefore significantly improve the treatment of those with CHD. Tissue engineering has shown promise in
achieving some but not all of the required characteristics for a functional tissue engineered vascular graft
(TEVG). A particularly challenging aspect in the development of a functional TEVG is the design of a fully
biodegradable biopolymer graft that can be tuned to a desired compliance pre-implantation and subsequently
maintain its compliance as it degrades and remodels in-vivo. As such there is a critical need to develop a
compliance matched TEVG that remains compliance matched throughout the host remodeling process while
also maintaining a functional endothelium. To meet this need we will develop and functionally assess a
tropoelastin layered and endothelialized TEVG that is and remains compliance matched. We will utilize
computational simulation to optimize the compliance of a biodegradable gelatin/tropoelastin layered TEVG that
elutes TGFb2 in a controlled manner to promote early cell infiltration and late matrix deposition in our graft,
thus stabilizing its compliance as our graft degrades. The overall working hypothesis of our research is that the
intravital (in-vitro and in-vivo) compliance of our graft can be maintained by temporally controlling TGFb2
elution from a computationally optimized TEVG. We will test this hypothesis by completing the following
Specific Aims. Aim 1 of our research project will assess if compliance and TGFb2 elution can maintain the
compliance of our TEVG in-vivo using a rat aortic interpositional implantation model. Aim 2 of our proposed
work will assess the function of our TEVG in a preclinical large animal (sheep carotid) implantation model. The
proposed studies will establish a novel pre- and post-implantation compliance controlled fully biodegradable
biopolymer TEVG with excellent patency, anti-thrombogenicity, vasoreactivity, and functional performance.
项目摘要
每年进行大约250,000例冠状动脉旁路移植术(CABG),以治疗
冠状动脉心脏病(CHD)移植失败率高达42.8%。贪污的主要原因
冠状动脉旁路移植术的失败归因于移植物顺应性不匹配,导致随后的内膜增生
和移植物血栓形成。顺应性匹配的功能性小直径血管移植物的开发将
从而显著改善冠心病患者的治疗。组织工程学已经显示出在
实现功能性组织工程血管移植物的一些但不是全部所需特征
(TEVG).在功能性TEVG的开发中,一个特别具有挑战性的方面是设计一个完整的
可生物降解的生物聚合物移植物,其可在植入前和随后调节至所需的顺应性,
在体内降解和重塑时保持其顺应性。因此,迫切需要制定一项
在整个主机改造过程中保持合规性匹配的TEVG,
还维持功能性内皮。为了满足这一需求,我们将开发和功能评估
弹性蛋白原分层和内皮化的TEVG是并保持顺应性匹配。我们将利用
计算模拟以优化可生物降解的明胶/原弹性蛋白分层的TEVG的顺应性,
以受控的方式洗脱TGF β 2以促进我们移植物中的早期细胞浸润和晚期基质沉积,
从而在移植物降解时稳定其顺应性。我们研究的总体工作假设是,
我们的移植物的活体内(体外和体内)顺应性可以通过暂时控制TGF β 2来维持
从计算优化的TEVG洗脱。我们将通过完成以下操作来检验此假设
具体目标。我们研究项目的目标1将评估依从性和TGF β 2洗脱是否可以维持
使用大鼠主动脉间置植入模型的体内TEVG的顺应性。我们的目标2
工作将评估我们的TEVG在临床前大型动物(绵羊颈动脉)植入模型中的功能。的
拟议的研究将建立一种新的植入前和植入后的依从性控制完全可生物降解
生物聚合物TEVG具有优异的通畅性、抗血栓形成性、血管反应性和功能性能。
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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Jonathan Pieter Vande Geest其他文献
Characterizing Bruch's membrane: State-of-the-art imaging, computational segmentation, and biologic models in retinal disease and health
布鲁赫膜的特征描述:视网膜疾病与健康状态中的先进成像、计算分割及生物学模型
- DOI:
10.1016/j.preteyeres.2025.101358 - 发表时间:
2025-05-01 - 期刊:
- 影响因子:14.700
- 作者:
Joshua Ong;Amrish Selvam;Matthew Driban;Arman Zarnegar;Susana Isabel Morgado Mendes Antunes Da Silva;Jincy Joy;Ethan A. Rossi;Jonathan Pieter Vande Geest;José-Alain Sahel;Jay Chhablani - 通讯作者:
Jay Chhablani
Jonathan Pieter Vande Geest的其他文献
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{{ truncateString('Jonathan Pieter Vande Geest', 18)}}的其他基金
Biocarpet: The Next Generation Endovascular Device for Peripheral Arterial Disease
Biocarpet:治疗外周动脉疾病的下一代血管内装置
- 批准号:
10744597 - 财政年份:2023
- 资助金额:
$ 63.64万 - 项目类别:
Preclinical Assessment of a Compliance Matched Biopolymer Vascular Graft
顺应性匹配的生物聚合物血管移植物的临床前评估
- 批准号:
10366911 - 财政年份:2021
- 资助金额:
$ 63.64万 - 项目类别:
Preclinical Assessment of a Compliance Matched Biopolymer Vascular Graft
顺应性匹配的生物聚合物血管移植物的临床前评估
- 批准号:
10731964 - 财政年份:2021
- 资助金额:
$ 63.64万 - 项目类别:
Extracelluar Matrix Organization and Biomechanics of the Lamina Cribrosa and Peripapillary Sclera in Populations at High Risk for Primary Open Angle Glaucoma
原发性开角型青光眼高危人群筛板和视乳头周围巩膜的细胞外基质组织和生物力学
- 批准号:
9293031 - 财政年份:2016
- 资助金额:
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Development of a Microstructurally Inspired and Compliance Matched Tissue Enginee
开发受微观结构启发且顺应性匹配的组织工程
- 批准号:
8444206 - 财政年份:2013
- 资助金额:
$ 63.64万 - 项目类别:
Development of a Microstructurally Inspired and Compliance Matched Tissue Enginee
开发受微观结构启发且顺应性匹配的组织工程
- 批准号:
8603278 - 财政年份:2013
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$ 63.64万 - 项目类别:
Extracelluar Matrix Organization and Biomechanics of the Lamina Cribrosa and Peri
筛板和周周的细胞外基质组织和生物力学
- 批准号:
8188325 - 财政年份:2011
- 资助金额:
$ 63.64万 - 项目类别:
Extracelluar Matrix Organization and Biomechanics of the Lamina Cribrosa and Peri
筛板和周周的细胞外基质组织和生物力学
- 批准号:
8703108 - 财政年份:2011
- 资助金额:
$ 63.64万 - 项目类别:
Extracelluar Matrix Organization and Biomechanics of the Lamina Cribrosa and Peri
筛板和周周的细胞外基质组织和生物力学
- 批准号:
8304189 - 财政年份:2011
- 资助金额:
$ 63.64万 - 项目类别:
Extracelluar Matrix Organization and Biomechanics of the Lamina Cribrosa and Peri
筛板和周周的细胞外基质组织和生物力学
- 批准号:
8509699 - 财政年份:2011
- 资助金额:
$ 63.64万 - 项目类别:
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