Heparin-free extracorporeal circulation via combined nitric oxide releasing/generating surfaces
通过组合的一氧化氮释放/生成表面进行无肝素体外循环
基本信息
- 批准号:10184748
- 负责人:
- 金额:$ 36.42万
- 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:2021-05-01 至 2025-04-30
- 项目状态:未结题
- 来源:
- 关键词:2019-nCoVAddressAdhesionsAnti-Bacterial AgentsAnticoagulationAttentionBacteriaBacterial InfectionsBindingBloodBlood Coagulation DisordersBlood PlateletsBlood VesselsBlood-Borne PathogensCOVID-19COVID-19 pandemicCOVID-19 patientCandida albicansCannulasCathetersCellsClinicalCoagulation ProcessComplicationCritical IllnessDataDevicesEmbolismExhibitsExtracorporeal CirculationExtracorporeal Membrane OxygenationFormulationGenerationsGoalsHeart failureHemodialysisHemorrhageHeparinImmobilizationIn VitroInfectionLeadLifeMeasuresMechanical ventilationMicrobial BiofilmsModelingN-acetylpenicillamineNitric OxideNitric Oxide DonorsNosocomial InfectionsObstructionOryctolagus cuniculusOxygenatorsPatient CarePatientsPlatelet ActivationPolymersPreventionPropertyPseudomonas aeruginosaPulmonary ThromboembolismReportingResearch Project GrantsRespiratory FailureRiskS-NitrosothiolsS-nitro-N-acetylpenicillamineSafetySavingsSeleniumSepsisStaphylococcus aureusStaphylococcus epidermidisSterilizationSurfaceSystemTechnologyTestingTherapeuticThrombophiliaThrombosisThrombusTimeTranslationsVascular Endothelial CellWorkanalytical methodantimicrobialbasecatalystclinical applicationclinical developmentcovalent bondearly phase clinical trialhemocompatibilityhigh riskimprovedin vitro Bioassayinfection ratepolydimethylsiloxanepreventsuccesssynergismthrombogenesisthrombotic complications
项目摘要
Project Summary/Abstract
The major limiting factors to clinical applications of blood-contacting materials, ranging from small catheters to
large extracorporeal circulation (ECC) devices, include platelet activation leading to thrombosis and infection.
Thrombus formation can further lead to obstruction of blood vessels, device malfunction, or even life-threatening
situations such as embolism. Systemic anticoagulation is required to prevent clotting in the devices; however,
one of the resulting major complications of this is bleeding. During the COVID-19 pandemic, extracorporeal
membrane oxygenation (ECMO) has received critical attention as a therapy for patients where mechanical
ventilation alone is ineffective. Significant challenges remain due to the increased risks of thrombosis in the
circuitry that can be further exacerbated by hypercoagulable blood exhibited by COVID-19 patients. Therefore,
there is an urgent necessity and opportunity to combine strategies for preventing thrombosis and infection into
multifunctional device coatings for enhanced patency and safety.
Our work and others have demonstrated that nitric oxide (NO) release from polymers prevent platelets activation
and infection. This technology mimics the vascular endothelial cells lining the blood vessels, as well as other
cells in our bodies, producing NO locally to prevent clotting and bacterial biofilm and subsequent infections.
Recently we discovered that all of the positive effects can be achieved from polymers physically blended with
the NO donor molecule S-nitroso-N-acetylpenicillamine (SNAP), which is nontoxic, inexpensive, and easy to
synthesize. Active NO release from the NO donor functionalities in the polymer reduces thrombosis and bacterial
infection polymer-blood interface; however, the NO-release strategy alone is limited by the finite reservoir of NO
donor functionalities within the polymer that limit the duration of the NO availability at the polymer-blood interface.
Our recent work has shown the potential of combining active NO-release with catalytic NO-generating
mechanism in a single polymer. The goal of this proposal is to develop a polymer comprised of a NO donor
covalently bonded to the polymer to provide active NO-release (without leaching) in combination with
immobilized selenocystamine moieties to provide long-term NO-generation. This polymer will combine
NO-release and NO-generating strategies for the first time, resulting in a new generation of polymers
that possess potent broad-spectrum antimicrobial properties and reduce thrombosis by inhibiting
platelet adhesion/activation. The new polymers will be applicable to any blood-contacting device; however,
this proposal will focus on studying the combined NO-releasing/NO-generating strategy in vitro for antimicrobial
properties and in a rabbit extracorporeal circulation model for prevention of thrombosis. Successful completion
of this project will allow progression to early clinical trials and development of a new generation of extracorporeal
circuits that can reduce complications while improving the success of patient care.
项目总结/文摘
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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Elizabeth Joy Brisbois其他文献
Elizabeth Joy Brisbois的其他文献
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{{ truncateString('Elizabeth Joy Brisbois', 18)}}的其他基金
Prevention of catheter related infections via photoactive nitric oxide delivery device
通过光敏一氧化氮输送装置预防导管相关感染
- 批准号:
10753081 - 财政年份:2023
- 资助金额:
$ 36.42万 - 项目类别:
Heparin-free extracorporeal circulation via combined nitric oxide releasing/generating surfaces
通过组合的一氧化氮释放/生成表面进行无肝素体外循环
- 批准号:
10608084 - 财政年份:2021
- 资助金额:
$ 36.42万 - 项目类别:
Heparin-free extracorporeal circulation via combined nitric oxide releasing/generating surfaces
通过组合的一氧化氮释放/生成表面进行无肝素体外循环
- 批准号:
10394301 - 财政年份:2021
- 资助金额:
$ 36.42万 - 项目类别:
Bioinspired antifouling and thromboresistant polymers for blood-contacting interfaces
用于血液接触界面的仿生防污和抗血栓聚合物
- 批准号:
10292846 - 财政年份:2020
- 资助金额:
$ 36.42万 - 项目类别:
Bioinspired antifouling and thromboresistant polymers for blood-contacting interfaces
用于血液接触界面的仿生防污和抗血栓聚合物
- 批准号:
10591536 - 财政年份:2020
- 资助金额:
$ 36.42万 - 项目类别:
Bioinspired antifouling and thromboresistant polymers for blood-contacting interfaces
用于血液接触界面的仿生防污和抗血栓聚合物
- 批准号:
10377491 - 财政年份:2020
- 资助金额:
$ 36.42万 - 项目类别:
Thromboresistant/Bactericidal Intravascular Catheters Based on Electrochemical Nitric Oxide Generation
基于电化学一氧化氮生成的抗血栓/杀菌血管内导管
- 批准号:
9147476 - 财政年份:2015
- 资助金额:
$ 36.42万 - 项目类别:
Thromboresistant/Bactericidal Intravascular Catheters Based on Electrochemical Nitric Oxide Generation
基于电化学一氧化氮生成的抗血栓/杀菌血管内导管
- 批准号:
8981223 - 财政年份:2015
- 资助金额:
$ 36.42万 - 项目类别:
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