Increasing biocompatibility of stents via CD47 surface functionalization: Mechanistic and Preclinical studies
通过 CD47 表面功能化提高支架的生物相容性:机理和临床前研究
基本信息
- 批准号:9565589
- 负责人:
- 金额:$ 72万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2017
- 资助国家:美国
- 起止时间:2017-09-15 至 2021-05-31
- 项目状态:已结题
- 来源:
- 关键词:AddressAdhesionsAdvocateAffectAmino AcidsAnatomyAnimal ModelAnimalsAnti-inflammatoryAntimitotic AgentsArteriesAutomobile DrivingBiologicalBloodBlood PlateletsBlood flowCD47 geneCarotid stentCell CommunicationCellsClinicalCoronaryDataDevelopmentDevicesDiseaseEffectivenessEventExtracellular ProteinFamily suidaeFunctional disorderFutureGoalsHarvestHumanImmobilizationImmune responseImmunologicsInflammationInflammatoryInflammatory ResponseIntegral Membrane ProteinLaboratoriesMalignant NeoplasmsMediatingMedical DeviceMedicineMetalsMissionModelingModificationMolecularOryctolagus cuniculusOutcomePathogenesisPathologyPatientsPeptidesPeripheralPharmaceutical PreparationsPhysiologyPolymersProcessPropertyPublic HealthRattusReceptor SignalingRecombinantsReperfusion InjuryResearchRiskSHPS-1 proteinSignal TransductionSiteSmooth Muscle MyocytesSolidStentsSterilizationSurfaceSystemTestingTherapeuticTherapeutic StudiesThrombosisTimeTissuesUnited States National Institutes of HealthWorkagedbiomaterial compatibilitycell typeclinically relevantdesigndiabetichuman modeliliac arteryimplantationimprovedin vivoinnovationinterestmetallicitymonocyteneutrophilnovel strategiesparacrinepre-clinicalpreclinical studypreventprogramsprotein aminoacid sequenceprotein biomarkersreceptor bindingrecruitresponserestenosistherapeutic effectivenesstranslational impactvalidation studies
项目摘要
Abstract/Summary
The pathophysiology associated with endovascular stent usage is well documented and is observed in up to
50% of all patients receiving the medical device. CD47 is a ubiquitously expressed transmembrane protein,
that when bound to its cognate receptor Signal Regulatory Protein alpha (SIRP), inhibits the immune
response. We have shown, both ex vivo and in a rat carotid stent model, that immobilized recombinant CD47,
or a 21 amino acid peptide sequence (pepCD47) thereof, significantly inhibited restenosis and thrombosis. The
overall objective of the proposed research is to investigate the anti-restenotic capacity of a pepCD47
functionalized endovascular stent in rabbit and porcine animal models. Three Specific Aims (SA) will test our
central hypothesis that immobilized pepCD47 represents a pragmatic surface modification strategy that will
control adverse immunological and hemocompatibility responses and thus significantly contribute to
biocompatibility of endovascular stents. In SA 1 we will fabricate and perform efficacy and stability analysis
on CD47 functionalized metal surface to test our working hypothesis that rabbit and pig CD47, immobilized
on the bare metal surfaces, will confer a similar anti-platelet and anti-inflammatory activity as human CD47 and
will be amenable to clinically relevant challenges. SA 2 will determine how immobilized CD47 affects
cellular interactions at the blood/stent interface. Our working hypothesis is that immobilized CD47 confers
a biocompatible microenvironment that inhibits inflammatory cell and platelet interactions and permits re-
endothelialization. SA 3 will demonstrate in vivo efficacy of CD47 functionalized stents in the large
animal models. Our working hypothesis is that CD47 modified stents would confer significantly greater
biocompatibility, compared to commercially available bare metal stents and drug eluting stents (DES), which
will be demonstrated by a significant reduction in ISR of the stented site. The rationale for the proposed
research is that demonstration of pepCD47 mediated inhibition of ISR in a large animal model would provide
necessary preclinical and usage data to advance the application of the CD47-functionalized stents into the
clinical realm. The research is significant because it will demonstrate the broad translational importance of
CD47 in regulating the cellular/molecular response to synthetic surfaces that are used in clinically relevant
biomedical devices. The research proposed herein is innovative because it challenges and redirects current
therapeutic strategies, such as DES, by identifying candidate molecular signaling mechanisms that actively
regulate cellular interactions with solid synthetic surfaces, and then incorporating these concepts into the
design and fabrication of metallic stents.
抽象/总结
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 }}
Ilia Fishbein其他文献
Ilia Fishbein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('Ilia Fishbein', 18)}}的其他基金
Increasing biocompatibility of stents via CD47 surface functionalization: Mechanistic and Preclinical studies
通过 CD47 表面功能化提高支架的生物相容性:机理和临床前研究
- 批准号:
9448802 - 财政年份:2017
- 资助金额:
$ 72万 - 项目类别:
Increasing biocompatibility of stents through CD47 functionalization
通过 CD47 功能化提高支架的生物相容性
- 批准号:
8512290 - 财政年份:2013
- 资助金额:
$ 72万 - 项目类别:
相似海外基金
How tensins transform focal adhesions into fibrillar adhesions and phase separate to form new adhesion signalling hubs.
张力蛋白如何将粘着斑转化为纤维状粘连并相分离以形成新的粘连信号中枢。
- 批准号:
BB/Y004841/1 - 财政年份:2024
- 资助金额:
$ 72万 - 项目类别:
Research Grant
Defining a role for non-canonical mTORC1 activity at focal adhesions
定义非典型 mTORC1 活性在粘着斑中的作用
- 批准号:
BB/Y001427/1 - 财政年份:2024
- 资助金额:
$ 72万 - 项目类别:
Research Grant
How tensins transform focal adhesions into fibrillar adhesions and phase separate to form new adhesion signalling hubs.
张力蛋白如何将粘着斑转化为纤维状粘连并相分离以形成新的粘连信号中枢。
- 批准号:
BB/Y005414/1 - 财政年份:2024
- 资助金额:
$ 72万 - 项目类别:
Research Grant
Development of a single-use, ready-to-use, sterile, dual chamber, dual syringe sprayable hydrogel to prevent postsurgical cardiac adhesions.
开发一次性、即用型、无菌、双室、双注射器可喷雾水凝胶,以防止术后心脏粘连。
- 批准号:
10669829 - 财政年份:2023
- 资助金额:
$ 72万 - 项目类别:
Regulating axon guidance through local translation at adhesions
通过粘连处的局部翻译调节轴突引导
- 批准号:
10587090 - 财政年份:2023
- 资助金额:
$ 72万 - 项目类别:
Improving Maternal Outcomes of Cesarean Delivery with the Prevention of Postoperative Adhesions
通过预防术后粘连改善剖宫产的产妇结局
- 批准号:
10821599 - 财政年份:2023
- 资助金额:
$ 72万 - 项目类别:
Regulating axon guidance through local translation at adhesions
通过粘连处的局部翻译调节轴突引导
- 批准号:
10841832 - 财政年份:2023
- 资助金额:
$ 72万 - 项目类别:
Prevention of Intraabdominal Adhesions via Release of Novel Anti-Inflammatory from Surface Eroding Polymer Solid Barrier
通过从表面侵蚀聚合物固体屏障中释放新型抗炎剂来预防腹内粘连
- 批准号:
10532480 - 财政年份:2022
- 资助金额:
$ 72万 - 项目类别:
I-Corps: A Sprayable Tissue-Binding Hydrogel to Prevent Postsurgical Cardiac Adhesions
I-Corps:一种可喷雾的组织结合水凝胶,可防止术后心脏粘连
- 批准号:
10741261 - 财政年份:2022
- 资助金额:
$ 72万 - 项目类别:
Sprayable Polymer Blends for Prevention of Site Specific Surgical Adhesions
用于预防特定部位手术粘连的可喷涂聚合物共混物
- 批准号:
10674894 - 财政年份:2022
- 资助金额:
$ 72万 - 项目类别: