Enhanced endothelialization for tissue engineering

增强组织工程内皮化

基本信息

  • 批准号:
    7011892
  • 负责人:
  • 金额:
    $ 21.13万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2006
  • 资助国家:
    美国
  • 起止时间:
    2006-05-01 至 2010-04-30
  • 项目状态:
    已结题

项目摘要

DESCRIPTION (provided by applicant): Biodegradable polymers including poly(l-lactic acid) (PLLA) have been used to develop cardiovascular prostheses such as vascular grafts and stents. However, implant-associated thrombosis, inflammation, and restenosis are still a major obstacle for the patency of these prostheses. Our long-term goal is to reduce these complications by rapid endothelialization. Our hypothesis is that rapid endothelialization on the prosthetic surfaces is possible by incorporation of the prosthetic materials with endothelial cell (EC) adhesion (fibronectin) and growth factors (vascular endothelial growth factor, VEGF) and by seeding of genetically modified ECs with growth factor receptors (VEGF receptors, KDR/flk-1) on the prosthetic surfaces. Specifically, aim #1 is to incorporate fibronectin and VEGF onto PLLA surfaces using different immobilized techniques: coating, cross-linking, and electrostatic self-assembly (ESA). Cell adhesion and proliferation on these surfaces will be investigated using PicoGreen DNA assays, whereas cell retention under physiological flow conditions will be studied using an in vitro parallel flow system. To assess whether seeded cells maintain functional characteristics of ECs, we will determine: (1) the cellular uptake of acetylated LDL (ac-LDL), (2) histamine-mediated release of von Willerbrand factor (vWF), and (3) the expression of vWF (endothelial marker) and endothelium constitutive NO synthase (ecNOS) using immunocytochemistry. Aim #2 is to develop genetically modified ECs with VEGF receptors (KDR/flk-1 plasmids) using Lipofectamine(tm) transfection reagent. Expression of transduced genes will be confirmed using Western blotting. Aim #3 is to seed genetically modified ECs on the optimal surface developed in Aim #1 and evaluate their performance. EC adhesion, retention, proliferation, and functionality will be assessed as described in Aim #1. The proposed biodegradable PLLA materials will have several benefits as these materials will stimulate the vessel healing by creating a vessel wall-protecting neoendothelium and thus can be used in the future as a way to modify surfaces for vascular tissue engineering. We believe that surface modification with the combination of adhesion and growth factors and gene transfer of growth factor receptors used in our strategies will improve endothelialization, and thereby reduce the body's adverse reactions toward the prostheses.
描述(由申请人提供):包括聚(l-乳酸)(PLLA)在内的可生物降解聚合物已用于开发心血管假体,如血管移植物和支架。然而,与植入物相关的血栓形成、炎症和再狭窄仍然是这些假体通畅的主要障碍。我们的长期目标是通过快速内皮化减少这些并发症。我们的假设是,假体表面上的快速内皮化是可能的,通过将假体材料与内皮细胞(EC)粘附(纤连蛋白)和生长因子(血管内皮生长因子,VEGF)结合,并通过在假体表面上接种具有生长因子受体(VEGF受体,KDR/flk-1)的遗传修饰的EC。具体而言,目标#1是使用不同的固定化技术将纤连蛋白和VEGF结合到PLLA表面上:涂覆、交联和静电自组装(ESA)。这些表面上的细胞粘附和增殖将使用PicoGreen DNA测定法进行研究,而生理流动条件下的细胞保留将使用体外平行流动系统进行研究。为了评估接种的细胞是否保持EC的功能特征,我们将使用免疫细胞化学确定:(1)乙酰化LDL(ac-LDL)的细胞摄取,(2)组胺介导的von Willerbrand因子(vWF)的释放,以及(3)vWF(内皮标志物)和内皮组成型NO合酶(ecNOS)的表达。目的#2是使用Lipofectamine(tm)转染试剂开发具有VEGF受体(KDR/flk-1质粒)的遗传修饰的EC。将使用蛋白质印迹法确认转导基因的表达。目标#3是在目标#1中开发的最佳表面上接种遗传修饰的EC并评估其性能。EC粘附、保留、增殖和功能性将按照目标#1中所述进行评估。所提出的可生物降解的PLLA材料将具有几个益处,因为这些材料将通过产生血管壁保护性新内皮来刺激血管愈合,因此可以在未来用作血管组织工程的表面改性的方式。我们相信,结合粘附和生长因子以及我们策略中使用的生长因子受体的基因转移的表面改性将改善内皮化,从而减少身体对假体的不良反应。

项目成果

期刊论文数量(4)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(1)
Enhanced endothelialization on surface modified poly(L-lactic acid) substrates.
  • DOI:
    10.1089/ten.tea.2010.0129
  • 发表时间:
    2010-07
  • 期刊:
  • 影响因子:
    0
  • 作者:
    Hao Xu;R. Deshmukh;R. Timmons;K. Nguyen
  • 通讯作者:
    Hao Xu;R. Deshmukh;R. Timmons;K. Nguyen
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Kytai Truong Nguyen其他文献

Shear Stress Reduces Protease Activated Receptor-1 Expression in Human Endothelial Cells
  • DOI:
    10.1114/1.1349700
  • 发表时间:
    2001-02-01
  • 期刊:
  • 影响因子:
    5.400
  • 作者:
    Kytai Truong Nguyen;Suzanne G. Eskin;Cam Patterson;Marschall S. Runge;Larry V. McIntire
  • 通讯作者:
    Larry V. McIntire
Lung Cancer Targeted Chemoradiotherapy via Dual-Stimuli Responsive Biodegradable Core-Shell Nanoparticles.
  • DOI:
    10.3390/pharmaceutics14081525
  • 发表时间:
    2022-07-22
  • 期刊:
  • 影响因子:
    5.4
  • 作者:
    Iyer, Roshni;Ramachandramoorthy, Harish;Trinh Nguyen;Xu, Cancan;Fu, Huikang;Kotadia, Tanviben;Chen, Benjamin;Hong, Yi;Saha, Debabrata;Kytai Truong Nguyen
  • 通讯作者:
    Kytai Truong Nguyen

Kytai Truong Nguyen的其他文献

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{{ truncateString('Kytai Truong Nguyen', 18)}}的其他基金

Synergistic Upregulation of EpoR /RopE NPs for Enhancing Effective Angiogenesis to treat PAD
EpoR /RopE NP 的协同上调可增强有效的血管生成以治疗 PAD
  • 批准号:
    10113347
  • 财政年份:
    2021
  • 资助金额:
    $ 21.13万
  • 项目类别:
Interdisciplinary Training in Nanotechnology for Cardiovascular and Lung Diseases in North Texas
北德克萨斯州心血管和肺部疾病纳米技术跨学科培训
  • 批准号:
    9355415
  • 财政年份:
    2017
  • 资助金额:
    $ 21.13万
  • 项目类别:
Interdisciplinary Training in Nanotechnology for Cardiovascular and Lung Diseases in North Texas
北德克萨斯州心血管和肺部疾病纳米技术跨学科培训
  • 批准号:
    10206233
  • 财政年份:
    2017
  • 资助金额:
    $ 21.13万
  • 项目类别:
Novel Engineered Particle Platform for Endothelium Regeneration
用于内皮再生的新型工程颗粒平台
  • 批准号:
    9198993
  • 财政年份:
    2014
  • 资助金额:
    $ 21.13万
  • 项目类别:
Novel Engineered Particle Platform for Endothelium Regeneration
用于内皮再生的新型工程颗粒平台
  • 批准号:
    8632706
  • 财政年份:
    2014
  • 资助金额:
    $ 21.13万
  • 项目类别:
Novel Engineered Particle Platform for Endothelium Regeneration
用于内皮再生的新型工程颗粒平台
  • 批准号:
    8788441
  • 财政年份:
    2014
  • 资助金额:
    $ 21.13万
  • 项目类别:
Nanoparticles for targeting drug delivery to the injured vascular wall
用于将药物递送至受损血管壁的纳米颗粒
  • 批准号:
    7837498
  • 财政年份:
    2009
  • 资助金额:
    $ 21.13万
  • 项目类别:
Nanoparticles for targeting drug delivery to the injured vascular wall
用于将药物递送至受损血管壁的纳米颗粒
  • 批准号:
    7569399
  • 财政年份:
    2008
  • 资助金额:
    $ 21.13万
  • 项目类别:
Nanoparticles for targeting drug delivery to the injured vascular wall
用于将药物递送至受损血管壁的纳米颗粒
  • 批准号:
    7354589
  • 财政年份:
    2008
  • 资助金额:
    $ 21.13万
  • 项目类别:
TISSUE ENGINEERED VASCULAR GRAFTS
组织工程血管移植物
  • 批准号:
    6491785
  • 财政年份:
    2001
  • 资助金额:
    $ 21.13万
  • 项目类别:
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