Stents are the most common cardiovascular implants used in the treatment of cardiovascular diseases. However, there are concerns about in-stent restenosis with bare metal stents (BMS) and late stent thrombosis and late inflammatory responses with drug-eluting stents (DES). Despite the promise of recently developed strategies to overcome the challenges of current stents, there remain many emerging concerns and limitations. Development of innovative strategies to restore endothelial healing while limiting the risk of late stent thrombosis, inflammatory responses, and restenosis is critical for the long-term success of stents. In nature, the endothelium is the thin layer of endothelial cells and underlying nanofibrillar basement membrane that modulates vascular tone by release of soluble factors, such as nitric oxide (NO). Endothelial dysfunction or the injury of endothelium is a hallmark of vascular diseases. The inevitable injury to this multifunctional endothelium associated with stent deployment triggers the cascade of restenosis and thrombosis. The goal of this application is to demonstrate the prohealing effects of the novel multifunctional endothelium nanomatrix coated stent, which will minimize the risks of late stent thrombosis, restenosis, inflammatory responses, and incomplete endothelialization. The overall hypothesis of this application is that the prohealing multifunctional endothelium nanomatrix can enhance the efficacy of the stent by promoting endothelial healing on the surface of the stent.
Three specific aims are proposed to test this hypothesis:
Specific Aim 1 : To evaluate the synergistic prohealing effects of multiple components of the endothelium mimicking, self-assembled nanomatrix.
Specific Aim 2 : To determine the influence of hemodynamics on the prohealing multifunctional endothelium nanomatrix coated stent using a rabbit artery simulating bioreactor.
Specific Aim 3 : To validate the efficacy of the prohealing multifunctional endothelium nanomatrix coated stent on vasodilation of rabbit arteries ex vivo and enhanced endothelial healing in a rabbit iliac artery balloon injury model in vivo.
These aims provide a paradigm changing approach that will circumvent the significant healthcare risks of current stents.

Public Health Relevance

Stents are the most common cardiovascular implants used in the treatment of cardiovascular diseases. However, there are concerns about complications with current stents. Development of innovative strategies to minimize the risk of late stent thrombosis, inflammatory responses, restenosis, and incomplete endothelialization are critical for success of stents.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL125391-03
Application #
9235296
Study Section
Biomaterials and Biointerfaces Study Section (BMBI)
Program Officer
Lee, Albert
Project Start
2015-01-15
Project End
2019-12-31
Budget Start
2017-01-01
Budget End
2017-12-31
Support Year
3
Fiscal Year
2017
Total Cost
Indirect Cost
Name
University of Alabama Birmingham
Department
Biomedical Engineering
Type
Schools of Medicine
DUNS #
063690705
City
Birmingham
State
AL
Country
United States
Zip Code
35294
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