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 #
5R01HL125391-05
Application #
9625518
Study Section
Biomaterials and Biointerfaces Study Section (BMBI)
Program Officer
Lee, Albert
Project Start
2015-01-15
Project End
2019-12-31
Budget Start
2019-01-01
Budget End
2019-12-31
Support Year
5
Fiscal Year
2019
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
Chen, Jun; Deng, Lily; Porter, Catherine et al. (2018) Angiogenic and Osteogenic Synergy of Human Mesenchymal Stem Cells and Human Umbilical Vein Endothelial Cells Cocultured on a Nanomatrix. Sci Rep 8:15749
Park, Misun; Yoon, Young Sup (2018) Cardiac Regeneration with Human Pluripotent Stem Cell-Derived Cardiomyocytes. Korean Circ J 48:974-988
Lee, Shin-Jeong; Sohn, Young-Doug; Andukuri, Adinarayana et al. (2017) Enhanced Therapeutic and Long-Term Dynamic Vascularization Effects of Human Pluripotent Stem Cell-Derived Endothelial Cells Encapsulated in a Nanomatrix Gel. Circulation 136:1939-1954
Cho, Do-Yeon; Hoffman, Kyle; Skinner, Daniel et al. (2017) Tolerance and pharmacokinetics of a ciprofloxacin-coated sinus stent in a preclinical model. Int Forum Allergy Rhinol 7:352-358
Kaushik, Sagar N; Kim, Bogeun; Walma, Alexander M Cruz et al. (2016) Biomimetic microenvironments for regenerative endodontics. Biomater Res 20:14
Hwang, Patrick T J; Lim, Dong-Jin; Fee, Timothy et al. (2016) A bio-inspired hybrid nanosack for graft vascularization at the omentum. Acta Biomater 41:224-34
Alexander, Grant C; Vines, Jeremy B; Hwang, Patrick et al. (2016) Novel Multifunctional Nanomatrix Reduces Inflammation in Dynamic Conditions in Vitro and Dilates Arteries ex Vivo. ACS Appl Mater Interfaces 8:5178-87
Hwang, Patrick T J; Murdock, Kyle; Alexander, Grant C et al. (2016) Poly(?-caprolactone)/gelatin composite electrospun scaffolds with porous crater-like structures for tissue engineering. J Biomed Mater Res A 104:1017-29
Hwang, Patrick T J; Shah, Dishant K; Garcia, Jacob A et al. (2016) Progress and challenges of the bioartificial pancreas. Nano Converg 3:28
El-Ferzli, George T; Andukuri, Adinarayana; Alexander, Grant et al. (2015) A Nitric Oxide-Releasing Self-Assembled Peptide Amphiphile Nanomatrix for Improving the Biocompatibility of Microporous Hollow Fibers. ASAIO J 61:589-95

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