한빛사 논문
Xixi Zhang 1, Jun Chen 1, Brigitta C Brott 2 3, Peter G Anderson 4, Patrick T J Hwang 3, Jennifer Sherwood 3, Gillian Huskin 1, Young-Sup Yoon 5, Renu Virmani 6, Ho-Wook Jun 1 3
1Department of Biomedical Engineering, University of Alabama at Birmingham, Birmingham, Alabama, 35294, United States.
2Department of Medicine and Division of Cardiovascular Disease, University of Alabama at Birmingham, Birmingham, Alabama, 35233, United States.
3Endomimetics, LLC, Birmingham, Alabama, 35242, United States.
4Department of Medicine, Department of Pathology3, University of Alabama at Birmingham, Birmingham, Alabama, 35294, United States.
5School of Medicine, Division of Cardiology, Emory University, Atlanta, Georgia, 30322, United States.
6CVPath Institute, Inc., Gaithersburg, Maryland, 20878, United States.
Corresponding Author : Ho-Wook Jun
Abstract
Cardiovascular stent technologies have significantly improved over time. However, their optimal performance remains limited by restenosis, thrombosis, inflammation, and delayed re-endothelialization. Current stent designs primarily target inhibition of neointimal proliferation but do not promote functional arterial healing (pro-healing) in order to restore normal vascular reactivity. The endothelial lining that does develop with current stents appears to have loose intracellular junctions. We have developed a pro-healing nanomatrix coating for stents that enhances healing while limiting neointimal proliferation. This builds on our prior work evaluating the effects of the pro-healing nanomatrix coating on cultures of vascular endothelial cells (ECs), smooth muscle cells (SMCs), monocytes, and platelets. However, when a stent is deployed in an artery, multiple vascular cell types interact, and their interactions affect stent performance. Thus, in our current study, an in vitro vascular double-layer (VDL) system was used to observe stent effects on communication between different vascular cell types. Additionally, we assessed the pro-healing ability and vascular cell interactions after stent deployment in the VDL system and in a rabbit model, evaluating the nanomatrix-coated stent compared to a commercial bare metal stent (BMS) and a drug eluting stent (DES). In vitro results indicated that, in a layered vascular structure, the pro-healing nanomatrix-coated stent could (1) improve endothelialization and endothelial functions, (2) regulate SMC phenotype to reduce SMC proliferation and migration, (3) suppress inflammation through a multifactorial manner, and (4) reduce foam cell formation, extracellular matrix remodeling, and calcification. Consistent with this, in vivo results demonstrated that, compared with commercial BMS and DES, this pro-healing nanomatrix-coated stent enhanced re-endothelialization with negligible restenosis, inflammation, or thrombosis. Thus, these findings indicate the unique pro-healing features of this nanomatrix stent coating with superior efficacy over commercial BMS and DES.
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