Atherosclerotic three-layer nanomatrix vascular sheets for high-throughput therapeutic evaluation

Jun Chen; Xixi Zhang; Robbie Cross Jr; Yujin Ahn; Gillian Huskin; Will Evans; Patrick Taejoon Hwang; Jeong-A Kim; Brigitta C Brott; Hanjoong Jo; Young-Sup Yoon; Ho-Wook Jun

doi:10.1016/j.biomaterials.2023.122450

Atherosclerotic three-layer nanomatrix vascular sheets for high-throughput therapeutic evaluation

Biomaterials. 2024 Mar:305:122450. doi: 10.1016/j.biomaterials.2023.122450. Epub 2023 Dec 27.

Authors

Affiliations

¹ Department of Biomedical Engineering, The University of Alabama at Birmingham, Birmingham, AL, USA; Endomimetics, LLC., Birmingham, AL, USA.
² Department of Biomedical Engineering, The University of Alabama at Birmingham, Birmingham, AL, USA.
³ Augusta University/University of Georgia Medical Partnership, Athens, GA, USA.
⁴ Endomimetics, LLC., Birmingham, AL, USA.
⁵ Department of Medicine, Division of Endocrinology and Metabolism, UAB Comprehensive Diabetes Center, Birmingham, AL, USA.
⁶ Endomimetics, LLC., Birmingham, AL, USA; Department of Medicine and Division of Cardiovascular Disease, The University of Alabama at Birmingham, AL, USA.
⁷ Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA, USA.
⁸ Division of Cardiology, School of Medicine, Emory University, Atlanta, GA, USA.
⁹ Department of Biomedical Engineering, The University of Alabama at Birmingham, Birmingham, AL, USA; Endomimetics, LLC., Birmingham, AL, USA. Electronic address: hwjun@uab.edu.

Abstract

In vitro atherosclerosis models are essential to evaluate therapeutics before in vivo and clinical studies, but significant limitations remain, such as the lack of three-layer vascular architecture and limited atherosclerotic features. Moreover, no scalable 3D atherosclerosis model is available for making high-throughput assays for therapeutic evaluation. Herein, we report an in vitro 3D three-layer nanomatrix vascular sheet with critical atherosclerosis multi-features (VSA), including endothelial dysfunction, monocyte recruitment, macrophages, extracellular matrix remodeling, smooth muscle cell phenotype transition, inflammatory cytokine secretion, foam cells, and calcification initiation. Notably, we present the creation of high-throughput functional assays with VSAs and the use of these assays for evaluating therapeutics for atherosclerosis treatment. The therapeutics include conventional drugs (statin and sirolimus), candidates for treating atherosclerosis (curcumin and colchicine), and potential gene therapy (miR-146a-loaded liposomes). The high efficiency and flexibility of the scalable VSA functional assays should facilitate drug discovery and development for atherosclerosis.

Keywords: 3D in vitro models; Atherosclerosis; Drug evaluation; High-throughput; Vascular sheet.

MeSH terms

Atherosclerosis* / drug therapy
Foam Cells
Gene Expression
Humans
Macrophages
Monocytes
Myocytes, Smooth Muscle
Plaque, Atherosclerotic*

Grants and funding

R01 HL163802/HL/NHLBI NIH HHS/United States