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

Jun Chen; Xixi Zhang; Robbie Cross; 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

Jun Chen, Xixi Zhang, Robbie Cross, Yujin Ahn, Gillian Huskin, Will Evans, Patrick Taejoon Hwang, Jeong a. Kim, Brigitta C. Brott, Hanjoong Jo, Young sup Yoon, Ho Wook Jun

Virtua Operations

Rowan University

Research output: Contribution to journal › Article › peer-review

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.

Original language	American English
Article number	122450
Journal	Biomaterials
Volume	305
DOIs	https://doi.org/10.1016/j.biomaterials.2023.122450
State	Published - Mar 2024

ASJC Scopus subject areas

Biophysics
Bioengineering
Ceramics and Composites
Biomaterials
Mechanics of Materials

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10.1016/j.biomaterials.2023.122450

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title = "Atherosclerotic three-layer nanomatrix vascular sheets for high-throughput therapeutic evaluation",

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.",

author = "Jun Chen and Xixi Zhang and Robbie Cross and Yujin Ahn and Gillian Huskin and Will Evans and Hwang, {Patrick Taejoon} and Kim, {Jeong a.} and Brott, {Brigitta C.} and Hanjoong Jo and Yoon, {Young sup} and Jun, {Ho Wook}",

note = "Publisher Copyright: {\textcopyright} 2023 The Authors",

year = "2024",

month = mar,

doi = "10.1016/j.biomaterials.2023.122450",

language = "American English",

volume = "305",

journal = "Biomaterials",

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AU - Chen, Jun

AU - Zhang, Xixi

AU - Cross, Robbie

AU - Ahn, Yujin

AU - Huskin, Gillian

AU - Evans, Will

AU - Hwang, Patrick Taejoon

AU - Kim, Jeong a.

AU - Brott, Brigitta C.

AU - Jo, Hanjoong

AU - Yoon, Young sup

AU - Jun, Ho Wook

PY - 2024/3

Y1 - 2024/3

N2 - 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.

AB - 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.

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VL - 305

JO - Biomaterials

JF - Biomaterials

M1 - 122450

ER -

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

Abstract

ASJC Scopus subject areas

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