A novel human arterial wall-on-a-chip to study endothelial inflammation and vascular smooth muscle cell migration in early atherosclerosis

Su, Chengxun; Menon, Nishanth Venugopal; Xu, Xiaohan; Teo, Yu Rong; Cao, Huấn; Dalan, Rinkoo; Tay, Chor Yong; Hou, Han Wei

doi:10.1039/d1lc00131k

Cited by 39 publications

(48 citation statements)

References 57 publications

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“…While the dual-lane stepped-height based hydrogel chip have been reported for arterial wall-on-a-chip [ 29 ], we further demonstrated the scalability of this method to pattern multiple adjacent lanes of hydrogel using single or dual stepped heights. An injection-molded culture platform for patterning three adjacent lanes of hydrogel have been reported [ 37 ], but it lacks the flexibility to pattern two different hydrogels for the first two lanes.…”

Section: Discussionmentioning

confidence: 68%

“…Our group previously developed a hydrogel patterning method based on channel stepped heights and capillary burst valve (CBV) effect for blood vessel studies [ 28 , 29 ]. Herein, we further explore the versatility and scalability of the stepped-height based technique for 3D cell cultures in enclosed microchannels and spheroid-in-gel cultures in an open-channel microarray format.…”

Section: Introductionmentioning

confidence: 99%

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A Facile and Scalable Hydrogel Patterning Method for Microfluidic 3D Cell Culture and Spheroid-in-Gel Culture Array

Chuah

Ong

et al. 2021

Biosensors

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Incorporation of extracellular matrix (ECM) and hydrogel in microfluidic 3D cell culture platforms is important to create a physiological microenvironment for cell morphogenesis and to establish 3D co-culture models by hydrogel compartmentalization. Here, we describe a simple and scalable ECM patterning method for microfluidic cell cultures by achieving hydrogel confinement due to the geometrical expansion of channel heights (stepped height features) and capillary burst valve (CBV) effects. We first demonstrate a sequential “pillar-free” hydrogel patterning to form adjacent hydrogel lanes in enclosed microfluidic devices, which can be further multiplexed with one to two stepped height features. Next, we developed a novel “spheroid-in-gel” culture device that integrates (1) an on-chip hanging drop spheroid culture and (2) a single “press-on” hydrogel confinement step for rapid ECM patterning in an open-channel microarray format. The initial formation of breast cancer (MCF-7) spheroids was achieved by hanging a drop culture on a patterned polydimethylsiloxane (PDMS) substrate. Single spheroids were then directly encapsulated on-chip in individual hydrogel islands at the same positions, thus, eliminating any manual spheroid handling and transferring steps. As a proof-of-concept to perform a spheroid co-culture, endothelial cell layer (HUVEC) was formed surrounding the spheroid-containing ECM region for drug testing studies. Overall, this developed stepped height-based hydrogel patterning method is simple to use in either enclosed microchannels or open surfaces and can be readily adapted for in-gel cultures of larger 3D cellular spheroids or microtissues.

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Section: Discussionmentioning

confidence: 68%

Section: Introductionmentioning

confidence: 99%

A Facile and Scalable Hydrogel Patterning Method for Microfluidic 3D Cell Culture and Spheroid-in-Gel Culture Array

Chuah

Ong

et al. 2021

Biosensors

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“…Su et al first reported a microfluidic EC-SMC co-culture device for a normal artery wall model. Then they stimulated the model with pro-inflammatory cytokines (such as TNF-α and IL1-β) and oxidized LDL for studying endothelial inflammation in early atherosclerosis [151]. Furthermore, drug screening was also applied in this model and confirmed that Vitamin D, a drug known as anti-atherogenic, could inhibit monocytes-EC adhesion and SMC migration.…”

Section: Atherosclerosismentioning

confidence: 92%

The Biofabrication of Diseased Artery In Vitro Models

et al. 2022

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As the leading causes of global death, cardiovascular diseases are generally initiated by artery-related disorders such as atherosclerosis, thrombosis, and aneurysm. Although clinical treatments have been developed to rescue patients suffering from artery-related disorders, the underlying pathologies of these arterial abnormalities are not fully understood. Biofabrication techniques pave the way to constructing diseased artery in vitro models using human vascular cells, biomaterials, and biomolecules, which are capable of recapitulating arterial pathophysiology with superior performance compared with conventional planar cell culture and experimental animal models. This review discusses the critical elements in the arterial microenvironment which are important considerations for recreating biomimetic human arteries with the desired disorders in vitro. Afterward, conventionally biofabricated platforms for the investigation of arterial diseases are summarized, along with their merits and shortcomings, followed by a comprehensive review of advanced biofabrication techniques and the progress of their applications in establishing diseased artery models.

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“…Notably, the SMC migration into the EC layer could be easily quantified using such a system, which cannot be achieved through a traditional transwell assay. Moreover, the potential of this system as a drug screening tool was demonstrated by the atheroprotective effect of vitamin D, and metformin was observed when tested using this model (158). However, the main limitation of this study is that the EC layer is not monolayer and is as thick as the SMC layer, and lacks tunica adventitia.…”

Section: In Vitro 3d Cell-laden Hydrogel Constructsmentioning

confidence: 95%

Recent Progress in in vitro Models for Atherosclerosis Studies

Zhang

Millican

Lynd

et al. 2022

Front. Cardiovasc. Med.

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Atherosclerosis is the primary cause of hardening and narrowing arteries, leading to cardiovascular disease accounting for the high mortality in the United States. For developing effective treatments for atherosclerosis, considerable efforts have been devoted to developing in vitro models. Compared to animal models, in vitro models can provide great opportunities to obtain data more efficiently, economically. Therefore, this review discusses the recent progress in in vitro models for atherosclerosis studies, including traditional two-dimensional (2D) systems cultured on the tissue culture plate, 2D cell sheets, and recently emerged microfluidic chip models with 2D culture. In addition, advanced in vitro three-dimensional models such as spheroids, cell-laden hydrogel constructs, tissue-engineered blood vessels, and vessel-on-a-chip will also be covered. Moreover, the functions of these models are also summarized along with model discussion. Lastly, the future perspectives of this field are discussed.

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A novel human arterial wall-on-a-chip to study endothelial inflammation and vascular smooth muscle cell migration in early atherosclerosis

Abstract: Mechanistic understanding of atherosclerosis is largely hampered by the lack of suitable in vitro human arterial model that recapitulates the arterial wall structure, and the interplay between different cell types...

Cited by 39 publications

References 57 publications

A Facile and Scalable Hydrogel Patterning Method for Microfluidic 3D Cell Culture and Spheroid-in-Gel Culture Array

A Facile and Scalable Hydrogel Patterning Method for Microfluidic 3D Cell Culture and Spheroid-in-Gel Culture Array

The Biofabrication of Diseased Artery In Vitro Models

Recent Progress in in vitro Models for Atherosclerosis Studies

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