Device-Based In Vitro Techniques for Mechanical Stimulation of Vascular Cells: A Review

Abstract

The most common cause of death in the developed world is cardiovascular disease. For decades, this has provided a powerful motivation to study the effects of mechanical forces on vascular cells in a controlled setting, since these cells have been implicated in the development of disease. Early efforts in the 1970 s included the first use of a parallel-plate flow system to apply shear stress to endothelial cells (ECs) and the development of uniaxial substrate stretching techniques (Krueger et al., 1971, "An in Vitro Study of Flow Response by Cells," J. Biomech., 4(1), pp. 31-36 and Meikle et al., 1979, "Rabbit Cranial Sutures in Vitro: A New Experimental Model for Studying the Response of Fibrous Joints to Mechanical Stress," Calcif. Tissue Int., 28(2), pp. 13-144). Since then, a multitude of in vitro devices have been designed and developed for mechanical stimulation of vascular cells and tissues in an effort to better understand their response to in vivo physiologic mechanical conditions. This article reviews the functional attributes of mechanical bioreactors developed in the 21st century, including their major advantages and disadvantages. Each of these systems has been categorized in terms of their primary loading modality: fluid shear stress (FSS), substrate distention, combined distention and fluid shear, or other applied forces. The goal of this article is to provide researchers with a survey of useful methodologies that can be adapted to studies in this area, and to clarify future possibilities for improved research methods.

Microfluidic traction force microscopy to study mechanotransduction in angiogenesis

“…The effect of shear stress on EC has been the focus of much research, and as such, a range of microfluidic in vitro systems for the application of flow have been developed, some specific to the study of angiogenesis and others repurposed to that aim. Comprehensive reviews already exist, in which these techniques are described in detail . In brief, systems range from common planar flow chambers, in which shear stress is applied via the laminar flow of fluid between two parallel plates, to simple circular channels, microvascular networks, and patient‐specific geometries.…”

“…Comprehensive reviews already exist, in which these techniques are described in detail. 45 In brief, systems range from common planar flow chambers, 7 in which shear stress is applied via the laminar flow of fluid between two parallel plates, to simple circular channels, 46 microvascular networks, 47 and patient-specific geometries.…”

Application of Microfluidics in Wearable Devices

“…Nowadays, microfluidics has been widely applied in wearable devices . Microfluidics is a multidisciplinary technology for precise manipulation of minute amounts of fluids in a confined micro space, which has been widely applied in various areas, including but not limited to organ on Chip, drug delivery, cell biology, and electrochemical detection . Microdroplets is another big category in microfluidics and offers a great number of opportunities in chemical and biological research, such as chemistrode and single cell/molecule assays …”

Glioblastoma adhesion in a quick-fit hybrid microdevice

“…An in vitro cell-cell interaction model of glioblastoma and endothelial cells could further our understanding of the perivascular tumor microenvironment of glioblastoma (Tsai et al 2017). Endothelial cells cultured in vitro can be conditioned chemically or physically through mechanical or electrical stimulation to up-regulate expression of cell adhesion molecules or to promote cell morphology with more natural physiological conditions (Sheikh et al 2003; Zhao et al 2004; Bai et al 2011; Khan and Sefton 2011; Uzarski et al 2013; Jaczewska et al 2014; Davis et al 2015). We employ the quick-fit BMMD to demonstrate its robustness by applying concurrent electrical and mechanical conditioning on the endothelial cells and further investigate the adherence of glioblastoma cells on the conditioned endothelium.…”