Microfluidic Models of Vascular Functions

Abstract

In vitro studies of vascular physiology have traditionally relied on cultures of endothelial cells, smooth muscle cells, and pericytes grown on centimeter-scale plates, filters, and flow chambers. The introduction of microfluidic tools has revolutionized the study of vascular physiology by allowing researchers to create physiologically relevant culture models, at the same time greatly reducing the consumption of expensive reagents. By taking advantage of the small dimensions and laminar flow inherent in microfluidic systems, recent studies have created in vitro models that reproduce many features of the in vivo vascular microenvironment with fine spatial and temporal resolution. In this review, we highlight the advantages of microfluidics in four areas: the investigation of hemodynamics on a capillary length scale, the modulation of fluid streams over vascular cells, angiogenesis induced by the exposure of vascular cells to well-defined gradients in growth factors or pressure, and the growth of microvascular networks in biomaterials. Such unique capabilities at the microscale are rapidly advancing the understanding of microcirculatory dynamics, shear responses, and angiogenesis in health and disease as well as the ability to create in vivo–like blood vessels in vitro.

Optically clear biomicroviscometer with modular geometry using disposable PDMS chips

“…Because of its importance, various blood flow phenomena are of great scientific interest, and because of its complex behaviour, there is much left unknown about blood flow phenomena, making it a topic for current research and experimental modelling, particularly at the microcirculation scale [2]. Blood is comprised of solid particles (mainly flexible cells and platelets) suspended in liquid plasma (a Newtonian matrix).…”

“…Scale-dependent behaviour is especially important in the microcirculation, which is the main site for nutrient and gas exchange within the vascular network. As the size of the channel and/or the shear rate decreases, the non-homogeneity of the blood becomes increasingly important [2][3][4]. The size of the cellular components in comparison to the size of the channels, and the interactions between the cells with each other and with the vessel walls become significant.…”

“…It is hypothesized that the tissue perfusion (the passage of blood through the tissue) will be influenced by the network geometry, channel size, and bifurcation angles of the vessels within it [2], [15]. Changes to these factors affect the RBC interactions with both each other and with the vessel walls.…”

Towards engineering integrated cardiac organoids: beating recorded

“…To date, a variety of microphysiological systems have been developed that model their respective tissues and organs (and their disease states) of the human body, ranging from those mimicking the nervous system (11), the respiratory system (12,13), the digestive system (14,15), and the musculoskeletal system (16,17) to the cardiovascular system (18,19), covering essentially every single type of tissue and organ (4,5). Among all, the cardiac organoids have attracted increasing attention due to their critical roles in toxicology; for example, it is estimated that cardiotoxicity represents a major side effect of systemic drug toxicityin the past 40 years 19% of drug recalls were likely due to cardiotoxicity (20).…”

Osteocyte culture in microfluidic devices

“…Electronic addresses: youlidan@mie.utoronto.ca; jbwang@mail. ie.ac.cn; and chenjian@mail.ie.ac.cn 1932-1058/2015/9(1)/014109/10 V C Author(s) 2015 9, 014109-1 construct more in vivo like cell culture models, [18][19][20] enabling tumor, 21,22 neuron, 23 and vascular 24,25 studies. However, in the field of microfluidics based bone studies, preliminary demonstrations were focused to osteoblasts, [26][27][28][29] while no systematic study of on-chip culture of osteocytes has been demonstrated.…”