Microfluidic devices for modeling cell–cell and particle–cell interactions in the microvasculature

Abstract

Cell-fluid and cell-cell interactions are critical components of many physiological and pathological conditions in the microvasculature. Similarly, particle-cell interactions play an important role in targeted delivery of therapeutics to tissue. Development of in vitro fluidic devices to mimic these microcirculatory processes has been a critical step forward in our understanding of the inflammatory process, development of nano-particulate drug carriers, and developing realistic in vitro models of the microvasculature and its surrounding tissue. However, widely used parallel plate flow based devices and assays have a number of important limitations for studying the physiological conditions in vivo. In addition, these devices are resource hungry and time consuming for performing various assays. Recently developed, more realistic, microfluidic based devices have been able to overcome many of these limitations. In this review, an overview of the fluidic devices and their use in studying the effects of shear forces on cell-cell and cell-particle interactions is presented. In addition, use of mathematical models and Computational Fluid Dynamics (CFD) based models for interpreting the complex flow patterns in the microvasculature are highlighted. Finally, the potential of 3D microfluidic devices and imaging for better representing in vivo conditions under which cell-cell and cell-particle interactions take place are discussed.

Platelet bioreactor-on-a-chip

“…PLT bioreactor models the physiological characteristics of human BM PLT bioreactors were designed to recapitulate the dimensions of human venules 29 in the BM ( Figure 1A) and are comprised of upper and lower microfluidic channels separated by a series of columns (spaced 2 mm apart) ( Figure 1B-C) to model proPLT extension through gaps in vascular endothelium under controlled flow conditions. To scale PLT production the bioreactor was lengthened, and upper and lower microfluidic channels were mirrored as outlined in Figure 1D.…”

Tumour-on-a-chip: microfluidic models of tumour morphology, growth and microenvironment

“…Common methods to create capillary lumen structures as microvasculatures include moulding the capillaries in hydrogels by needles or rods [95][96][97][98], by photoresists [99][100][101], by sacrificial carbohydrates [102] or creating lumens based on viscous fingering instabilities [103,104]. Alternatively, an endothelial vascular network as the microvasculature can be formed by endothelial sprouting in hydrogels [105][106][107][108][109][110][111][112], monolayer on ECM hydrogel [113][114][115] or on a porous membrane [116,117], and monolayer in microchannels [118,119] (figure 2l ).…”

Integrative Utilization of Microenvironments, Biomaterials and Computational Techniques for Advanced Tissue Engineering

“…The key role of microfluidic platforms along with the significance of three-dimensional matrices in studding cell-cell communications have been reviewed by Guo et al [112]. Various microfluidic designs have been proposed to study cell-cell communications [113][114][115][116]. For example, Byrne et al proposed a microfluidic platform to study communications via soluble factors using autocrine and paracrine signaling molecules in the absence of physical contacts between the cells [117].…”