Emerging Microfluidic Approaches for Platelet Mechanobiology and Interplay With Circulatory Systems

Abstract

Understanding how platelets can sense and respond to hemodynamic forces in disturbed blood flow and complexed vasculature is crucial to the development of more effective and safer antithrombotic therapeutics. By incorporating diverse structural and functional designs, microfluidic technologies have emerged to mimic microvascular anatomies and hemodynamic microenvironments, which open the floodgates for fascinating platelet mechanobiology investigations. The latest endothelialized microfluidics can even recapitulate the crosstalk between platelets and the circulatory system, including the vessel walls and plasma proteins such as von Willebrand factor. Hereby, we highlight these exciting microfluidic applications to platelet mechanobiology and platelet–circulatory system interplay as implicated in thrombosis. Last but not least, we discuss the need for microfluidic standardization and summarize the commercially available microfluidic platforms for researchers to obtain reproducible and consistent results in the field.

Microfluidic post method for 3-dimensional modeling of platelet–leukocyte interactions

“…Such an assay system would not only complement the in vivo needle injury model but would be readily ‘humanized’ to allow the analysis of human neutrophil–platelet interactions in a tunable 3D hydrodynamic environment. 15 In this context, parallel-plate flow chambers and capillary microslides are the conventional methods employed to characterize adhesion dynamics between blood cells with cultured endothelial cells, subendothelial matrix proteins or platelet monolayers. 11,16–18 In the context of neutrophil–platelet interactions, platelets are usually pre-coated to form a 2D monolayer followed by neutrophil perfusion, 19,20 as the platelet thrombi that form on collagen substrates are heterogeneous and difficult to standardize.…”

Dynamic Vortex Generation, Pulsed Injection, and Rapid Mixing of Blood Samples in Microfluidics Using the Tube Oscillation Mechanism

“…Equally important, the pulsed injection and rapid mixing of cell suspensions facilitate performing multistep assays, involving injection, dilution, drug stimulation, labeling, washing, and imaging of cells in a highly programmable manner. Furthermore, the versatility of our system provides opportunities for studying the response of mechanosensitive cells to vortical flows , and various shear levels , using microfluidic vessel models. , …”

Platelet Mechanobiology Inspired Microdevices: From Hematological Function Tests to Disease and Drug Screening

“…Conventional methods such as PFA-100/200 ® do not capture the geometric characteristics of the vessel, preventing the mimicking of platelet responses to their microenvironment. In contrast, latest soft lithography enables multifaceted, high-fidelity and customized microfluidic designs to imitate various vascular anatomies, such as straight ( Jain et al, 2016b ; Li et al, 2017 ; Zhang and Neelamegham, 2017 ; Albers et al, 2019 ; Dupuy et al, 2021 ), bifurcated ( Tsai et al, 2012 ), stenosed ( Tovar-Lopez et al, 2010 ; Jain et al, 2016b ) and net ( Zilberman-Rudenko et al, 2017 ; Zhang et al, 2021 ) channels. 2) Microfluidics can recapitulate hemodynamic microenvironment.…”

“…Endothelialized microfluidics are rapidly evolving as humanized screening platforms ( Albers et al, 2019 ; Jenny et al, 2020 ; Dupuy et al, 2021 ). Increasing evidences demonstrate their great potential in simulating the interplays between platelets and circulatory systems ( Zhang et al, 2021 ). 5) Existing platelet function tests are bulky, expensive, and require specialized operators and a large volume of blood samples.…”