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The role of the circulatory system, containing the blood and lymphatic vasculatures, within the body, has become increasingly focused on by researchers as dysfunction of either of the systems has been linked to serious complications and disease. Currently, in vivo models are unable to provide the sufficient monitoring and level of manipulation needed to characterize the fluidic dynamics of the microcirculation in blood and lymphatic vessels; thus in vitro models have been pursued as an alternative model. Microfluidic devices have the required properties to provide a physiologically relevant circulatory system model for research as well as the experimental tools to conduct more advanced research analyses of microcirculation flow. In this review paper, the physiological behavior of fluid flow and electrical communication within the endothelial cells of the systems are detailed and discussed to highlight their complexities. Cell co-culturing methods and other relevant organ-on-a-chip devices will be evaluated to demonstrate the feasibility and relevance of the in vitro microfluidic model. Microfluidic systems will be determined as a noteworthy model that can display physiologically relevant flow of the cardiovascular and lymphatic systems, which will enable researchers to investigate the systems' prevalence in diseases and identify potential therapeutics.

 

Surface coating with dopamine conjugated hyaluronic acid (HA–DP) can interact with lymphatic vessel endothelial hyaluronan receptor-1 (LYVE-1) to preserve the phenotypes and functionality of lymphatic endothelial cells (LECs).

 

Encapsulation of single cells in a thin hydrogel provides a more precise control of stem cell niches and better molecular transport. Despite the recent advances in microfluidic technologies to allow encapsulation of single cells, existing methods rely on special crosslinking agents that are pre-coated on the cell surface and subject to the variation of the cell membrane, which limits their widespread adoption. This work reports a high-throughput single-cell encapsulation method based on the “tip streaming” mode of alternating current (AC) electrospray, with encapsulation efficiencies over 80% after tuned centrifugation. Dripping with multiple cells is curtailed due to gating by the sharp conic meniscus of the tip streaming mode that only allows one cell to be ejected at a time. Moreover, the method can be universally applied to both natural and synthetic hydrogels, as well as various cell types, including human multipotent mesenchymal stromal cells (hMSCs). Encapsulated hMSCs maintain good cell viability over an extended culture period and exhibit robust differentiation potential into osteoblasts and adipocytes. Collectively, electrically induced tip streaming enables high-throughput encapsulation of single cells with high efficiency and universality, which is applicable for various applications in cell therapy, pharmacokinetic studies, and regenerative medicine.