Monitoring Of Random Microvessel Network Formation By In-Line Sensing Of Flow Rates: A Numerical And In Vitro Investigation

The directed or de novo formation of microvasculature in engineered tissue constructs is essential for accurately replicating physiological function. A limiting factor of a system relying on spontaneous microvessel formation is the inability to precisely quantify the development of the microvascular network and control fluid moving through formed vessels. Herein, we report a strategy to monitor the dynamic formation of microscale fluid networks, which can be translated to the monitoring of microvasculature development in engineered tissue constructs. The non-invasive, non-destructive monitoring and characterization of the fluid network is achieved via in-line sensing of fluid flow rate and correlating this measurement to the hydrodynamic resistance of the fluid network to model the progression of microvessel formation and connectivity. Computational fluid dynamics, equivalent circuit, and experimental models were compared, which simulated multi-generational branching or splitting microvessel networks. The networks simulated vessels with varying cross-sectional area, up to 16 branching vessels, and microvessel network volume ranging from 20-30 mm(3). In all models, the increasing degree of network complexity and volume corresponded to a decrease in jumper flow-rate measured; however, vessel cross-section also impacted the measured jumper flow rate, i.e. at low vessel height (<200 mu m) response was dominated by increased network volume and at higher vessel height (>200 mu m) the response was dominated by resistance of narrow channels. An approximately 2% error was exhibited between the models, which was attributed to variation in the geometry of the fabricated models and illustrates the potential to precisely and non-destructively monitor microvessel network development and volumetric changes. (C) 2021 Elsevier B.V. All rights reserved.