Clot Accumulation in 3D Microfluidic Bifurcating Microvasculature Network

Author:

Belenkovich Merav1,Veksler Ruth1ORCID,Kreinin Yevgeniy1,Mekler Tirosh1,Flores Mariane2,Sznitman Josué1ORCID,Holinstat Michael234ORCID,Korin Netanel1ORCID

Affiliation:

1. Faculty of Biomedical Engineering, Technion-Israel Institute of Technology, Haifa 32000, Israel

2. Department of Pharmacology, University of Michigan Medical School, Ann Arbor, MI 48109, USA

3. Department of Internal Medicine, Division of Cardiovascular Medicine, University of Michigan Medical School, Ann Arbor, MI 48109, USA

4. Department of Surgery, Division of Vascular Surgery, University of Michigan Medical School, Ann Arbor, MI 48109, USA

Abstract

The microvasculature, which makes up the majority of the cardiovascular system, plays a crucial role in the process of thrombosis, with the pathological formation of blood clots inside blood vessels. Since blood microflow conditions significantly influence platelet activation and thrombosis, accurately mimicking the structure of bifurcating microvascular networks and emulating local physiological blood flow conditions are valuable for understanding blood clot formation. In this work, we present an in vitro model for blood clotting in microvessels, focusing on 3D bifurcations that align with Murray’s law, which guides vascular networks by maintaining a constant wall shear rate throughout. Using these models, we demonstrate that microvascular bifurcations act as sites facilitating thrombus formation compared to straight models. Additionally, by culturing endothelial cells on the luminal surfaces of the models, we show the potential of using our in vitro platforms to recapitulate the initial clotting in diseases involving endothelial dysfunction, such as Thrombotic Thrombocytopenic Purpura.

Funder

University of Michigan–Israel Partnership for Research Collaborative Research Grant

Publisher

MDPI AG

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