Effects of biomechanical and biochemical stimuli on angio- and vasculogenesis in a complex microvasculature-on-chip

Dario Ferrari; Arunima Sengupta; Lyong Heo; Laszlo Pethö; Johann Michler; Thomas Geiser; Vinicio A de Jesus Perez; Wolfgang M Kuebler; Soheila Zeinali; Olivier T Guenat

doi:10.1016/j.isci.2023.106198

Effects of biomechanical and biochemical stimuli on angio- and vasculogenesis in a complex microvasculature-on-chip

iScience. 2023 Feb 13;26(3):106198. doi: 10.1016/j.isci.2023.106198. eCollection 2023 Mar 17.

Authors

Affiliations

¹ Organs-on-chip Technologies Laboratory, ARTORG Center, University of Bern, Bern, Switzerland.
² Stanford Center for Genomics and Personalized Medicine, Palo Alto, CA, USA.
³ Empa, Swiss Federal Laboratories for Materials Science and Technology, Laboratory for Mechanics of Materials and Nanostructures, Thun, Switzerland.
⁴ Department of Pulmonary Medicine, Inselspital, University Hospital of Bern, Bern, Switzerland.
⁵ Department for BioMedical Research, University of Bern, Bern, Switzerland.
⁶ Division of Pulmonary, Allergy, and Critical Care Medicine, Stanford University Medical Center, Stanford, CA, USA.
⁷ Institute of Physiology, Charité - Universitätsmedizin Berlin, Berlin, Germany.
⁸ Department of General Thoracic Surgery, Inselspital, University Hospital of Bern, Bern, Switzerland.

Abstract

The endothelium of blood vessels is a vital organ that reacts differently to subtle changes in stiffness and mechanical forces exerted on its environment (extracellular matrix (ECM)). Upon alteration of these biomechanical cues, endothelial cells initiate signaling pathways that govern vascular remodeling. The emerging organs-on-chip technologies allow the mimicking of complex microvasculature networks, identifying the combined or singular effects of these biomechanical or biochemical stimuli. Here, we present a microvasculature-on-chip model to investigate the singular effect of ECM stiffness and mechanical cyclic stretch on vascular development. Following two different approaches for vascular growth, the effect of ECM stiffness on sprouting angiogenesis and the effect of cyclic stretch on endothelial vasculogenesis are studied. Our results indicate that ECM hydrogel stiffness controls the size of the patterned vasculature and the density of sprouting angiogenesis. RNA sequencing shows that the cellular response to stretching is characterized by the upregulation of certain genes such as ANGPTL4+5, PDE1A, and PLEC.

Keywords: Biotechnology; Transcriptomics; Vascular anatomy.

Abstract

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