Topography-driven alterations in endothelial cell phenotype and contact guidance

Ana Maria Almonacid Suarez; Iris van der Ham; Marja G L Brinker; Patrick van Rijn; Martin C Harmsen

doi:10.1016/j.heliyon.2020.e04329

Topography-driven alterations in endothelial cell phenotype and contact guidance

Heliyon. 2020 Jun 29;6(6):e04329. doi: 10.1016/j.heliyon.2020.e04329. eCollection 2020 Jun.

Authors

Ana Maria Almonacid Suarez¹, Iris van der Ham¹, Marja G L Brinker¹, Patrick van Rijn², Martin C Harmsen¹

Affiliations

¹ University of Groningen, University Medical Center Groningen, Department of Pathology and Medical Biology, Hanzeplein 1 (EA11), 9713 GZ, Groningen, the Netherlands.
² University of Groningen, University Medical Center Groningen, Department of Biomedical Engineering-FB40, W.J. Kolff Institute for Biomedical Engineering and Materials Science-FB41, A. Deusinglaan 1, 9713 AV, Groningen, the Netherlands.

Abstract

Understanding how endothelial cell phenotype is affected by topography could improve the design of new tools for tissue engineering as many tissue engineering approaches make use of topography-mediated cell stimulation. Therefore, we cultured human pulmonary microvascular endothelial cells (ECs) on a directional topographical gradient to screen the EC vascular-like network formation and alignment response to nano to microsized topographies. The cell response was evaluated by microscopy. We found that ECs formed unstable vascular-like networks that aggregated in the smaller topographies and flat parts whereas ECs themselves aligned on the larger topographies. Subsequently, we designed a mixed topography where we could explore the network formation and proliferative properties of these ECs by live imaging for three days. Vascular-like network formation continued to be unstable on the topography and were only produced on the flat areas and a fibronectin coating did not improve the network stability. However, an instructive adipose tissue-derived stromal cell (ASC) coating provided the correct environment to sustain the vascular-like networks, which were still affected by the topography underneath. It was concluded that large microsized topographies inhibit vascular endothelial network formation but not proliferation and flat and nano/microsized topographies allow formation of early networks that can be stabilized by using an ASC instructive layer.

Keywords: Bioengineering; Biomedical engineering; Biophysics; Cell biology; Contact guidance; Directional topography; Endothelial cells; Regenerative medicine; Vascular-like networks; Vascularization.