Anisotropic topographies restore endothelial monolayer integrity and promote the proliferation of senescent endothelial cells

Vasileios Exarchos; Sebastian Neuber; Heike Meyborg; Costanza Giampietro; Nafsika Chala; Silvia Moimas; Hristian Hinkov; Friedrich Kaufmann; Francesca M Pramotton; Katrin Krüger; Hector Rodriguez Cetina Biefer; Nikola Cesarovic; Dimos Poulikakos; Volkmar Falk; Maximilian Y Emmert; Aldo Ferrari; Timo Z Nazari-Shafti

doi:10.3389/fcvm.2022.953582

Anisotropic topographies restore endothelial monolayer integrity and promote the proliferation of senescent endothelial cells

Front Cardiovasc Med. 2022 Oct 5:9:953582. doi: 10.3389/fcvm.2022.953582. eCollection 2022.

Authors

Vasileios Exarchos^{1

2}, Sebastian Neuber^{1

2}, Heike Meyborg^{1

2}, Costanza Giampietro^{3

4}, Nafsika Chala⁵, Silvia Moimas⁵, Hristian Hinkov^{1

2}, Friedrich Kaufmann¹, Francesca M Pramotton^{3

4}, Katrin Krüger^{1

2

6}, Hector Rodriguez Cetina Biefer^{1

2

7}, Nikola Cesarovic^{1

8}, Dimos Poulikakos⁵, Volkmar Falk^{6

8

9}, Maximilian Y Emmert^{1

2

6

8

10}, Aldo Ferrari^{3

4

5}, Timo Z Nazari-Shafti^{1

2

11}

Affiliations

¹ Cardiosurgical Research Group, Department of Cardiothoracic and Vascular Surgery, German Heart Center Berlin, Berlin, Germany.
² Translational Cardiovascular Regenerative Technologies Group, BIH Center for Regenerative Therapies, Berlin Institute of Health at Charité-Universitätsmedizin Berlin, Berlin, Germany.
³ Experimental Continuum Mechanics, Empa Swiss Federal Laboratories for Materials Science and Technology, Dübendorf, Switzerland.
⁴ Department of Mechanical and Process Engineering, Institute for Mechanical Systems, ETH Zürich, Zurich, Switzerland.
⁵ Laboratory of Thermodynamics in Emerging Technologies, Department of Mechanical and Process Engineering, ETH Zürich, Zurich, Switzerland.
⁶ Clinic for Cardiovascular Surgery, Charité-Universitätsmedizin Berlin, Berlin, Germany.
⁷ Department of Cardiac Surgery, City Hospital of Zürich, Site Triemli, Zurich, Switzerland.
⁸ Department of Health Sciences and Technology, ETH Zürich, Zurich, Switzerland.
⁹ Department for Cardiovascular and Thoracic Surgery, German Heart Center Berlin, Berlin, Germany.
¹⁰ Institute for Regenerative Medicine, University of Zurich, Zurich, Switzerland.
¹¹ BIH Biomedical Innovation Academy, BIH Charité (Junior) (Digital) Clinician Scientist Program, Berlin Institute of Health at Charité-Universitätsmedizin Berlin, Berlin, Germany.

Abstract

Thrombogenicity remains a major issue in cardiovascular implants (CVIs). Complete surficial coverage of CVIs by a monolayer of endothelial cells (ECs) prior to implantation represents a promising strategy but is hampered by the overall logistical complexity and the high number of cells required. Consequently, extensive cell expansion is necessary, which may eventually lead to replicative senescence. Considering that micro-structured surfaces with anisotropic topography may promote endothelialization, we investigated the impact of gratings on the biomechanical properties and the replicative capacity of senescent ECs. After cultivation on gridded surfaces, the cells showed significant improvements in terms of adherens junction integrity, cell elongation, and orientation of the actin filaments, as well as enhanced yes-associated protein nuclear translocation and cell proliferation. Our data therefore suggest that micro-structured surfaces with anisotropic topographies may improve long-term endothelialization of CVIs.

Keywords: aging; anisotropy; endothelial cells; monolayer integrity; proliferation; senescence; telomere; topography.