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Development of a Bi-Layered Cryogenic Electrospun Polylactic Acid Scaffold to Study Calcific Aortic Valve Disease in a 3D Co-Culture Model

50 Pages Posted: 13 May 2021 Publication Status: Under Review

See all articles by Kathrin Stadelmann

Kathrin Stadelmann

University of Tübingen - NMI Natural and Medical Sciences Institute; Eberhard Karls University of Tübingen - Department of Women’s Health

Adrian Weghofer

Eberhard Karls University of Tübingen - Department of Women’s Health

Peter Loskill

University of Tübingen - NMI Natural and Medical Sciences Institute; Eberhard Karls University of Tübingen - Department of Women’s Health

Peter D. Jones

University of Tübingen - NMI Natural and Medical Sciences Institute

Katja Schenke-Layland

University of Tübingen - NMI Natural and Medical Sciences Institute; Eberhard Karls University of Tübingen - Department of Women’s Health

Abstract

Calcified aortic valve disease (CAVD) is the most prevalent valve disease in the elderly in the western world. Targeted pharmacological therapies are limited since the underlying mechanisms of CAVD are not well understood. Appropriate 3D in vitro models could potentially improve our knowledge of the disease. Here, we developed a 3D in vitro heart valve model that resembles the morphology of the valvular extracellular matrix and mimics the mechanical and physiological behavior of the aortic valve fibrosa and spongiosa. We employed cryogenic electrospinning to engineer a bi-layered cryogenic electrospun scaffold (BCES) with defined morphologies that allowed valvular endothelial cell (VEC) adherence and valvular interstitial cell (VIC) ingrowth into the scaffold. Using a self-designed cell culture insert allowed us to establish the valvular co-culture simultaneously by seeding VICs on one side and VECs on the other side of the electrospun scaffold. Proof-of-principle calcification studies were successfully performed using an established osteogenic culture protocol and the here designed 3D in vitro heart valve model.

Keywords: CAVD, heart valve, valvular interstitial cell, cryogenic electrospinning, cell culture

Suggested Citation

Stadelmann, Kathrin and Weghofer, Adrian and Loskill, Peter and Jones, Peter D. and Schenke-Layland, Katja, Development of a Bi-Layered Cryogenic Electrospun Polylactic Acid Scaffold to Study Calcific Aortic Valve Disease in a 3D Co-Culture Model. Available at SSRN: https://ssrn.com/abstract=3845715 or http://dx.doi.org/10.2139/ssrn.3845715

Kathrin Stadelmann

University of Tübingen - NMI Natural and Medical Sciences Institute ( email )

Reutlingen
Germany

Eberhard Karls University of Tübingen - Department of Women’s Health ( email )

Germany

Adrian Weghofer

Eberhard Karls University of Tübingen - Department of Women’s Health ( email )

Germany

Peter Loskill

University of Tübingen - NMI Natural and Medical Sciences Institute ( email )

Reutlingen
Germany

Eberhard Karls University of Tübingen - Department of Women’s Health ( email )

Germany

Peter D. Jones

University of Tübingen - NMI Natural and Medical Sciences Institute ( email )

Reutlingen
Germany

Katja Schenke-Layland (Contact Author)

University of Tübingen - NMI Natural and Medical Sciences Institute ( email )

Reutlingen
Germany

Eberhard Karls University of Tübingen - Department of Women’s Health ( email )

Germany

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