In Situ Remodeling Overrules Bioinspired Scaffold Architecture of Supramolecular Elastomeric Tissue-Engineered Heart Valves

Marcelle Uiterwijk; Anthal I P M Smits; Daphne van Geemen; Bas van Klarenbosch; Sylvia Dekker; Maarten Jan Cramer; Jan Willem van Rijswijk; Emily B Lurier; Andrea Di Luca; Marieke C P Brugmans; Tristan Mes; Anton W Bosman; Elena Aikawa; Paul F Gründeman; Carlijn V C Bouten; Jolanda Kluin

doi:10.1016/j.jacbts.2020.09.011

In Situ Remodeling Overrules Bioinspired Scaffold Architecture of Supramolecular Elastomeric Tissue-Engineered Heart Valves

JACC Basic Transl Sci. 2020 Nov 25;5(12):1187-1206. doi: 10.1016/j.jacbts.2020.09.011. eCollection 2020 Dec.

Authors

Marcelle Uiterwijk¹, Anthal I P M Smits^{2

3}, Daphne van Geemen², Bas van Klarenbosch⁴, Sylvia Dekker², Maarten Jan Cramer⁴, Jan Willem van Rijswijk¹, Emily B Lurier^{2

5}, Andrea Di Luca², Marieke C P Brugmans⁶, Tristan Mes⁷, Anton W Bosman⁷, Elena Aikawa⁸, Paul F Gründeman⁹, Carlijn V C Bouten^{2

3}, Jolanda Kluin^{1

3}

Affiliations

¹ Department of Cardiothoracic Surgery, Amsterdam University Medical Center, Amsterdam, the Netherlands.
² Department of Biomedical Engineering, Eindhoven University of Technology, Eindhoven, the Netherlands.
³ Institute for Complex Molecular Systems, Eindhoven University of Technology, Eindhoven, the Netherlands.
⁴ Department of Cardiology, University Medical Center Utrecht, Utrecht, the Netherlands.
⁵ School of Biomedical Engineering, Science and Health Systems, Drexel University, Philadelphia, Pennsylvania, USA.
⁶ Xeltis B.V., Eindhoven, the Netherlands.
⁷ SupraPolix B.V., Eindhoven, the Netherlands.
⁸ Center for Excellence in Vascular Biology, Division of Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
⁹ Department of Cardiothoracic Surgery, University Medical Center Utrecht, Utrecht, the Netherlands.

Abstract

In situ tissue engineering that uses resorbable synthetic heart valve scaffolds is an affordable and practical approach for heart valve replacement; therefore, it is attractive for clinical use. This study showed no consistent collagen organization in the predefined direction of electrospun scaffolds made from a resorbable supramolecular elastomer with random or circumferentially aligned fibers, after 12 months of implantation in sheep. These unexpected findings and the observed intervalvular variability highlight the need for a mechanistic understanding of the long-term in situ remodeling processes in large animal models to improve predictability of outcome toward robust and safe clinical application.

Keywords: GPC, gel permeation chromatography; SEM, scanning electron microscopy; TEHV, tissue-engineered heart valve; TTE, transthoracic echocardiography; aTEHV, anisotropic tissue-engineered heart valve; cell biology/structural biology; rTEHV, random tissue-engineered heart valve; valvular heart disease.