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, E.B. Lurier, A. Di Luca, M.C.P. Brugmans, T. Mes, Anton W. Bosman, Elena Aikawa, P.F. Grundeman, Carlijn V.C. Bouten (Corresponding author), Jolanda Kluin (Corresponding author)

Research output: Contribution to journalArticleAcademicpeer-review

47 Citations (Scopus)

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.
Original languageEnglish
Pages (from-to)1187-1206
Number of pages20
JournalJACC: Basic to Translational Science
Volume5
Issue number12
Early online dateNov 2020
DOIs
Publication statusPublished - Dec 2020

Funding

The authors would like to acknowledge Bente de Kort for performing the elastin assay, Marloes Janssen-van den Broek and Dr. Vivian Mouser for their expert help with the biaxial tensile tests, and Dr. Mark van Turnhout for his expert help in the quantifications of collagen and scaffold alignment. This research forms part of the iValve-II project, powered by Health∼Holland, top sector Life Sciences and Health (Grant number TTTI1403B), supported by the Dutch Ministry of Economic Affairs. This work was supported by the Netherlands Cardiovascular Research Initiative (CVON 2012-01): The Dutch Heart Foundation, Dutch Federation of University Medical Centers, the Netherlands Organization for Health Research and Development, the Royal Netherlands Academy of Sciences, and by the Gravitation Program “Materials Driven Regeneration,” funded by the Netherlands Organization for Scientific Research (024.003.013). Dr. Aikawa is supported by grants from the National Institutes of Health (R01 HL114805, R01 HL136431, R01 HL147095). Dr. Bouten is a shareholder of Xeltis BV. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. Drs. Tristan and Mes are employees of Suprapolix BV. Dr. Brugmans is an employee of Xeltis BV.

FundersFunder number
Dutch Federation of University Medical Centers
Dutch Heart Foundation
Dutch Ministry of Economic Affairs
Netherlands Cardiovascular Research InitiativeCVON 2012-01
Netherlands Organization for Health Research and Development
Nederlandse Organisatie voor Wetenschappelijk Onderzoek024.003.013
Royal Netherlands Academy of Arts and Sciences
National Institutes of HealthR01 HL114805, R01 HL136431, R01 HL147095

    Keywords

    • cell biology/structural biology
    • valvular heart disease

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