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; Jolanda Kluin

doi:10.1016/j.jacbts.2020.09.011

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 journal › Article › Academic › peer-review

60 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 language	English
Pages (from-to)	1187-1206
Number of pages	20
Journal	JACC: Basic to Translational Science
Volume	5
Issue number	12
Early online date	Nov 2020
DOIs	https://doi.org/10.1016/j.jacbts.2020.09.011
Publication status	Published - 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.

Funders	Funder number
Dutch Federation of University Medical Centers
Dutch Heart Foundation
Ministerie van Economische Zaken en Klimaat
Netherlands Cardiovascular Research Initiative	CVON 2012-01
ZonMw : Dutch Organisation for Health Research and Development
Nederlandse Organisatie voor Wetenschappelijk Onderzoek	024.003.013
Koninklijke Nederlandse Akademie van Wetenschappen
National Institutes of Health	R01 HL114805, R01 HL136431, R01 HL147095

Keywords

cell biology/structural biology
valvular heart disease

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Uiterwijk, M., Smits, A. I. P. M., van Geemen, D., van Klarenbosch, B., Dekker, S., Cramer, M. J., van Rijswijk, J. W., Lurier, E. B., Di Luca, A., Brugmans, M. C. P., Mes, T., Bosman, A. W., Aikawa, E., Grundeman, P. F., Bouten, C. V. C., & Kluin, J. (2020). In Situ Remodeling Overrules Bioinspired Scaffold Architecture of Supramolecular Elastomeric Tissue-Engineered Heart Valves. JACC: Basic to Translational Science, 5(12), 1187-1206. https://doi.org/10.1016/j.jacbts.2020.09.011

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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.",

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Uiterwijk, M, Smits, AIPM , van Geemen, D, van Klarenbosch, B, Dekker, S, Cramer, MJ, van Rijswijk, JW, Lurier, EB, Di Luca, A, Brugmans, MCP, Mes, T, Bosman, AW, Aikawa, E, Grundeman, PF, Bouten, CVC & Kluin, J 2020, 'In Situ Remodeling Overrules Bioinspired Scaffold Architecture of Supramolecular Elastomeric Tissue-Engineered Heart Valves', JACC: Basic to Translational Science, vol. 5, no. 12, pp. 1187-1206. https://doi.org/10.1016/j.jacbts.2020.09.011

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AU - Smits, Anthal I.P.M.

AU - van Geemen, Daphne

AU - van Klarenbosch, Bas

AU - Dekker, Sylvia

AU - Cramer, Maarten Jan

AU - van Rijswijk, Jan Willem

AU - Lurier, E.B.

AU - Di Luca, A.

AU - Brugmans, M.C.P.

AU - Mes, T.

AU - Bosman, Anton W.

AU - Aikawa, Elena

AU - Grundeman, P.F.

AU - Bouten, Carlijn V.C.

AU - Kluin, Jolanda

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KW - valvular heart disease

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

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