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Transcatheter implantation of homologous "off-the-shelf" tissue engineered heart valves with self-repair capacity: long term functionality and rapid in vivo remodeling in sheep


Driessen-Mol, Anita; Emmert, Maximilian Y; Dijkman, Petra E; Frese, Laura; Sanders, Bart; Weber, Benedikt; Cesarovic, Nikola; Sidler, Michele; Leenders, Jori; Jenni, Rolf; Grünenfelder, Jürg; Falk, Volkmar; Baaijens, Frank P T; Hoerstrup, Simon P (2014). Transcatheter implantation of homologous "off-the-shelf" tissue engineered heart valves with self-repair capacity: long term functionality and rapid in vivo remodeling in sheep. Journal of the American College of Cardiology, 63(13):1320-1329.

Abstract

OBJECTIVES: To evaluate long-term in-vivo functionality, host cell repopulation and remodeling of "off-the-shelf" tissue-engineered transcatheter homologous heart-valves.
BACKGROUND: Transcatheter valve implantation has emerged as minimally-invasive alternative to conventional surgery in particular in elderly high-risk patients. However, currently used bio-prosthetic transcatheter valves are prone to progressive dysfunctional degeneration limiting their use in younger patients. To overcome these limitations the concept of tissue-engineered heart-valves with self-repair capacity has been introduced as next generation technology.
METHODS: In-vivo functionality, host cell repopulation, and matrix remodeling of tissue
engineered homologous transcatheter heart valves (TEHVs) was evaluated up to 24weeks as pulmonary-valve replacements (transapical access) in sheep (n=12). As a control, tissue-composition and -structure were analyzed in identical not implanted TEHVs (n=5).
RESULTS: Transcatheter implantation was successful in all animals. Valve functionality was excellent displaying sufficient leaflet motion and coaptation with only minor paravalvular leakage in some animals. Mild central regurgitation was detected after 8 weeks increasing to moderate after 24weeks, correlating to a compromised leaflet coaptation. Mean and peak transvalvular pressure-gradients were 4.4±1.6 and 9.7±3.0mmHg. Significant matrix-remodeling was observed in the entire valve and corresponded with the rate of host cell repopulation.
CONCLUSION: For the first time, the feasibility and long-term functionality of transcatheter based homologous off-the-shelf tissue-engineered heart-valves are demonstrated in a relevant preclinical-model. Such engineered heart-valves may represent an interesting alternative to current prostheses because of their rapid cellular repopulation, tissue remodeling and therewith self-repair capacity. The concept of homologous off-the-shelf tissue engineered heart-valves may therefore substantially simplify previous tissue-engineering concepts towards clinical translation.

Abstract

OBJECTIVES: To evaluate long-term in-vivo functionality, host cell repopulation and remodeling of "off-the-shelf" tissue-engineered transcatheter homologous heart-valves.
BACKGROUND: Transcatheter valve implantation has emerged as minimally-invasive alternative to conventional surgery in particular in elderly high-risk patients. However, currently used bio-prosthetic transcatheter valves are prone to progressive dysfunctional degeneration limiting their use in younger patients. To overcome these limitations the concept of tissue-engineered heart-valves with self-repair capacity has been introduced as next generation technology.
METHODS: In-vivo functionality, host cell repopulation, and matrix remodeling of tissue
engineered homologous transcatheter heart valves (TEHVs) was evaluated up to 24weeks as pulmonary-valve replacements (transapical access) in sheep (n=12). As a control, tissue-composition and -structure were analyzed in identical not implanted TEHVs (n=5).
RESULTS: Transcatheter implantation was successful in all animals. Valve functionality was excellent displaying sufficient leaflet motion and coaptation with only minor paravalvular leakage in some animals. Mild central regurgitation was detected after 8 weeks increasing to moderate after 24weeks, correlating to a compromised leaflet coaptation. Mean and peak transvalvular pressure-gradients were 4.4±1.6 and 9.7±3.0mmHg. Significant matrix-remodeling was observed in the entire valve and corresponded with the rate of host cell repopulation.
CONCLUSION: For the first time, the feasibility and long-term functionality of transcatheter based homologous off-the-shelf tissue-engineered heart-valves are demonstrated in a relevant preclinical-model. Such engineered heart-valves may represent an interesting alternative to current prostheses because of their rapid cellular repopulation, tissue remodeling and therewith self-repair capacity. The concept of homologous off-the-shelf tissue engineered heart-valves may therefore substantially simplify previous tissue-engineering concepts towards clinical translation.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Clinic for Cardiovascular Surgery
04 Faculty of Medicine > University Hospital Zurich > Division of Surgical Research
Dewey Decimal Classification:610 Medicine & health
Language:German
Date:2014
Deposited On:05 Feb 2014 14:31
Last Modified:05 Apr 2016 17:31
Publisher:Elsevier
ISSN:0735-1097
Publisher DOI:https://doi.org/10.1016/j.jacc.2013.09.082
PubMed ID:24361320

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