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Canadian Journal of Cardiology

Recent Progress Toward Clinical Translation of Tissue-Engineered Heart Valves

  • Author Footnotes
    ‡ These authors contributed equally to this work.
    Bahram Mirani
    Footnotes
    ‡ These authors contributed equally to this work.
    Affiliations
    Translational Biology and Engineering Program, Ted Rogers Centre for Heart Research, Toronto, Ontario, Canada

    Institute of Biomedical Engineering, University of Toronto, Toronto, Ontario, Canada

    Department of Mechanical and Industrial Engineering, University of Toronto, Toronto, Ontario, Canada
    Search for articles by this author
  • Author Footnotes
    ‡ These authors contributed equally to this work.
    Shouka Parvin Nejad
    Footnotes
    ‡ These authors contributed equally to this work.
    Affiliations
    Translational Biology and Engineering Program, Ted Rogers Centre for Heart Research, Toronto, Ontario, Canada

    Institute of Biomedical Engineering, University of Toronto, Toronto, Ontario, Canada
    Search for articles by this author
  • Craig A. Simmons
    Correspondence
    Corresponding author: Dr Craig A. Simmons, Translational Biology and Engineering Program, Ted Rogers Centre for Heart Research, University of Toronto, 661 University Avenue, 14th Floor, Toronto, Ontario M5G 1M1, Canada. Tel.: +1-416-946-0548; fax: +1-416-978-7753.
    Affiliations
    Translational Biology and Engineering Program, Ted Rogers Centre for Heart Research, Toronto, Ontario, Canada

    Institute of Biomedical Engineering, University of Toronto, Toronto, Ontario, Canada

    Department of Mechanical and Industrial Engineering, University of Toronto, Toronto, Ontario, Canada
    Search for articles by this author
  • Author Footnotes
    ‡ These authors contributed equally to this work.
Published:April 07, 2021DOI:https://doi.org/10.1016/j.cjca.2021.03.022

      Abstract

      Surgical replacement remains the primary option to treat the rapidly growing number of patients with severe valvular heart disease. Although current valve replacements—mechanical, bioprosthetic, and cryopreserved homograft valves—enhance survival and quality of life for many patients, the ideal prosthetic heart valve that is abundantly available, immunocompatible, and capable of growth, self-repair, and life-long performance has yet to be developed. These features are essential for pediatric patients with congenital defects, children and young adult patients with rheumatic fever, and active adult patients with valve disease. Heart valve tissue engineering promises to address these needs by providing living valve replacements that function similarly to their native counterparts. This is best evidenced by the long-term clinical success of decellularised pulmonary and aortic homografts, but the supply of homografts cannot meet the demand for replacement valves. A more abundant and consistent source of replacement valves may come from cellularised valves grown in vitro or acellular off-the-shelf biomaterial/tissue constructs that recellularise in situ, but neither tissue engineering approach has yet achieved long-term success in preclinical testing. Beyond the technical challenges, heart valve tissue engineering faces logistical, economic, and regulatory challenges. In this review, we summarise recent progress in heart valve tissue engineering, highlight important outcomes from preclinical and clinical testing, and discuss challenges and future directions toward clinical translation.

      Résumé

      Le remplacement chirurgical reste l'option première pour traiter le nombre de patients atteints de cardiopathies valvulaires graves qui croît rapidement. Bien que les remplacements valvulaires actuels - mécaniques, bioprothétiques et valves homogreffes cryoconservées - améliorent la survie et la qualité de vie de nombreux patients, la prothèse valvulaire idéale, disponible en abondance, immunocompatible, capable de croître, de s'autoréparer et de fonctionner toute la vie, n'a pas encore été mise au point. Ces caractéristiques sont essentielles pour les patients pédiatriques présentant des anomalies congénitales, les enfants et les jeunes adultes atteints de fièvre rhumatismale et les adultes actifs souffrant de valvulopathie. L'ingénierie tissulaire des valves cardiaques promet de répondre à ces besoins en fournissant des substituts valvulaires vivants qui fonctionnent de manière similaire à leurs homologues natifs. La meilleure preuve en est le succès clinique à long terme des homogreffes pulmonaires et aortiques décellularisées, mais l'offre d'homogreffes peine à répondre à la demande de remplacement de valves. Une source plus abondante et harmonisée de valves de remplacement pourrait provenir de valves cellulaires cultivées in vitro ou de constructions acellulaires de biomatériaux/tissus disponibles dans le commerce qui se recellularisent in situ, mais aucune de ces deux approches d'ingénierie tissulaire n'a encore obtenu de succès à long terme lors d'essais précliniques. Au-delà des défis techniques, l'ingénierie tissulaire des valves cardiaques est confrontée à des défis logistiques, économiques et réglementaires. Dans cette revue, nous résumons les progrès récents dans le domaine de l'ingénierie tissulaire des valves cardiaques, soulignons les résultats importants des tests précliniques et cliniques, et discutons des défis et des orientations futures vers une application clinique.
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