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.
To read this article in full you will need to make a payment
Purchase one-time access:
Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online accessOne-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:
Subscribe to Canadian Journal of CardiologyAlready a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
References
- Global, regional, and national burden of calcific aortic valve and degenerative mitral valve diseases 1990-2017.Circulation. 2020; 141: 1670-1680
- The incidence of congenital heart disease.J Am Coll Cardiol. 2002; 39: 1890-1900
- Epidemiology of valvular heart disease in the adult.Nat Rev Cardiol. 2011; 8: 162-172
- Will heart valve tissue engineering change the world?.Nat Clin Pract Cardiovasc Med. 2005; 2: 60-61
- Thrombosis of prosthetic heart valves: diagnosis and therapeutic considerations.Heart. 2007; 93: 137-142
- Infective endocarditis in adults: diagnosis, antimicrobial therapy, and management of complications: a scientific statement for healthcare professionals from the American Heart Association.Circulation. 2015; 132: 1435-1486
- 2020 ACC/AHA guideline for the management of patients with valvular heart disease: executive summary: a report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines.J Am Coll Cardiol. 2021; 77: 450-500
- Durability of prostheses for transcatheter aortic valve implantation.Nat Rev Cardiol. 2016; 13: 360-367
- Allograft heart valves: current aspects and future applications.Biopreserv Biobank. 2017; 15: 148-157
- Long-term outcomes after autograft versus homograft aortic root replacement in adults with aortic valve disease: a randomised controlled trial.Lancet. 2010; 376: 524-531
- Functional living trileaflet heart valves grown in vitro.Circulation. 2000; : 44-49
- Minimally-invasive implantation of living tissue engineered heart valves a comprehensive approach from autologous vascular cells to stem cells.J Am Coll Cardiol. 2010; 56: 510-520
- In vivo remodeling and structural characterization of fibrin-based tissue-engineered heart valves in the adult sheep model.Tissue Eng Part A. 2009; 15: 2965-2976
- In vivo monitoring of function of autologous engineered pulmonary valve.J Thorac Cardiovasc Surg. 2010; 139: 723-731
- From stem cells to viable autologous semilunar heart valve.Circulation. 2005; 111: 2783-2791
- Tissue-engineered heart valve with a tubular leaflet design for minimally invasive transcatheter implantation.Tissue Eng Part C Methods. 2015; 21: 530
- Development of a completely autologous valved conduit with the sinus of valsalva using in-body tissue architecture technology: a pilot study in pulmonary valve replacement in a beagle model.Circulation. 2010; 122: S100-S106
- Development of an in vivo tissue-engineered, autologous heart valve (the biovalve): preparation of a prototype model.J Thorac Cardiovasc Surg. 2007; 134: 152-159
- Sutureless aortic valve replacement using a novel autologous tissue heart valve with stent (stent biovalve): proof of concept.J Artif Organs. 2015; 18: 185-190
- Implantation of a tissue-engineered tubular heart valve in growing lambs.Ann Biomed Eng. 2017; 45: 439-451
- 6-Month aortic valve implantation of an off-the-shelf tissue-engineered valve in sheep.Biomaterials. 2015; 73: 175-184
- Human cell–derived tissue-engineered heart valve with integrated Valsalva sinuses: toward native-like transcatheter pulmonary valve replacements.NPJ Regen Med. 2019; 4: 14
- Computational modeling guides tissue-engineered heart valve design for long-term in vivo performance in a translational sheep model.Sci Transl Med. 2018; 10: eaan4587
- Development of an off-the-shelf tissue-engineered sinus valve for transcatheter pulmonary valve replacement: a proof-of-concept study.J Cardiovasc Transl Res. 2018; 11: 182-191
- Percutaneous pulmonary valve replacement using completely tissue-engineered off-the-shelf heart valves: six-month in vivo functionality and matrix remodelling in sheep.EuroIntervention. 2016; 12: 62-70
- 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.J Am Coll Cardiol. 2014; 63: 1320-1329
- Off-the-shelf human decellularized tissue-engineered heart valves in a nonhuman primate model.Biomaterials. 2013; 34: 7269-7280
- In situ heart valve tissue engineering using a bioresorbable elastomeric implant—from material design to 12 months follow-up in sheep.Biomaterials. 2017; 125: 101-117
- In situ remodeling overrules bioinspired scaffold architecture of supramolecular elastomeric tissue-engineered heart valves.JACC Basic Transl Sci. 2020; 5: 1187-1206
- A novel restorative pulmonary valved conduit in a chronic sheep model: mid-term hemodynamic function and histologic assessment.J Thorac Cardiovasc Surg. 2018; 155 (2591-601.e3)
- Midterm performance of a novel restorative pulmonary valved conduit: preclinical results.EuroIntervention. 2017; 13: e1418-e1427
- JetValve: rapid manufacturing of biohybrid scaffolds for biomimetic heart valve replacement.Biomaterials. 2017; 133: 229-241
- Early insight into in-vivo recellularization of cell-free allogenic heart valves.Ann Thorac Surg. March 2019;
- Performance of SynerGraft decellularized pulmonary allografts compared with standard cryopreserved allografts: results from multiinstitutional data.Ann Thorac Surg. 2017; 103: 869-874
- Ten years of clinical results with a tissue-engineered pulmonary valve.Ann Thorac Surg. 2011; 92: 1308-1314
- Performance of SynerGraft decellularized pulmonary homograft in patients undergoing a ross procedure.Ann Thorac Surg. 2011; 91: 416-423
- Fifty-two months’ mean follow up of decellularized SynerGraft-treated pulmonary valve allografts.J Heart Valve Dis. 2008; 17 (discussion 104): 98-104
- Decellularized fresh homografts for pulmonary valve replacement: a decade of clinical experience.Eur J Cardiothoracic Surg. 2016; 50: 281-290
- Mid-term clinical results using a tissue-engineered pulmonary valve to reconstruct the right ventricular outflow tract during the ross procedure.Ann Thorac Surg. 2007; 84: 729-736
- In vivo performance of freeze-dried decellularized pulmonary heart valve allo- and xenografts orthotopically implanted into juvenile sheep.Acta Biomater. 2018; 68: 41-52
- The immune response to crosslinked tissue is reduced in decellularized xenogeneic and absent in decellularized allogeneic heart valves.Int J Artif Organs. 2015; 38: 199-209
- Adverse results of a decellularized tissue-engineered pulmonary valve in humans assessed with magnetic resonance imaging.Eur J Cardiothoracic Surg. 2013; 44: e272-e279
- Right ventricular outflow tract reconstruction with decellularized porcine xenografts in patients with congenital heart disease.J Heart Valve Dis. 2011; 20: 341-347
- Decellularized xenogenic heart valves reveal remodeling and growth potential in vivo.Tissue Eng. 2006; 12: 2059-2068
- Early failure of the tissue engineered porcine heart valve SynerGraft in pediatric patients.Eur J Cardiothoracic Surg. 2003; 23: 1002-1006
- Molecular and functional characteristics of heart-valve interstitial cells.Philos Trans R Soc B Biol Sci. 2007; 362: 1437-1443
- Mesenchymal stem cells in health and disease.Nat Rev Immunol. 2008; 8: 726-736
- Prenatally fabricated autologous human living heart valves based on amniotic fluid derived progenitor cells as single cell source.Circulation. 2007; 116 (I-64-70)
- Living autologous heart valves engineered from human prenatally harvested progenitors.Circulation. 2006; 114 (I-125-31)
- Use of human umbilical cord blood–derived progenitor cells for tissue-engineered heart valves.Ann Thorac Surg. 2010; 89: 819-828
- Living patches engineered from human umbilical cord derived fibroblasts and endothelial progenitor cells.Eur J Cardiothoracic Surg. 2005; 27: 795-800
- Human umbilical cord perivascular (HUCPV) cells: a source of mesenchymal progenitors.Stem Cells. 2005; 23: 220-229
- Porcine umbilical cord perivascular cells for preclinical testing of tissue engineered heart valves.Tissue Eng Part C Methods. 2021; 27: 35-46
- Engineering pulmonary valve tissue sheets from human umbilical cord perivascular cells and electrospun polyurethane.Struct Heart. 2020; 4: 203
- BMP10 signaling promotes the development of endocardial cells from human pluripotent stem cell-derived cardiovascular progenitors.Cell Stem Cell. 2021; 28 (96-111.e7)
- Hemodynamic and cellular response feedback in calcific aortic valve disease.Circ Res. 2013; 113: 186-197
- Inhibition of pathological differentiation of valvular interstitial cells by C-type natriuretic peptide.Arterioscler Thromb Vasc Biol. 2011; 31: 1881-1889
- Deficiency of natriuretic peptide receptor 2 promotes bicuspid aortic valves, aortic valve disease, left ventricular dysfunction, and ascending aortic dilatations in micenovelty and significance.Circ Res. 2018; 122: 405-416
Nataly M. Siqueira, Chung S, Simmons CA, Santerre JP. Heparin-coated, self-assembled nanoparticle-delivery system for in situ supply of exogenous C-type natriuretic peptide during myocardial remodeling. Poster presented at: Biomedical Engineering Society 2020 Annual Meeting. October 14--19, 2020; Virtual.
- Tissue-engineered fibrin-based heart valve with bio-inspired textile reinforcement.Adv Healthc Mater. 2016; 5: 2113-2121
- Engineering of a bio-functionalized hybrid off-the-shelf heart valve.Biomaterials. 2014; 35: 2130-2139
- 3D Bioprinting of heterogeneous aortic valve conduits with alginate/gelatin hydrogels.J Biomed Mater Res Part A. 2013; 101A: 1255-1264
- Three-dimensional printed trileaflet valve conduits using biological hydrogels and human valve interstitial cells.Acta Biomater. 2014; 10: 1836-1846
- Differential regulation of macrophage inflammatory activation by fibrin and fibrinogen.Acta Biomater. 2017; 47: 14-24
- Elastic fiber production in cardiovascular tissue-equivalents.Matrix Biol. 2003; 22: 339-350
- Fibrin as a cell carrier in cardiovascular tissue engineering applications.Biomaterials. 2005; 26: 3113-3121
- Synthetic biomaterials as instructive extracellular microenvironments for morphogenesis in tissue engineering.Nat Biotechnol. 2005; 23: 47-55
- In vitro model of a fibrosa layer of a heart valve.ACS Appl Mater Interfaces. 2015; 7: 20012-20020
- Fabrication and in vitro characterization of a tissue engineered PCL-PLLA heart valve.Sci Rep. 2018; 8: 8187
- Anisotropic poly(ethylene glycol)/polycaprolactone hydrogel–fiber composites for heart valve tissue engineering.Tissue Eng Part A. 2014; 20: 2634-2645
- Rapid 3D printing of anatomically accurate and mechanically heterogeneous aortic valve hydrogel scaffolds.Biofabrication. 2012; 4035005
- Electrospun polyurethane and hydrogel composite scaffolds as biomechanical mimics for aortic valve tissue engineering.ACS Biomater Sci Eng. 2016; 2: 1546-1558
- Heart valve scaffold fabrication: bioinspired control of macro-scale morphology, mechanics and micro-structure.Biomaterials. 2018; 150: 25-37
- Taking bioengineered heart valves from faulty to functional.Nature. 2018; 559: 42-43
- In vivo repopulation of xenogeneic and allogeneic acellular valve matrix conduits in the pulmonary circulation.Ann Thorac Surg. 2003; 75: 1457-1463
- In vivo recellularization of plain decellularized xenografts with specific cell characterization in the systemic circulation: histological and immunohistochemical study.Artif Organs. 2006; 30: 233-241
- Biomechanical conditioning of tissue engineered heart valves: too much of a good thing?.Adv Drug Deliv Rev. 2016; 96: 161-175
- Controlled cyclic stretch bioreactor for tissue-engineered heart valves.Biomaterials. 2009; 30: 4078-4084
- Tissue engineering of human heart valve leaflets: a novel bioreactor for a strain-based conditioning approach.Ann Biomed Eng. 2005; 33: 1778-1788
- Heart valve mechanobiology in development and disease.Molecular and Cellular Mechanobiology. Springer, New York2016: 255-276
- An overview of tissue and whole organ decellularization processes.Biomaterials. 2011; 32: 3233-3243
- Effects of decellularization on the mechanical and structural properties of the porcine aortic valve leaflet.Biomaterials. 2008; 29: 1065-1074
- Improved geometry of decellularized tissue engineered heart valves to prevent leaflet retraction.Ann Biomed Eng. 2016; 44: 1061-1071
- Next-generation tissue-engineered heart valves with repair, remodelling and regeneration capacity.Nat Rev Cardiol. 2021; 18: 92-116
- Biologically inspired scaffolds for heart valve tissue engineering via melt electrowriting.Small. 2019; 151900873
- Endothelial nitric oxide signaling regulates Notch1 in aortic valve disease.J Mol Cell Cardiol. 2013; 60: 27-35
- Challenges in translating tissue engineered heart valves into clinical practice.Eur Heart J. 2017; 38: 619-621
- Bioengineered human blood vessels.Science. 2020; 370: eaaw8682
Article info
Publication history
Published online: April 07, 2021
Accepted:
March 14,
2021
Received:
January 11,
2021
Footnotes
See page 1074 for disclosure information.
Identification
Copyright
© 2021 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.
