Biological tissue engineering for Fontan failure using decellularized extracellular matrix: a systematic review

Journal of Translational Medicine, vol. 24

Abstract

BACKGROUND: Functional univentricular heart disease is the most severe congenital condition, managed by Fontan surgery, which is life-sustaining by creating a non-contractile conduit yet limited by long-term complications. Decellularized ECM (dECM) scaffolds reseeded with contractile human cells offer a promising solution, but key factors for such a biological tube remain undefined. AIM: To evaluate the potential of cardiac dECM as a scaffold for recellularization in the development of a contractile Fontan conduit. METHODS: A systematic review was performed of studies identified in PubMed, Embase, Web of Science, and the Cochrane Library on human or porcine cardiac tissue engineering. Decellularization outcome parameters included efficiency of DNA removal, ECM preservation, and cytocompatibility; recellularization parameters focused on cell viability, co-culture strategies, maturation, and contractility. RESULTS: Fifty-eight studies on decellularization of porcine or human cardiac tissue were included; 13 also investigated recellularization. Most studies reported more than 90% reduced DNA content and preserved ECM architecture, though quantitative ECM analyses and toxicity assessments were not often reported. Recellularization with cardiomyocyte (like) cells showed high viability, especially in slice monocultures. Co-culture with other cell types improved organization and sarcomere maturation. Functionality assessment in most studies showed spontaneous and synchronized contractions however remaining under normal physiological values. CONCLUSION: Cardiac dECM scaffolds hold promise for contractile Fontan conduits; however, standardized decellularization protocols, enhanced recellularization strategies, and integration of vascular and supportive cells are needed to advance clinical translation.

Authors 12

1. Elizaveta Polyakova Aachen Department of Anatomy and Embryology

   Leiden University Medical Center

   Affiliation as printed

   Department of Anatomy & Embryology, Leiden University Medical Center (LUMC), Leiden, The Netherlands

2. Marlon J.A. de Haan Aachen Department of Internal Medicine (Nephrology) & Einthoven Laboratory of Vascular and Regenerative Medicine

   Leiden University Medical Center

   Affiliation as printed

   Department of Internal Medicine (Nephrology) & Einthoven Laboratory of Vascular and Regenerative Medicine, Leiden University Medical Center (LUMC), Leiden, The Netherlands

3. Janine Maria van Gils Aachen Department of Anatomy and Embryology

   Leiden University Medical Center

   Affiliation as printed

   Department of Anatomy & Embryology, Leiden University Medical Center (LUMC), Leiden, The Netherlands

4. Boudewijn P. T. Kruithof Aachen Department of Cell and Chemical Biology Heart Lung Centre Department of Cardiology, Leiden University Medical Center

   Leiden University Medical Center

   Affiliation as printed

   Department of Cell and Chemical Biology, Leiden University Medical Center (LUMC), Leiden, The Netherlands

   Heart-Lung Center, Department of Cardiology, Leiden University Medical Center (LUMC), Leiden, The Netherlands

5. Mark Hazekamp Aachen Heart Lung Centre Department of Thoracic Surgery

   Leiden University Medical Center

   Affiliation as printed

   Heart-Lung Center, Department of Thoracic Surgery, Leiden University Medical Center (LUMC), Leiden, The Netherlands

6. Arno A.W. Roest Aachen Department of Pediatric Cardiology

   Leiden University Medical Center

   Affiliation as printed

   Department of Pediatric Cardiology, Leiden University Medical Center (LUMC), Leiden, The Netherlands

7. Jolanda J. Wentzel

   Erasmus MC

   Affiliation as printed

   Department of Cardiology, Erasmus Medical Center, Rotterdam, The Netherlands

8. M J Goumans Aachen Department of Cell and Chemical Biology

   Leiden University Medical Center

   Affiliation as printed

   Department of Cell and Chemical Biology, Leiden University Medical Center (LUMC), Leiden, The Netherlands

9. Daniel Biermann

   Universität Hamburg · University Medical Center Hamburg-Eppendorf

   Affiliation as printed

   Department of Congenital and Pediatric Heart Surgery, Children's Heart Clinic, University Heart & Vascular Center Hamburg, Hamburg, Germany

10. Marco C. DeRuiter Aachen Center of Congenital Heart Disease Amsterdam Leiden (CAHAL) Department of Anatomy and Embryology

    Leiden University Medical Center

    Affiliation as printed

    Center of Congenital Heart Disease Amsterdam Leiden (CAHAL), Location Leiden University Medical Center (LUMC), Leiden, The Netherlands

    Department of Anatomy & Embryology, Leiden University Medical Center (LUMC), Leiden, The Netherlands

11. Marten A. Engelse Aachen Department of Internal Medicine (Nephrology) & Einthoven Laboratory of Vascular and Regenerative Medicine

    Leiden University Medical Center

    Affiliation as printed

    Department of Internal Medicine (Nephrology) & Einthoven Laboratory of Vascular and Regenerative Medicine, Leiden University Medical Center (LUMC), Leiden, The Netherlands

12. Monique R.M. Jongbloed corresponding Aachen Center of Congenital Heart Disease Amsterdam Leiden (CAHAL) Department of Anatomy and Embryology Heart Lung Centre Department of Cardiology, Leiden University Medical Center

    Leiden University Medical Center

    Affiliation as printed

    Center of Congenital Heart Disease Amsterdam Leiden (CAHAL), Location Leiden University Medical Center (LUMC), Leiden, The Netherlands. m.r.m.jongbloed@lumc.nl

    Department of Anatomy & Embryology, Leiden University Medical Center (LUMC), Leiden, The Netherlands. m.r.m.jongbloed@lumc.nl

    Heart-Lung Center, Department of Cardiology, Leiden University Medical Center (LUMC), Leiden, The Netherlands. m.r.m.jongbloed@lumc.nl