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

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. To evaluate the potential of cardiac dECM as a scaffold for recellularization in the development of a contractile Fontan conduit. 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. 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. 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.