Towards a Tissue-Engineered Contractile Fontan-Conduit: The Fate of Cardiac Myocytes in the Subpulmonary Circulation

Abstract

The long-term outcome of patients with single ventricles improved over time, but remains poor compared to other congenital heart lesions with biventricular circulation. Main cause for this unfavourable outcome is the unphysiological hemodynamic of the Fontan circulation, such as subnormal systemic cardiac output and increased systemic-venous pressure. To overcome this limitation, we are developing the concept of a contractile extracardiac Fontan-tunnel. In this study, we evaluated the survival and structural development of a tissue-engineered conduit under in vivo conditions. Engineered heart tissue was generated from ventricular heart cells of neonatal Wistar rats, fibrinogen and thrombin. Engineered heart tissues started beating around day 8 in vitro and remained contractile in vivo throughout the experiment. After culture for 14 days constructs were implanted around the right superior vena cava of Wistar rats (n = 12). Animals were euthanized after 7, 14, 28 and 56 days postoperatively. Hematoxylin and eosin staining showed cardiomyocytes arranged in thick bundles within the engineered heart tissue-conduit. Immunostaining of sarcomeric actin, alpha-actin and connexin 43 revealed a well -developed cardiac myocyte structure. Magnetic resonance imaging (d14, n = 3) revealed no constriction or stenosis of the superior vena cava by the constructs. Engineered heart tissues survive and contract for extended periods after implantation around the superior vena cava of rats. Generation of larger constructs is warranted to evaluate functional benefits of a contractile Fontan-conduit.

In vitro validation of a self-driving aortic-turbine venous-assist device for Fontan patients

“… 39 Furthermore, poor power transmission efficiency has the potential to limit the hydrodynamic performance of ventricular assist. Cardiac assist systems that harvest the skeletal muscle power 40 , 41 , 42 to drive an IVC cuff, 43 , 44 atrial cardiomyoplasty, 45 or tissue-engineered beating TCPC conduits, 46 can eliminate the need for external power. However, these systems also have poor power transmission efficiency and for any meaningful IVC support, require pacing systems and valves to synchronize with the venous pulsatility.…”

Progress in experimental and clinical subpulmonary assistance for Fontan circulation

“…Several investigators are attempting to apply TERM technologies to advance the care of patients with congenital heart disease. [77][78][79] In an intriguing study, Biermann and colleagues 80 described attempts to create a ''contractile extracardiac Fontan-tunnel'' with engineered heart tissue. Further, some investigators, including those in our group, are using TERM technologies with the intent to recapitulate the entire heart, 81,82 which would obviate the need for a subpulmonary assist device.…”

Noteworthy Literature Published in 2016

“…This interesting work is starting to describe a way to potentially create a contractile Fontan-conduit for single-ventricle anatomy patients in the not too distant future. 13 Developing a living contractile conduit in humans will be challenging. It will need to come from an autologous cell source to avoid immune suppression medications being administered to the patient, and it must be able to grow as the child develops.…”