The Use of Human Decellularized Amniotic Membrane as Pulmonary Valve Leaflets in Right Ventricular Outflow Tract Reconstruction – An in vivo Proof of Concept Study

Mohamed T Ghorbel^1*Tasneem Salih¹Giulia Parolari¹Katie Skeffington¹Sofia Di Leonardo²Danila Vella²Gaetano Burriesci²Massimo Caputo¹DOMINGA IACOBAZZI^3*

• ¹Bristol Medical School, Translational Health Sciences, University of Bristol, Bristol, United Kingdom
• ²Fondazione Ri.MED, Palermo, Italy
• ³University of Bristol, Bristol, United Kingdom

Abstract Introduction. Despite fundamental improvements in surgical treatment of Congenital Heart Defects, there are still challenges related to premature failure of the material used for such corrections, thus resulting in repeated operations during a patient's life. This is particularly the case for complex defects with Right Ventricular Outflow Tract (RVOT) obstruction, such as in Tetralogy of Fallot/Pulmonary Atresia, whereby the pulmonary valve reconstruction remains problematic due to short-term durability of the currently used replacement solutions. We set out to test, for the first time, the suitability of amniotic membrane derived from human placenta for use in cardiovascular replacement of pulmonary valve. Methods. The decellularized and preserved amniotic membrane, obtained through our optimised protocol, was characterised for mechanical and hydrodynamic properties in vitro, and then implanted in the RVOT position of two Landrace piglets for in vivo feasibility and performance evaluation. Results. Both the in vitro and in vivo assessments showed favourable outcomes. The decellularized amniotic membrane had mechanical properties comparable to the native porcine pulmonary valve leaflets. In hydrodynamic testing, the decellularized amniotic membrane-made valve exhibited favourable opening dynamics, with smooth and coordinated leaflet motion throughout the cycle. In vivo, the decellularized amniotic membrane-based valved conduit showed patency in the short-and long-term with no sign of stenosis or regurgitation. Discussion. This study provides an in vivo proof of concept that the decellularized amniotic membrane can be implanted and perform as functional pulmonary valve in a porcine animal model mimicking the clinical scenario of Tetralogy of Fallot surgical correction in infants.