Transplantation of Decellularized Venous Valvular Grafts in an Ovine Model

Abstract

The surgical treatment of end-stage chronic venous insufficiency involves valvular repair or transplantation to restore venous valve function and structure. Current valve substitutes can have issues with durability, thrombogenicity, susceptibility to infection, and a lack of growth potential. Therefore, the development of tissue-engineered venous valves represents a promising solution. Before clinical use of these grafts, in vivo animal testing is necessary. Here we describe the development of different surgical techniques for tissue-engineered venous valve transplantation in a low-pressure system (venous circulation) in a large animal model. Tissue-engineered vein valves prostheses were generated using decellularized jugular ovine Vein Valves (oVV) reseeded with ovine peripheral Blood-derived Endothelial Cells (oBEC). oVV were transplanted orthotopically and heterotopically in an ovine model. Four oVV were transplanted into the jugular position (two decellularized and two decellularized/reseeded vein valves). Two decellularized oVV were heterotopically transplanted into the superior vena cava after induction of Tricuspid Valve Insufficiency (TVI). All animals survived the surgery. After three months, grafts were explanted for histological evaluation. All grafts were permeable and the vascular wall was thickened compared with the native vein. Macroscopic examination revealed loss of valve cusps in all cases. Despite a postoperative regimen of anticoagulants, intraluminal thrombi of various dimensions were found in two implants. In all cases, the histology showed a distinct cell infiltration of the vein wall. Intrathoracic implantation and increase of venous pressure in systole did not prevent venous valve alteration. These findings suggest that proposed approaches are not a suitable for in vivo testing of such grafts.

Advances in Engineering Venous Valves: The Pursuit of a Definite Solution for Chronic Venous Disease

“…99 Decellularized ovine jugular vein segments containing bileaflet valves were preseeded with ovine peripheral bloodderived ECs for 12 h and cultured in a flow-loop bioreactor for 5 days. 100 In a pilot study, the reseeded grafts and the cell-free counterparts were implanted in an ovine model. Upon explantation at 3 months, all the grafts featured thickening of the vascular wall and loss of valvular leaflets.…”

“…Upon explantation at 3 months, all the grafts featured thickening of the vascular wall and loss of valvular leaflets. 100 The aforementioned studies have in common the use of decellularized native tissue as scaffold for cell ingrown and remodeling. However, the use of decellularized native tissue (derived from humans or animals) is still linked to concerns regarding immunorejection or disease transmission.…”