Tissue-engineered bioprosthetic venous valve: A long-term study in sheep

Abstract

Objective: to develop a graft bearing an immunologically tolerated tissue-engineered venous valve (TE graft) that will be incorporated into a native vessel, and restore normal valve function for the treatment of chronic venous insufficiency. Methods: twenty-four TE grafts were grown using decellularised allogeneic ovine veins as donor matrix, which was subsequently repopulated with the future recipient's myofibroblasts (MFB) and endothelial cells (EC). TE grafts were implanted into the external jugular vein. Animals were sacrificed at 1, 6, and 12 weeks (n = 4, each). Autografts served as controls (1 week, n = 4; 6 weeks, n = 4). Specimen for histology and immunohistochemistry were taken. Results: the matrix was successfully repopulated with MFB and EC (n = 8). Patency on venography in the TE graft-group was 4/4, 4/4, and 3/4 at 1, 6, and 12 weeks, and 4/4 (4/4) in autografts at 1 (6) weeks, respectively. Except for 2 TE grafts after 12 weeks, valves were competent (duplex ultrasound). Patent TE grafts were merely distinguishable from autografts with minor inflammatory reactions. Reflux was caused by neo-intima formation related to the basis of the TE graft. Conclusion: acellularisation and consecutive in vitro autogenic re-seeding of valved venous conduits can lead to immunologically acceptable, patent, and competent implants in sheep.