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RESEARCH PRODUCT

Unseeded Elastomeric Single Leaflets Retain Function and Remodel After Implant In Ovine Pulmonary Outflow Tract

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description

Current materials for heart valve replacement and repair are limited by the inability to grow or remodel. Tissue engineered valves offer the potential to overcome these disadvantages by creating living structures, but is limited by the availability of biocompatible scaffold materials with desirable biomechanical properties. We assessed the in vivo performance of a novel scaffold poly(carbonate urethane) urea (PCUU), fabricated by electrospinning and implanted in the pulmonary outflow tract of sheep. PCUU was electrospun into elastomeric sheets of thickness ranging from 120-180 μm. Using cardiopulmonary bypass we replaced the native anterior pulmonary leaflet with an acellular PCUU leaflet. Valve function was evaluated by epicardial echocardiography at implant and explant at weeks 1 (n=3), 3 (n=3), 6 (n=3) and 16 (n=3). Histological, immunohistochemical, molecular imaging analyses and multi-photon imaging were performed on the explanted leaflets. Echocardiography demonstrated mobile functioning leaflets, with zero to mild pulmonary regurgitation. Molecular imaging showed increased levels of proteolytic activity and macrophage accumulation. Histology showed persistence of scaffold material up to 16 weeks with cellular infiltration throughout the leaflet. Picrosirius red revealed mature collagen deposition along the arterial surface of the construct at 6 and 16 weeks. These findings were corroborated by multi-photon analysis showing highly aligned collagen fibers across the leaflets. Both surfaces of the engineered leaflets were consistently covered with CD31 positive cells. The majority of cells expressed α-SMA and MMP2. CD45 positive cells, suggesting hematogenous origin, were found throughout the leaflet. These results suggest that: 1) PCUU can be a suitable polymer for valve bioengineering; 2) cell pre-seeding may not be required for tissue formation or remodeling for a functional engineered valve; 3) host cells seem to populate the leaflet either by migration from adjacent tissue or by attachment from circulating blood; 4) mature matrix orientation and increased proteolytic activity suggests active tissue remodeling. Longer term implants and the role of scaffold pre-seeding will require further study.