In vitro investigation of aortic valve annuloplasty using prosthetic ring devices

Objectives: The remodeling of the dilatated valve annulus with a prosthetic ring for the repair of valve insufficiency is a well-established concept in mitral valve surgery, and may also be suitable for aortic valve reconstruction. In this study, two models of prosthetic aortic annuloplasty devices were investigated. Methods: Fresh porcine aortic roots (n = 16) were investigated in a pulsatile flow simulator after patch dilatation of the annulus and subsequent reconstruction using both an external and an internal prosthetic ring. For each configuration, leakage was determined by ultrasonic flow measurements and leaflet co-aptation by transesophageal echocardiography. In addition, valves’ motions were recorded by high-speed video. Results: By the use of the prosthetic annuloplasty rings, leakage volumes decreased significantly compared with the dilatated root, more pronounced with the intra-annular ring. Similarly, the co-aptation height of the leaflets increased. Pressure gradients were not significantly influenced by the ring application, but leaflet motion patterns changed from the usual trapezoid to a more rectangular opening characteristic, visible at both echocardiographic and high-speed video analysis. Conclusions: The reconstruction of a dilatated aortic valve annulus using external and internal ring devices is feasible and effective for reduction of regurgitation at which the internal ring provides a greater potential to decrease valve insufficiency.     

Engineering of large osteogenic grafts with rapid engraftment capacity using mesenchymal and endothelial progenitors from human adipose tissue

We investigated whether the maintenance in culture of endothelial and mesenchymal progenitors from the stromal vascular fraction (SVF) of human adipose tissue supports the formation of vascular structures in vitro and thereby improves the efficiency and uniformity of bone tissue formation in vivo within critically sized scaffolds. Freshly-isolated human SVF cells were seeded and cultured into hydroxyapatite scaffolds (1 cm-diameter, 1 cm-thickness) using a perfusion-based bioreactor system, which resulted in maintenance of CD34(+)/CD31(+) endothelial lineage cells. Monolayer-expanded isogenic adipose stromal cells (ASC) and age-matched bone marrow stromal cells (BMSC), both lacking vasculogenic cells, were used as controls. After 5 days in vitro, SVF-derived endothelial and mesenchymal progenitors formed capillary networks, which anastomosed with the host vasculature already 1 week after ectopic nude rat implantation. As compared to BMSC and ASC, SVF-derived cells promoted faster tissue ingrowth, more abundant and uniform bone tissue formation, with ossicles reaching a 3.5 mm depth from the scaffold periphery after 8 weeks. Our findings demonstrate that maintenance of endothelial/mesenchymal SVF cell fractions is crucial to generate osteogenic constructs with enhanced engraftment capacity. The single, easily accessible cell source and streamlined, bioreactor-based process makes the approach attractive towards manufacturing of clinically relevant sized bone substitute grafts.