Functional Living Trileaflet Heart Valves Grown In Vitro

I chose this paper because it was relevant to two of the classes I am taking right now. We have been talking about heart valves and heart-related mechanics in bioe 102, and the tissue engineering part is definitely related to our class. It might be relatively an old paper (2000) but I thought some of the techniques they used, like the pulse duplicator, were pretty interesting and overall an informative read.

In this study this group fabricated tri-leaflet heart valves by seeding autologous myofibroblasts and endothelial cells from sheep on a bioabsorbable polymer graft. A pulse duplicator was used to gradually increase the pressure and flow in order to mimic the function of heart so that the cells adjust themselves to in vivo conditions.

The major advancement of this approach over other tissue engineering attempts was that it does not have the shortcomings of mechanical valve replacements. Mechanical valve replacements have the risk of thromboembolism due to structural dysfunction and other mechanical shortcomings. Also these replacements often require anticoagulation therapy. Some valves may calcify prematurely and have limited durability. This approach eliminates these shortcomings by using autologous transplantation and mimicking in-vivo conditions using the pulse replicator.

This paper was actually a follow-up on another study. In the previous study the group had tried a transplantation of a single pulmonary valve. In this study they improved the original polymer graft to decrease the absorbability and strength of the graft. After cells were harvested for 14 days on the heart valve constructs they were implanted into the same lambs. The polymer graft would temporarily provide mechanical support and would gradually get absorbed as the cells produce their own ECM, which replaces the polymer. After transplantation different analysis were done on the TE valve periodically. These test compared different properties of the TE heart valve with normal heart valves and a control experiment. Control experiment was done using the same material, except that the cells and polymer graft were not put on the pulse duplicator. Some of these test included Polymer degradation analysis, tissue microconstructure, mechanical properties, and tissue analysis. Histology results showed that the cells were organized in a layered fashion, denser in the outer layer compared to inner layers. Mechanical tensile testing revealed that the strength of the implants were originally higher than normal tissue, but gradually leveled off to normal. Tissue analysis also showed collagen content 140% of normal tissue in 4 week, which increased to 180% (plateau level). DNA content was initially 65%, but rose up to 150% in 20 weeks.

Overall the valves showed higher formation of matrix proteins, a more organized structure, and favorable mechanical properties over the control experiment (static cell culture) The study only reported follow up until week 20 over which no evidence of thrombus, stenosis, or aneurysm, however at 16-20 weeks, central pulmonary regurgitation was reported.