Autologous Human Tissue-Engineered Heart Valves: Prospects for Systemic Application

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Past efforts on heart valve replacement have concentrated on the development of pulmonary (to the lungs) rather than systemic valves and the resultant valves have also proved unable to properly grow, adapt, and heal. In their July 2006 article, Anita et al. successfully incorporated several recently published techniques of cell seeding using fibrin gel (as a cell carrier), cell culture on a biodegradable scaffold, and mechanical cell conditioning to induce more anisotropy and valve-like behavior. Cells simply cultured statically were compared with cells subject mechanical conditioning in a bioreactor that simulates blood flow in a human heart, especially during diastole (when the heart dilates as it is filled with blood).

The original cells were harvested from the vena saphena magma of a 77 year old man and then isolated using an automated cell staining system and three primary antibodies. The trileaflet heart valves were grown into the correct shape using a mold, stents to hold up each leaflet, and scaffolds that had been sterilized with 70% ethanol. These cells were allowed to grow with media which among other components, contained 10% fetal bovine serum. Cells were than either a.)simply left to grow on culture flasks, b.) simply left to grow in the aforementioned bioreactor, and c.) grown in the bioreactor mimicking the heart’s diastolic phase with pressure differences of 5 to 30 mm Hg. The cells in group c.) were analyzed after 2, 4, and 6 weeks while the a.) and b.) cells were analyzed at the 4 week mark only.

While the conditioning proved to have little effect on cell growth or collagen content, it did succeed in generating tissue with more uniform mechanical properties than the statically grown controls. While the tissue engineered valves were able to generate similar stress strain curves in the radial direction as compared real heart valves, they performed less strongly in the circumferential direction. This most likely contributed to a larger problem - the valves opened correctly but failed to close completely, allowing blood to flow in the opposite direction. While further efforts must obviously be made in perfecting this technique, this new method of valve replacement culture shows great promise.

I first chose this article for its creative application of recent advances to tailor and design a new way to create a sorely needed tissue engineered device; reading widely and applying previously proven results to our project design is something we could all come into the habit of doing as engineers. The methods of tissue culture and testing were too numerous to mention completely, but this article is a great example of a large scale combination of various analytic tools we have learned about in class including histology, recognition using antibodies, mechanical stress/strain testing, cell counting by dyes to determine DNA amount (similar to our technique of nuclear staining with DAPI).

(Terry sez: a direct link to the paper can be found here - http://circ.ahajournals.org/cgi/content/full/114/1_suppl/I-152)