CREATION OF VIABLE PULMONARY ARTERY AUTOGRAFTS THROUGH TISSUE ENGINEERING
CREATION OF VIABLE PULMONARY ARTERY AUTOGRAFTS THROUGH TISSUE ENGINEERING
Toshiharu Shinoka, MDa
Dominique Shum-Tim, MDa
Peter X. Ma, PhDb
Ronn E. Tanel, MDc
Noritaka Isogai, MDd
Robert Langer, PhDb
Joseph P. Vacanti, MD,
John E. Mayer, Jr., MDa
Problems with the cardiac system are one of the most common medical problems in the
They harvested cells from small sections of carotid artery or of the jugular vein in young lambs, homogenized these tissues and then used flow cytometry to sort out the epthilial cells from the fibroblasts. The epthilial cells were then seeded onto a tubular scaffold made of polyglactin woven mesh and sealed with a non-woven PGA mesh inside the lumen. This matrix was roughly 95% porous before seeding and was designed to biodegrade over 6 to 8 weeks. After the cells became confluent on the scaffolds, the TE arteries were implanted into the same lambs they had been harvested from and were allowed to grow for between 75 to 169 days before the lambs were killed and the TE arteries removed and examined.
They found that these artificial ateries show no signs of thrombus formation or calcification and that the original polymer scaffold had disappeared. All of the arteries showed an increase over their original diameter, although they still were not quite as large as the native arteries and they were somewhat thinner as well. Histological examination showed that the TE vessels resembled normal arteries in structure. Further testing revealed that they had about 70% of the normal collagen content and that they contained more calcium as well, although no overt calcification was visible.
The authors hope that this method could solve problems with immune rejection and donor scarcity for blood vessels. By employing a biodegradable scaffold, they can allow the TE vessels to grow and expand more than other implants are capable of, making them potentially useful in children with cardiac problems. These arteries can use the existing systems in the body to grow, repair and maintain themselves, giving them much better long term potential than inert implants. A major limitation right now with these blood vessels is their stiffness before implantation, when the polymer scaffold is still present.
I remember from previous BioE classes that tissue engineers have had a great deal of trouble creating artificial blood vessels that can take the strain put upon them by the pulsing pressure effects generated by the heart. The group in this article succeeded in this area and their technique offers considerable promise for clinical applications. I think they mostly need to investigate ways to reduce the amount of time it takes to prepare a device, since growing up an appropriate number of cells from the patients took several weeks in this case.
4 comments:
Have the authors also investigated the behaviors of endothelial cells for their artificial arteries? I'm curious because I've read that endothelial cells can express a wide array of genes in response to mechanical stresses. I suspect the stiffness of the artificial vessels before implantation have negatively affected the mechanotransduction pathways of the endothelial cells, and thus causing the final arteries to be smaller/thinner than the native ones.
Did the authors mention the possibility of developing a new polymer for the scaffold that would be more flexible yet still possess enough of the necessary original characteristics to allow the growth of arteries? Perhaps the thinness of the arteries is due to the difficulty getting growth factors and media to the interior cells while within the scaffold?
The challenge of creating something for children is quite difficult. The fact that children can grow, and thus their physiology, can be a problem in designing that most shy from. I like how this paper addressed that issue--very cool. But I have a question of the expansion mechanism. I can see that expanding radially would be easy to come by, given that tissue can take place of the biodegradable scaffold, so getting girth in that direction is no problem. But my question relates to the longitudinal expansion of the device. Is the in growth tissue supposed to provide support of its stretching? Also, how did they experimenters fix it into the body? Standard produced for tubular tissues use sutures, but one must also take into consideration their own material viability in bearing internal pressure loads. Was another route taken?
I believe that the cells they harvested from the arteries they collected from young lambs were endothelial cells, since they were part of the original arteries.
The authors did not mention exploring other scaffold materials, they seemed more interested in the method for seeding the cells onto the scaffold and growing them up rather than the actual scaffold material in this case. They did not mention any problems with nutrients diffusing into the cells. They did not try to introduce any vascularization before the arteries were implanted, so I believe they hoped the body would do this naturally.
The implantation of the arteries was accomplished in the usual manner, suturing them in place, I assume with sutures that biodegraded over time. The experimental period of this study was not long enough to see any substantial amount of longitudinal growth in the arteries, since the lambs would also have to grow a large amount for this to be necessary. They probably will try to study this in the future studies they alluded to.
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