Currently, when small diameter blood vessels are obstructed, we sometimes have to replace them. The best option is to use a “less important” vessel and transplant it within the same patient. This is done, for example, when a vein from the leg is used to replace one on the heart. We also sacrifice healthy vessels to connect people with failed kidneys to a hemodialysis machine. Of course, we do not have a large supply of vessels that can be spared, and, unfortunately, these transplanted vessels most often do not last for the rest of the life of the patient. When biological vessels are not (no longer) available, surgeons use special plastic tubing. Unfortunately, the body recognizes these so-called “biomaterials” as foreign and will try to degrade them. This will cause inflammation, fibrosis, and thrombosis that can all lead to failure of the conduit. In addition, these materials can hide microorganism from the immune system and cause deadly infection. Also, these materials are very stiff compared to biological tissues and this will add to the poor ability of these synthetic grafts to work as blood vessels, especially when diameters are smaller than 5-6 mm.
With our current eating habits and more sedentary lifestyle, disease of the blood vessels (cardiovascular) is the most important cause morbidity and mortality in the richer countries. The need for hemodialysis, which linked to diabetes and hypertension, is also very important (about 2 million worldwide) and will likely increase at the population ages. Clearly, finding better blood vessel replacements would improve the life of millions.
Our approach is to produce biological vessels in the lab by using human cells in culture. This would avoid the use of synthetic materials that the body recognized as foreign while insuring an infinite supply of replacement vessels. We have previously shown that cells can lay down a sheet of material (called extracellular matrix) in the right culture conditions. We have previously shown that this cell-assembled matrix (CAM) can be used to produce vessel by rolling the sheets and that these vessels can perform well in humans. In this project, we want to create blood vessels by weaving yarn made from CAM because this will allow the production of vessels much more rapidly (so less expensively), reliably, and with better control over their properties. Our objectives are to 1) Create and characterize CAM yarn made in the lab with human and a large animal cells, 2) Test the biocompatibility (under the skin) of theses yarns in vivo (test human in an immunosuppressed rat model and the large animal yarn in the same selected large animal species), 3) Weave small diameter vessels with human and animal yarn, characterize them in vitro, and optimize their properties, and 4) Implant large animal woven vessels in the arterial circulation of the same species and evaluate their performance.
