Juliana Blum

Readily Available Tissue-Engineered Vascular Grafts

Nonimmunogenic, tissue-engineered vascular grafts stored long-term maintain their patency, strength, and function after transplant in large-animal models. Grow Your Own Blood Vessels Growing your own vegetables may be a well-established approach for a healthier life, but growing blood vessels for surgical transplantation is a more unusual pastime. But the idea of growing a readily available supply of blood vessels for surgical transplant into patients requiring, for example, a cardiac bypass or dialysis is not as far-fetched as it sounds. Although a patient’s own blood vessels can sometimes be used for the graft, often this is not possible. Engineered autologous blood vessels can be grown from endothelial cells taken from the patient and cultured on scaffolds, but this process takes 9 months or more, and often the patients cannot wait that long for surgery. Enter Dahl and her team with a new approach that provides readily available, off-the-shelf vascular grafts that retain their strength and patency during long-term storage and function successfully after vascular surgery in baboon and dog animal models. The authors grew their human vascular grafts by culturing smooth muscle cells from human cadavers (that is, allogeneic cells) on tubular scaffolds made from a biodegradable polymer called polyglycolic acid (PGA). The smooth muscle cells produced collagen and other molecules that formed an extracellular matrix. When the scaffold degraded, fully formed vascular grafts were left behind. The investigators then stripped the cells from the grafts, using detergent to make sure the grafts would not elicit an immune response when transplanted. These human vascular grafts were 6 mm or greater in diameter and retained their strength, elasticity, and patency even after storage in phosphate-buffered saline solution for a year. The human vascular grafts were tested in a baboon model of arteriovenous bypass in which the graft formed a direct conduit between an artery and a vein (an approach that enables human patients with kidney disease to undergo dialysis). The authors showed that the grafts in baboons restored blood flow and retained their patency and strength for up to 6 months. When the grafts were removed and examined histologically, they did not show evidence of fibrosis, calcification, or thickening of the vessel wall intima. But the authors wanted to test engineered vascular grafts with smaller diameters, which are often plagued by thrombi (blood clots) after transplant. To do this, they turned to a dog model of peripheral and coronary artery bypass, surgeries that require smaller-diameter vascular grafts. Using dog smooth muscle cells cultured on PGA scaffolds, they created canine vascular grafts with small diameters (3 to 4 mm). They then seeded these grafts with endothelial cells (from the dogs due to be recipients) because an endothelial cell lining helps to prevent blood clot formation. Using the engineered grafts, the investigators then conducted either peripheral or coronary artery bypass in the dog recipients and showed that they functioned effectively for at least 1 month. Together, these results demonstrate that durable vascular grafts derived from allogeneic donors and rendered nonimmunogenic by removal of donor cells are suitable for surgical transplant. The added advantage of being able to store these off-the-shelf vascular grafts long-term in a simple saline solution means that these can be made ahead of time and then are ready to go whenever they are needed. Growing blood vessels for a healthier life is as real as the home-grown asparagus in your garden. Autologous or synthetic vascular grafts are used routinely for providing access in hemodialysis or for arterial bypass in patients with cardiovascular disease. However, some patients either lack suitable autologous tissue or cannot receive synthetic grafts. Such patients could benefit from a vascular graft produced by tissue engineering. Here, we engineer vascular grafts using human allogeneic or canine smooth muscle cells grown on a tubular polyglycolic acid scaffold. Cellular material was removed with detergents to render the grafts nonimmunogenic. Mechanical properties of the human vascular grafts were similar to native human blood vessels, and the grafts could withstand long-term storage at 4°C. Human engineered grafts were tested in a baboon model of arteriovenous access for hemodialysis. Canine grafts were tested in a dog model of peripheral and coronary artery bypass. Grafts demonstrated excellent patency and resisted dilatation, calcification, and intimal hyperplasia. Such tissue-engineered vascular grafts may provide a readily available option for patients without suitable autologous tissue or for those who are not candidates for synthetic grafts.