Vascudyne, Inc.

Researchers at the University of Minnesota Twin Cities recently received a $3.7 million grant to prepare for a human clinical trial of artificial, bioengineered blood vessels. The new funding is through the U.S. Dept. of Defense’s Congressionally Directed Medical Research Programs. It will go toward the preparation needed for a human clinical trial of artificial, bioengineered blood vessels that grow with a patient. If the trial is successful, the vessel grafts could be used to prevent repeated surgeries in children with congenital heart defects. Patients who have heart defects at birth can often grow out of current vessel grafts and need to have larger vessels implanted several times while still growing, according to the researchers. “This grant is a major step forward and will allow us to do everything that’s necessary to get to day one of a first clinical trial where we would implant one of our lab-created blood vessels into an infant with a heart defect,” said Robert Tranquillo, a Distinguished McKnight University professor in the department of biomedical engineering and the department of chemical engineering and materials science. A University of Minnesota startup company, Vascudyne, will manufacture the vessel-like tubes to prepare for the clinical trial. The tubes will be grown using a donor’s skin cells in a lab. The cells are then removed to reduce the chance of rejection. Once the tube is implanted, it will be repopulated by the recipient’s own skin cells to allow it to grow. Funding from the grant will cover any remaining pre-clinical studies needed before proceeding to the human clinical trials. Tranquillo and Zeeshan Syedain, Vascudyne’s chief scientific officer and a senior research associate, will partner with Experimental Surgical Services in the University of Minnesota Medical School to test the tubes in lambs. “This research could have a major impact for children with heart defects. Instead of three, four or even five surgeries or interventions during their childhood, children would only need one surgery,” Tranquillo said. “This would substantially reduce trauma and risk for children and the overwhelming health care costs for families.” The study is a replication of a 2016 study when lamb’s cells repopulated tubes implanted into the main pulmonary artery and proved that the tubes grew in size with the lamb. Two lambs have been implanted with the tubes in the current clinical study. The tubes were placed in the left pulmonary artery branch that has grown with the lambs into adulthood. The research team is partnering with pediatric cardiac surgeons at Children’s Minnesota and Boston Children’s Hospital to help understand the pre-clinical data and design the first human clinical trial. If successful, Tranquillo hopes to move toward clinical trials with similar research involving bio-artificial pediatric heart valves that grow with a child.

A new report from University of Minnesota researchers shows that artificial heart valves implanted in lambs continued to grow and function for at least a year after surgery, a promising finding for pediatric patients in need of heart valve replacements. The procedure to make the valves has already been patented to University of Minnesota spinout Vascudyne, which is planning clinical trials. Vascudyne launched in 2018 to manufacture growing artificial arteries and valves. The valves were derived from post-natal lamb skin cells. Collagen from the cells can form into tubes in fibrin, creating an extracellular matrix. Donor cells were washed away to avoid stimulating an immune response, and three tubes were sutured together to form the artificial valve. Researchers also tested a more advanced version that covered the tubes in a sleeve. In the paper, published online in Science Translational Medicine, the University of Minnesota researchers showed that after implantation in pulmonary arteries, both versions of the engineered allograft valves recellularized and maintained function in growing lambs when tested a year after implantation. In the tubes-only cohort, two of four lambs experienced mild regurgitation in the valve and systolic pressure drops after a year, during which time the valves grew from 19mm to about 25mm. Two of three lambs receiving the sheathed valves had even less regurgitation and lower systolic pressure drops, with the same growth, while the third experienced moderate regurgitation in the valve. Valves that grow along with pediatric patients would address a major challenge for children requiring heart valve replacement. The current standard of care is replacement with chemically treated animal valves that do not grow, meaning the patients often require multiple open-heart surgeries to replace them as they grow. These animal valves frequently calcify over time and stop functioning. But in the trial, researchers also tested the valves against pediatric bioprosthetics used in humans, and the new valves had both lower levels of calcification and better blood flow. Robert Tranquillo, the senior researcher for the University of Minnesota team and professor of biological engineering, called the results “a huge step forward in pediatric heart research,” and said it was the first large animal model demonstration of an implanted valve growing with the animal into adulthood. Tranquillo and Zeeshan Syedain, the lead author on the paper and a senior research associate in Tranquillo’s lab, are co-inventors of Vascudyne’s foundational IP. Both Syedain and Tranquillo were coauthors on a 2016 Nature Communications proof-of-concept paper showing comparable grafts could grow in lambs.