DALLAS – An investigational tissue-engineered vascular graft has enduring potential for vascular access for hemodialysis in patients with end-stage renal disease, based on early clinical results.
Moreover, other potential uses are on the horizon. The big picture involves subsequent extrapolation of this technology from the large-diameter, high-flow bioengineered vessels required for hemodialysis to the creation of small-diameter, low-flow vessels for coronary artery and peripheral arterial graft surgery, Dr. Jeffrey H. Lawson explained at the American Heart Association scientific sessions.
"Our goal is to make a tissue-engineered conduit that could be used widely throughout the body," said Dr. Lawson, professor of surgery and of pathology at Duke University Medical Center, Durham, N.C.
He presented the results from the first-in-man, ongoing phase I clinical experience with the Humacyte graft, which to date has been implanted to provide vascular access for hemodialysis in 28 patients, with 6-month patency as the primary study endpoint. This was a challenging study population, with an average of 4.1 previous access procedure failures per patient. The presentation at the AHA was the first public disclosure of the results of a project Dr. Lawson has been working on for more than 15 years. His surgical colleagues from Poland, who have done the implantations in patients with end-stage renal disease, were in attendance.
The overall 6-month patency was 100%, with no infections, no sign of an immune response, and no aneurysms or other indication of structural degeneration, he said.
Of the 28 patients, 20 had no further interventions, yielding a primary unassisted 6-month patency rate of 71%. Eight patients collectively underwent 10 interventions to maintain patency: eight had thrombectomies for graft- or surgically related thrombosis and two had venous anastomoses. Flow rates have remained suitable for dialysis in all patients, and the grafts are being used for dialysis three times per week. Dr. Lawson described the grafts as easy to cannulate via standard techniques.
He characterized these initial results as "quite remarkable" compared with the outcomes in two large studies of the current benchmark technologies, which are synthetic grafts made of PTFE (polytetrafluoroethyline). In those studies, the primary patency rate at 6 months was less than 50%, with a secondary patency rate of 77% and a 10% infection rate. In other studies, 30%-40% of PTFE grafts are abandoned within 12 months due to loss of patency.
The process of creating the bioengineered grafts begins with harvesting human aortic vascular smooth muscle cells, seeding them on a biodegradable matrix, then culturing them under pulsatile conditions. When the biodegradable matrix melts away, what remains is a tube comprised of vascular smooth muscle cells and extracellular matrix. This is then decellularized, yielding a tube of extracellular matrix that can be shipped off the shelf and around the world.
In primate models, the implanted bioengineered graft has been shown to repopulate with the host’s own vascular smooth muscle cells lined intimally by endothelium.
"Where we implanted an acellular structure, it appears to now be a living tissue, suggesting [the graft] has become their tissue, not ours," Dr. Lawson said.
To date, none of the bioengineered grafts implanted in patients has been explanted, so it’s unknown whether the favorable histologic changes seen in primates’ grafts also occur in humans. Larger clinical trials with longer follow-up are planned in order to assess the bioengineered graft’s durability.
Dr. Lawson’s study is funded by a Department of Defense research grant and by Humacyte. He serves as a consultant to the company.