The Future of Tissue Engineering
Over the course of just one month, physician-scientist Jeffrey Lawson, a vascular surgeon and vascular biologist out of Duke University, successfully implanted three bioengineered blood vessels in human patients – a milestone that marks the culmination of a 15-year project and a breakthrough that Lawson calls “the end of the beginning” in the field of human tissue engineering.
Lawson, who claims to live in the place between the blood and the blood vessel, is a practicing MD in vascular surgery with a PhD in cell and molecular biology. Combined, his specialties have allowed him to both perform surgeries and maintain an active vascular research lab. It is this combination that ultimately fostered ideal conditions for the creation and implantation of the bioengineered blood vessels.
The ideal lab
Lawson’s laboratory at Duke concentrates on basic research related to blood, blood clotting, bleeding related to surgery, blood vessels and blood vessel structure.
“Our lab was uniquely suited to help do some of the basic science related to this tissue engineering project,” he says. “The research team was able to do all the surgical implants in the animal models that were required by the FDA before getting to humans.”
And, when it got to humans, Lawson was there to be the clinical vascular surgeon who could implant the graft himself, in his own patient, as part of the human clinical research. “This tissue engineering project has been intimately involved with my own research about how to put blood in a foreign tube and not have the blood clot,” he says.
Working in partnership with Laura Niklason, another physician-scientist and founder of the biotech tissue product company Humacyte, Lawson and his research team began to explore the possibility of engineering a blood vessel that would have the structural and biological requirements needed to be implanted as a replacement in a human.
The process was not easy. Lawson says the initial goal was to make “your blood vessel for you,” a goal that morphed and changed over time.
“We would make a prototype, implant it, it would fail, and we would make a new prototype – we did this for many years. We eventually got to the point where we could make a blood vessel for an animal from its own cells…but the cultivation of that, the growing time, it just takes too long,” Lawson says. “If you need a new vessel, you don’t always have a three-month window to grow it. So we had to back up and reconfigure.”
Building a cellular house
The final product implanted in Lawson’s three patients is a “vascular graft” that the human body can repopulate with its own cells after it is implanted; and, Lawson says, from a manufacturing standpoint, the graft can be available on demand.
The graft is developed on a biodegradable matrix that melts away over a period of weeks. The matrix is constructed using a bioabsorbable mesh that can be molded into any shape. Once the matrix is shaped into the blood vessel prototype size – about the diameter of a pinky – the matrix is seeded with screened, banked vascular human muscle cells, provided by Humacyte. After cell culture media, vitamins and other essential nutrients are added, the muscular cells begin to grow into the mesh and eventually replace the initial foreign materials with their own collagen.
“They set up their own structural network of cells,” Lawson says. “It’s basically like a cell house – in each room a cell lives and around them is the structure of the house.”
After the cells have built this house, Lawson says there is only one way to ensure the graft will not be rejected by its host, like so many other implanted organs often are: “We kill all the cells.”
“If you leave the cells in there and implant the graft with them, it can work, but it can also put that tube at risk of being identified or rejected by the host you put it in. So, to make it inert, we kill all the cells and we wash them away from the collagen tube that’s left,” he says.
The leftover tube is the structure that Lawson implants into the circulation system of a person or animal.
“The live cells grow into that structure just like it was a house waiting to be repopulated, which is really the magic in all this,” Lawson explains.
The “first-in-man” surgical implantations of the vascular grafts are considered successful and are being monitored closely. According to Lawson, the three patients currently show no signs of infection or clotting.
“Patients who are willing to help us advance medical technology by participating in clinical research are important – they’re as important as we [doctors] are,” Lawson says. “Having someone say, ‘I don’t know anything about this tissue engineering, but I trust you and it’s okay if you perform the surgery on me,’ takes a lot of courage. Those people understand the need and want for new medical technologies. I give them a lot of credit.”
Understanding the future
Despite the success of the bioengineered vascular grafts, Lawson knows there are plenty of hurdles to come in his field.
“We’ve been able to recreate the fundamental properties of a blood vessel both structurally and biologically, so I think we’ve got that first hurdle well controlled. There are still 1,000 questions we have to answer before we can evolve into creating other organs or tissues,” he says, “but I know it’s possible because every day in the world there’s a little fetus that knows how to grow not just a blood vessel, but a kidney and an eye, and all of that genetic programming lives within our own tissues – we just don’t understand it yet.”