Self-Regeneration: Coaxing the Body to Fix Itself

Kevin Rocco builds blood vessels in a laboratory. Sitting at his sunlit workbench, he offers up one of his meticulous creations in the palm of his hand. The white tube, made of soft elastic, is big enough for you to stick your thumb through. It looks like a worn-down pencil grip, but it’s actually one of the latest feats of engineering.

Compared to traditional blood vessels grafts, which are engineered to just sit in the body and serve as an artificial replacement for a natural vessel, Rocco’s designs may seem a little unusual: they’re meant to break down, and over a relatively short period of time. His lab-engineered arterial graft—or, transplanted blood vessel—is actually more like a specially crafted framework that coaxes the body into growing its own tissue, and it gradually gets chipped away as the body regenerates its own healthy blood vessel. Eventually, there won’t even be a hint of anything but the body’s regrown architecture.

“We’re providing the opportunity for your body to really heal itself,” said Rocco, who is a biomedical engineering graduate student at Yale University.

Rocco’s work on arterial grafts is at the forefront of a burgeoning field known as tissue engineering, or regenerative medicine. For the past few decades, the goal of tissue engineering has been to grow replacement body parts such as kidneys, livers, and muscles through a complex recipe of chemical solutions and electrical impulses in the laboratory.[1] This goal has been achieved for some organs, such as the first lab-grown human bladder[2]  that was successively transplanted back in 2006. However, regenerative medicine is shifting its focus to a more elegant approach: letting the body’s amazing healing capability do most of the work.[1] Naturally degradable structures, called scaffolds, are part of this shift.

“Degradable blood vessels use the same concept as degradable sutures you get after your wisdom teeth are pulled,” he explained. “But instead of having only your gums heal themselves and your sutures degrading away, we want to do something more complex than that.”

The shift in tissue engineering to focus on degradable devices grown inside the body isn’t arriving a moment too soon. Implantations of blood vessel transplants are the most common type of open-heart surgery in the United States.[3] Dialysis patients often need replacement veins, and dozens of other conditions are also typically treated with arterial grafts. Most of these grafts are either small veins plucked from a patient’s lower leg or synthetic blood vessels. However, these grafts are prone to clotting and infection and some patients, especially obese and diabetic patients, can’t depend on self-transplantation because their blood vessels are too weak to be relocated.[4]

 Despite the previous successes of growing human organs in lab, growing human blood vessel in a lab hasn’t been widespread. It’s expensive to try to recreate the conditions inside of the body—internal temperature, nutrient and oxygen supply, electrical stimulation—outside of the body, especially if scientists tried to mass-produce organs. It’s so complicated and time-consuming that although lab-grown organs are an exciting accomplishment, most researchers believe growing organs in a lab is cost-prohibitive.

These complications led Rocco and other people in his field to ask a simple question: Why grow a blood vessel in a jar when you can make your body grow a better one?

That’s where degradable, regenerative tissue engineering comes into play. In the simplest terms, all Rocco has to do is design the vessel, implant it in the body, and let nature run its course.

To make a degradable blood vessel graft, Rocco begins with a simple tube made out of special fabric. The fabric is white, thin, and porous; its holes, though naked to our eyes, are large enough to let cells that will help regenerate the tissue zoom in and out of the tube. Rocco soaks the tube in solution, encrusting it with a chainmail of naturally occuring polymers found in the body and thus strengthening the tube. Finally, Kevin seeds the graft with bone marrow stem cells from the patient’s body, which will prime the body to build natural tissue upon the scaffold.

Think about how you heal from a paper cut. Your body senses the wound, and then it sends the right cells to grow new tissue, flush out old cells, and your body has just regenerated

part of itself. This exact same principle applies to Rocco’s blood vessel grafts: the implanted graft tricks the body into thinking it’s wounded, coaxing the right cells to journey into the nest, flushing out old cells, and kick-starting regeneration of a new blood vessel.

“I’m really just building a nest for the body’s own cells by building the right structure, physically,” Rocco said. “The idea is that any cells that end up around the graft just think they’re repairing a very small portion of the artery.”

The nest is made of polymers naturally found in the body. Only when the new blood vessel is fully generated and functioning does the nest fully dissolve on its own, a time period that depends on the size and thickness of the vessel itself. This method of coaxing the body to regenerate its own tissue is a huge advantage over tissues grown outside the body: you don’t have to surgically remove the scaffolding, making the recovery process much easier.

These grafts just started being used in clinical trials in the United States in 2011, although there have already been 25 other successful trials in Japan. Dr. Christopher Breuer, Rocco’s mentor and a pediatric surgeon at the Yale School of Medicine, successfully designed and implanted a degradable, regenerative blood vessel in the heart of a 4-year-old girl. Six months later, doctors couldn’t even tell a difference between her regenerated tissue and her other blood vessel tissues.[4] 

As these medical devices shuffle through the process of FDA approval, scientists are expanding and improving the degradable and regenerative properties of the technology. Rocco’s next goal is to make a thicker-walled, stronger blood vessel graft that can be used to replace arteries, which must withstand higher blood pressure than veins. Furthermore, because the entire process of designing and then implanting these regenerative blood vessel scaffolds is still highly uncommon, other engineers are searching for ways to make the process as easily reproducible as possible. The hope is that one day, surgeons won’t have to wait for an expensive organ to grow in a lab; instead, they can take a ready-made blood vessel off a shelf and immediately implant it into a patient.[5] 

The future of engineering is headed down a path to take advantage of the innate healing power of our bodies — and it’s a future that we’ll likely reach in our lifetimes.

“Anybody who says we [as scientists] do all the work is crazy,” Rocco said, “because really it’s just about giving the cells the right opportunity — and they’ll do it all.”

References

  1. National Institutes of Health, Regenerative medicine, Accessed 18 Sept. 2012.
  2. R. Weiss, First bladders grown in lab transplanted, Washington Post, 2006.
  3. National Institutes of Health, What is coronary artery bypass grafting?, National Heart Lung Blood Disease, 23 Feb. 2012.
  4. H. Dodson, Rebuilding a heart, saving a life, Yale News, 2012.
  5. G. Vogel, Off-the-shelf blood vessels, Science Now, 2011.

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