Building heart tissue from scratch is hard work. Not only are chemistry, biology and all sorts of other -ologies involved, there's physics, too.
For instance, how do you mold a living, functioning hunk of heart tissue into just the right shape and get it to grow exactly how you want it to grow?
The answer, according to some University of Toronto engineers: Velcro.
Researchers at the Institute of Biomaterials and Biomedical Engineering at the U of T have been working on a method that would enable lab-built heart tissue to grow in three dimensions, just like real heart tissue. (So far, the stuff engineered in labs doesn't grow that way, and it's neither as strong nor as defined as real heart tissue.) They've found a way to link microscopic platforms — they are, in effect, scaffolds for the heart tissue — in a system reminiscent of the tiny hooks and loops that characterize Velcro.
They've laid out their findings in a recent research article in Science Advances. The goal spurring all that research and all that science is simple: to fix broken hearts.
"We'd have this functional tissue that would repair the damaged muscle of the heart after you have, say, a heart attack," says University of Toronto doctoral student Boyang Zhang, the lead author of the paper. "The other thing we're working on is how to deliver this in a minimally invasive way."
Yes, if Zhang and the other members of his team are ultimately successful, someday a surgeon could implant a preformed and flexible bit of robust heart tissue through a small incision in a patient's chest and use it to repair a damaged heart.
How far in the future?
"There are," Zhang warns, "a lot of hurdles we have to overcome."
T-shaped Hooks to the Rescue
The team at the University of Toronto's Laboratory for Functional Tissue Engineering, led by professor Milica Radisic, has overcome a lot already. First, two years ago, they discovered a way to get tissue to grow along a strand of surgical suture, like a single fiber in a heart muscle. They dubbed it the "biowire."
Next, they created a flat, kind of honeycombed-looking structure made out of a biodegradable flexible polymer to grow cells around. That was the "two-dimensional" part of the puzzle solved.
And then they ran into a wall in trying to get all 3-D.
They tried stacking individual sheets of cells on top of each other, but the cells took a lot of time to integrate with each other to form tissue. They tried 3-D printing in a gel, but while the cells were growing, they became deformed. With both of those methods, it was harder to see how each layer was performing by itself, too. Researchers had to rip apart the whole structure.
Sometime in 2014, the scientists came up with the right process.
"To scale that up to a 3-D structure, we had to think about how we can assemble these meshes together, somehow link them together," Zhang says. "That's when we came up with these T-shaped hooks. These hooks can go through the holes in the meshes and then grab onto another mesh, so you can lock two meshes together. That's kind of the idea of Tissue-Velcro."
Each flat mesh had T-shaped hooks engineered onto it. It was tricky. The T's are tiny — some less than 100 microns long, the diameter of a human hair. (A micron is one-millionth of a meter.)
"Initially, we made the hook too shallow," Zhang says. "So we had to play around with the height of the hooks."
Eventually, it worked. Cells grew around the scaffolds, and when researchers sent electrical impulses through the cells (to mimic the electrical impulses in a heart muscle), the entire structure beat in rhythm.
For one of their next steps, the engineers will see how Tissue-Velcro works in a living organism.
It's hard, painstaking work.
"But I think the results are meaningful. It's worth doing," Zhang says. "This entire field of tissue engineering has been around for almost a decade now. A lot of progress has been made. There's still a lot more to do. But the ultimate goal is very exciting."