Jul 13, 2016 | By Alec

3D bioprinted organs could be called the Holy Grail of additive manufacturing, and numerous research teams around the world are working hard to realize 3D printed implantable tissue – though virtually all experts believe it will take several years before patients will actually benefit from it. But of all 3D printed organs, the heart would be the most desirable, and a team of Harvard researchers just completed an important step in that direction. As an exercise in exploring heart tissue engineering, a team led by professor Kit Kevin Parker just built a miniature ‘living’ stingray, a biohybrid creature made from a rat’s heart muscle tissue and 3D printed gold cartilage that responds to light ques.

Living is necessarily surrounded by quotation marks, because this mini stingray – the size of a coin – isn’t actually completely alive. The tissue cells are, and they can respond to light ques to facilitate movement, but the creature can’t actually make autonomous decisions, reproduce or anything else. It makes this breakthrough a whole lot less creepy, but it can certainly be called a disruptive breakthrough that could facilitate more innovations in the fields of robotics, artificial intelligence, bioengineering and 3D bioprinting.

An actual ray on the right, with its artificial cousin on the left.

Like most disruptive breakthroughs, it also started with a simple idea. Professor Parker’s young daughter loves the New England Aquarium in Boston, where he saw his daughter become completely entranced by stingrays. Watching the display, the professor started thinking about engineering muscles to move in the same sinuous pattern. “It struck me like a thunderbolt that I could build that system in the musculature, and that it would look very much like the [muscular] layer of the heart,” he recalled.

This unusual concept was taken to fellow Wyss researcher Sung-Jin Park, and quickly became a new project for researchers from the Disease Biophysics Group at the School of Engineering and Applied Sciences at Harvard. Also involved were researchers from the University of Illinois, the University of Michigan, and Stanford University’s Medical Center.

So how does it work? In a nutshell, this little stingray combines the latest advances in engineering, cell culture, genetics, and biomechanics in a single creature. Weighing just ten grams, the cyborg stingray is made from a very thin 3D printed gold skeleton, that has been overlaid with two thin layers of stretchy polymer. That polymer is covered with about 200,000 living cardiomyocyte cells, taken from a rat’s heart muscle. While it could’ve been built using electronics and motors, these would’ve made the ray much bulkier and less maneuverable.

Indeed, the real breakthrough can be found in those cells and what they do. They have been placed in a very specific pattern around the fins and have been genetically engineered to respond to light cues, which prompt contraction or release – resulting in movement. This technique comes out of a very recently pioneered genetic engineering method called optogenetics, which makes cells light-sensitive.

As a result, the cardiomyocyte cells push the fins up and down, propelling the little creature through water when exposed to certain light cues. Flashing lights even cause it to swim faster, which shining lights causes the ray to turn around corners. The 3D printed gold skeleton plays a crucial role in that process, as it effectively acts as cartilage and provides recoil – enabling the pectoral fins to bounce back to their original positions. Through this intricate set up, the ‘animal’ can even be guided to swim through an obstacle course .

It’s a remarkable creation that has just been detailed in the latest issue of the Science journal, in an article called Heartmaker's next step: a ray ‘biohybrid’, by Elizabeth Pennisi. As the researchers explained, “our ray outperformed existing locomotive biohybrid systems in terms of speed, distance traveled, and durability (six days), demonstrating the potential of self-propelled, phototactically activated tissue-engineered robots.”

The implications of this breakthrough are obviously enormous. Scientists have been increasingly looking into artificial lifeforms that can perform certain tasks inside the human body – such as worms that eat cancer cells, or nanoswimmers that attack hostile cells in your blood stream. Sensor-rich tissue creations are exactly what those researchers are looking for, and this miniature stingray could point them in the right direction. This is certainly not the last we’ve seen of 3D printed biohybrid creatures. As a side note, this creation could also help marine biologists better understand a ray’s swimming patterns.

An actual stingray.

But Parker is obviously focusing on the cardiomyocytes taken from a rat’s heart, as these provide him with a better understanding of how heart muscles move and how they can be genetically engineered. This could pave the way for synthetic pumps used in heart disease patients, built from a mixture of mechanical elements and organic tissue. “I want to build an artificial heart, but you're not going to go from zero to a whole heart overnight. This is a training exercise,” the professor said. “The heart's built the way it is for a reason. And we're trying to replicate as much of that function as we possibly can.”

While it will take years before Parker can really build his artificial heart, this 3D printed almost-living stingray is certainly a very important step in the right direction.



Posted in 3D Printing Application



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