We’re at the cusp of integrating miniaturized electronics and monitoring into engineered tissues and organs.
At the start of the 2009 Star Trek reboot (this is relevant, trust me), the USS Kelvin’s captain meets the enemy on their ship to try to negotiate a cease-fire. His crew uses a kind of sensing technology to track his vital signs—like heart rate, breathing, body temperature—right up to the moment of his untimely demise.
While we’re not quite up to the technology level of the Star Trek universe, the ability to remotely sense what’s going on in tissues and organs is something of a holy grail for bioengineers. This is especially true for artificial or engineered organs: If you’d grown a new kidney for a patient needing a transplant, for example, you’d want some way to monitor it and make sure it’s working properly. It’s something that the body does naturally, but that bioengineers have struggled to replicate.
“In the body, the autonomic nervous system keeps track of pH, chemistry, oxygen and other factors, and triggers responses as needed,” says Daniel Kohane, MD, PhD, a biomaterials researcher in Boston Children’s Hospital’s Anesthesia Department. “We need to be able to mimic the kind of intrinsic feedback loops the body has evolved in order to maintain fine control at the cellular and tissue level.”
The main challenge has been designing sensors that merge directly with engineered tissues. But it’s a challenge that Kohane and collaborators at Harvard and MIT may have overcome by building, in essence, cyborg tissues.
The autonomic nervous system (or ANS) Kohane referred to is the unconscious part of our nervous system. It works in the background, quietly coordinating all of our body’s vital functions and adjusting them as necessary.
With that as inspiration, Bozhi Tian, PhD, a postdoctoral fellow in the Kohane lab (now at the University of Chicago), worked with collaborators in the labs of Harvard’s Charles M. Lieber, PhD, and Robert Langer, ScD, to create the beginnings of an artificial ANS. Their system, reported in Nature Materials, consists of mesh-like networks of nanoscale silicon wires—about 80 nm in diameter, roughly 1,000 times narrower than a human hair—shaped into flat planes or puffy balls like cotton candy.
The wires are so small that, according to Kohane, they’re close in size to parts of the extracellular matrix—the lattice of materials that surrounds cells, helping regulate their function. And the networks are porous enough that the researchers were able to seed them with heart, nerve and smooth-muscle cells and get those cells to grow three-dimensionally around the networks.
On top of that, once the wires were incorporated into tissues, the team could measure electrical activity in the heart and nerve tissues, even tracking changes in response to heart and nerve-stimulating drugs. They could even detect changes in the acidity of fluids passing through an engineered, sensor-laden blood vessel—the kind of changes that our bodies might detect in tissues that are inflamed or don’t have enough oxygen.
“This represents the first example of truly merging electronics and tissue in 3D,” adds Bozhi, who was recently named one of Technology Review‘s top 35 innovators under 35 this year.
The team members see a big future for this tiny technology. Imagine, for instance, bioengineered cyborg blood vessels that could sense glucose levels and activate an implanted insulin pump, or nanoscale pacemakers coupled to nanoscale defibrillators within artificial heart tissue. Kohane also envisions “lab-on-a-chip” systems that would use engineered tissues to measure cellular reactions to potential new drugs.
With their strategy, Bozhi, Kohane and their colleagues have reversed some of the guiding principles of bioengineering. “Most of the time, your goal is to create scaffolds on which to grow tissues and then have those scaffolds degrade and dissolve away,” Kohane explains. “Here, the scaffold stays in the form of an embedded nanoscale network, and actually plays an active role in the tissue.”