Elephant trunks and garden hoses hardly seem like inspirations for a miniature 3D bioprinter.
Yet they’ve led scientists at McGill University to engineer the smallest reported bioprinting head to date. Described in the journal Devices, the device has a flexible tip just 2.7 millimeters in diameter—roughly the length of a sesame seed.
Bioprinters can deposit a wide range of healing materials directly at the site of injury. Some bioinks combat infections in lab studies; others deliver chemotherapy to cancerous sites, which could prevent tumors from recurring. On the operating table, biocompatible hydrogels injected during surgery help heal wounds.
The devices are promising but most are rather bulky. They struggle to reach all the body’s nooks and crannies—including, for example, the vocal cords.
It’s easy to take our ability to speak for granted and only appreciate its loss after catching a bad cold. But up to nine percent of people develop vocal-cord disorders in their lifetimes. Smoking, acid reflux, and chronic coughing tear at the delicate folds of tissue. Abnormal growths and cancers also contribute. These are usually removed with surgery that comes with a significant risk of scarring.
Hydrogels can help with healing. But because throat and vocal cord tissue is so intricate, current treatments inject it through the skin, rather than precisely into damaged regions.
But the new device can, in theory, sneak into a patient’s throat during surgery. Its tiny printhead doesn’t block a surgeon’s view, allowing near real-time printing after the removal of damaged tissues.
“I thought this would not be feasible at first—it seemed like an impossible challenge to make a flexible robot less than 3 mm in size,” Luc Mongeau, who led the study, said in a press release.
Although just a prototype, the device could one day help restore people’s voices after surgery and improve quality of life. It also could lead to the delivery of bioinks containing medications or even living cells to other tissues through the nose, mouth, or a small surgical cut.
Squishy Band-Aid
Surgery inevitably results in scars. While these are an annoyance on the skin, excessive scarring—called fibrosis—seriously limits how well tissues can do their jobs.
Fibrosis in lungs after surgery, for example, leads to infections, blood clots, and a general decline in normal breathing. Scarring of the heart tampers with its electrical signals and often leads to irregular heartbeats. And for delicate tissues like vocal cords, fibrosis causes lasting stiffness, making it difficult to intonate, sing, or talk like before—essentially robbing the person of their voice.
Scientists have found a range of molecules that could aid the healing process. Hydrogels are one promising candidate. Soft, flexible, and biocompatible, hydrogel injections provide a squishy but structured architecture supporting vocal cords. Studies also suggest hydrogels boost the growth the healthy tissues and reduce fibrosis.
But because vocal cords are difficult to target, injections are handled through the skin, making it difficult to control where the hydrogel goes.
An alternative is to 3D print hydrogels directly in the body and repair damage during surgery. Both handheld and robotic systems have been successfully tested in labs, and minimally invasive versions are on the rise. One design uses air pressure to bioprint hydrogels inside the intestines. Another taps into magnets to repair the liver. But existing devices are too large to accommodate vocal cords.
Surgical Trunks
To heal vocal cords, an ideal mini 3D bioprinter must seamlessly integrate into throat surgeries. Here, surgeons insert a microscope through the mouth and suspend it inside the throat. While it sounds uncomfortable, the procedure is highly efficient with little pain afterward.
The printhead needs to snake around the microscope but also flexibly adjust its position to target injured sites without blocking the surgeon’s view. Finally, the speed and force of the hydrogel spray should be controllable—avoiding the equivalent of accidentally squeezing out too much superglue.
The new bioprinter’s has a printhead a bit like an elephant’s trunk. It has a flexible arm that easily slips into the throat with a 2.7-millimeter arched nozzle at the end. Picture it as a fine-point Sharpie connected to a flexible tube. Three cables operate the printhead and control nozzle movement by applying tension, like strings on a puppet.
The system’s brain is in the actuator housing, which looks like a tiny plastic gift box. It holds a syringe of hydrogel for the printhead and pilots the adjustable cables using motors that precisely move the printhead to its intended location with a custom algorithm. Other electronics allow the team to control the setup using a wireless gaming controller in real time.
The actuator can be mounted under a standard throat surgery microscope so it’s out of the way during an operation, wrote the team.
To put the device through its paces, the team used the mini bioprinter to draw a range of shapes, including a square, heart, spiral, and various letters on a flat surface. The printhead accurately deposited thin lines of hydrogel, which can be stacked to form thicker lines—like repeatedly tracing drawings using a fine-tipped pen.
The team also tried it out in a mock vocal cord surgery. The “patient” was an accurate 3D model of a person’s throat but with different types of wounds to its vocal cords, including one that completely lacked half of the tissue. The bioprinter successfully made the repairs and reconstructed the missing vocal cord without issue.
“Part of what makes this device so impressive is that it behaves predictably, even though it’s essentially a garden hose—and if you’ve ever seen a garden hose, you know that when you start running water through it, it goes crazy,” said study author Audrey Sedal.
The flexibility comes at a cost. Though the printhead design deforms to prevent injury to tissues, this also means it’s more prone to mechanical vibrations from the actuator’s motors, which dings its accuracy.
As of now the mini printer requires manual control, but the team is working on a semi-autonomous version. More importantly, it needs to be pitted against standard hydrogel injection methods in living animals to show it’s safe and effective.
“The next step is testing these hydrogels in animals, and hopefully that will lead us to clinical trials in humans to test the accuracy, usability, and clinical outcomes of the bioprinter and hydrogel,” said Mongeau.
