A plump piece of farm-fresh chicken leg lay on a pristine surface at Harvard Medical School. With skin and bone, it was cut open precisely so that the bone hardly broke.
A robotic arm turned around, scanned the fracture, and carefully injected a liquid cocktail of ingredients into the crack, including some ingredients isolated from algae. With multiple ultrasound pulses, the fluid hardened into a bone-like material and sealed the fracture.
This wasn’t an avant-garde dinner show. Rather, it was an innovative experiment to find out whether ultrasound could one day be used to 3D print implants directly in our bodies.
Under the direction of Dr. Yu Shrike Zhang of Brigham and Women’s Hospital and Harvard Medical School, a recent study combined the unique properties of ultrasound and 3D printing to repair damaged tissue. At the heart of the technology is a mixture of chemicals that gel in response to sound waves – a mixture called “Sono-Ink”.
In one test, the team 3D printed a cartoon bone shape into a thick piece of isolated pork belly, with ultrasound easily penetrating layers of fatty skin and tissue. The technology also created hive-like structures in isolated pig livers and a heart shape in kidneys.
It may sound macabre, but the goal is not to 3D print emojis in living tissue. Instead, doctors could one day use ultrasound and sonic ink to directly repair damaged organs in the body, as an alternative to invasive surgeries.
As a proof of concept, the team used sono-ink to repair a broken region of an isolated goat heart. After a few ultrasound blasts, the resulting patch gelled and seamlessly interlocked with the surrounding heart tissue, essentially becoming a biocompatible, stretchy bandage.
In another test, the Sono-Ink was loaded with a chemotherapy drug and the concoction was injected into a damaged liver. Within minutes, the ink delivered the drug to injured areas while sparing most healthy surrounding cells.
The technology offers a way to convert open surgery into less invasive treatments, Drs. Yuxing Yao and Mikhail Shapiro from the California Institute of Technology, who were not involved in the study. It could also be used to print body-machine interfaces that respond to ultrasound, create flexible electronics for heart injuries, or efficiently deliver cancer drugs directly to the source after surgery to limit side effects.
“We are still a long way from bringing this tool to the clinic, but these tests have reaffirmed the potential of this technology,” Zhang said. “We’re very excited to see where we can go from here.”
From light to sound
Thanks to its versatility, 3D printing has captured the imagination of bioengineers when it comes to building artificial biological parts – such as stents for life-threatening heart diseases.
The process is usually iterative. An inkjet 3D printer – similar to an office printer – sprays a thin layer and “cures” it with light. This causes the liquid ink to solidify and then the printer builds up an entire structure layer by layer. However, for many materials, light can only illuminate the surface, making it impossible to create a fully printed 3D structure with one beam.
The new study turned to volumetric printing, in which a printer projects light into a volume of liquid resin and solidifies the resin into the object’s structure – and voilà, the object is built as a whole.
The process is much faster and creates objects with smoother surfaces than traditional 3D printing. However, it is limited by how far the light can shine through the ink and surrounding material – such as skin, muscle and other tissue.
This is where ultrasound comes into play. Ultrasound is best known for maternal care and, at low intensity, easily penetrates opaque layers such as skin or muscles without causing damage. Researchers are exploring so-called focused ultrasound technology to monitor and stimulate the brain and other tissues.
It has disadvantages. Sound waves blur as they travel through fluids, which are abundant in our bodies. When 3D printing structures, the sound waves could create an abnormality in the original design. To build an acoustic 3D printer, the first step was to redesign the ink.
A well-founded recipe
The team initially experimented with ink designs that cure using ultrasound. The recipe they came up with is a soup of molecules. Some solidify when heated; others absorb sound waves.
The Sono-Ink turns into a gel within a few minutes of the ultrasound pulses.
The process is self-propelled, Yao and Shapiro explained. Ultrasound triggers a chemical reaction that produces heat, which is absorbed by the gel and speeds up the cycle. Because the ultrasound source is controlled by a robotic arm, it is possible to focus the sound waves to a resolution of one millimeter – slightly thicker than the average credit card.
The team tested several sono-ink recipes and 3D printed simple structures, such as a multicolored three-piece gear and glow-in-the-dark structures that resemble blood vessels. This helped the team push the limits of the system and explore potential uses: a fluorescent 3D-printed implant, for example, could be easier to track in the body.
Good success
Next, the team turned to isolated organs.
In one test, they injected sono-ink into a damaged goat heart. A similar condition can lead to fatal blood clots and heart attacks in humans. The usual treatment is open-heart surgery.
The team injected sono-ink directly into the goat’s heart via blood vessels. Using precisely focused ultrasound pulses, the ink gels to protect the damaged region – without harming neighboring parts – and bonds to the heart’s own tissue.
In another test, they injected the ink into a fracture of a chicken leg and reconstructed the bone “with a seamless connection to the natural parts,” the authors write.
In a third test, they mixed doxorubicin, a chemotherapy drug commonly used for breast cancer, into the sono-ink and injected it into damaged parts of a pig’s liver. Using ultrasound beams, the ink settled into the damaged regions and gradually delivered the drug to the liver over the next week. The team believes this method could help improve cancer treatment after surgical removal of tumors, they explained.
The system is just a start. Sono-Ink has not yet been tested in a living body and could cause toxic effects. And while ultrasound is generally safe, the stimulation can increase sound wave pressure and heat tissue to a very toasty 158 degrees Fahrenheit. For Yao and Shapiro, these challenges can guide the technology.
The ability to quickly print soft 3D materials opens the door to new body-machine interfaces. Organ patches with embedded electronics could support long-term care for people with chronic heart disease. Ultrasound could also stimulate tissue regeneration in deeper parts of the body without invasive surgery.
Aside from biomedical applications, sono-ink could even make a splash in our everyday world. For example, 3D printed shoes are already on the market. It’s possible that “the running shoes of the future could be printed using the same acoustic method that repairs bones,” Yao and Shapiro wrote.
Image source: Alex Sanchez, Duke University; Junjie Yao, Duke University; Y. Shrike Zhang, Harvard Medical School