Developed by engineers at Duke University and Harvard Medical School, the ink can be used in deep tissues for biomedical purposes ranging from bone healing to heart valve repair. The team’s findings are detailed in Science.
Dubbed deep-penetrating acoustic volumetric printing (DVAP), the process has been developed by Y. Shrike Zhang, associate bioengineer at Brigham and Women’s Hospital and associate professor at Harvard Medical School, and Junjie Yao, associate professor of biomedical engineering at Duke.
This new technique involves a specialised ink that reacts to soundwaves rather than light, enabling them to create biomedically useful structures at unprecedented tissue depths.
“DVAP relies on the sonothermal effect, which occurs when soundwaves are absorbed and increase the temperature to harden our ink,” Yao said in a statement. “Ultrasound waves can penetrate more than 100 times deeper than light while still spatially confined, so we can reach tissues, bones and organs with high spatial precision that haven’t been reachable with light-based printing methods.”
The first component of DVAP involves the sono-ink (a sonicated ink) which is a combination of hydrogels, microparticles and molecules designed to react to ultrasound. Once the sono-ink is delivered into the target area, a specialised ultrasound printing probe sends focused ultrasound waves into the ink, hardening portions of it into intricate structures.
“The ink itself is a viscous liquid, so it can be injected into a targeted area fairly easily, and as you move the ultrasound printing probe around, the materials in the ink will link together and harden,” said Zhang. “Once it’s done, you can remove any remaining ink that isn’t solidified via a syringe.”
According to Duke, the different components of the sono-ink enable the researchers to adjust the formula for a variety uses; if they want to create a scaffold to help heal a broken bone or make up for bone loss, they can add bone mineral particles to the ink. This flexibility also allows them to engineer the hardened formula to be more durable or more degradable, depending on its use. They can also adjust the colours of their final print.
The team conducted three tests as a proof-of-concept of their new technique. The first involved using the ink to seal off a section in a goat’s heart. When a human has nonvalvular atrial fibrillation, the heart will not beat correctly, causing blood to pool in the organ. Traditional treatment often requires open-chest surgery to seal off the left atrial appendage to reduce the risk of blood clots and heart attack.
Instead, the team used a catheter to deliver their sono-ink to the left atrial appendage in a goat heart that was placed in a printing chamber. The ultrasound probe then delivered focused ultrasound waves through 12mm of tissue, hardening the ink without damaging any of the surrounding organ. Once the process was complete, the ink was bonded to the heart tissue and was flexible enough to withstand movements that mimicked the heart beating.
The team then tested the potential for DVAP’s use for tissue reconstruction and regeneration. After creating a bone defect model using a chicken leg, the team injected the sono-ink and hardened it through 10mm of sample skin and muscle tissue layers. The resulting material bonded seamlessly to the bone and did not negatively impact any of the surrounding tissues.
Yao and Zhang also showed that DVAP could also be used for therapeutic drug delivery. In their example, they added a common chemotherapy drug to their ink, which they delivered to sample liver tissue. Using their probe, they hardened the sono-ink into hydrogels that slowly released the chemotherapy and diffused into the liver tissue.
“We’re still far from bringing this tool into the clinic, but these tests reaffirmed the potential of this technology,” said Zhang.
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