Scientists in the US have created a way to 3D print materials inside the body using ultrasound. Tests in mice and rabbits suggest the technique could deliver cancer drugs directly to organs and repair injured tissue.
Dubbed deep tissue in vivo sound printing (DISP), the method involves injecting a specialized bioink. Ingredients can vary depending on their intended function in the body, but the non-negotiables are polymer chains and crosslinking agents to assemble them into a hydrogel structure.
To keep the hydrogel from forming instantly, the crosslinking agents are locked inside lipid-based particles called liposomes, with outer shells designed to leak when heated to 41.7 °C (107.1 °F) – a few degrees above body temperature.
The team, led by scientists from the California Institute of Technology (Caltech), used a beam of focused ultrasound to heat and create holes in the liposomes, releasing the crosslinking agents, and forming a hydrogel right there in the body.
While previous studies have used infrared light to 3D print hydrogels in the body, ultrasound was chosen as the trigger mechanism this time because it can activate bioinks injected deeper, down to muscles and organs.
“Infrared penetration is very limited. It only reaches right below the skin,” says Wei Gao, a biomedical engineer at Caltech. “Our new technique reaches the deep tissue and can print a variety of materials for a broad range of applications, all while maintaining excellent biocompatibility.”
By precisely controlling the ultrasound beam, the team was able to 3D print complex shapes, like stars and teardrops.
DISP isn’t just a fun new body mod tool, though – animal tests using different versions of the hydrogel showed it could help replace or repair damaged tissue, deliver drugs, or monitor electrical signals for tests like electrocardiography.
The researchers used tiny gas vesicles as an imaging contrast agent, allowing them to see when the system was working.
These vesicles change their contrast when exposed to chemical reactions from the polymer crosslinking. Ultrasound picks these signals up and confirms that the reaction has worked.
In rabbits, the researchers printed pieces of artificial tissue at depths of up to 4 centimeters (about 1.6 inches) below the skin. This could help speed up healing of wounds and injuries – especially if cells are incorporated into the bioink first.
In tests on 3D cell cultures of bladder cancer, the team administered a version of the bioink loaded with the chemotherapy drug doxorubicin. Using the DISP method to harden it into hydrogel, the drug was released slowly over a few days. That led to significantly more cancer cell death than regular injection of the drug.
Adding other ingredients to the bioink can give DISP even more uses. The researchers also made conductive bioinks using carbon nanotubes and silver nanowires, which could be used for implantable sensors for temperature or electrical signals from the heart or muscles.
Importantly, no toxicity from the hydrogel was detected, and leftover liquid bioink is naturally flushed from the body within seven days, the team says.
Of course, the researchers still need to cross the chasm between tests in animals and tests in humans, but 3D printing biomedical devices right there in the body is an intriguing idea.
“Our next stage is to try to print in a larger animal model, and hopefully, in the near future, we can evaluate this in humans,” says Gao. “In the future, with the help of AI, we would like to be able to autonomously trigger high-precision printing within a moving organ such as a beating heart.”
The research was published in the journal Science.
