What if doctors could treat deep injuries or repair tissues without making a single cut on your body? It may sound impossible, but a team of researchers from the California Institute of Technology (Caltech) just showed this is achievable. 

Without any surgery or stitches, they 3D printed tissues inside disease-affected areas of a mouse’s bladder and a rabbit’s leg muscles using a special injectable bioink. What’s interesting about the bioink is that it stays liquid at body temperature, but when exposed to ultrasound, it begins forming desirable shapes and solidifies.

This novel method is called deep tissue in vivo sound printing (DISP), and in the future, it could be used to deliver drugs and repair (or replace) damaged cells, tissues, and organs in humans. 

The researchers suggest that DISP could take healthcare to the next level by making treatments faster, less invasive, and even possible in places where surgery isn’t an option, like on the battlefield or in remote locations.

“We validated DISP by successfully printing near diseased areas in the mouse bladder and deep within rabbit leg muscles in vivo, demonstrating its potential for localized drug delivery and tissue replacement. DISP’s ability to print conductive, drug-loaded, cell-laden, and bioadhesive biomaterials demonstrates its versatility for diverse biomedical applications,” the researchers note.

How does DISP work?

The key to DISP’s effectiveness lies in its bioink. This bioink contains long-chain polymers and special chemicals known as crosslinkers, which help the polymers stick together and form a gel. 

However, to keep the ink from turning solid too early, the crosslinkers are safely sealed inside tiny, heat-sensitive capsules called liposomes. 

These liposomes are designed such that they burst only when they are warmed to just a few degrees above body temperature. Once the bioink is injected into the body, a focused ultrasound beam is used to heat a specific area. This causes the liposomes at that location to open and release the crosslinkers, which then react with the polymers to form a solid gel-like structure right there in the tissue. 

To test this idea, the researchers also carried out experiments on rabbits, mice, and lab-grown cancer cells. In rabbits, they successfully printed artificial tissue structures four centimeters beneath the skin to patch wounds or repair internal damage. The team further tested whether DISP could be used to deliver cancer drugs more precisely.

They prepared a version of the bioink that contained doxorubicin, a widely used chemotherapy medication, and applied it to cells with bladder cancer. Using ultrasound, they solidified the drug-containing gel exactly where the cancer cells were located. This setup allowed the drug to be released gradually over several days, leading to much effective cancer cell death than when doxorubicin was injected all at once. 

In additional experiments, the researchers added materials like carbon nanotubes and silver nanowires to the bioink. These made the printed gels electrically conductive, which could be useful in the future for building implantable sensors that track temperature, muscle activity, or heart signals from inside the body.

“Importantly, no toxicity from the hydrogel was detected, and leftover liquid bioink is naturally flushed from the body (of animals) within seven days,” the study author said.

Sound is better than light

What makes DISP more promising than previous methods is its ability to reach deep into the body. Earlier techniques used light, such as infrared, to perform similar tasks, but light cannot travel far beneath the skin. Ultrasound, on the other hand, is already used in medical imaging for its deep penetration and safety. 

“Infrared penetration is very limited. It only reaches right below the skin. 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,” Wei Gao, one of the study authors and a biomedical engineer at Caltech, said.

However, the results are still early and limited to animals and lab models. The next steps would be to test DISP in larger animals and, eventually, in humans. 

Also, “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,” Gao added. 

The study is published in the journal Science.