As if by magic, replacement elements for bones and tissue could be built inside the body: Researchers have developed a special “ink” that can be transformed into biocompatible 3D structures in tissue by irradiation with focused ultrasound waves. The developers have already been able to impressively demonstrate the potential of the process through various application examples.
3D printing is booming: In recent years, many exciting processes have been developed for producing complex structures from many different materials. Most are based on the substances being applied in layers or steps to gradually produce a desired three-dimensional structure. In addition, an alternative process has already been developed that does not require a stable base: the three-dimensional objects are created in a volume of light-sensitive ink. Precisely focused rays cause the substance to harden in certain places.
With this concept, however, the ink must be transparent and must not be obscured by objects so that the light rays can ensure curing at the focal point. But now a team of US researchers has developed a process that can circumvent this limitation. Instead of light, they use ultrasonic waves to cure the ink, which are known for their penetrating yet gentle potential. Their printing method, called “Deep-Penetrating Acoustic Volumetric Printing,” is based on the development of a so-called sono-ink made from biologically compatible components. It is a hydrogel substance that contains special microparticles and molecules that respond to ultrasonic waves.
Focused sound waves instead of light
“The system is based on a sonothermal effect, which occurs when sound waves are absorbed and thereby increase the temperature. This then leads to the hardening of our ink,” explains co-author Junjie Yao from Duke University in Durham. “Ultrasonic waves can penetrate more than 100 times deeper than light and still be spatially confined, allowing us to reach tissues, bones and organs with high spatial precision that are not accessible with light-based printing methods,” says Yao.
The process of the concept is concrete: The viscous sono-ink is injected with a syringe at the site of use. Focused ultrasound waves are then sent into the ink volume using a special ultrasonic pressure probe. Due to the hardening effect in the focus, the desired structures can then be built up by moving the ultrasonic pressure probe. Depending on the intensity of irradiation and the formulation of the ink, different degrees of hardness can be achieved. For example, three-dimensional structures with the hardness of bone material or more flexible structures that can be combined with organs can be created. “Once the structure is complete, the remaining unsolidified ink can be removed with a syringe,” says co-author Shrike Zhang from Harvard Medical School in Cambridge.
Depending on the intended use, the Sono-Ink can also be optimized with certain additional ingredients, say the developers: If, for example, a framework is to be created to support the healing of a bone or to compensate for bone loss, bone mineral particles can be added to the ink. You can also set how long the 3D object should last. For some applications it can be designed to be robust and for others it can dissolve again after its function has been fulfilled.
Potential demonstrated
The team has already demonstrated the potential of the process through three example applications: In the first use, the ink was used to seal a section in a removed goat heart. The sono-ink was brought to the site using a catheter. The material was then hardened by the focused ultrasound waves through the covering tissue. There were no signs of tissue damage to the surrounding organ, the researchers say. Once the process was complete, the structure adhered to the heart tissue and was flexible enough to withstand movements that mimicked the heartbeat.
Next, the team tested the procedure's potential for bone regeneration. A broken chicken leg was used as a model. Here too, the sono-ink sprayed at the site of action could be transformed into a connecting material between the fracture surfaces using ultrasound activation from the outside, without damaging the surrounding tissue. The third possible application that the team tested was a special process for the continuous release of drugs from a reservoir in the body. The researchers added a common chemotherapy drug to their ink and applied it to experimental liver tissue. They then used their probe to harden the material into a hydrogel that could slowly release the active ingredient and allow it to diffuse into the liver tissue.
According to the researchers, the results of all three tests were extremely promising and other possible uses for the concept are also conceivable. “Because we can print through tissue, this opens up many potential applications in surgery and therapy that traditionally require very invasive and disruptive methods,” says Yao. “This work opens up an exciting new path in the world of 3D printing and we look forward to further exploring the potential of this tool.” In conclusion, however, the scientists emphasize that a lot of research is still needed: “We are still a long way from there "We are looking forward to bringing this tool into the clinic, but our testing so far has definitely highlighted the potential of this technology," Zhang concluded.
Source: Duke University, specialist article: Science, doi: 10.1126/science.adi1563