Imagine if doctors could accurately print the miniature capsules capable of managing cells necessary for fabric repair exactly where they are needed inside A heartbeat. A team of scientists led by Caltech has taken a significant step towards that final goal, since it has developed a method for 3D printing polymers in specific places in depth within living animals. The technique is based on the sound for location and has already been used to print polymers capsules for selective drug administration, as well as glue -shaped polymers to seal internal wounds.
Previously, scientists have used infrared light to trigger polymerization, the linking of the basic units or monomers of polymers within living animals. “But infrared penetration is very limited. It only arrives just below the skin,” says Wei Gao, a professor of medical engineering at Caltech and researcher at the Heritage Medical Research Institute. “Our new technique reaches deep tissue and can print a variety of materials for a wide range of applications, all while maintaining excellent biocompatibility.”
Gao and his colleagues report their new 3D in vivo printing technique in the newspaper Science. Together with bioadhesive gels and polymers for the supply of drugs and cells, the document also describes the use of the technique to print bioelectric hydrogels, which are polymers with integrated conductive materials for use in internal monitoring of physiological vital signs such as electrocardiograms (ECGS). The main author of the study is Elham Davoodi, assistant professor of mechanical engineering at the University of Utah, who completed the work while he was postdoctoral academic in Caltech.
The origin of a novel idea
Wanting to find a way to make an in vivid impression of deep tissue, Gao and his colleagues became ultrasound, a platform that is widely used in biomedicine for a deep tissue penetration. But they needed a way of triggering the reticulation, or the union of monomers, in a specific location and only when they wanted it.
They came up with a novel approach: combine ultrasound with low temperature liposomes. These liposomes, spherical vesicles similar to cells with protective fatty layers, are often used for drug administration. In the new work, the scientists loaded the liposomes with a reticulation agent and integrated them into a polymer solution containing the monomers of the polymer they wanted to print, an image contrast agent that would reveal when the reticulation and load that they expected to deliver a therapeutic medication had occurred, for example. Additional components, such as cells and conductive materials such as carbon or silver nanotubes can be included. The compound bioink was injected directly into the body.
Raise the temperature only one touch for activation printing
Liposomas particles are sensitive at low temperature, which means that when using ultrasound focused on raising the temperature of a small region directed in approximately 5 degrees Celsius, scientists can trigger the release of their payload and initiate polymers.
“Increasing the temperature in a few degrees Celsius is enough for the liposomes particle to release our reticulation agents,” says Gao. “Where the agents are released, that is where polymerization or localized printing will occur.”
The equipment uses gas -derived gas vesicles as an image contrast agent. The vesicles, capsules full of protein air, appear strongly in the ultrasound image and are sensitive to the chemical changes that take place when the liquid monomer solution is transmitted to form a gel network. Vesicles really change the contrast, detected by ultrasound images, when transformation is performed, allowing scientists to easily identify when and precisely where the reticulation of polymerization has occurred, which allows them to customize printed patterns in living animals.
The team calls the new technique the sound printing platform (Discom) of deep tissue.
When the team used the DIST platform to print polymers charged with doxorubicin, a chemotherapeutic drug, near a bladder tumor in mice, found substantially more death of tumor cells for several days compared to animals that received the drug through direct injection of drug solutions.
“We have already demonstrated in a small animal that we can print drugs loaded with drugs for tumor treatment,” says Gao. “Our next stage is to try to print in a larger and, hopefully, in the near future animals model, we can evaluate this in humans.”
The team also believes that automatic learning can improve the capacity of the PLAT platform to locate and apply ultrasound accurately focused. “In the future, with the help of AI, we would like to be able to unleashed the impression of high precision within a moving organ, such as a heart of beating,” says Gao.
The work was supported by the financing of the National Institutes of Health, the American Cancer Society, the Institute for Medical Heritage Research and the Challenge Initiative in UCLA. The fluorescence microscopy was carried out in the Advanced Optical Microscopy/Spectroscopy Laboratory and the Leica of Excellence Center at the California Nanosystems Institute in UCLA.