3D printing in vivo with sound

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Imagine that doctors can precisely print miniature capsules able to providing the cells needed to repair the tissue exactly where the beating is required. A team of scientists under the leadership of Caltech took a major step towards this final goal, developing a technique for 3D printing polymers in specific locations of deep living animals. This technique relies on a position for location and has already been used to print polymer capsules for selective delivery of medication, in addition to glue -like polymers to seal internal wounds.

Earlier, scientists used infrared light to liberate polymerization, combining basic units or polymers monomers in living animals. “But infrared penetration is very limited. It will only reach right under the skin,” says Wei Gao, a professor of medical engineering at Caltech and investigators Heritage Medical Research Institute. “Our new technique reaches deep tissue and can print a variety of materials to a wide range of applications, while maintaining excellent biocompatibility.”

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Gao and his colleagues report their recent 3D in vivo printing technique in the journal. Along with bioadhesian gels and polymers for the provision of medication and cells, the article also describes the usage of bioelectric hydrogel printing technique, that are polymers with embedded conductive materials to be used in internal monitoring of physiological life symptoms as in electrocardiograms (ECG). The essential creator of the study is Elham Davoodi, an assistant to a mechanical engineering professor on the University of Utah, who finished his work throughout the post -coat scholar in Caltech.

The origin of an modern idea

In order to come back up with a approach to realize the deep print tissue in vivo, GAO and his colleagues turned to ultrasound, a widely used platform in biomedicine for deep tissue penetration. But they needed a approach to free the network or bind monomers, in a selected place and only then.

They got here up with a brand new approach: mix ultrasound with liposomes sensitive to low temperature. Such liposomes, spherical cell follicles with protective layers of fat are sometimes used to offer drugs. In the brand new work, scientists loaded liposomes with a network agent and placed them in a polymer solution containing polymer monometers that they desired to print, for instance, a contrasting agent that will reveal when networking, and a load that they hoped to offer – a therapeutic drug. Additional elements, reminiscent of cells and conductive materials, reminiscent of carbon nanotrons or silver, may be taken under consideration. The folded bioink was then injected directly into the body.

Lift the temperature only somewhat to call printing

Liposome particles are sensitive to low temperature, which suggests that due to the focused ultrasound in order to extend the temperature of a small -targeted region by about 5 degrees Celsius, scientists can start releasing their charge and initiate printing polymers.

“Increasing the temperature by a few degrees Celsius is enough for a particle of liposome to free our network,” says Gao. “Where agents are released, it will happen that the polymerization or printing will happen.”

The team uses gas bacteria as a contrasting agent of imaging. Bubbles, protein capsules filled with air strongly appear in ultrasonic imaging and are sensitive to chemical changes that occur when the liquid agents of the monomer solution to create a gel network. The bubbles actually change the contrast, detected by ultrasonic imaging, when the transformation takes place, enabling scientists to simply determine when and exactly where polymerization has taken place, enabling them to adapt printed patterns on live animals.

The team calls the brand new strategy of the deep tissue platform in vivo (DISP).

When the team used the DISP platform for printing polymers burdened with doxorubicin, a chemotherapeutic drug, near the bladder tumor on the mice, they found far more death of cancer cells for several days in comparison with animals that received the drugs by direct injection of drug solutions.

“We have already shown at a small animal that we can print hydrogels with a drug for the treatment of cancer,” says Gao. “Our next stage is printing in a larger animal model and I hope that in the near future we can assess it in humans.”

The team also believes that machine learning can increase the DISP platform’s ability to exactly locate and use a targeted ultrasound. “In the future, with the help of artificial intelligence, we would like to be able to autonomously release very precise printing in movable organs, such as heartbeat,” says Gao.

The work supported financing from the National Institutes of Health, American Cancer Society, Heritage Medical Research Institute and the UCLE challenges initiative. Fluorescent microscopy was carried out in advanced light microscopy/spectroscopy laboratory and Leica Center of Excellence on the California Nanosystems Institute in Ucla.

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