A research team led by the California Institute of Technology (Caltech) has developed a method that can be used to precisely print polymer structures directly in deep body tissue. The approach uses focused ultrasound to trigger local polymerization, enabling the targeted release of active substances, the sealing of internal injuries or the integration of bioelectric components.
“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,” says Wei Gao, professor of medical engineering at Caltech and a Heritage Medical Research Institute Investigator.
The new technique, called “deep tissue in vivo sound printing” (DISP), combines biocompatible polymer solutions with temperature-sensitive liposomes containing a special cross-linking agent. Targeted heating of the tissue by a few degrees Celsius using ultrasound activates these liposomes, releasing the cross-linking agent they contain and triggering polymerization. The reaction only takes place in the selected tissue area, enabling highly localized structuring.
“Increasing the temperature by a few degrees Celsius is enough for the liposome particle to release our crosslinking agents,” says Gao. “Where the agents are released, that’s where localized polymerization or printing will happen.”
“We have already shown in a small animal that we can print drug-loaded hydrogels for tumor treatment,” Gao says. “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.”
The researchers use gas-filled vesicles of bacterial origin as a contrast agent, which are visible in ultrasound imaging and change their acoustic contrast during the crosslinking reaction. This allows the spatial expansion of the printed polymer to be controlled in real time during the process. In animal models, the structures generated in this way have already been successfully used for the targeted delivery of chemotherapeutics.
The team also believes that machine learning can enhance the DISP platform’s ability to precisely locate and apply focused ultrasound. “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 says.
The research was funded by the US National Institutes of Health and the American Cancer Society, among others. The next step is to apply the technology in larger animal models, with the prospect of using it in human tissue. In the future, AI-supported systems will also be used to control the printing process autonomously and synchronously with moving organs such as the heart.
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