Caltech team 3D-prints drug depots deep inside living tissue

Caltech engineers have turned focused ultrasound into a noninvasive “printhead,” raising tissue temperature by only a few degrees to solidify injectable bio-inks several centimeters beneath the skin. The deep-tissue in-vivo sound-printing (DISP) technique shaped drug-loaded hydrogels next to mouse bladder tumors—killing more cancer cells than a direct doxorubicin shot—and built conductive gels inside rabbit muscle without harming nearby tissue, the team reports May 8 in Science.

The bio-ink blends polymer precursors with temperature-sensitive liposomes carrying a cross-linker and gas vesicles that double as ultrasound contrast agents. A brief, focused ultrasound pulse warms the target, releases the cross-linker and locks the material in place. In mice, printed doxorubicin gels beat direct injections on tumor-cell kill; in rabbits, printed conductive gels left tissue architecture intact, and unpolymerized ink cleared within a week—underscoring DISP’s promise for localized drug delivery and tissue repair.

“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, Caltech

This ability to precisely sculpt functional materials deep inside the body, such as cell-laden constructs for tissue regeneration or bioadhesive polymers to seal internal wounds, distinguishes DISP. It effectively overcomes the penetration depth limitations of light-based in vivo printing, offering a pathway to more complex, minimally invasive therapeutic interventions and the fabrication of internal biomedical devices.