A new ultrasound-guided 3D printing technique could make it possible to fabricate medical implants in vivo and deliver tailored therapies to tissues deep inside the body – all without invasive surgery, researchers report. 3D bioprinting technologies offer significant promise to modern medicine by enabling the creation of customized implants, intricate medical devices, and engineered tissues tailored to individual patients. However, most current approaches require invasive surgical implantation. Although in vivo bioprinting – “3D printing” tissue directly within the body – offers a less invasive alternative, it has been limited by challenges like poor tissue penetration depth, a narrow range of biocompatible bioinks, and the need for printing systems that operate at high resolution with precise, real-time control. To address these barriers, Elham Davoodi and colleagues developed a novel imaging-guided platform called Imaging-Guided Deep Tissue In Vivo Sound Printing (DISP), which uses focused ultrasound and ultrasound-responsive bioinks to precisely fabricate biomaterials directly within the body. These bioinks, or US-inks, combine biopolymers, imaging contrast agents, and temperature-sensitive liposomes carrying crosslinking agents and can be delivered to targeted tissue sites deep within the body via injection or catheter. A focused ultrasound transducer, guided by automated positioning and a predefined digital blueprint, triggers localized low-temperature heating (slightly above body temperature) that releases the crosslinker, initiating immediate in situ gel formation. Moreover, the bioinks and their resulting gels can be tailored for various functions, including conductivity, localized drug delivery, and tissue adhesion, as well as real-time imaging capabilities. Davoodi et al. validated DISP by successfully printing drug-loaded and functional biomaterials near cancerous sites in a mouse bladder and deep within rabbit muscle tissue, demonstrating potential applications for drug delivery, tissue regeneration, and bioelectronics. Further biocompatibility tests revealed no signs of tissue damage or inflammation, and the body cleared unpolymerized US-ink within a week, illustrating the platform's safety. “Although Davoodi et al. advanced ultrasound 3D printing toward clinical translation, additional refinements are needed to implement the technology for clinical use,” writes Xiao Kuang in a related Perspective. “A detailed relationship between process conditions, the structure of the printed material, and the resulting properties must be elucidated through careful testing.”