3D bioprinting technologies hold considerable promise for advancing modern medicine by enabling the production of customized implants, intricate medical devices, and engineered tissues designed to meet the specific needs of individual patients. However, most of the current approaches still necessitate invasive surgical procedures for implantation. In contrast, in vivo bioprinting – the process of 3D printing tissue directly within the body – provides a less invasive solution, yet it has been constrained by various challenges. These include limited tissue penetration depth, a restricted selection of biocompatible bioinks, and the need for printing systems capable of operating at high resolution with precise, real-time control. Now, a newly developed ultrasound-guided 3D printing technique offers a promising method to fabricate medical implants in vivo and deliver targeted therapies to tissues deep inside the body – all without the need for invasive surgery, according to research published in Science.

Researchers at the California Institute of Technology (Pasadena, CA, USA) have pioneered an innovative platform called Imaging-Guided Deep Tissue In Vivo Sound Printing (DISP), which employs focused ultrasound and ultrasound-responsive bioinks to precisely fabricate biomaterials within the body. These bioinks, known as US-inks, are a combination of biopolymers, imaging contrast agents, and temperature-sensitive liposomes containing crosslinking agents. The bioinks are delivered via injection or catheter directly to the targeted tissue sites deep within the body. The focused ultrasound transducer, guided by automated positioning and a predefined digital blueprint, triggers localized low-temperature heating (slightly above body temperature) to release the crosslinkers, prompting immediate gel formation at the targeted site.

Additionally, the bioinks and their resulting gels can be engineered for various functionalities, such as conductivity, localized drug delivery, tissue adhesion, and real-time imaging capabilities. The team demonstrated the effectiveness of DISP by successfully printing drug-loaded and functional biomaterials in proximity to cancerous sites in a mouse bladder and deep within rabbit muscle tissue. These tests revealed the potential applications of this technology in drug delivery, tissue regeneration, and bioelectronics. Subsequent biocompatibility assessments showed no indications of tissue damage or inflammation, and the body was able to clear the unpolymerized US-ink within a week, indicating the platform’s safety. The researchers believe that integrating machine learning could further enhance the DISP platform, improving its ability to accurately locate and apply focused ultrasound in real-time.

"We have already shown in a small animal that we can print drug-loaded hydrogels for tumor treatment," said Wei Gao, professor of medical engineering at Caltech, who led the team"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. 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." 

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