3D Printing deep tissue In Vivo Using ultrasound

Amazing stuff!

"... Gao and his colleagues report their new in vivo 3D-printing technique in the journal Science. Along with bioadhesive gels and polymers for drug and cell delivery, the paper also describes the use of the technique for printing bioelectric hydrogels, which are polymers with embedded conductive materials for use in the internal monitoring of physiological vital signs as in electrocardiograms (ECGs).  ...

They came up with a novel approach: Combine ultrasound with low-temperature–sensitive liposomes. Such liposomes, spherical cell-like vesicles with protective fat layers, are often used for drug delivery. In the new work, the scientists loaded the liposomes with a crosslinking agent and embedded them in a polymer solution containing the monomers of the polymer they wanted to print, an imaging contrast agent that would reveal when the crosslinking had occurred, and the cargo they hoped to deliver—a therapeutic drug, for example. Additional components can be included, such as cells and conductive materials like carbon nanotubes or silver. The composite bioink was then injected directly into the body.

Raise the Temperature Just a Touch to Trigger Printing

The liposome particles are low-temperature sensitive, which means that by using focused ultrasound to raise the temperature of a small targeted region by about 5 degrees Celsius, the scientists can trigger the release of their payload and initiate the printing of polymers."

From the perspective abstract:

"Tailoring implants to an individual’s anatomy can offer better surgical outcomes and patient satisfaction.

Traditionally, patient-specific artificial components, such as breast implants or hip joints, are sculpted outside of a body and inserted by open surgery.

Additive manufacturing, or three-dimensional (3D) printing, offers an alternative to quickly build personalized implants with complex shapes. 3D printing using infrared light has enabled the patterning of complex shapes underneath submillimeter-thick skins or muscles. In this approach, irradiating tissue-embedded polymer inks with light triggers polymerization. However, considerable attenuation and scattering of light beams by intervening tissues limit direct printing of implants beneath millimeter-thick tissues. ... Davoodi et al. report 3D printing using ultrasound rather than light to create complex structures underneath centimeter thick tissues inside an animal body. This process could potentially be combined with conventional ultrasound imaging to customize the shapes of implants on demand."

From the editor's summary and abstract:

"Editor’s summary

Three-dimensional (3D) printing is a valuable tool for generating patient-specific implants, either externally or even directly inside the body. The limitation of the former approach is the need for surgical implantation, whereas the latter approach is limited by the need for precursor materials and a polymerization method safe for in vivo use that can be activated with precision from outside of the body. Davoodi et al. developed a platform that uses imaging-guided ultrasound printing, which is capable of penetration depths much greater than the other approaches (see the Perspective by Kuang). The authors loaded cross-linking agents loaded into low-temperature–sensitive liposomes for incorporation into tunable bioinks. In vivo demonstrations included printing near diseased areas in a mouse bladder and deep within rabbit leg muscles. ...

Abstract

Three-dimensional printing offers promise for patient-specific implants and therapies but is often limited by the need for invasive surgical procedures. To address this, we developed an imaging-guided deep tissue in vivo sound printing (DISP) platform. By incorporating cross-linking agent–loaded low-temperature–sensitive liposomes into bioinks, DISP enables precise, rapid, on-demand cross-linking of diverse functional biomaterials using focused ultrasound.

Gas vesicle–based ultrasound imaging provides real-time monitoring and allows for customized pattern creation in live animals.

We validated DISP by successfully printing near diseased areas in the mouse bladder and deep within rabbit leg muscles in vivo, demonstrating its potential for localized drug delivery and tissue replacement.

DISP’s ability to print conductive, drug-loaded, cell-laden, and bioadhesive biomaterials demonstrates its versatility for diverse biomedical applications."

3D Printing In Vivo Using Sound - www.caltech.edu "Imagine if doctors could precisely print miniature capsules capable of delivering cells needed for tissue repair exactly where they are needed inside a beating heart. A team of scientists led by Caltech has taken a significant step toward that ultimate goal, having developed a method for 3D printing polymers at specific locations deep within living animals. The technique relies on sound for localization and has already been used to print polymer capsules for selective drug delivery as well as glue-like polymers to seal internal wounds."

Replicating a tissue with sound waves (no public access)

Imaging-guided deep tissue in vivo sound printing (no public access, but this link provides access to PDF) "Ultrasound waves can penetrate thick tissues and print implants on demand inside a body"

The deep tissue in vivo sound printing (DISP) platform. The technique combines ultrasound with low-temperature–sensitive liposomes loaded with crosslinking agents. The liposomes, often used for drug delivery, are embedded in a polymer solution containing the monomers of the desired polymer, an imaging contrast agent that reveals when crosslinking has occurred (here, the gas vesicles used for this purpose are shown as hexagons), and the cargo they hope to deliver—a therapeutic drug, for example. Scientists use focused ultrasound to increase the temperature in a targeted area by a few degrees, causing the liposomes to release their contents and initiate printing in a precise location.