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The world’s tiniest 3D bio-printer delivers a good gut feeling [unsw.edu.au]:

A big step in 3D bioprinting

The F3BD has been developed to proof-of-concept stage by a team led by Dr Thanh Nho Do [unsw.edu.au], Director of the UNSW Medical Robotics Lab, and his PhD student, Mai Thanh Thai, in collaboration with colleagues including Scientia Professor Nigel Lovell [unsw.edu.au], Dr Hoang-Phuong Phan [unsw.edu.au], and Associate Professor Jelena Rnjak-Kovacina [unsw.edu.au].

When the team published their research in early 2023, they knew they had delivered a game changer.

“Existing 3D bioprinting techniques create the patch outside the body. Placing that patch in a patient usually requires large open surgery that increases infection risks,” explains Do. “There is also the risk that a patch or structure will be contaminated or damaged during manual handling, or that it will not perfectly match the affected tissue as it’s meant to. Our F3DB prototype will avoid all those issues as its flexible body means it can 3D print multilayered biomaterials even in hard-to-reach areas.”

Developing an all-in-one endoscopic tool

The researchers are keen to turn the FD3B into an all-in-one surgical tool that can be used as an electric scalpel to remove lesions, direct water through a nozzle to clean the site, then print biomaterials to promote healing of the wound. There are also plans to integrate a camera and real-time scanning system.

“Evolving the F3DB into an all-in-one endoscopic tool will avoid the use of changeable tools which are normally associated with longer procedural time and infection risks,” adds Mai.

The system has already gained a provisional patent. The next stage along the path to commercialisation involves testing with animals. The team anticipates that with further funding and development, clinicians could be using the F3DB as part of routine practice within just five to seven years.

The potential for soft robotics systems is huge, according to Do.

“They are less bulky and more responsive than conventional cable mechanisms and, being soft, they are safe to use inside the human body,” he says. “I’m using soft robotics to address some of the limitations of existing devices and to broaden treatment options for people living with disease,” he explains.

“Ultimately, my research vision is to combine robotic, surgical and wearable devices to improve Australians’ quality of life.”

One step closer to 3D printing inside the body [healthcare-in-europe.com]:

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.

Previously, scientists have used infrared light to trigger polymerization, the linking of the basic units, or monomers, of polymers within living animals. "But infrared penetration is very limited. It only reaches right below the skin," says Wei Gao, professor of medical engineering at Caltech and a Heritage Medical Research Institute Investigator. "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."

Gao and his colleagues report their new in vivo 3D-printing technique in the journal Science [science.org]. 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). The lead author of the study is Elham Davoodi, an assistant professor of mechanical engineering at the University of Utah, who completed the work while a postdoctoral scholar at Caltech.

Wanting to figure out a way to realize deep tissue in vivo printing, Gao and his colleagues turned to ultrasound, a platform that is widely used in biomedicine for deep tissue penetration. But they needed a way to trigger crosslinking, or binding of monomers, at a specific location and only when desired.

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.

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°C, the scientists can trigger the release of their payload and initiate the printing of polymers. "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.".

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°C, the scientists can trigger the release of their payload and initiate the printing of polymers. "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.".

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

The team uses gas vesicles derived from bacteria as an imaging contrast agent. The vesicles, air-filled capsules of protein, show up strongly in ultrasound imaging and are sensitive to chemical changes that take place when the liquid monomer solution crosslinks to form a gel network. The vesicles actually change contrast, detected by ultrasound imaging, when the transformation takes place, allowing scientists to easily identify when and precisely where polymerization crosslinking has occurred, enabling them to customize the patterns printed in live animals. The team calls the new technique the deep tissue in vivo sound printing (DISP) platform.

When the team used the DISP platform to print polymers loaded with doxorubicin, a chemotherapeutic drug, near a bladder tumor in mice, they found substantially more tumor cell death for several days as compared to animals that received the drug through direct injection of drug solutions. "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 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.

Source: Caltech

10.05.2025

• 3D (249) [healthcare-in-europe.com]
• printing (92) [healthcare-in-europe.com]
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Contact … Read all latest stories [healthcare-in-europe.com]

Journal Reference:
Mai Thanh Thai, Phuoc Thien Phan, Hien Anh Tran, et al. Advanced Soft Robotic System for In Situ 3D Bioprinting and Endoscopic Surgery [open], Advanced Science (DOI: 10.1002/advs.202205656 [doi.org])
Imaging-guided deep tissue in vivo sound printing, Science (DOI: https://www.science.org/doi/10.1126/science.adt0293 [doi.org])

Original Submission