3D printers can print prototypes of medical devices, design flexible and lightweight electronics, and even create tissues for wound healing. However, many of these printing technologies require a slow and painstaking process of building objects point by point, which often requires a robust printing platform.
In the past few years, to circumvent these problems, researchers have developed a photosensitive ink that reacts directly to the target beam and quickly hardens into the desired structure. While this printing technology can greatly improve the speed and quality of prints, researchers can only print with clear inks, and its biomedical use is limited because light cannot penetrate a few millimeters deep into tissue.
A few days ago, Harvard Medical School YShrike Zhang and Junjie Yao, an associate professor in the Department of Biomedical Engineering at Duke University, have developed a new 3D printing method called Deep Penetration Acoustic Volumetric Printing (DVAP) that solves these problems. The new technology uses a special ink that reacts to sound waves rather than light, allowing them to create structures with biomedical uses at unprecedented depth of tissue.
In detail, the researchers report a design of a self-enhancing acoustic ink (or acoustic ink) for d**p and a corresponding focused ultrasound writing technique. They used experiments and acoustic modeling to investigate acoustic printing behavior in relation to frequency and scan rate. The key features of low acoustic flow, fast acoustothermal polymerization, and large print depths are achieved by d**p, enabling the printing of volumetric hydrogels and nanocomposites in a variety of shapes, regardless of their optical properties. D**P can also print centimeter depths in biological tissues, paving the way for minimally invasive medicine. The research results were published in the latest issue of Science under the title "Self-enhancing Sono-inks Enable Deep-penetration Acoustic Volumetric Printing", and the first authors are Xiao Kuang and Qiangzhou Rong.
Fig. D**P prints 3D structures by using focused ultrasonic-cured sonic inks.
DVAP composition
The first component of DVAP involves an ultrasonic ink, called ultrasonic ink, which is a combination of hydrogels, particles, and molecules designed to respond specifically to ultrasound. Once the sonic ink is delivered to the target area, a dedicated ultrasonic printing probe sends focused ultrasound into the ink, partially hardening it into a complex structure. These structures range from hexagonal scaffolds that mimic bone hardness to hydrogel bubbles that can be placed on organs.
The ink itself is a viscous liquid, so it can be injected into the target area fairly easily, and when the ultrasonic printing probe is moved, the materials in the ink are joined together and hardened, and when finished, any remaining uncured ink can be removed by the scientist through a syringe.
Figure 1D**P working principle and self-reinforcing sonogram ink design.
This focused ultrasound 3D printing technique requires a high level of energy, which has the potential to overheat the surrounding tissue. To solve this problem, the researchers built a confocal high-intensity ultrasonic printer. The system uses two ultrasonic transducers, which are arranged in a crosshead pattern, allowing the two ultrasonic fronts to overlap. This design not only reduces the amount of energy required for each sensor, but also improves the resolution and speed of the ultrasonic printer.
Figure 2Characterization of d**p print resolution.
3D shapes
First, the researchers suspended a focused ultrasound transducer above a room filled with a new type of ink. There is a "matching medium" between the transducer and the ink, a substance used in most ultrasonic methods to ensure the efficient transmission of ultrasonic waves. By using a computer program to precisely control the complex 3D motion of the ultrasonic transducer, the researchers were able to create a variety of different structures at different depths in the ink chamber. These structures come in a variety of sizes and complex geometries, including objects such as multi-layered honeycombs, branching vascular networks, and complex models that resemble hands or spiders.
Next, the researchers wanted to determine if their technology could be used to 3D print biological tissues. They placed porcine tissue of varying thicknesses (up to 17 mm) on top of an ink-filled chamber. The transducer is placed above, and the researcher directs the ultrasound through the tissue and into the chamber below. They successfully printed a variety of different structures from several different types of tissue, including porcine liver and a porcine tissue model consisting of multiple layers such as **, fat, and muscle.
Figure 3d**p performance and material versatility.
Proof of concept
As a proof of concept for the new technology, the researchers conducted three tests.
The first trial was to seal a part of a goat's heart with ink. When a person has non-valvular atrial fibrillation, the heart is unable to beat properly, causing blood to build up inside the organs. The traditional method usually requires thoracotomy to close the left atrial appendix to reduce the risk of blood clots and heart attack. Instead, the researchers used a catheter to deliver sonic ink to the left atrium wall of the goat's heart placed in a printing chamber. The ultrasound probe will then focus the ultrasound waves through the 12 mm tissue, hardening the ink without damaging any surrounding organs. Once this process is complete, the ink is securely bonded to the heart tissue and is flexible enough to withstand movements that mimic the beating of the heart.
Next, the researchers tested the potential of DVAP for tissue reconstruction and regeneration. After making a model of the bone defect from a chicken leg, the researchers injected sonic ink and hardened it through a 10 mm sample** and layers of muscle tissue. The resulting material is seamlessly integrated with the bone and does not negatively affect any surrounding tissue.
Finally, the researchers showed that DVAP can also be used for drug delivery. In their case, they added a common chemotherapy drug to the ink and delivered it into a liver tissue sample. They used probes to harden the acoustic ink into a hydrogel that slowly releases the chemotherapy drug and spreads into the liver tissue.
Figure 4d**p was used for proof-of-concept by tissue printing and minimally invasive**.
Summarize and look forward to the future
Taking advantage of the deep penetration of fus waves, low acoustic flow, and fast acoustic aggregation of viscoelastic self-enhancing acoustic inks, the authors developed a D**P technique that can construct volumetric constructs with high print fidelity and resolution without a build platform. The use of thermally responsive acoustic absorbers solves the contradiction between acoustic wave flow and deep penetration when FUS is exposed. Together, self-reinforcing acoustic inks and nonlinear acoustic wave propagation enhance the acoustic thermal heating at the focal point of the fus, resulting in the rapid and selective solidification of the material into constituent voxels. The curing mechanism based on heat accumulation results in millimeter-level anisotropic print resolution, which can be further improved by optimizing print parameters for FUS frequency and scan speed, as well as using a confocal dual-sensor configuration. The deep penetration of fus waves enables volumetric fabrication of opaque (nano) composites and the printing of centimeter-thick tissues, which is not possible with state-of-the-art light-based printing technologies. The self-reinforcing acoustic ink design can be used in different systems, greatly expanding the material library for acoustic printing technology.
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