A 2D vessel network (82 mm by 68 mm by 1 mm) was printed on a 3.41-MHz FUS using a PEGDA-based sono-ink.
A 2D vessel network (82 mm by 68 mm by 1 mm) was printed on a 3.41-MHz FUS using a PEGDA-based sono-ink [Qiangzhou Rong]

A new 3D printing technique that uses ultrasound and “sono-ink” could one day be used to build bones, blood vessels, and other tissues within the body.

Researchers developed a technique to quickly and precisely print biomaterial inside ex-vivo living tissue using a deep-penetrating acoustic volumetric printing (DAVP) method.

Xiao Kuang, PhD, from Harvard Medical School, and colleagues were able to print at centimeter depths through biological tissues, “paving the way toward minimally invasive medicine.”

Reporting in the journal Science, they suggest the technique could be used to correct bone defects or treating non-valvular atrial fibrillation without surgery.

Ultrasound is often used for diagnostic imaging and therapy due to its ability to penetrate a variety of materials deeply. Compared with light, ultrasound waves can penetrate more than 100 times deeper into optically scattering materials and could therefore be useful for depositing energy to trigger polymerization at depths.

But using ultrasound for 3D printing poses several challenges. For the material to polymerize, ultrasound energy needs to be converted into chemical reactions that do not happen directly, as with photochemistry.

Secondly, as ultrasound travels through a liquid it can cause streaming flows that disturb the medium and blur resolution, which can impact accuracy.

To address this, the researchers developed phase-transition viscoelastic sonicated inks formed from a mixture of polymers, particles and chemical initiators to absorb sound waves and form a gel.

The “sono-ink” is able to penetrate deeply and harnesses the effects of ultrasound-generated heat to control fluid flow and drive acrylate polymerization, so that material is fabricated on-site.

A small temperature increase at the ultrasound focus causes a heat-responsive polymer in the ink to form a gel, which reduces streaming and keeps the heat-driven chemistry precise. The gel absorbs the ultrasound and converts it into more heat, keeping the process localized and speeding polymerization. This allows it to print voxels of approximately 1 mm, which are only two to three times the wavelength of the ultrasound used, at a depth of several centimeters to form complex geometries.

The team was able to print bone-shaped constructs through ex-vivo tissue derived from a pig and a hollow, heart-shaped model through 17mm porcine kidney tissue.

They also examined use of the technique in treating large bone defects, printing a bone scaffold for a hypothetical bone-loss treatment and in left atrial appendage closure for nonvalvular atrial fibrillation.

Additionally, the researchers demonstrated the potential for drug delivery by printing drug-eluting filler hydrogels on liver lesions.

In an accompanying Perspective article, Yuxing Yao and Mikhail Shapiro, PhD, from the California Institute of Technology, note that concerns over the toxicity of infusing high concentrations of sono-ink need to be addressed before it can be used in patients.

The temporary high ultrasound pressure at the focus of 35 to 55 MPa and accompanying temperature increase, which exceeds 70 degrees centigrade locally, could also cause tissue damage if not adequately targeted and confined.

Nonetheless, Yao and Shapiro add: “If optimized and demonstrated in live animal models, these approaches could be a promising way to convert open surgeries to less-invasive ultrasound-based treatments.”

They further note that the technology has potential beyond biomedical applications. “It is conceivable that the running shoes of the future could be printed with the same acoustic method that repairs bones.”

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