September 30, 2015

Granular gel as a 3D writing medium to create fragile and complex things like artificial jelly fish and can write and grow living tissue cells

University of Florida Researcher Angelini came up with the idea to use microscopic hydrogel particles as a medium for 3-D printing of soft matter. These particles are 99.8 percent water and 20 times smaller than the diameter of a human hair. He found that he could manufacture soft materials into shapes more fragile than anything found in nature, all with structural integrity. The discovery is reported today in a paper in the journal Science Advances.

3-D printing soft matter leads to new engineering discipline. The discovery will require new tools, theory and modeling techniques in mechanical engineering. Hahn said much of that work will take place in the College of Engineering’s new Soft Matter Engineering Research Group, which already has attracted collaborators across several disciplines. The group’s work also has attracted financial support from two international companies intrigued by the prospects for soft matter manufacturing.

Building it soft and letting it stay soft and not collapse

“In simple terms, a hundred-plus years that we’ve built a foundation on in traditional mechanics is largely off the table with soft matter,” Hahn said. “It really is a whole new frontier of engineering.”

“What if I could print you a structure that never solidified but it still held into place? That’s a new idea. It’s no longer about solidification, it’s more about placing things in space and leaving them where you put them. They aren’t going to move,” said Angelini, who conducted the work using his National Science Foundation Early Career Development Award, NSF’s most prestigious award for promising junior faculty. “This level of control is the foundation of all manufacturing.”

Sawyer, pointing to one of the laboratory jellyfish, adds, “Nobody in the world can make that jellyfish. We make them everyday. When we have soft matter manufacturing, we can make things, and then it is the realm of the engineer. It’s kind of like an

Gels made from soft microscale particles smoothly transition between the fluid and solid states, making them an ideal medium in which to create macroscopic structures with microscopic precision. While tracing out spatial paths with an injection tip, the granular gel fluidizes at the point of injection and then rapidly solidifies, trapping injected material in place. This physical approach to creating three-dimensional (3D) structures negates the effects of surface tension, gravity, and particle diffusion, allowing a limitless breadth of materials to be written. With this method, we used silicones, hydrogels, colloids, and living cells to create complex large aspect ratio 3D objects, thin closed shells, and hierarchically branched tubular networks. We crosslinked polymeric materials and removed them from the granular gel, whereas uncrosslinked particulate systems were left supported within the medium for long times. This approach can be immediately used in diverse areas, contributing to tissue engineering, flexible electronics, particle engineering, smart materials, and encapsulation technologies.

To explore the stability of writing in granular gels, they have generated several complex structures that would otherwise disperse, sag, or fall apart. For example, they created a 4-cm-long model of DNA by arranging long thread-like features about 100 μm in diameter made entirely from uncrosslinked 1-μm fluorescent polystyrene microspheres

Granular gel as a 3D writing medium. (A) A microscale capillary tip sweeps out a complex pattern as material is injected into the granular gel medium. Complex objects can be generated because the drawn structure does not need to solidify or generate support on its own. (B) As the tip moves, the granular gel locally fluidizes and then rapidly solidifies, leaving a drawn cylinder in its wake. The reversible transition allows the tip to traverse the same regions repeatedly. (C) The soft granular gel is a yield stress material, which elastically deforms at low shear strains and fluidizes at high strains. (D) Stress-strain measurements reveal a shear modulus of 64 Pa and a yield stress of 9 Pa for 0.2% (w/v) Carbopol gel. (E) The cross-sectional area of written features exhibits nearly ideal behavior over a wide range of tip speeds, v, and flow rates, Q. The trend line corresponds to the volume conserving relationship

Writing solid shells and capsules. (A) A thin-shell model octopus is made from multiple connected hydrogel parts with a complex, stable surface before polymerization. (B) A fluorescence image of the octopus model after polymerization, still trapped in granular gel, exhibits no structural changes from the polymerization process. (C) The polymerized octopus model retains integrity after removal from the granular gel, shown floating in water. (D) A model jellyfish incorporates flexible high aspect ratio tentacles attached to a closed-shell body. (E) Freely floating in water, the jellyfish model exhibits robustness and flexibility. (F) Model Russian dolls demonstrate the ability to encapsulate with nested thin shells. Photographs in (A), (C), and (E) were illuminated with white light, and those in (B), (D), and (F) were illuminated with UV light, shown with false-color look-up table (LUT) to enhance weak features

Science Advances - "Writing in the granular gel medium" by Tapomoy Bhattacharjee1, Steven M. Zehnder, Kyle G. Rowe, Suhani Jain, Ryan M. Nixon, W. Gregory Sawyer and Thomas E. Angelini

Making impossible things for new art, medicine, tissue replacement, human organs and all kinds of fields

It is possible to both write and grow living tissue cells in a granular gel culture medium, which is prepared by using cell growth media as a solvent
Angelini’s team has already used the technique to print material out of living cells – including human blood-vessel and canine kidney cells. The researchers can also use silicone, hydrogel and other polymers, and made a replica of a colleague’s brain in the soft, tissue-like consistency of hydrogel to test it out. Internal organs are as individual as faces, so they based the brain on detailed images of the professor’s grey matter.

“We could foresee a future in which, before brain surgery, the surgeon 3D prints a brain out of hydrogel and then practises on it,” says Angelini. “Then the surgeon knows exactly how that surgery is going to happen.”

The use of 3D printing to make working tissue and organs is still a long way off, but Angelini is optimistic. “Our method, I think, represents a path towards that,” he says. “I really think we are going to get there.”

Angelini said the printing medium is the key. Printing a soft object in three dimensions had been out of the question because, by its nature, 3-D printing requires an object to solidify layer by layer, with the printing tip depositing a material such as a plastic or metal, which hardens to provide its own support. A top-heavy object like a jellyfish, for instance, would be too soft to print using traditional 3-D methods because the thin tentacles on the bottom would not support the bulk at the top. Even if you printed the jellyfish upside down the thin, flexible legs could never stay still in a fluid or stand upright.

Angelini, however, decided to try 3-D printing in a medium of densely packed, microscopic hydrogel particles, or granular gel for short. The granular gel provides a stable, water-based environment that provides support for soft objects. As the printing tip injects a fluid into the granular gel, the gel traps the fluid in place, allowing for deposition of subsequent layers of fluid, without regard for support.

Angelini has used the new method to create numerous objects, including a jellyfish and a hollow, tubular knot, which could not be printed outside the granular gel environment.

It’s a revolution that has attracted attention outside engineering. Neurosurgery professor Frank Bova said he is excited about using the technology for education, perhaps creating artificial brains and other phantom organs that medical students can use for hands-on experience.

“For years, we have made models of bone and cartilage, but we’ve never been able to print soft tissue models,” Bova said.

“With this process, we can take a brain scan with a tumor and make tissue that looks like that of a real patient, and that will help us better train surgeons,” Bova said. “One problem with teaching medical students and residents is having the right case at the right time. Complicated cases come in when you’d rather be teaching simple things, so this process allows us to create a library of appropriate cases that can provide practice at the appropriate time in a student’s medical education.”

Bova said he has faith in the process in part because he has seen it work. He sent Angelini a scan of his brain and got back a soft matter model.

The objects printed in the lab so far are orders of magnitude softer than any man-made object. Angelini says he doesn’t know of a lower limit to the mechanical integrity of the objects the lab can make, and Sawyer adds, “We can make a cloud.”

A tantalizing question, Sawyer says, is what will be the smartest thing to do with this technology. For their part, Sawyer and Angelini are developing ways to print living cells using the granular gel technique.

“In science, you’re either leading or you’re following, and you hope that if you do things right, every 10 years or so, you get a chance to lead for a while,” Hahn said. “With this new discipline we will be in the lead, and we are seizing the opportunity to make it a big strategic thrust for UF.”

SOURCES - Science Advances, University of Florida, Youtube, New Scientist

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