Aspiration of spheroids used to 3D print artificial tissues

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Aspiration of spheroids, cells and tissue strands is being used to precisely place these biologics in 3D patterns on scaffolding - or without - to create artificial tissues with natural properties.

PSU aspiration bioprinted on the bottom of a glass Petri dish. The spheroids of tissue can be seen (Image: Ozbolat’s lab/Penn State)

According to Penn State University’s Ibrahim T. Ozbolat, tissue spheroids have been increasingly used as building blocks for fabrication of tissues, but their precise bioprinting has been a major limitation.

"In addition, these spheroids have been primarily bioprinted in a scaffold-free manner and could not be applied for fabrication with a scaffold," said Ozbolat, Penn State’s Hartz Family Career Development Associate Professor of Engineering Science and Mechanics.

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Scaffolding is necessary for applications in regenerative medicine and tissue engineering, and in fabrication of microphysiological systems for disease modelling or drug screening.

Ozbolat and his team used aspiration-assisted bioprinting along with conventional micro-valve printing to create homogeneous tissues and tissues containing a variety of cells.

As demonstrated in the video below, aspiration-assisted bioprinting uses suction to move tiny microscopic spheroids. Aspiration-assisted bioprinting picks up the tissue spheroid, holds the suction on the spheroid until it is placed in exactly the proper location and then releases it. The researchers report their findings in Science Advances.

"Of course, we have to gently aspirate the spheroids according to their viscoelastic properties, so no damage occurs in transferring the spheroids to the gel substrate," Ozbolat said in a statement. "The spheroids need to be structurally intact and biologically viable."

By controlling the exact placement and type of spheroid, the researchers have been able to create samples of heterocellular tissues, those containing different types of cells.

"We demonstrated for the first time that by controlling the location and distance between spheroids we can mediate collective capillary sprouting," said Ozbolat.

The researchers created a matrix of spheroids with capillary growth in the desired directions. Capillaries, which are necessary for the creation of tissues that can grow and survive, deliver oxygen and nutrients to the cells. Without capillaries, only the outermost cells will receive oxygen and nutrients.

Precise placement of spheroids also allows creation of heterocellular tissues like bone. Penn State add that by beginning with human mesenchymal stem cells, the cells differentiated and self-assembled bone tissue.

The ability to produce artificial living tissues has applications beyond regenerative medicine, such as in drug testing or the screening of chemical products where specific tissues could be produced for the purpose.

The researchers suggest that this method can be cost-effective because the equipment required costs under $1,000 and is easy to use. They report that the system "can be useful in a wide variety of applications, including but not limited to organ-on-a-chip devices, drug testing devices, microfluidic, in vitro human disease models, organoid engineering, biofabrication and tissue engineering, biocomputing and biophysics."

The team note that the system needs improvement to print spheroids in high-throughput to create larger tissues in a shorter time.