Dec 29, 2017 | By Benedict

Bioengineers from UC San Francisco are using a 3D cell-patterning technology called DNA-programmed assembly of cells (DPAC) to 3D print complex folding shapes out of living tissue. The research could help scientists create complex and functional synthetic tissues.

3D bioprinting has already come a long way in allowing scientists to create synthetic tissues from human or animal cells. But even the most advanced bioprinters often fall short in successfully replicating the key structural features of tissues that grow according to developmental programs. Natural folds in human tissue, for example, the many stretchy and wrinkly parts of our body that help us to function, are not easy to replicate using a 3D printer.

New research carried out at UC San Francisco could mark an important turning point in tissue engineering, specifically regarding those difficult-to-replicate folding structures. Scientists at the university have discovered that by patterning mechanically active mouse or human cells—specifically mesenchymal cells—to thin layers of extracellular matrix fibers, they are able to create bowls, coils, and ripples from living tissue.

“We're beginning to see that it's possible to break down natural developmental processes into engineering principles that we can then repurpose to build and understand tissues,” said first author Alex Hughes, a postdoctoral fellow at UCSF. "It's a totally new angle in tissue engineering.”

The research involves the use of a 3D cell-patterning technology called DNA-programmed assembly of cells, which can be employed to set up a spatial template of a tissue. This tissue template then folds itself into complex shapes, mimicking the way in which tissues assemble themselves hierarchically during development.

It works because the mesenchymal cells effectively “tug” on the network of ropelike extracellular matrix (ECM) fibers around them, causing the entire structure to arch or deform.

Most excitingly, the scientists already have a firm grasp on how they can program the cellular assembly in order to manipulate its folding behavior. The researchers say that, by arranging the mesenchymal cells in particular ways, they are able to make living constructs that “shape-shift” in ways that are very similar to what their simple models predict.

“Development is starting to become a canvas for engineering, and by breaking the complexity of development down into simpler engineering principles, scientists are beginning to better understand, and ultimately control, the fundamental biology,” said senior author Zev Gartner, who described the new process as “a fantastic chassis for building complex and functional synthetic tissues.”

From here, the researchers have several avenues to explore. Firstly, they want to find out if they can incorporate the folding tissue development program into other programs that control tissue patterning, in order to manipulate cells in a comprehensive way. And secondly, they want to spend more time figuring out how cells differentiate in response to the mechanical changes that occur during in vivo tissue folding.

Ultimately, this important work could have knock-on effects anywhere from 3D bioprinted organs or miniature “organoids” for drug testing, all the way to the development of biological soft robots.

“It was astonishing to me about how well this idea worked and how simply the cells behave,” Gartner added. “This idea showed us that when we reveal robust developmental design principles, what we can do with them from an engineering perspective is only limited by our imagination.”

The researchers’ study, “Engineered Tissue Folding by Mechanical Compaction of the Mesenchyme,” has been published in the journal Developmental Cell.



Posted in 3D Printing Application



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