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Bio-Ink for 3-D Printing Inside the Body

Bioprinting could happen via minimally invasive surgery

3 min read
A lattice structure implanted directly into soft living tissue.
A lattice structure implanted directly into soft living tissue.
Image: Ohio State University

Right now, almost 70,000 people in the United States alone are on active waiting lists for organ donations. The dream of bio-printing is that one day, instead of waiting for a donor, a patient could receive, say, a kidney  assembled on demand from living cells using 3-D printing techniques. But one problem with this dream is that bio-printing an organ outside the body necessarily requires surgery to implant it.  This may mean large incisions, which in turn adds the risk of infection and increased recovery time for patients. Doctors would also have to postpone surgery until the necessary implant was bio-printed, vital time patients might not have. 

A way around this problem could be provided by new bio-ink, composed of living cells suspended in a gel, that is safe for use inside people and could help enable 3-D printing in the body. Doctors could produce living parts inside patients through small incisions using minimally invasive surgical techniques. Such an option might prove safer and faster than major surgery.

One challenge with bio-printing inside the body is that current bio-inks often require ultraviolet light in order to solidify, but ultraviolet rays can damage internal organs. Another problem is how to attach printed tissues effectively to soft live organs and tissues.

According to a new study published in the journal Biofabrication, researchers developed a bio-ink they could solidify using visible light. Moreover, the ink was printable at the kinds of temperatures found within the body—previous bio-inks were too liquid at body temperature to hold their shape when printed, says study senior author David Hoelzle, a mechanical engineer at Ohio State University.

The scientists used a 3-D printing nozzle affixed onto robotic machinery. This strategy dispensed bio-ink much like an icing tube squeezes out frosting, only in a controlled, programmable manner. The researchers experimented with bio-printing onto soft materials, such as raw chicken breast strips and a gel similar to agar jelly. They first pierced the surfaces of these materials with the nozzle and extruded a little “interlock” knob into the punctured space. Next, they slowly withdrew the nozzle from the materials, trailing behind a filament of material they could keep on printing with.

The knobs left beneath the surface anchored the printed structure to the body, acting a bit like surgical staples, “but with a different type of material and with more flexibility with the shape of material,” Hoelzle says.

The scientists made their bio-printed structures porous to help immerse the cells in fluids carrying nutrients, oxygen and other molecules. Up to 77 percent of mouse cells in the bio-ink remained viable in the structures after 21 days, and the researchers found their strategy of using interlocks resulted in an up to four-fold boost in adhesion strength.

Hoelzle notes they can definitely optimize the interlocks to boost adhesion. “Just like different stitch patterns for textiles have different strengths, there are bound to be different interlocking patterns that improve upon these results,” he says.

The researchers caution they do not aim to bio-print an entire heart or kidney in the body in a minimally invasive manner. “Even more traditional methods of delivery of tissue-engineering materials are years away from this accomplishment,” he says. Instead, “consider the ability to augment a standard surgery by delivering a biomaterial with a tethered growth factor to jumpstart healing, or a tethered drug to prevent infection.”

The scientists foresee bio-printing inside the body using robotic surgery instruments. “In a typical robotic surgery operation, the surgeon is operating four arms, two of them simultaneously,” Hoelzle says. “Each of the arms has an interchangeable tool, so the surgeon can swap out tools depending on what he or she needs at the moment. We envision a biomaterial-bioink printing tool as another tool in the surgeon’s toolset.”

Hoelzle and his colleagues are currently working on the first generation of an interchangeable bio-printing attachment for robotic surgery they aim to report before the end of this year, “although research restrictions from COVID are slowing us down,” he says.

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This CAD Program Can Design New Organisms

Genetic engineers have a powerful new tool to write and edit DNA code

11 min read
A photo showing machinery in a lab

Foundries such as the Edinburgh Genome Foundry assemble fragments of synthetic DNA and send them to labs for testing in cells.

Edinburgh Genome Foundry, University of Edinburgh

In the next decade, medical science may finally advance cures for some of the most complex diseases that plague humanity. Many diseases are caused by mutations in the human genome, which can either be inherited from our parents (such as in cystic fibrosis), or acquired during life, such as most types of cancer. For some of these conditions, medical researchers have identified the exact mutations that lead to disease; but in many more, they're still seeking answers. And without understanding the cause of a problem, it's pretty tough to find a cure.

We believe that a key enabling technology in this quest is a computer-aided design (CAD) program for genome editing, which our organization is launching this week at the Genome Project-write (GP-write) conference.

With this CAD program, medical researchers will be able to quickly design hundreds of different genomes with any combination of mutations and send the genetic code to a company that manufactures strings of DNA. Those fragments of synthesized DNA can then be sent to a foundry for assembly, and finally to a lab where the designed genomes can be tested in cells. Based on how the cells grow, researchers can use the CAD program to iterate with a new batch of redesigned genomes, sharing data for collaborative efforts. Enabling fast redesign of thousands of variants can only be achieved through automation; at that scale, researchers just might identify the combinations of mutations that are causing genetic diseases. This is the first critical R&D step toward finding cures.

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