Sticky cells are the key to printing 3D organs

Author: Paul Krzyzanowski, 07/23/15

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3d-printed-bionic-ear-from-princetonIt’s been about 50 years since Philip K. Dick, one of the greatest science fiction authors, introduced the idea of artificial organs replacing failing or diseased organs. In his novel, Ubik, the author writes:

“[Glen] Runciter’s body contained a dozen artiforgs, artificial organs grafted into place in his physiological apparatus as the genuine, original ones, failed”.

Biological 3D printing, or bioprinting, has recently become possible on a scale that’s still nowhere near ordering bespoke organs, but nevertheless can potentially make a huge difference for people facing major surgeries or in need of skin grafts. Regenerative medicine researchers are keeping a close watch on the progress of this technology.

The 3D printing currently used to print replacement body parts uses materials that are largely inert: titanium, ceramic materials, and polymers. The Financial Times recently covered many of these applications, which are mostly structural (i.e. ears and nose bridges), claiming that 3D printing of complex organs is still far into the future.

Maybe so, but surgeons in the UK 3D-printed a copy of a two year old’s defective heart to plan and practice the complex operation beforehand. In Japan, researchers are printing model livers to help surgeons visualize blood vessel structure. These are both excellent applications of 3D-printed organs. However, these practice models are still made of plastics, not cells.

Bioprinting is more akin to what regenerative medicine researchers envision when describing the potential of 3D-printed organs: using live cells to create a product that goes beyond making a structural model to mimicking a natural organ’s function. This feat is much more difficult than simply printing an accurate model of an organ in plastic, the current popular practice.

One of the biggest companies working in this space is Organovo who, in 2013, publicly presented a small (0.5mm deep by 4mm wide) piece of bioprinted liver tissue that retained function for 40 days. This level of success hints that printed tissues might actually take hold and survive if transplanted into a native environment like a recipient’s liver.

More recently, the company has also demonstrated that these tissues work particularly well for toxicology experiments, flagging Rezulin (a drug withdrawn from the market in 2000 for liver toxicity) as a liver-damaging agent after only seven days of experimentation. As we know, induced pluripotent stem (iPS) derived cells have proved useful for drug screening.

skin7As always, there’s a market for printed tissues that is different from that which regenerative medicine researchers strive for: Organovo is partnering with L’Oreal to develop printed skin tissue. The cosmetics company already cultures skin donated by surgery patients, mostly to test cosmetics, according to this excellent overview of the deal in Wired. This collaboration will be an interesting one to follow as it evolves.

It’s starting to be obvious that the key obstacle to real 3D bioprinting lies in keeping cells alive, happy, and doing what they are intended for during and after the printing process. The actual tissue printing process isn’t much different from the additive manufacturing process most consumer printers make use of.

Converting cells into “bioink” that bioprinters can actually use is challenging, explains Michael Renard, a VP at Organovo, to Wired: “In concept, [bioprinting uses] the same idea of programming the 3-D printer to print architecture on an X-Y-Z axis. We just happened to use living human cells. There’s delicacy involved.” Critically, cells need to be nourished and kept at stable temperatures so they can actually fuse when printed, but the exact details of how Organovo does this aren’t divulged here.

What I find very interesting in the bioprinting market is that competitors don’t appear to be competing on printing capabilities, but rather via their bioink compounds.

For instance BioBots, a Philadelphia-based startup, produces a $25,000 printer that prints using whatever cells you choose, but converts them into printable bioink using their proprietary cartridges of reagents. Earlier this year, BioBots founder Danny Cabrera explained that the company’s innovative feature was using a blue light activated adhesive to form cells instead of chemicals activated by UV light (which can obviously damage printed cells); the printer was secondary.

Other competitors are emerging: CELLINK is commercializing bioink composed of cellulose fibres and alginate as a cross-linking agent, which can be used to print chondrocytes into cartilaginous shapes including the classic human ear, with little to no cytotoxicity, and a report in Nature Communications used tissue specific bioinks to print several types of cells last year.

If you’re into the bioprinting field, you’re probably correct in thinking that startups in the bioprinting space will be developing technology that keeps cells functioning after printing. A printed organ may give researchers the hot headline for an academic publication, but finding the right adhesive to do so is the leap that will actually make a difference.

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Paul Krzyzanowski

Paul is a computational biologist and writer living in Toronto. He's been a contributor to Signals for three years, writing articles for the general public about how biotechnology and biomedical research can be used to solve pressing medical problems. Alongside Paul's experience in computational biology,
 bioinformatics, and molecular genetics, he's interested in how academic research develops into real world, commercial technology, and what's needed for the Canadian biotech industry needs to grow. Paul is currently a Post-doctoral Fellow at the Ontario Institute of Cancer Research. Prior to joining the OICR, he worked at the Ottawa Hospital Research 
Institute and earned a Ph.D. from the University of Ottawa, specializing in computational biology. And finally, Paul earned an H.B.Sc. from the University of Toronto a long time ago. Paul's blog can be read at www.checkmatescientist.net
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