A View of Commercial Efforts in Organ Bioprinting and Recellularization

A fair number of companies are at work on various approaches to bioprinting larger tissue structures, stepping stones on the way to the construction of patient-matched organs to order. New organs on demand is clearly the goal on the horizon, but many hard problems have to be solved before that can be accomplished for even relatively less complex internal organs. At the moment, while functional tissues for several organ types can be produced from cells in the lab, in the form of tiny organoid structures, there is no reliable methodology for the production of blood vessel and capillary networks needed to supply large tissue sections. Printing structures of the same complexity as the natural extracellular matrix of decellularized donor organs is also a work somewhere in progress. Nonetheless, a great deal of funding is devoted to these and other challenges; progress is likely over the decade to come.

Last month I had the chance to hold a replica of the upper part of a human airway - the windpipe plus the first two bronchi. It had been made from collagen, the biological cement that holds our bodies together. It was slippery and hollow, with the consistency of undercooked pasta. The structure had emerged from a refrigerator-size 3-D printer at an outpost of United Therapeutics, a company that earns more than a billion dollars a year selling drugs to treat lung ailments. One day, the company says, it plans to use a printer like this one to manufacture human lungs in "unlimited quantities" and overcome the severe shortage of donor organs. Bioprinting tissue isn't a new idea. 3-D printers can make human skin, even retinas. Yet the method, so far, has been limited to tissues that are very small or very thin and lack blood vessels.

United instead is developing a printer that it believes will be able, within a few years, to manufacture a solid, rubbery outline of a lung in exquisite detail, including all 23 descending branches of the airway, the gas-exchanging alveoli, and a delicate network of capillaries. A lung made from collagen won't help anyone: it's to a real lung what a rubber chicken is to an actual hen. So United is also developing ways to impregnate the matrix with human cells so they'll attach and burrow into it, bringing it alive.

United has already made some risky organ bets. One of its subsidiaries, Revivicor, supplies surgeons with hearts, kidneys, and lungs from genetically engineered pigs (these have been used in baboons, so far). Another, Lung Bioengineering, refurbishes lungs from human donors by pumping warm solution into them. About 250 people have already received lungs that would otherwise have been designated medical waste. Don't expect fully manufactured organs soon. United, in its company projections, predicts it won't happen for another 12 years. The printed structure I saw is just a start. Even so, United's effort to print entire organs, which got under way last year, may be the industry's largest.

Link: https://www.technologyreview.com/s/611236/inside-the-effort-to-print-lungs-and-breathe-life-into-them-with-stem-cells/

Comments

See Techcrunch's recent piece on Prellis Biologics using holographic printing technology to create capillaries:

https://techcrunch.com/2018/06/25/implantable-3d-printed-organs-could-be-coming-sooner-than-you-think/

"Now, Prellis has published findings indicating that it can manufacture those capillaries at a size and speed that would deliver 3D-printed organs to the market within the next five years.

Prellis uses holographic printing technology that creates three-dimensional layers deposited by a light-induced chemical reaction that happens in five milliseconds.

This feature, according to the company, is critical for building tissues like kidneys or lungs. Prellis achieves this by combining a light-sensitive photo-initiator with traditional bioinks that allows the cellular material to undergo a reaction when blasted with infrared light, which catalyzes the polymerization of the bioink."

Posted by: Jim at July 2nd, 2018 6:14 AM

Fun nature paper on a TGF-B small molecule inhibitor that slows senescence in mice (open access):

http://www.nature.com/articles/s41467-018-04994-z
TGF-β signaling alters H4K20me3 status via miR-29 and contributes to cellular senescence and cardiac aging

Posted by: Chris at July 2nd, 2018 9:14 AM

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