Published online 20 March 2008 | Nature | doi:10.1038/news.2008.675

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How to print out a blood vessel

New work moves closer to the age of organs on demand.

Blood vessels can now be 'printed out' by machine. Could bigger structures be in the future?SUSUMU NISHINAGA / SCIENCE PHOTO LIBRARY

A tissue-engineering group has succeeded in creating functional blood vessels and cardiac tissue, using a 'printer' that dispenses cells instead of ink. The work, published this month in Tissue Engineering, is among the first to produce functional three-dimensional tissue using a printer, and a milestone on the way to the goal of printing out whole organs1.

Gabor Forgacs from the University of Missouri in Columbia and his colleagues printed various tissue structures, including blood vessels and sheets of cardiac tissue. When they printed out cardiac and endothelial cells, the cells fused into a tissue after 70 hours, and began beating in time like regular heart tissue after 90 hours.

Their work relies on the innate capacities of the cells to create capillaries and other finishing touches on their own. "We will never be able to print a liver with all of its many details," says Forgacs. "But it is not necessary. If you initiate the process, nature will do it for you."

What makes this work different from that done in most other tissue-engineering labs is that Forgacs's team does everything without a scaffold — they don't start with an object shaped like the tissue or organ they are aiming to create, but instead plan to print the whole thing from scratch, from the vasculature up. This should make it easier to print any type of organ, they say, as they don't have to develop different scaffolds for each tissue type. "Often when you implant a scaffold you get inflammation," says Forgacs.

The work also uses a printer that dispenses blobs (or 'spheroids') of cells, rather than spraying out one cell at a time. This is faster, can be gentler on the cells, and seems to encourage them to fuse together.

Made to order

In December, the team demonstrated their technique after their paper first appeared online.

The centrepiece of the lab is the 2-metre-wide printer, a custom-made device from a company based in Orlando, Florida, called nScrypt, which usually specializes in printers that make microelectronics. The printer has three heads, each of which is controlled by an attached computer, that can lay down spheroids of cells much as a desk printer would lay down ink.

Two of the heads print out tissue cells (mixtures including, for example, cardiac and endothelial cells), while the third prints a 'gap-filler' (such as collagen) that fills a space temporarily until the other cells have fused. So to make a blood vessel, for example, lines of cells are laid down with lines of collagen in the middle, which will later be extracted to make way for blood.

Francoise Marga, one of Forgac's team, watches the demonstration printing anxiously. When one of her cell lines smears a bit, she swoops in with a toothpick to tidy it up. After all the lines are laid down, the result is a tiny, flaccid-looking white tube. This is a simple example of what the team can achieve: they can create branched tubes to order.

Paul Calvert of the University of Massachusetts Dartmouth, who has reviewed the field of tissue engineering, says that the work is a definite step towards the ultimate goal of printing organs. He says that both cell-by-cell 'inkjet' printing, and the dispensing of spheroids of cells, will likely be used together, in future, to make fused tissues.

Home grown

Once Forgacs and his lab have printed branched tubes, the tubes can be left on their own to arrange their cell types in the right orientation and grow basic vasculature including capillaries, following the same internal instructions that produce complex tissues when an embryo develops. "It is tissue engineering based on developmental biology," says Forgacs.

The team is now working on ways to exercise the muscle in their resulting blood-vessel tubes to make them tough enough to sew onto natural blood vessels as a graft. They are focusing on vessels narrower than 6 millimetres, as there are synthetic grafts that work quite well for larger vessels.

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Forgacs and several others have formed a Missouri-based company, called Organovo, to bring such developments to market. They predict that their first product, which they hope to have for sale within a few years, will be simple, no-frills tissue structures for toxicology tests. Such simple models of livers, for example, could be used to test the effects of a drug on a human organ, without having to rely on animal tests. Implantable blood vessels won't be too far behind, he says.

Beyond that, Forgacs has his eye on fully implantable whole organs printed from a patient's own cells. "You give us your cells: we grow them, we print them, the structure forms and we are ready to go," he says. "I am pretty sure that full organs will be on the market [one day]." The kidney may be one of the first, he predicts, as its filtering function is relatively simple. "It may not look exactly like a kidney, but it will function exactly like one." 

  • References

    1. Jakab, K. et al. [journal]Tissue Eng.[/journal] 14, 413-421 (2008).
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