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http://cen.acs.org/articles/93/i10/Print-Heart.html?h=-265035111 

It was an honest question. But the way Stuart K. Williams asked it sounded like the prelude to a wager: Which organ will researchers first replicate with three-dimensional bioprinting?

Williams, the director of the Bioficial Organs Program at the University of Louisville, posed the question to Gabor Forgacs of the University of Missouri at last month’s Select Biosciences Tissue Engineering & Bioprinting Conference in Boston. Forgacs, having just delivered the keynote speech, mulled the question over.

Some believe 3-D printers will one day create viable organ transplants using a patient’s own cells. This would alleviate complications that arise when a patient’s immune system rejects a donor organ. And it would put an end to growing transplant wait lists. For every organ donor in 2012, there were more than eight patients on the transplant wait list, according to the U.S. Department of Health & Human Services.

Williams’s question hung in the air for a moment. The conference hall overlooking the Charles River was packed even though the latest in a series of record-setting snowstorms kept many would-be attendees away. The crowd waited silently for Forgacs’s answer, but everyone there had an inkling of what it would be.

Forgacs, a pioneer in bioengineering who’s printed 3-D structures with “inks” made of living cells, hedged the question, reminding the audience of comments he made during his talk. “Everybody’s dream is the 3-D printed organ. Are we ever going to get there?” he asked himself. “I’m not so sure.”

Bioprinting’s more immediate impact will be in making small patches of tissue for screening drugs or for better understanding biology, Forgacs said. Before researchers can even hope to tackle the far more complex problem of printing an entire organ, he added, they will need to confront some daunting challenges, such as figuring out how to print blood vessels capable of supplying artificial organs with essential nutrients.

These challenges influence the decisions researchers make in every phase of the printing process: from concocting a suitable bioink to printing the ink to goading the printed cells to act like an organ. This last bit, Forgacs said, is the most important and most difficult challenge.

He’s not convinced that researchers will ever duplicate an organ with bioprinting, but he doesn’t believe that they should try to copy organs exactly. “There’s no reason we can’t make something that functions exactly the same, if not better, than the natural organ,” Forgacs told C&EN. The day when an improved heart or liver can be printed on demand is several decades away, but Forgacs is optimistic it’s coming. “We are fantastic engineers.”

Researchers’ engineering ingenuity is evidenced by how far bioprinting has come since its birth about 15 years ago. It’s tough to pin down an exact starting point for the field, but many researchers point to the early-2000s work of Thomas Boland, who was then working as a bioengineer at Clemson University.

Boland swapped out the contents of an ink-jet printer cartridge for a bioink containing bovine cells suspended in a mixture of serum and cell-culture medium. After installing the cartridge in a modified Hewlett-Packard desktop printer, his team printed a 2-D pattern of the ink on a biopaper—a substrate that makes cells feel more at home outside the body. In this case, the biopaper was a gelatinous mixture of collagen and a protein matrix to help anchor cells. Within a few years, the ink-jet technology could print stacks of these cellular patterns to make 3-D structures.

Boland’s experiments would essentially define the criteria needed for a method to truly be considered bioprinting. First, the bioink must contain cells. Metals, plastics, and ceramics have been printed without cells to repair or replace biological structures such as teeth, windpipes, and skulls. Many consider these uses to be examples of conventional 3-D printing with biological applications rather than bioprinting.

Second, the bioprinter must be able to pattern a user-defined 3-D structure on demand. This means that organs made from cells cultured in molds don’t get the “bioprinted” label. This method has been used by researchers at Wake Forest University toproduce bladders for transplantation.

And finally, the cells must survive the printing process and remain viable. In other words, a printer shouldn’t murder cells with heat, laser light, or mechanical stress. Cells also need a print medium that fosters a nurturing biological environment, which can be provided by the bioink, the biopaper, or some combination thereof.

Since Boland’s ink-jet innovation, researchers have developed a variety of inks, papers, and printers that work together to satisfy the basic requirements of bioprinting. Some of these products have even been commercialized.

There are currently more than a dozen 3-D bioprinting companies, according to a list provided by Select Biosciences.Organovo, a company founded in 2007 based on technology developed by Forgacs, is the most notable among these, according to many in the field.

In November of last year, Organovo started selling a 3-D bioprinted liver tissue called exVive3D. The tissue accurately predicts human response to drugs that are toxic to the liver, according to the company’s chief executive officer, Keith Murphy.

Pharmaceutical companies could thus use the tissue to test drugs at a stage between preclinical animal trials and clinical human trials. Catching adverse effects in human tissue before moving a drug into clinical trials would not only better protect patients but also save companies time and money in drug development.

So far, the response to the exVive product has been good, Murphy said. The printed tissue accounted for nearly $140,000 of Organovo’s revenue between its November launch date and the end of the calendar year, according to the company’s most recent quarterly report.