The Next Frontier for 3-D Printing: Human Organs

Scientists are on their way to 3-D printing functioning large organs. In the meantime, the technology is being used to test drug responses in mini-systems.

A 3D printer constructs a model human figure in the exhibition '3D: printing the future' in the Science Museum on October 8, 2013 in London, England.
National Journal
Sophie Novack
See more stories about...
Sophie Novack
Dec. 27, 2013, midnight

Re­search­ers at Wake Forest Baptist Med­ic­al Cen­ter are em­bark­ing on a pro­ject that is so over­loaded with sci-fiesque ele­ments that if it were a movie, you might ques­tion the screen­writer’s cred­ib­il­ity.

The “body on a chip” pro­ject will use 3-D print­ing — or bioprint­ing — tech­no­logy to cre­ate mini hu­man-or­gan sys­tems about the size of a quarter to test the body’s re­sponse to drugs. It’s fun­ded by a $24 mil­lion grant from the De­fense De­part­ment to de­vel­op an­ti­dotes to very strong agents in the areas of chem­ic­al and bio­lo­gic­al war­fare.

The ul­ti­mate goal of bioprint­ing is to cre­ate large, func­tion­al, im­plant­able or­gans that will ad­dress the grow­ing gap between vi­able or­gan sup­ply and de­mand for trans­plants. Along the way, the sim­pler, mini-ver­sions can be used to more ef­fect­ively test drugs.

A few groups have been ex­per­i­ment­ing with bioprint­ing tis­sues and or­gans, but the body-on-a-chip pro­ject is unique in con­nect­ing the struc­tures to­geth­er. The chip will be able to test the im­pact of agents — in­clud­ing in­tense chem­ic­al weapons, more main­stream drugs, and treat­ments — on the hu­man body. The pro­ject of­fers an al­tern­at­ive to an­im­al test­ing — which is of­ten in­ef­fi­cient and in­ac­cur­ate for meas­ur­ing hu­man re­sponses — and en­ables the lab to test the full sys­tem’s re­sponse, rather than just one type of or­gan.

Sci­ent­ists star­ted mak­ing tis­sues by hand about 25 years ago. Us­ing a tech­nique known as scaf­fold­ing, cells from a pa­tient’s tis­sue were layered on 3-D molds and grown in an in­cub­at­or out­side the body. Us­ing bioprint­ing tech­no­logy, they are now able to feed the same in­form­a­tion in­to a com­puter to build the tis­sue.

Print­ing came about as a way to scale up the tis­sues and or­gans we were already cre­at­ing by hand,” says An­thony Atala, dir­ect­or of the Wake Forest In­sti­tute of Re­gen­er­at­ive Medi­cine in North Car­o­lina and the lead in­vest­ig­at­or on the pro­ject. Bioprint­ing en­ables re­search­ers to cre­ate tis­sues with much great­er pre­ci­sion and ac­cur­acy.

Atala ex­plains the four tis­sues types in or­der of com­plex­ity: Simplest are flat struc­tures like skin; second are tu­bu­lar struc­tures, such as blood ves­sels or wind­pipes; third are hol­low non-tu­bu­lar or­gans, such as the stom­ach, blad­der, and uter­us; and last and most com­plex by far are sol­id or­gans, such as the heart, kid­ney, and liv­er. These have more cells per area, more cell types, and high­er nu­tri­tion re­quire­ments, and they need much more vas­cu­lar­ity and blood sup­ply.

To this point, sci­ent­ists have only im­planted the first three types from hand­made tis­sues in pa­tients. No bioprin­ted struc­ture has been im­planted.

The mini-or­gans are small enough that they don’t re­quire a com­plex vas­cu­lar tree to sur­vive. The mini-liv­ers, hearts, lungs, and kid­neys are not fully func­tion­al nat­ive or­gans, but they mim­ic the func­tion­al­ity for the test­ing ap­plic­a­tion.

The Wake Forest lab has de­veloped one ma­chine to bioprint dif­fer­ent types of tis­sues. “It’s like with an inkjet print­er, where you have dif­fer­ent col­ors,” says Sang Jin Lee, a coin­vestig­at­or on the pro­ject. “Here we have dif­fer­ent nozzles and dif­fer­ent ma­ter­i­als and cells.”

The re­search­ers are bor­row­ing from com­puter mi­cro­chip and bi­o­sensing tech­no­logy. They will fo­cus on one or­gan type at a time, be­gin­ning with the liv­er. As each is de­veloped, it will be used to test drug re­sponses in­di­vidu­ally; once they are com­pleted, they will be con­nec­ted on the chip to test the full sys­tem re­sponse.

A small hand­ful of oth­er groups are de­vel­op­ing tech­no­lo­gies to print tis­sues, al­though gen­er­ally with a fo­cus on in­di­vidu­al or­gans, rather than the full sys­tem.

Or­gan­ovo, a start-up in San Diego, is us­ing bioprint­ing of tis­sues to im­prove re­search on drugs, with a re­cent fo­cus on the liv­er.

“Re­li­ance on an­im­al mod­els and cells in a petri dish [for test­ing] is prob­lem­at­ic, be­cause many dis­eases can’t get good an­im­al mod­els or don’t be­have sim­il­arly in petri dishes,” says Or­gan­ovo CEO Keith Murphy. The com­pany has suc­ceeded in bioprint­ing liv­er tis­sue that las­ted 40 days in a dish. Murphy says nor­mally the tis­sue stops func­tion­ing in two days, which is not help­ful for test­ing a drug that is ad­min­istered for two years.

Or­gan­ovo is fo­cused on the im­me­di­ate com­mer­cial im­pact of bioprint­ing, with test­ing done on each tis­sue in­de­pend­ently. “We’ve con­tem­plated put­ting [the parts] to­geth­er over time, but you don’t need 10 things to study the liv­er — you need the liv­er,” ex­plains Murphy.

“You can make liv­ing struc­tures act like liv­ing tis­sues,” he says. “You don’t need the full or­gan to have an im­pact.”

The Ad­vanced Man­u­fac­tur­ing Tech­no­logy Group at the Uni­versity of Iowa is bioprint­ing tis­sue with this idea in mind. Ibrahim Ozbolat, AMTech co­dir­ect­or and as­sist­ant pro­fess­or of mech­an­ic­al and in­dus­tri­al en­gin­eer­ing, is fo­cused on cre­at­ing tis­sue that would ac­com­pany — not ne­ces­sar­ily re­place — the pan­creas and pro­duce in­sulin to help pa­tients with dia­betes.

“We’re not in­ter­ested in mak­ing a full nat­ur­al pan­creas,” he says. “We’re work­ing on mak­ing something that is large enough and pro­duces enough in­sulin that is trans­plant­able.”

These pro­jects are all steps along the path to­ward bioprint­ing large or­gans, al­though that goal and its clin­ic­al ap­plic­a­tion is years in the fu­ture.

“[Bioprint­ing or­gans] is still sev­er­al bil­lion dol­lars away,” Murphy says. “If the fund­ing is provided in five years, it could hap­pen quickly. If it takes 20 years, it will be more over that time frame.”

The hope is that as the tech­no­lo­gies con­tin­ue to de­vel­op, the man­u­fac­tur­ing of or­gans could help solve the prob­lem of rap­idly grow­ing trans­plant wait-lists.

Atala notes that over two sets of 10 years, the num­ber of pa­tients on wait-lists has doubled, while the num­ber of or­gans trans­planted has in­creased by only 1 per­cent — a prob­lem the Amer­ic­an Hos­pit­al As­so­ci­ation has de­clared a pub­lic health crisis.

“This is really what drives us to do this,” he says. “Everything builds on the next step.”

What We're Following See More »
‘PRESUMPTIVE NOMINEE’
Priebus Asks Party to Unite Behind Trump
7 hours ago
THE LATEST
FEELING THE MIDWESTERN BERN
Sanders Upsets Clinton in Indiana
8 hours ago
THE LATEST

Despite trailing Hillary Clinton by a significant margin, Bernie Sanders wasn't going the way of Ted Cruz tonight. The Vermont senator upset Clinton in Indiana, with MSNBC calling the race at 9pm. Sanders appears poised to win by a five- or six-point spread.

Source:
TRUMP IS PRESUMPTIVE NOMINEE
Ted Cruz Bows Out, Effectively Ceding the Contest to Trump
9 hours ago
THE LATEST

And just like that, it's over. Ted Cruz will suspend his presidential campaign after losing badly to Donald Trump in Indiana tonight. "While Cruz had always hedged when asked whether he would quit if he lost Indiana; his campaign had laid a huge bet on the state." John Kasich's campaign has pledged to carry on. “From the beginning, I’ve said that I would continue on as long as there was a viable path to victory,” said Cruz. “Tonight, I’m sorry to say it appears that path has been foreclosed."

Source:
TAKES AT LEAST 45 DELEGATES
Trump Wins Indiana, All but Seals the Nomination
9 hours ago
THE LATEST

The Republican establishment's last remaining hope—a contested convention this summer—may have just ended in Indiana, as Donald Trump won a decisive victory over Ted Cruz. Nothing Cruz seemed to have in his corner seemed to help—not a presumptive VP pick in Carly Fiorina, not a midwestern state where he's done well in the past, and not the state's legions of conservatives. Though Trump "won't secure the 1,237 delegates he needs to formally claim the nomination until June, his Indiana triumph makes it almost impossible to stop him. Following his decisive wins in New York and other East Coast states, the Indiana victory could put Trump within 200 delegates of the magic number he needs to clinch the nomination." Cruz, meanwhile, "now faces the agonizing choice of whether to remain in the race, with his attempt to force the party into a contested convention in tatters, or to bow out and cede the party nomination to his political nemesis." The Associated Press, which called the race at 7pm, predicts Trump will win at least 45 delegates.

Source:
THE QUESTION
What’s the Average Household Income of a Trump Voter?
14 hours ago
THE ANSWER

Seventy-two thousand dollars, according to FiveThirtyEight. That's higher than the national average, as well as the average Clinton or Sanders voter, but lower than the average Kasich voter.

Source:
×