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
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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.”

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