Printing Bodies

They are some way off making hearts, kidneys or livers to order, but scientists are

continuing to experiment with three-dimensional printing of organs and tissue,

from blood vessels to ears. Now, Science reports that scientists from the University

of Oxford have succeeded in printing a material that behaves like real human

tissue, with the ability to respond to stimuli and communicate in the same way as

neurons.

Doctor Curt Connors lost an arm in the war and, after coming back to his native New

York, he became a scientist obsessed with regenerating missing limbs. Connors ended

up turning into the villainous Lizard, an enemy of Spiderman in the Marvel Comics

universe. He based himself around reptiles as, unlike humans, they are able to

regenerate a limb if they lose it.

“Actually we can regenerate. For example your skin regenerates every two weeks, and

your bones regenerate every 10 years,” states Antony Atala, Director of the Wake

Forest Institute for Regenerative Medicine (USA) in one of the famous TED Talks.

However “it will still take some years before the organs that we’re printing in three

dimensions enter clinical trials with humans”, he explained to SINC.

While the cartoonists Stan Lee and Steve Ditko were dreaming up the character of

Connors, the real world had already seen the first human kidney transplant. It was in

that decade, the 60s, when tissue engineering was born. Over half a century later, people

walk down the street with tracheas created entirely in the lab, or with urethras and

bladders built in a Petri dish. Scientists throughout the world are starting to play with

3D printers, loading their cartridges not with ink, but with cells.

This week, the journal Science carried a study in which a team from the University of

Oxford, led by the scientist Gabriel Villar, printed a three-dimensional material capable

of imitating the behaviour of real human tissue. It has the consistency of soft rubber,

and physically it resembles adipose and brain tissue. Most interestingly, it is able to

make folding movements and is equipped with communication networks that work like

neurons.

Villar’s team used a printer to arrange thousands of tiny droplets of water into rows and

layers, which held together thanks to a lipid membrane (i.e. made from fat). This results

in a macroscopic network that makes up “a cohesive material with cooperating microcompartments”

in the words of the researchers.

By including proteins in this lipid layer, the structure can respond to certain stimuli.

“The printed network presented here is functionally analogous to a nerve axon in

enabling rapid, long-distance electrical communication along a defined path”, claim the

authors in their paper.

This material can be integrated into the tissue of live organisms in order to interact with

the individual and the environment, for example “by delivering drugs upon a specific

signal” or even “working to support failing tissues”.

Supply and demand of organs

Like everything, organs wear out as they are used. “While the number of donors

remains at the same level, as life expectancy increases the need for transplants does

too”, notes Anthony Atala. According to this expert, the number of patients needing a

transplant has doubled in the last decade.

“If we were some day able to create organs using cells from the individual themselves,

we would be able to cure many chronic and degenerative diseases on demand”, explains

Mike Renard, Executive Vice President of Organovo, to SINC.

One of the founders of this regenerative medicine company was the scientist Gabor

Forgacs, who in 2008 first used a printer to create functional blood vessels. Organovo

repeated the feat in 2010 with their own printer, which, instead of ink, was loaded with

the cells that make up an artery: endothelial, muscle and fibroblast cells.

“Before considering the therapeutic applications of this technology, we need to perfect

it, and this is what we are doing by creating relatively simple and useful tissue that, for

now, could work as support for tissue that’s already been damaged, for example nerves,

bone, cartilage, or parts of the heart or kidney”, explains Renard.

For the time being, one of Organovo’s most immediate aims is to print complete human

tissue that could help develop new drugs. Renard believes that “this technology could

be very useful considering how difficult it is to obtain relevant and extrapolatable

biological information from two-dimensional cell cultures”.

Printed skin and ears

In any case, how far we are from clinical application for this printing technology will

depend on which organ we are talking about, as some are more complex than others.

For example, it is hoped that printing skin directly onto wounds or burns will be ready

for clinical trials with human patients in less than five years.

“We have already started pre-clinical trials,” says Mohammad Albanna, researcher from

the Wake Forest Institute, which in 2012 announced the use of this method in pigs. “The

advantage of this technique compared to current skin replacement products is that it can

cover large areas in a short amount of time”.

This project depends on interest and funding from the military industry as “soldiers

often suffer burns over a large portion of their body, which require immediate action”

states Albanna in an email to SINC.

Although reproducing living skin is still a little ways off, as early as last month the

journal PLOS ONE reported on the success of 3D printing of ears to be implanted onto

human patients. Between 1 and 4 in 10,000 newborns suffer from microtia, a congenital

deformity of the outer ear that can be treated with this technique.

The authors of the study, scientists from the Weill Cornell Medical College in New

York, are specialists in cartilage-based human structures such as joints, the trachea and

the nose, and are very proud of the result, which is practically identical to the human

ear. “It could be the solution that surgeons have been waiting for to help children who

are born with this defect, or people who have lost their outer ear through an accident or

cancer”, declared Jason Spector, coordinator of the study.

Hollow and solid organs

It may be a step further in complexity, but the generation of hollow organs using the

patient’s own cells and biomaterials is already producing proven clinical results. These

materials, which Antony Atala describes as “intelligent”, serve as a mould that the cells

can cover in order to form the organ, and eventually disintegrate without causing

rejection. Using this method, Atala and his team created and transplanted bladders into

seven patients in 2006.

The scientists from Wake Forest Institute have applied this technology in order to create

aortic valves, muscles, blood vessels and urethras. The next challenge is generating

solid organs, such as the kidney, the liver or the heart, which are highly vascularised

and made up of not two, but multiple types of cells.

One of the steps towards this is using the structure of an organ which, for whatever

reason, is not suitable for transplant. It could be a liver, for example. The scientists

remove its cells, leaving just the collagen structure. The next stage is to extract cells

from the liver of the patient due to receive the transplant and use them to repopulate the

structure, thus creating a new liver. This would prevent rejection and treatment with

immunosuppressants, which are two common causes of failure in transplants.

Every cell in its place

Another step forward is, again, three-dimensional printing. “The important thing in

tissue engineering is to control the precise location of each cell in order to imitate the

natural complexity of the tissue so that it works at a biological level”, explains the

director of the Wake Forest Institute in an email. “Printing allows you to do exactly

this”.

At the start of this year, he and his team announced in the journal Biomaterials that

printing had allowed them to obtain a three-dimensional tissue made up of various types

of cells that functioned biologically. “This study shows that it is possible to construct

complex and functional tissue in this way,” affirms Atala.

“So far, in the Wake Forest Institute we have managed to print muscle tissue, bone, an

ear, a nose, and kidney structures,” James Yoo, one of the inventors and owners of the

patent for this technology, told SINC. Although the aim is to resolve the problems of

organ shortage, Yoo admits that “it’s difficult to know which one will the first to be

fully built using this technology”.

“I honestly believe that 3D printing will have a large role to play in tissue and organ

engineering, but science is so unpredictable that I’ve learned not to make prophesies”,

states Atala. What this respected scientist wants to make clear is that it will take some

years for this technology to be put into clinical practice and the most important thing is

“to make sure that we don’t harm any patients”.