In the film, ‘The Fifth Element’, Mila Jovovich’s character is
in a pretty bad state. After her spaceship is shot down and crashes on Mars,
all that can be recovered from the wreckage is a solitary hand. There is no cause for alarm (although cue
spoiler alert), because thanks to the magic of science fiction she is saved! In
the following scenes, government scientists from the year 2263 place the
surviving limb in a perspex tube, and use DNA from the cells clinging on to
life to completely reconstruct her body, albeit without clothing. In mere
minutes, her modesty is hidden by a few strategically placed bandages, and she
fights on as the female protagonist till the end of the film.
All operations in the
year 2263 allow you to emerge looking like a supermodel.
Could science fiction ever become fact? Perhaps not at this
scale or speed, but human organs may one day be manufactured simply by using
3D-printing. Traditionally used with plastics and polymers, 3D-printing is
particularly special because at the stroke of a few computer keys, objects are
easily customised and made unique. Besides the manufacture of bespoke and
on-demand plastics, other ‘inks’ have been formulated for these machines to
produce clothing, food and even buildings. Specially adapted 3D-printers can
now use living cells as a ‘bio-ink’, and are close to being capable of printing
entire human organs for transplantation. By using cells harvested from an
individual, organ donations, organ rejection and immunosuppressant drugs may
one day be a thing of the past.
Several names have been coined for the fledgling technology,
such as ‘bio-printing’ or ‘organ-printing’, as well as ‘computer-aided tissue
engineering’. This multitude of names reflects the numerous approaches to
building complex organs out of living raw materials. In general, temporary scaffolding
materials such as agarose gel or starch, are printed alongside a bio-ink containing
cells to form the working organ, such as liver or kidney cells. As layers are
printed consecutively on top of one another, the cells anchor around the
scaffolding, forming the 3D structure. The scaffolding is then simply dissolved
away, leaving the tissue in a formation that mimics that of the organ. Producing
vascular structures, such as blood vessels and capillaries is critical to surmount
the greatest challenge in bio-printing fully-sized organs: keeping cells alive.
After printing layers of cells on top of each other, the cells buried within
the tissue are cut off from nutrients and oxygen supplies, causing them to die.
Bio-printing blood vessels and capillaries in organs can evade this problem,
and allows the production of bigger tissues that stay alive.
Printing something
less complex than a supermodel using an agarose scaffolding.
This has been successful in many applications, such as the creation
of artificial liver tissue at the University of Pennsylvania using a
scaffolding of sugars (1); dissolving the sugar leaves ‘holes’ where blood
vessels are required. Other techniques to create blood vessels have also been
explored. For instance, artificial capillaries have been constructed in Germany
at the Fraunhofer Institute, using photons to stimulate scaffolding materials into
fine flexible structures. This allows the capillary to infiltrate surrounding
tissue, alongside a bio-molecular coating to subdue rejection by the immune
system (2). However, in addition to their structure, capillaries contain layers
of different cell types like the endothelium, which all perform important
functions for vascularisation. At Harvard University, an approach where the
holes in bio-printed organs are ‘seeded’ with endothelial cells has been
successful, as the cells spontaneously cover the lining of artificial blood
vessels if the right conditions are provided (3).
The innate self-organising abilities of cells are enabling
this technology to go even further towards bio-printing entire organs. Simply
by using several bio-inks containing the constituent cells of vascular
structures like the endothelium, including smooth muscle cells and fibroblasts,
complete capillaries can be printed within organs. Like the endothelial cell-seeding
approach, when these cell types are printed around artificial capillaries, they
autonomously organise themselves into the distinct layers found in vascular
structures. Finally, bio-printing is coming of age, and is now commercially
available from the biotechnology firm Organovo, with their ‘Novogen’
bio-printers. However, many researchers have produced bio-printing machines of
a similar calibre, many of which are ‘hacked’ 3D-printers. Unfortunately, they
all share the same caveat; no bio-printers can produce anything on the scale of
human organs, and are only readily useful to researchers who require home-grown
tissues for experimental work, rather than using cells cultured in the
traditional way.
Even with the small-scale capabilities of bio-printing, it
is already set to revolutionise medical care. A bio-printing spray from the
Wake Forest Institute for Regenerative Medicine has shown great promise in
animal studies. By directly spraying cells onto wounds, this may speed up the
healing process and eliminate the need for painful skin grafts (4). A scanning
laser directly analyses the exposed tissue in the wound, and a 3D map is
generated to determine where certain cell types are appropriate to print
directly onto the area. A future development for this technology promises even
greater things; it may be possible to have ‘tissue on demand’ within the
operating theatre, not unlike the donated blood that is readily available today.
Further uses for bio-printing technology – even at this
small scale – are also revolutionising other fields of medical science.
Complete human organs may be many years away, but the ‘body-on-a-chip’ concept
is rapidly becoming reality, and is also under development at the Wake Forest
Institute (5). This technology is a tiny bio-printed collection of human organ chambers,
connected with a minute blood system. These bio-printed systems could provide a
more valuable drug testing environment, as they would both imitate the effects
of disease or chemical agents on the entire human body, and also reproduce the effects
of any potential drugs, including any side-effects. Furthermore, if the body-on-a-chip
originated from one person, the efficacy of medicines could be tailored to the
individual, making a highly personalised treatment.
Even without personalising medicine to this extent, the
body-on-a-chip could make drugs more specific to our species. Animal testing
has been a mainstay of drug development, as drugs can have considerably
different effects within organ systems in comparison to cells in a petri dish. This
means any drug approved for clinical trials must demonstrate both safety and effectiveness
in animals, which is not completely fool-proof. Investigated treatments can become
tailored to animals rather than humans (with potentially fatal consequences), or
may be effective in humans but fail animal tests. As it is made from human
cells, the body-on-a-chip could circumvent these problems, and may even replace
the need for animals altogether. There are many possibilities, ripe for
exploration.
All of these prospective applications would revolutionise medicine,
but bio-printing entire organs for transplantation is urgently needed. From the
first kidney transplant in the 1950s to today, organ transplants have undoubtedly
saved countless lives, but sadly many die before reaching the end of the
waiting list for a suitable donor. Even those that are successful face a
lifetime of immunosuppressants, and the threat of organ rejection. Hopefully,
thanks to the magic of real science, by the middle of the 21st
Century these lives can all be saved, like Mila Jovovich. Saying that, I’d
avoid flying around in spaceships when someone clearly wants to kill you, as
complete bodily reconstruction might take a little longer to develop.
2) Moskvich, Katia (2011) Artificial blood vessels created on a 3D printer. BBC News. [Online]Available at: http://www.bbc.co.uk/news/technology-14946808 [Accessed February 25th, 2014]
3)Kolesky, D.B. et al. (2014) 3D Bioprinting of Vascularized, Heterogeneous Cell-LadenTissue Constructs. Advanced Materials. 26 (8): pp 1-7
4)Rosenblatt, Dana (2011) Researchers aim to ‘print’ human skin. CNN. [Online]Available at: http://edition.cnn.com/2011/TECH/innovation/02/19/bioprinting.wounded.soldiers/ [Accessed February 25th, 2014]
5)Hsu, J. (2013) Tiny 3D-Printed Organs Aim for ‘Body on a chip’. LiveScience. [Online]Available at: http://www.livescience.com/39660-3d-printed-body-on-a-chip.html [Accessed February 25th, 2014]
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