Article

World of Bioprinting : Myth or Reality?

  • Nimish Sany
  • 24 June , 2016

So we’ve had movies where the very machines we make take us over, destroy our cities, wipes out the human race and all that kind of stuff. And then there are machines that beat the bad ones, save our lives, save the day, etc, etc.  Ironically enough, this seems to be a ‘pop-fictionally’ exaggerated truth. There are machines with flipsides and then there are machine which are real life savers, and I mean literally. What if, you have in home a printer that prints out the very organs that hold up our life? Livers, kidneys, tissues, you-name-it. And not the metal or plastic ones either. Carefully designed, precisely engineered live pieces of printed cellulose made to work 24/7 for lifetime in a human body. A whole new level of cloning; welcome to bioprinting- probably the most valuable and sophisticated application of 3d printing to date.

Bioprinting is the

  • designing
  •  development &
  • printing of targeted tissues.

Where the targeted tissues forms the building blocks of the organ to be printed. Organ to be printed- what are the odds of reading this phrase elsewhere? Exactly why a need for advancement in this field was recognized. The basic principle of Bioprinting and 3D printing remains the same. The two major differences are the printer and the ink (additive material) used. The Bioprinter uses a ‘bio-ink’ for its printing processes. Bio-ink is a slurry of cells obtained from the targeted tissue. For example, a cell sample from the liver is obtained and cultured to form a slurry and is placed in the cartridge. This slurry, filled out through the cartridge form the bio-ink needed to print the liver. Arguably, designing of the organ and developing bio-ink constitutes a major portion of bioprinting.

So now we know the kind of technology we’re dealing with, but what made us push toward such a perplexing state of the art innovation? Demand indeed. Necessity is the mother of all inventions. Let's have a look at the donor statistics in the EU over a period of three years:

organ and tissue donation statistics in the EU till 2013

Organ and tissue donation in the EU  Image: nursingceu.com

The dependence on living donors for organs seemed to be climbing and is expected to have remained that way. The stat shows only a mere fraction of global demand. Sometimes this exponentially rising demand is met in the black market by exploiting or even torturing of living donors by rackets. The procedure and treatment expenses have also made organ transplantation a hardship for the poor and needy. So bioprinting came as a much needed and viable solution for a much pressing demand.

Bioprinting saw its outset in the late 2000s with Organovo, a San Diego based pioneer in this field. Organovo have successfully printed kidneys, muscle tissues and strips of human liver tissues which takes about two days to mature, and once printed, the strips can survive for about 40 days. By December 2010, the firm used cells cultivated from a single person to create the first ever 3D printed blood vessels tube.

And as to how such innovations have been made lies on the sophisticated yet successful bioprinting process. Like we discussed earlier, bioprinting is a 3-step process of designing, developing and printing of tissues; and once we’ve identified the target tissue (tissue to be printed, which later develops into the target organ), the process begins. The target tissue could be liver tissues, muscle fiber tissues, etc.

  • Designing

Every tissue has got its unique compositional and constructive elements. These elements are to be incorporated in the design of a tissue. Designs are often made with the help of CT scans, which gives a comprehensive design of the target organ. Sometimes the design from a CT scan itself is used or alterations are made using designing softwares.

  • Developing

 Once a design is chosen, the next step is to obtain the ‘ink’ to print our design. Keep in mind that the ink is for printing a chunk of tissue which expands, contracts and most importantly, breathe. What kind of ink could possibly print that? Obviously, the human kind; or the ‘bio-ink’. The bio-ink is made from the cells of the target tissue. Spheroids of this bio-ink are formed and loaded into the cartridge of a bioprinter.

  • Printing

The rest of the process is upto the bioprinter. The bioprinter dispense these bio-ink spheroids into a layer of ‘bio-paper’- a water based paper-like-layer made from collagen. More and more of these ’bio-paper’ containing bio-ink spheroids are printed layer by layer. Now, the bio-ink exhibits its exclusive property. The spheroids which are made of cells from the target tissue start exhibiting the property of those cells and fuse together to form the final tissue and the bio-paper dissolves away.

bioprint mechanism

Innovation of this printing technique is credited to Organovo and its first-of-a-kind bioprinter, called NovoGen MMX.

novogen bioprinter

The NovoGen MMX   Image: http://www.biotecnika.org/

Like in the picture, the NovoGen has got two printing heads, one prints out the spheroids while the other lays out the layer of bio-paper. NovoGen MMX is planning its commercial sales by the end of 2014. While NovoGen remain the pioneer in its field, there are other bioprinters with similar printing technology presently at use. Researchers at Wake Forest University uses ‘inkjet’ inspired printers which operate on the inkjet technology. Robot-printers have also found use at the University of Louisville's Cardiovascular Innovation Institute.

Check out this video demonstrating the bioprinting process: https://www.youtube.com/watch?v=s3CiJ26YS_U Video courtesy: Organovo.com              

The ‘abundant’ applications

As promising as it is, however, bioprinting is currently being used only for research and pharmaceutical testing. Organovo recently developed liver tissues for pharmaceutical testing for the first time in history. In 2010, the firm successfully bioprinted the first ever human blood vessels. Clearly, bioprinting it’s picking up its pace. Advancements in the field and exposure drew researchers everywhere towards bioprinting.

Regenovo, a bioprinter developed by researchers at the Hangzhou Dianzi University in China successfully bioprinted a human kidney that had a life of about 4 months. Recent developments also include a ‘bionic-ear’ from Princeton University printed using an ‘ink-jet’ inspired printer in 2013.

bioprinted kdney

The bioprinted kidney    Image: 3ders.org

Meanwhile, Organovo is planning to make its liver tissue available to pharmaceutical companies and research for testing purposes by the end of 2014; and once the human trials are over, the firm targets at commercial sales of its bioprinted blood vessel grafts for bypass surgeries. As far as research is concerned, the pioneer is currently putting its resources to successfully print breast cancer tissues in addition to lung and muscle tissues.

In practical usage, bioprinting is gaining popularity for surgical purposes and transplants globally. Surgeons have managed to implant a variety of bioprinted tissues into their patients. These include skin, muscle, cartilage, urethras and urinary bladders. It gained much attention when surgeons implanted a bioprinted windpipe into a two-year-old child in the US in earlier 2013. However, bioprinting a complete solid organ is still on the next shelf. “Bioprinting a solid organ is really the next frontier”, says Anthony Atala, of the Wake Forest Institute for Regenerative Medicine in North Carolina.

bioprinted ear

The Bionic-ear   Image: telegraph.co.uk

The ‘appealing’ advantages

Added to these heroics, bioprinting found its major uses in stem cell and developmental biology, cardiology, drug testing and more. The video on bioprinting from Organovo demonstrates how bioprinting is useful for stem cell and developmental biology. Drug testing could be done on printed tissues and thus provide an economic method as well as save animal and human testing.

Since, numerous tissues can be printed once the bio-ink is developed; bioprinting saves a lot of hassle and cost of obtaining these cells to pharmaceutical companies. Also, lab testing can be done upon organs as a whole instead of tissues which would give a collective reaction of the organ towards a drug.

Another huge crisis it could save is organ donation and transplantation. The ever-rising demand for organ transplantation could be met in the near future, hopefully with the help of bioprinting. Bioprinting life-like proaesthetics and limbs also seem possible in the near future.

 From a commercial perspective, ‘customizing’ the organ can be done from the designing phase itself. The automated and repeatable process of bioprinting makes it extremely appealing for a place in a commercial market.

A ‘fruitful’ future

With advancements and achievements following one by one, the future of bioprinting sure looks promising. Bio-degradable or bio-compatible substitutes for replacing damaged bones and cartilages are largely in use. In future, these could be bioprinted along with bio degradable materials which could increase bone and cartilage strength. The possibility of unconventional bioprinting using emerging nano-technology and genetic engineering techniques is also unquestionable. In 20-25 years time, we might be looking at an entirely new level of cloning, using bio-printed organs.

However these advancements have already led to debates on the ethics and morality of the future of bioprinting. "These initiatives are well-intentioned, but raise a number of questions that remain unanswered. What happens when complex 'enhanced' organs involving non-human cells are made? Who will control the ability to produce them? Who will ensure the quality of the resulting organs?”, asks Pete Basiliere, research director at Gartner. Once bioprinting reaches its prime, these questions need to be answered.

representational image

In the near future! Image: www.biospectrumasia.com

 However these question the ethics of man and not the science. So let’s hope resolutions will be found, bioprinting reaches its potential and ultimately, let’s hope we wouldn’t have to face our extermination by the ‘humans’ we create! 

Author

Nimish Sany: I bleed my thoughts on paper. And if I cant find a paper, blogs serve the purpose just fine.

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