Friday 3 April 2020

The Science Behind 3D Printing Organs


  Currently, there are hundreds of thousands of people on transplant lists all over the world, waiting for critical organs like kidneys, hearts, and livers that could save their lives. I was shocked to hear in a recent assembly that last year, over 400 people in the UK died waiting for a vital organ transplant and a further 777 people were removed form the waiting list due to deteriorating health that meant a transplant was no longer a viable option. As it stands, in the UK, 5693 patients are waiting for a transplant and statistics show that in the USA every 10 minutes another person is added to the transplant waiting list, since unfortunately, there aren’t nearly enough donor organs available to fill the growing demand.





This got me thinking; in this crazy and unprecedented world of modern research and development, surely there is a solution to this problem?

And yes, there is.

  Bioprinting is a branch of regenerative medicine currently under development that has the potential to create brand new, customised organs from scratch. Like modern 3D printing, bioprinting is a technique that deposits layers of material on top of each other to construct a 3D object one slice at a time, but instead of starting with plastic or ceramic based inks, a 3D printer for tissues and organs uses bioink.

  The main component of many bioinks are water-rich molecules called hydrogels. Millions of living cells are mixed into these, as well as numerous chemicals encouraging processes such as cell communication and growth. Engineering an organ or tissue is dependent upon having the right kinds of cells. In some cases, cells are isolated from a small tissue sample the size of a postage stamp. They are then mixed with growth factors and multiplied in the lab. The cells rapidly multiply in quantity so that, in about 6 weeks, a layer one cell thick could theoretically cover a football pitch. For cell types that cannot be substantially grown outside the body (e.g. heart, nerve, liver and pancreas cells), stem cells may be an option because of their pluripotency – the ability to become multiple cell types. Some inks contain just a single type of cell, whilst others combine several different kinds of cells, enabling scientists to create more complex structures.

  There are several printing techniques utilised in this field, the most popular being extrusion-based bioprinting. In this, bioink gets loaded into a printing chamber and pushed through a round nozzle attached to a printhead. It emerges from a tiny nozzle to produce a continuous fibre, the thickness of a human fingernail. 

  A computerised image guides the placement of the strands, either onto a flat surface or into a liquid bath that’ll help hold the structure in place until it stabilizes. After printing, some bioinks will stiffen immediately; others need UV light or an additional chemical or physical process to stabilise the structure. A successful printing process means that the cells in the synthetic tissue will begin to behave the same way cells do in real tissue: signalling to each other, exchanging nutrients, and multiplying.

  Most bioprinting uses a scaffold to hold cells in place. And once cells are ‘coaxed’ to a certain level, they begin to self-organise and assemble and then the scaffold can be removed. Dr Nakayama, a doctor and chairman of Saga University’s Regenerative Medicine and Biomedical Engineering department, has been developing a way to create 3D tissue without the need for scaffolds. Instead, he mounts small spheres on a fine array of needles called a kenzan and is now preparing the first human trial to implant dialysis tubes made entirely from a patient’s own skin cells. 

3D bioprinting using a kenzen rather than scaffolds
  The technology in this field already exists to print simple structures like lung tissue, skin, cartilage as well as miniature, semi-functional versions of solid organs, including kidneys livers and even hearts. Researchers have successfully used 15 different applications of cell/tissue therapy technologies in human patients - including a bioprinted bladder that was successfully implanted into 10-year-old Luke Massella in 2001.

  Luke Massella was born with a condition known as Spina Bifida, which left a gap in his spine. He is one of about 10 people alive walking around with a replacement bladder that has been grown from his own cells. At age 10, a malfunctioning bladder caused his kidneys to fail, and Luke faced a lifetime of dialysis treatment, that would have severely inhibited him from living a normal life. An enterprising surgeon, Dr Anthony Atala at Boston Children's Hospital, took a small piece of Luke's bladder, and over two months grew a new one in the lab, then in a 14-hour surgical procedure he replaced the defective bladder with the new one. In using the patient’s own cells this way, the issue of organ rejection (when the body’s immune system attacks transplanted cells from another organism) was minimised. Luke hasn’t had to have any surgery since and now, at 27, lives without complication.
Scientists at Wake Forest IRM using bioprinting to develop a replacement bladder.
  However, replicating the complex biochemical environment of a major organ is a harder feat, with so many more cells per centimetre. One of the biggest challenges is how to supply oxygen and nutrients to all the cells in a full-size organ and so the greatest successes so far have been with structures that are flat or hollow. To try and overcome this issue, researchers are working to incorporate blood vessels into the printed organs.  

  Ultimately, bioprinting organs from people's own cells will solve the huge lack of supply in organs for transplant and eliminate the need for anti-rejection immunosuppressant drugs. Specialist printers could even reproduce cancers tumours, giving doctors the chance to test treatments on specific patients. Bioprinters also provide a way of testing small quantities of fluid to test if a new antibiotic would work for a specific patient - this could help tackle the growing and serious problem of antimicrobial resistance.

  The potential to use bioprinting to save lives and advance our knowledge of organ function is huge. This kind of technology also opens up the possibility of augmentations similar to those seen in the classic science-fiction and superhero films, such as the printing of tissue with embedded electronics or the engineering of organs that exceed current human capability. Could we give ourselves futuristic qualities such as unburnable skin? And to what extent might we extend human life by printing and replacing our own organs when they start to fail with age?


References:
https://www.bbc.co.uk/news/business-45470799 https://www.ted.com/talks/taneka_jones_how_to_3d_print_human_tissue/transcript?language=en 
https://school.wakehealth.edu/Research/Institutes-and-Centers/Wake-Forest-Institute-for-Regenerative-Medicine/Research/ABCs-of-Organ-Engineering#Learn About the Steps Involved in Engineering Tissue and Organs

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