SC3: 3D Bioprinting

Written by Laura McKiel (Chair) and Leah Ferrie (Clerk)

Our Science Club topic last week was 3D Bioprinting. The TED talk “Printing a Human Kidney” by Anthony Atala was sent out for review by Science Club members prior to the session. The group was asked to discuss with the person beside them what they thought about the video, and any questions that came up. Some items discussed included:

  • How do you vascularize the printed organ?
  • How long can the cells survive without a nutrient supply (while being printed)?
  • Presented showed the kidney in his hands, so is the kidney actual functional? Or is it just the structure and shape?
  • How does cell attachment work?
  • Brought patient into the Ted Talk but not fully related to the topic because the patient received a bladder. The bladder may have been 3D printed in some aspects, but wasn’t bioprinted – disconnect between the 3D printed kidney and bladder
  • Regulatory considerations – can you cure everyone with this technology? How do you pick out the patient to trial this technology?

 

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Figure 1: Screenshot of an important message not highlighted originally in the TED talk. Source: https://www.ted.com/talks/anthony_atala_printing_a_human_kidney

 

There is a strong need for 3D bioprinting of organs. Currently there is an organ shortage, meaning that any patient requiring an organ transplant must be placed on a waiting list until one becomes available. In the US, 22 people die every day waiting for an organ transplant (Organ Procurement and Transplantation Network, 2017). Patient’s often need to have a certain health status in order to receive an organ transplant, meaning that the sickest patients who are in the most desperate need usually do not qualify to receive a transplant. There are also challenges following organ transplantation, namely the lifelong immune suppression after the procedure to prevent transplant rejection.

For patients who are unable to receive an organ transplant, medical treatments used to prolong and improve life (e.g. hemodialysis for kidney failure) are extremely costly and time consuming. One patient receiving hemodialysis costs approximately $70,000-$100,000 per year, and they must undergo treatment at least once per week (Chan, Training Program in Regenerative Medicine lecture, University of Toronto, 2016).

Additionally, the ability to 3D print human organs will improve current practices for drug discovery and clinical trials. Currently, a drug must be tested on cells, multiple animal models (e.g. mice and non-human primates) before being approved to begin clinical trials. Oftentimes the animal models are not an accurate model of how a drug will behave in humans. This can cause many drugs to fail in clinical trials, which wastes money that could have been otherwise used to discover, or test, more promising drugs (on the order of millions of dollars).

Current tissue engineering techniques (e.g. cell culture, pipetting, electrospinning) are not accurate enough to reproduce something as complex as an organ. The use of 3D bioprinting allows this process to be automated, providing high accuracy and reproducibility between trials.

 

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Figure 2: Model image of a 3D bioprinter. Source: http://www.explainingthefuture.com/bioprinting.html

 

The principles of 3D bioprinting are very similar to traditional 3D printing – an object is designed using software and then is printed in a layer-by-layer fashion. 3D bioprinting is unique because it incorporates living cells into the process. The cells, desired material, adhesive, and nutrients are combined into a bioink, which can then be printed similarly to any other liquid material. However, optimizing the bioink can be challenging due to the need to satisfy many conditions, including: cell type (stem cells or differentiated), mechanical properties of the organ, ability to easily flow through the printer, and ability to crosslink following material deposition (commonly induced with laser or UV light).

The 3 most common types of printers used for 3D bioprinting are shown in Figure 3. Inkjet bioprinters either use heat or piezoelectric forces to push out the material in a dropwise manner. Microextrusion bioprinters use mechanical methods, such as with a piston or a screw. Laser-assisted bioprinters use a laser focused at an absorbing surface to create pressure, allowing for the material to flow.

 

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Figure 3: The three different types of most commonly using setups for 3D bioprinting. Source: S. V. Murphy and A. Atala. Nat Biotechnol, 32(8), pp. 773-785, 2014.

 

A general overview of the 3D bioprinting process is given in Figure 4. The organ can be scanned with CT or MRI techniques to obtain an image, which can then be converted to a 3D CAD model. The path of the 3D bioprinter is then plotted, and the cell composition of each layer of the organ is designed (based on previous research). The cells and bioink are then loaded into the printer and the organ is printed. This process can take a very long time, depending on the complexity of the organ (e.g. printing the human kidney takes approximately 7 hours). The bioprinted organ is then incubated or conditioned for a set period. This allows the cells time to grow, form connections and tight junctions, and deposit extracellular matrix (ECM). If the printed scaffold material is degradable, the cells will degrade the initial scaffold over time and it will be replaced with ECM proteins.

 

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Figure 4: Overview of the 3D bioprinting process. Source: H.-W. Kang et al. Nat Biotechnol, 34(3), pp. 312-319, 2016.

 

The overall message from this session is that there is still a long way to go before we can create fully functioning and viable organs for human transplant. 3D bioprinting is still an emerging technology, and therefore has many inherent obstacles that must be overcome before it can be commercialized. Some of these challenges include:

  • Cell numbers – For example, to print a liver you would need millions or billions of cells. These cells would need to be biopsied (or differentiated from stem cells) and then cultured in a bioreactor specific to the application.
  • Bioink – As discussed above, the optimization of bioink for a specific organ can be very challenging as there are many factors to consider (cell type, location, mechanical properties).
  • Vascularization – The resolution of 3D bioprinters is not high enough to print the single cell thick capillaries that run through organs. Cells require a nutrient source within on average 200 microns, making it difficult to maintain cell viability in very thick, complex organs.
  • Immune tolerance – even with the potential to use a patient’s own cells to “customize” their organ, an immune response to cells from another area (e.g. stem cells) and the scaffold material is still likely.
  • Standardized practices and materials – currently the FDA does not even have a category for regulating 3D bioprinting. In turn, there are no “typical” bioink materials to use, making it challenging for new investigators to begin this research.

 

In the discussion portion of this session, a few key topics were covered:

  1. What are some ethical issues with 3D printing organs?
  • Ability to 3D print organs only available to those who can afford it because its so expensive
    • People who could afford it don’t require organ replacement as those who cannot
    • How do you subsidize this technology for those who cannot afford?
  • Potential for 3D printed organ black market
    • Ease of access – similar to printing guns, bombs, etc.
  • Potential for extremely elongated lifespan
    • Could humans live forever? Could easily 3D print an organ every time you need a replacement.
  • How do you decide who gets a 3D printed organ or the cells for the organ? How do you determine a waitlist and is it necessary?

 

  1. In the next 20 years, do you think 3D bioprinting will be commonly used?
  • 3D printing of all organs unlikely to be used in hospitals in 20 years
  • Potentially for simple organs such as skin, or blood vessels, but unlikely for larger organs (heart, lungs, liver)
  • Overcoming issues with vascularization will be difficult
  • Obtaining FDA approval will be challenging and take a long time
  • More likely to be a commonly used technology in the lab in 20 years – potential to replace animal models, useful for drug discovery

 

  1. After we can 3D print working organs, what’s next?
  • What organs do you stop at? Needs versus want – example: printing different colour eyes for aesthetic purposes rather than medical requirements
  • Potential for imaginary organs that could be used to live in space
  • Perhaps a better nose to filter pollution due to human presence
  • Can print better organs – an augmented human
  • Can we 3D print people?
  • 3D printing requires open surgery – try to make a material that has shape memory and insert by injection
  • Use a robot that could 3D print – eliminate the need for surgeons
  • Other 3D printing options:
    • 3D printed food – meat, leather – to overcome food shortages
    • 3D print anything you need – a home – could use in space application for Mars
    • 3D print bees, trees, etc.

 

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