Want to 3D Print Yourself a New Organ? Top 10 List of Challenges

3D printer

Need a new liver, pancreas, or other vital organ?

I’ll print one right up for you…that is in about 10 years.

My intern Lakshmi did a great job on her guest piece last week on the promise of 3D printing in stem cell-based bioengineering including organ and tissue production.

It’s an incredibly exciting area of biomedical science.

In theory in the future we could literally have new organs printed by specialized forms of 3D printers (e.g. see the image of a 3D printer at left from Wikipedia) or grown for us to replace old, diseased, or injured organs.

The organs could in principle even be made from our own cells so there would little if any danger of rejection.

The demand for organs for transplant has always far exceeded the supply and it’s a tragedy how many folks die waiting for a transplant.

Stem cell-based bioengineering might be a game changer here for hundreds of thousands of patients in coming decades.

But we have a ways to go to make this technology a reality in the clinic. Below are the top 10 hurdles.

  1. Function. Sure, you can print say some muscle off of that cool 3D printer you bought or produce some liver-like product, but does it actually work? Is it truly functional? That’s far harder than simply making something that looks like a real tissue. If the organ you printed doesn’t function like it is supposed to it is like a fancy looking new car with no engine. Pretty, but useless.
  2. Size matters. Most efforts to bioengineer tissues using 3D printing and other technologies have made tissue end products that are way too small. Scaling up is a huge challenge for a variety of reasons discussed more below.
  3. Contamination. Bioengineering a product to be transplanted into human patients is very different than just making some tissue blog in a lab. Of course we have to start somewhere, but to make a tissue to be used in human patients requires that the product not be contaminated with pathogens, xeno-antigens (e.g. from fetal bovine serum used to grow cells and to keep bioengineered tissues alive), and such. That’s much tougher. We need a pure, safe product.
  4. Integration. It’s still not enough to churn out a healthy, functional tissue to be used to treat a patient. That lab-produced issue/organ must integrate with the host patient or it will not work right and probably will die. So if you make the tissue outside the patient, you have to find a way to get the host body to meld into the transplanted organ and vice versa. Alternatively, you can try to make the organ de novo in the patient’s body, but that poses other challenges.
  5. Vasculature. Organs and tissues are not autonomous. They need nutrients to stay alive and those come from the bloodstream. This point links up with the integration issue in the point above. One of the key things tissues need is a blood supply. This is a huge challenge for bioengineers. Typically when making a tissue or organ in a lab, a bioengineer creates a product that is not vascularized. It’s very difficult to get blood vessels into the mix say if you are making a liver in a lab. However, without them the liver will never survive. This also gets back to the size issue. There’s a paradox here. Bioengineers need tissues and organs to be made that are big enough to have a meaningful impact on a patient’s health, but beyond a certain size, oxygen and other factors cannot diffuse so blood vessels are needed.
  6. Diversity. There is no such thing as an organ or tissue that is entirely composed of only one type of cell. As a result, you cannot just use one type of cell as a lego-like building block to make functional tissues. For example, liver is not just made of hepatocytes. They may be the most common cell in the liver, but there are many others too that perform much need functions. Some organs have dozens of types of cells, while even the need for just a few different cell types present big challenges to engineers.
  7. Immunity. Bioengineers need to find ways to avoid the patient’s body rejecting the transplant. Immunosuppressant drugs are an option as with traditional organ transplants, but are less than ideal. Sometimes the body rejects the organ anyone. One exciting option with bioengineered organs is to use the patient’s own cells to make them, likely avoiding the immune rejection issue. On the other hand, taking immunosuppressant drugs is an option.
  8. Complex architecture. Most organs and tissues need to be in a certain shape and with a specific organization to work properly. It’s not enough to 3D print a homogeneous product. Certain cells need to be in specific places, while other cells need to be somewhere else. Imagine, by analogy, 3D printing a plastic product like a specific part to a machine. All the plastic is the same so it is simple to make. Now imagine you need to print a plastic product that is composed of 10 different kinds of plastic and each kind must be present in only certain places in the product. That is orders of magnitude more difficult and that is the reality of biological products.
  9. Enervation. Ideally, bioengineers would want their lab-produced organs to have nerves as well to fully operate normally and respond to signals in the body. Generating nerves inside of tissues and having them integrate with the host is even more difficult than blood vessels. The expression “that takes some nerve!” takes on a whole new meaning here.
  10. Cost. To make functional organs via 3D printing and other bioengineering approaches will be very labor intensive and expensive. The first true engineered organs may cost millions of dollars each. At the same time serious organ disease and organ failure cost billions if not trillions of dollars in healthcare costs and untold suffering….so even if lab-grown organs are expensive, they may be relatively less expensive than one might imagine. And once they are made, over the subsequent years the costs will come down dramatically.

I’m confident that tissue engineers can overcome these problems in the coming decades. I’m not sure that all organs can be grown from stem cells in a lab, but I believe that in a few decades that there will be some organs available that truly work to help patients either by replacing faulty organs or supplementing their functions.

8 thoughts on “Want to 3D Print Yourself a New Organ? Top 10 List of Challenges


  1. Paul, it’s been done…
    http://www.dailymail.co.uk/health/article-2012415/Surgeons-implant-worlds-stem-cell-windpipe-grown-lab.html

    OK, sort of.

    Cartilage-type organs/tissue would seem to be the logical start-up project for this sort of technology because it obviates several of the difficulties you mention above.

    One thing I’ve always puzzled about, why the emphasis on using fetal calf serum? Basically we are talking about PRP (I’m just a layman, correct me if I’m wrong)? So why not explore other sources, including the autologous source?


    • Yeah, I should have mentioned the windpipe, but that is indeed a somewhat different case….still relevant though so thanks for mentioning it, Brian.

      Why the emphasis on fetal calf/bovine serum? Excellent question.

      It’s really cheap relatively speaking and although it is from cows, most mammalian species of cells including human respond great to it. It’s chalk full of growth factors and other cellular goodies including trophic factors that promote survival. Adult serum just does not compare (much lower concentration of factors) so PRP is not at all the same and autologous adult human serum would be relatively wimpy.

      Plus actual human serum is pretty hard to come by, expensive, and has a much higher relative health risk (HIV, HBV, et al) and as you can imagine fetal human serum is not exactly available.


  2. I guess no one reads these comments. The technology for 3D printing is very cool and in some small simple cases may be preferable. However, if you just want the organs, blastocyst complementation and the next generation of that technology will get us there, NOT 3D printing. If ANYONE actually reads these comments, please look at, http://www.ncbi.nlm.nih.gov/pubmed/?term=blastocyst+complementation. This is where you will find the technology that has a much better chance in resulting in the generation of transplantable organs. Please also see the research of Nakauchi, here is a good paper, “Generation of kidney from pluripotent stem cells via blastocyst complementation”, American Journal of Pathology – 2012 Jun;180(6):2417-26. doi: 10.1016/j.ajpath.2012.03.007. Epub 2012 Apr 14. This is somewhat new technology and needs much more confirmation – but that is coming into the literature more and more each day.


    • HI Matt,
      I do read these comments.

      You are overlooking the fact that human blastocyst complementation raises very serious ethical issues.

      The papers and research you cite is all murine too so who’s to say that’d even work in humans assuming we all decided it was even ethical in the first place.
      Paul


      • Hi Paul,

        Thank you for your reply! I do think that blastocyst complementation will work with human cells because it works in non-human primates – see Tachibana, et. al., “Generation of chimeric rhesus monkeys.”, http://www.ncbi.nlm.nih.gov/pubmed/22225614. I am surprised to hear anything negative from you as this research is the logical solution to the numbered problems in your article above except for: 5, 6, and 9. Moreover, it gives a method for studying and possibly overcoming, 5, 6, and 9. If one were afraid of negative regulation here in the US, it seems like using non-human primate stem cells into a donor instead of human embryonic stem cells may be preferable, “They were created completely differently, right?”. It doesn’t matter that much, because Hiromitsu Nakauchi’s lab is in Japan, and using human-pig blastocyst complementation to generate transplantable organs is his stated goal. I haven’t done any of this research, I have just read about it. There may be caveats – like 90% of the published literature. I am looking forward to hearing more about it.

        It isn’t that I don’t care about bioethics, it just that it changes all the time depending on who pays for it. You live in the country which ‘rescued’ Shiro Ishii, http://en.wikipedia.org/wiki/Unit_731#After_World_War_II. Also, this is an interesting philosophy of science question, can we choose not to progress, have we ever chosen not to?

        Matt


    • Matt, thank you for the list of references… which I am beginning to digest (in as much as I am capable of doing so).

      I note that Paul raises a question as to whether such blastocyst complementation technology would be “ethical” for engineering human organs.

      In this regard, I would ask whether such “ethical” arguments should based upon an analysis of what it is to be comprised of human tissue or what it is to be a person. This distinction refers back to my comment on another of Paul’s thought-provoking articles, about cloning John Lennon.
      http://www.ipscell.com/2013/08/imagine-cloning-john-lennon-from-old-molar/

      Matt, I see that you have also expressed a view on that article.


  3. Hi Brian,

    I do think that blastocyst complementation will work with human cells because it works in non-human primates – see Tachibana, et. al., “Generation of chimeric rhesus monkeys.”, http://www.ncbi.nlm.nih.gov/pubmed/22225614. If one were afraid of negative regulation here in the US, it seems like using non-human primate stem cells into a donor instead of human embryonic stem cells may be preferable. It doesn’t matter that much, because Hiromitsu Nakauchi’s lab is in Japan, and human-pig blastocyst complementation to generate transplantable organs is his stated goal.

    It isn’t that I don’t care about bioethics, it just that it changes all the time depending on who pays for it. You live in the country which ‘rescued’ Shiro Ishii, http://en.wikipedia.org/wiki/Unit_731#After_World_War_II.

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