Three-dimensional bioprinting and the future of organ transplants
3-D printing of cellular structures is changing the way we trial preclinical pharmaceuticals and consider the future of organ transplants.
Drug developers trying to make preclinical decisions about the efficacy and safety of their products now have a new way to test their drugs. Use a three-dimensional bioprinted cell structure.
3D PRINTING AT ORGANOVO
The use of additive manufacturing in the field of tissue engineering has the potential to revolutionize the health care industry.[1] Organovo utilizes three-dimensional printing technology to generate 3D tissue models that are much more representative of human tissue structure in the body. With this technology, drug developers can apply their drugs to human cells with a natural architecture prior to entering clinical trials and make more informed decisions regarding their drugs’ toxicity to certain cells. [2]
Utilization of 3D printing at Organovo is the backbone of the organization. Organovo’s patented bioprinters can arrange cellular structures in layers that are then fed nutrients to strengthen. By combining these cells in 3D structures, they are believed to behave more naturally and similarly to how cells behave inside the body. These 3D cell structures look to replace traditional lab cultures and animal tests when assessing the toxicity and efficacy of new drugs on cells. [3]
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The use and further development of 3D printing solutions is extremely important to Organovo’s success. The long term goal of this technology is to generate tissue replacement products for surgical implementation. These products can range from skin grafts all the way to entire organs. Demand for organs is expected to increase in the future, as existing donors age and supply of new organs decreases. [2]
By capitalizing on their patented bioprinters, improving the strength of their cell structures, and developing more tissue engineering products, Organovo is positioned to be a leader in creating organs for human transplants in the future.
CURRENT PRECLINICAL TESTING SOLUTIONS
Organovo has successfully printed liver and kidney tissues, and currently offers preclinical testing services for liver and kidney tissue-specific toxicity marker assessment. They have also partnered with L’Oreal to develop synthetic skin [4]. The use of bioprinted human liver tissue has continued to advance due to its ability to more accurately predict reactivity to new drugs due to the tissue’s complex architecture and lack of culture subsurfaces such as polymers.[5]
In late 2017, the FDA granted Organovo orphan drug status for their treatment of Deficiency of Alpha-1 Antitrypsin (AAT), a protein that protects the lungs and is generated by the liver, with 3D bioprinted liver tissue.[6] Orphan drug status incentivizes firms to pursue R&D of treatments for rare medical diseases that would not otherwise be achieved due to economic constraints [7]. Organovo plans to file for an Investigational New Drug application with the FDA in 2020, which would give Organovo permission to begin human clinical trials. [9]
WHERE TO GO FROM HERE?
Organovo is also pursuing a second orphan drug designation with the FDA and anticipates receiving it in the first half of 2019. Organovo believes that they will have enough funds to meet its capital and operating requirements through 2020. [9] Nevertheless they must continue to seek operating efficiencies in order to lower the costs of their printing services.
In the near term, Organovo is planning to support continued research and operations using its preclinical trial testing services. There appears to be enough demand to continue marketing their liver and kidney treatment preclinical trials. The estimated market for drug discovery assays and toxicity testing was valued at $11 billion [2]. Should Organovo be able to fully capture the market for liver and kidney treatment testing, they will be strongly positioned for future expansion. They must also continue seeking out new pharmaceutical partners to continue testing their own products.
In the medium term, there may be other opportunities for tissue engineering solutions outside of liver and kidney related disorders. Organovo could look to expand their operations into research and development of other organ disorders and seek additional first mover advantages. They would continue to strengthen their position in the biotechnology sphere by diversifying their product portfolio.
Still, Organovo must continue to pursue further liver and kidney treatments as they work towards their goal of printing organs to be used for transplants.
FUTURE QUESTIONS
As Organovo nears clinical trials of its own liver treatments, how will it deal with setbacks if not initially successful? Will they be able to continue to secure funding to get through clinical trials? How long until fully engineered organs can be successfully transplanted into humans? What are the ethical concerns related to implementation of tissue engineered transplants?
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[1] Murphy, and A. Atala. 3D bioprinting of tissues and organs. Nature Biotechnology 32, no. 8 (2014): 773.
[2] Organovo.Com. https://organovo.com/wp-content/uploads/2017/09/Organovo-ONVO-Fact-Sheet-0617.pdf.
[3] The Wall Street Journal, “Printing Evolves: An Inkjet for Living Tissue”. https://www.wsj.com/articles/SB10000872396390443816804578002101200151098
[4] The Medical Futurist. “The Top Bioprinting Companies”. https://medicalfuturist.com/top-biopriting-companies
[5] Retting et al. “Modeling Liver Biology and The Tissue Response to Injury in Bioprinted Human Liver Tissues”. Applied In Vitro Toxicology. Volume 4, Number 3, 2018. https://www.liebertpub.com/doi/pdf/10.1089/aivt.2018.0015
[6] Organovo Receives Orphan Designation From U.S. FDA for 3D Bioprinted Therapeutic Liver Tissue Treatment of Alpha-1 Antitrypsin Deficiency. http://ir.organovo.com/phoenix.zhtml?c=254194&p=irol-newsArticle&ID=2324035
[7] “Orphan Drug”. 2018.Wikipedia.Org. https://en.wikipedia.org/wiki/Orphan_drug.
[8] “Organovo 2018 Annual Report”. 2018.Com. https://organovo.com/onlineAR/.
[9] Organovo Affirms Key Clinical Development Goals; Company Reports Fiscal Second-Quarter 2019 Results. http://ir.organovo.com/phoenix.zhtml?c=254194&p=irol-newsArticle&ID=2376340
[10] “Bioprinting Process – Organovo”. 2018.Organovo. https://organovo.com/science-technology/bioprinting-process/.
I really enjoyed reading your piece about the promise and risks of bioprinting in the context of Organovo. You have hit on a topic of significant ethical debate in the medical world (up there with George Church’s genetics and stem cell research at Harvard, among other issues). These types of concepts — generating human tissue de novo — tend to be quite polarizing, as you’ve noted in your question at the end. One company that has also grappled with this question is called FluidForm, started by HBS grads, and you might consider looking at how they have dealt with some of these issues, though they are at an earlier stage compared to Organovo. My concern, as was yours, is the question about where this type of advance will lead us. After we can recreate human organs for transplant, what is next? Surely something is next. And I’m not sure I like that something.
Thanks for sharing this excellent commentary!
This was a really interesting read – thank you! My question for Organovo and their future is really regarding the presence of alternatives. The current organ transplant industry is unsustainable, with demand far out-numbering supply, and I think it’s fantastic that companies are experimenting with different ways to solve this problem. Due to the ethics question that you bring up at the end, and the amount of time it will take for this product to have the possibility of hitting the market, I would be concerned that there will be other medical breakthroughs that will render Organovo obsolete before they are able to reach the market. I am not aware of what those potential competitors could be, but to me that is what potential investors would be weighing when looking at investing in the company.
Great post about a very interesting application of 3D printing! The goal of 3D printing organs for transplant is certainly ambitious. One question/concern I have pertains to the cost – given how expensive 3D printing is, will they be able to demonstrate a cost advantage over a traditional transplant? Of course, the ability to print on demand rather than wait for a donor is a considerable advantage in and of itself. And perhaps I’m getting ahead of myself – they obviously have some intermediate hurdles to clear in the short to medium-term.
Fascinating post on the leaps made in this area! I am curious on Dave’s point regarding the cost advantage of 3D printing organs versus growing them in the lab in the conventional way. Does 3D printing lead to more standardized organ production or organs that perform more similarly in function? I feel this may be difficult given how cells can be similar but never identical. I am also curious as to the cost efficiency of using this approach.