OneBeacon first covered the topic of 3D printing in a previous whitepaper published in February 2014. Since that time, technological advancements now allow us to manufacture with an increasing number of materials using a variety of different technologies. Furthermore, 3D printers continue to drop in price, operate more quickly and produce more complicated and larger structures. However, the core technology remains unchanged—additive manufacturing or depositing materials in layers to form a finished product. In this paper, we explore the emerging ability to 3D print using biological materials and thereby build biological components and subsystems.
The 3D bioprinting market was roughly $411M in 2016 and expected to rise to $1.33B by 20211. Other firms estimate the global market to be $1.82B by 20222 or $1.8B by 20273. This increase will be fueled primarily by growth in institutional research and development (R&D), applications in the drug discovery process, toxicity testing, consumer product testing, tissue engineering and ultimately organ and tissue regeneration for transplantation (regenerative medicine). Key areas will be in medical, dental, biosensors, consumer product/personal product testing, bioinks and bioprinting of food/animal products4. A variety of new manufacturing techniques has emerged and continues to evolve, which will enable such applications.
In 2003, Thomas Boland, a bioengineering professor at Clemson University in South Carolina, filed a patent on using a custom inkjet printer capable of printing human cells using an ink where the cells were in a gel mixture5. Bioprinting is defined as the “deposition of living cells in a spatially controlled manner in absence of any pre-existing scaffold and in more than a single layer,”6 or simply, additive manufacturing/deposition using bioinks.
Bioinks include cells and biocompatible biomaterials consisting of natural and artificial polymers such as gelatin, collagen, alginates (made from brown algae), fibrin, chitson, hyaluronic acid7, nano cellulose, gelatin methacrylate and polyethylene glycol (PEG).
Bioinks serve one or more of these three basic cellular functions – matrix, sacrificial and/or support.8
Although the inkjet process sounds simplistic, it is quite complex as the key concern is to ensure that the cellular material is not damaged during the printing process. The issue with inkjets is the shear stress that is applied to the cellular material contained in the bioink as it is propelled through the nozzle jet. Although cell viability is greater than 85%10, it is lower than other technologies. However, it has a relatively faster printing speed than other technologies. Another issue is that the nozzle jets are prone to clogging over time, resulting in additional maintenance and downtime. Overall, it does have advantages in its simplicity, agility, versatility and greater control over the deposition pattern.11
Existing and new firms worldwide are venturing into the bioprinting space, given its high growth and market potential. Firms either are developing the bioprinters, the bioink materials, or providing services such as developing bioprinted tissue for research and industrial applications. The following offers a brief overview on some of the major firms in this industry:
Bioprinter manufacturing firms include Envisiontec, Gesim, Biobots, Cellink, RegenHU, Ourobotics, Dilab, Cyfuse, Organovo,20 Hewlett Packard (HP) and others. Universities and research institutions worldwide are also modifying traditional inkjet printers from firms like HP and Canon by for use in 3D bioprinting. Lastly, universities are developing R&D models of such products primarily for internal research, but may also market these to other research institutions.
Firms manufacture bioinks as proprietary or non-proprietary formulations. Proprietary formulations are used for either owned bioprinter equipment or are custom-developed for others. Stock on non-proprietary bioinks can be used by bioprinters from various manufacturers. Some of the bioink manufacturers include Bioink Solutions, CELLINK, RegenHU, Biobot22 and others.
The main application for bioprinting is the medical field. The importance of this technology in medical advancements cannot be overstated. There is significant research underway with transplantation success in animal models.
3D bioprinters deposit rows or filaments of living cells in layers onto a substrate to form tissue, muscles and eventually organs. The major challenge in the development of complex tissue or organs is the vasculature (blood vessels) needed to transport oxygen, nutrients and waste to and from the printed substitute product. This process is quite complicated and requires significantly more research and study before transplant-worthy organs can be mass developed.
Additionally, regulatory hurdles worldwide require investigation, review and approving the product before its use for human transplants. Within the U.S., the FDA would ideally regulate such products as a biologic, but depending on the application, it could be additionally construed as a drug or medical device, prompting different regulatory thresholds. Significant clinical trial data will likely be required especially since this is a brand new technology where the efficacy and safety of the device or biologic is unknown. There currently is no specific standard on 3D bioprinted biologics. The FDA released draft guidance on Additive Manufactured Devices (3D printed)29 30 in May 2016 but it does not specifically address bioprinted products.
The FDA did approve a 3D printed biodegradable airway splint made of PCL (polycaprolactone – a biodegradable polyester), for use in an infant under the emergency-use exemption, along with written consent of the patient’s parents.31 This was a one-off approval, however, and similar one-time signoffs for emergency-use are likely. However, for general clinical use, the FDA will require significant clinical trial data before approval. Until then, much of the hype surrounding 3D bioprinted materials will be primarily for research or trials with animal models.
Beyond regulatory hurdles, there could also be potential concerns from religious and other ethical groups arguing that bioprinting organs or using biomaterials from other animals (e.g. collagen scaffolding from pig hearts) in this process is unnatural. Such groups could exert pressure on governmental bodies and impede--or even ban--the bioprinting of such materials. An example is the case of the U.S. ban on the use of fetal stem cells. These arguments could negatively affect this field and greatly undermine the technology’s benefits.
Insurability of this technology remains a challenge due to safety, use of newer materials with unknown lifespans, and potential long-term quality and efficacy issues. For now, the leading exposure is likely to be from R&D use, drug/molecule toxicity testing applications and potential early stage clinical trials. There will be an increase in exposure once transplantable, bioprinted tissues and organs are approved and commercially available in the market. However, it will take time to fully understand the exposures associated with such products.
Due to projected market growth in this industry, it is likely we will continue to see a plethora of startups and investments, as well as existing firms venturing into this field. Opportunities for insurance coverage, for both new firms as well as new exposures, are already present and will continue to emerge. Remaining abreast of 3D printing technology will be incumbent on those servicing the life sciences industry and will present an exciting opportunity to appreciate the many benefits afforded by this process.
Imagine a world where sick or dying patients are saved by generating organs, tissues and muscles through 3D bioprinting. There have been major strides with this technology but we are not there yet. It may take up to ten years before FDA approved products are commercially available. Even then, these biologic products may be limited to simple organs such as skin and bladders. Complex organs such as livers, kidneys and hearts may take even more years before being commercially approved for the market.
For now, this technology can aid in various areas that will improve our lives. This can range from toxicity testing in drug development to ongoing R&D in existing and completely new areas. There are many unknowns regarding the success of this technology but the benefits should outweigh the concerns.
To learn more about how OneBeacon Technology Insurance can help you manage online and other technology risks, please contact Dan Bauman, VP of Risk Control for OneBeacon Technology Insurance at email@example.com or 262.966.2739.
1 (January 2017). “3D Bioprinting Market by Technology – Global Forecast to 2021.” Marketsandmarkets.com. Accessed May 2017. http://www.marketsandmarkets.com/Market-Reports/3d-bioprinting-market-170201787.html?gclid=CjwKEAjwr_rIBRDJzq-Z-LC_2HgSJADoL57HY4XMiFhUoiDwct1wkKQlhNBM7nm6xg5Feem9r9_E-BoCrdrw_wcB
2 (April 2016). “3D Bioprinting Market Size to be worth $1.82 Billion by 2022.” Grand View Research. Accessed May 2017 http://www.grandviewresearch.com/press-release/global-3d-bioprinting-market
3 Tsao, Nadia.(May 2017). “3D Bioprinting 2017-2027 Technologies, Markets, Forecasts.” IDTechEx. Accessed May 2017. http://www.idtechex.com/research/reports/3d-bioprinting-2017-2027-technologies-markets-forecasts-000537.asp
3 Ibid 2
4 Shaer, Matthew. (May 2015). “Soon, Your Doctor Could Print a Human Organ on Demand.” Smithsonian Magazine. Accessed May 2017. http://www.smithsonianmag.com/innovation/soon-doctor-print-human-organ-on-demand-180954951/
5 Ibid 3
6 “Bio-ink.” Wikipedia. Accessed May 2017. https://en.wikipedia.org/wiki/Bio-ink
7 “Bioinks.” Accessed May 2017. https://www.biobots.io/bioinks/
8 Holzl, Katja; Lin, Shengmao; Tytgat, Liesbeth; Vlierberghe, Sandra Van; Gu, Linxia; Ovsianikov, Aleksandr. (September 23, 2016). “Bioink properties before, during and after 3D bioprinting.” Biofabrication, IOP Publishing Ltd. Accessed May 2017. http://iopscience.iop.org/article/10.1088/1758-5090/8/3/032002/pdf, page 2
10 Ibid 9, page 3
11 Gudapati, Hemanth; Dey, Madhuri; Ozbolat, Ibrahim. (June 7, 2016). “A comprehensive review on droplet-based bioprinting: Past, present and future.” Biomaterials. Accessed May 2017. http://www.personal.psu.edu/ito1/Droplet-based%20Bioprinting.pdf, page 20
12 Ibid 9, page 3
13 Ibid 9, page 3
14 Ibid 9, page 3
15 Ibid11, page 23
16 “Electrospinning.” Accessed May 2017. http://www.nanojets.eu/electrospinning.html
17 (February 12, 2017). “San Diego researchers successfully 3D bioprint complete vascularized tissue.” 3D Printing Media Network. Accessed May 2017. http://www.3dprintingbusiness.directory/news/san-diego-researchers-successfully-3d-bioprint-complex-vascularized-tissue/
18 (August 25, 2015). “These microscopic fish are 3D-printed to do more than swim.” UC San Diego Jacob School of Engineering. Accessed May 2017. http://jacobsschool.ucsd.edu/news/news_releases/release.sfe?id=1797
19 Wang Brian. (March 23, 2017). “Tissue created with micro-blood vessel network and integrated the tissue into mice – a major advance for bioprinting organs.” Next Big Future. http://www.nextbigfuture.com/2017/03/tissue-created-with-microblood-vessel.html
20 Ibid 9, page 5
21 Ibid 9, page 6
22 Murphy, Sean V; Atala, Anthony. (August 5, 2014). “3D bioprinting of tissues and organs.” Nature Biotechnology. Accessed May 2017. http://www.nature.com/nbt/journal/v32/n8/full/nbt.2958.html?TB_iframe=true&width=921.6&height=921.6
23 Ibid 5
24 (January 18, 2017). “4 Ways 3D Printing will Revolutionize Modern Medicine.” 3D Printing.com. Accessed May 2017. https://3dprinting.com/bio-printing/4-ways-3d-printing-will-revolutionize-modern-medicine/
25 Skacel, Jiri. (November 24, 2016). “Czech scientist develops human lung models to aid treatments.” Reuters. Accessed May 2017. http://www.reuters.com/article/us-czech-medicine-lung-replica-idUSKBN13J108
26 Bigelow, Bruce V. (September 9, 2016). “Organovo to Test Preclinical Drugs on Bio-Printed Kidney Tissue.” Xconomy. Accessed May 2017. http://www.xconomy.com/san-diego/2016/09/09/organovo-to-test-pre-clinical-drugs-on-bio-printed-kidney-tissue/
27(October 5, 2016). “Organovo Introduces 3D Bioprinted Human Liver as Leading Therapeutic Tissue in Preclinical Development.” Accessed May 2017. http://ir.organovo.com/phoenix.zhtml?c=254194&p=irol-newsArticle&id=2209393
28 Visscher, Dafydd; and others. (September 2016). “Advances in Bioprinting Technologies for Craniofacial Reconstruction.” Trends in Biotechnology. Accessed May 2017. http://www.cell.com/trends/biotechnology/fulltext/S0167-7799(16)30005-1
29 “FDA’s role in 3D Printing.” FDA.gov. Accessed May 2017. https://www.fda.gov/MedicalDevices/ProductsandMedicalProcedures/3DPrintingofMedicalDevices/ucm500548.htm
30 (May 10, 2016). “Technical Considerations for Additive Manufactured Devices – Draft Guidance.” FDA.gov. Accessed May 2017. https://www.fda.gov/downloads/MedicalDevices/DeviceRegulationandGuidance/GuidanceDocuments/UCM499809.pdf
31 Ibid 9, page 37