This is an Expert’s Corner blog by professor Jorge M. Zuniga on the science and applications of antimicrobial materials for 3D printing medical devices.
The U.S. executive governmental branch has recently invoked the Defense Production Act to increase the domestic production of medical supplies necessary for fighting the current pandemic.1 The purpose of this invocation will likely be used to drive private businesses to increase U.S. production of Personal Protective Equipment (PPE) and other critical medical supplies and devices.
3D printing is uniquely well-positioned to support the shortage of medical devices2 and accelerate their production using conventional manufacturing methods, such as injection molding.2,3 Advancements in additive manufacturing technologies and antimicrobial materials offer the possibility of making and customizing a wide range of critical medical devices. The main limitation of using polymer materials for manufacturing medical devices using 3D printing is microbial contamination.4 Previous investigations have shown strong evidence that the use of different forms of copper as a biocidal agent4-11 and copper composites could enhance the antimicrobial properties of polymers for medical devices.8,10,11
New Antimicrobial Materials for 3D Printing Medical Devices
New advances in material technology have made significant progress in developing new antimicrobial materials for 3D printing medical devices. Previous researches have shown copper composites can enhance the antimicrobial properties of PLA and other polymers used in injection molding and 3D printing to develop medical devices.8,10 These polymers have shown to be up to 99.99% effective against Staphylococcus aureus and Escherichia coli. 10 PLA has been the primary commodity polymer derived from annually renewable resources, such as corn (Figure 1).12 Thus, using a renewable resource to produce antimicrobial materials for 3D printing medical devices could significantly assist the current medical product supply chain disruptions involving the manufacturing of critical medical devices in austere clinical settings.2
Antimicrobial Materials for 3D Printing Medical Devices in COVID Pandemic
COVID-19 is highly contagious. Patients experience pneumonia-like symptoms. An adequate supply of devices to provide supportive care and PPE is important as the virus spread to a larger population.3 We can use 3D Printable antimicrobial polymers for prototyping medical devices or as a final product (i.e., face masks, Figure 2).2
Face masks are the most commonly used PPE by the general population, as well as health care workers. Face and surgical masks effectively block large-particle droplets but do not block small particles in the air. The main reason why the standard surgical masks do not provide complete protection is the loose fit between the mask and face surface, allowing all particle and large droplets’ entrance.
The Centers for Disease Control and Prevention (CDC) recommends to safely discard used masks in a plastic bag and put it in the trash.13 Previous published research6 has suggested that the high viral load remaining in surgical masks can be a viral transmission source both to the health care worker wearing the mask and to patients.6 This may happen when healthcare workers touch their masks and then fail to wash their hands properly or when they dispose of the mask without proper safe disposal precautions.6 Thus, 3D printed open-sourced reusable face-masks using antimicrobial polymers with the right fit can significantly increase the protection level. These can also potentially reduce the viral load remaining on the mask, protecting the end-users from contamination during prolonged mask-wearing.6
Recent industrial efforts such as NanoHack Mask (Copper3D Inc) and SHABRI Last Resort Mask (SHABRI LLC) have made significant progress using additive manufacturing to develop open-sourced reusable face masks (Figure 2). The main characteristics of these 3D printable masks are the ability to customize the device to the end-user, washable and reusable, compatible with standard filtration systems, and use of biocompatible antimicrobial materials. The files of these mask designs are available at the National Institute of Health 3D Print Exchange website (NanoHack: https://3dprint.nih.gov/discover/3dpx-013667; SHABRI: https://3dprint.nih.gov/discover/3dpx-013937).
Copper-Based Composites as Antimicrobial Materials
The use of copper-based composites to develop antimicrobial materials has been extensively tested in viruses similar to the COVID-19 virus (SARS-CoV-2). In an investigation examining the viral deactivation properties of copper oxide particles infused in N95 respirators6, researchers found that copper oxide’s addition to face-masks resulted in potent anti-influenza properties against human influenza A (H1N1) and avian influenza (H9N2) without altering their physical barrier properties.8,10 When examining the capacity of copper oxide-containing filters to neutralize viruses in suspension, the researchers found that these filters resulted in a significant reduction of the infectious titers, ranging from 1.1 log10 to 4.6 log10 for Yellow Fever, Influenza A virus, Measles, Respiratory Syncytial Virus, Parainfluenza 3, HIV-1, Adenovirus type 1 and Cytomegalovirus.5
A recent publication in The New England Journal of Medicine by Doremalen et al.,7 suggested that copper was more effective than Stainless Steel and polypropylene polymers in reducing the COVID-19 virus viability. Specifically, the authors reported that after exposure to a copper surface, there was no viable COVID-19 virus detected after 4 hours. Stainless Steel, however, showed no viability after 72 hours. Polypropylene polymer was the worst, showing viruses detected even after 72 hours.7 Thus, standard polymers have the potential problem of promoting COVID-19 virus viability for up to 3 days, while copper surfaces reduce viral viability to only 4 hours.
Maverick is an injection-molded facemask using non-porous biocompatible antimicrobial elastomer. The filtration system used is a triple layer non-woven polypropylene embedded with a copper-based additive. This injection-molded facemask was initially made using additive manufacturing and is currently produced using injection molding. Material science companies have already fully implemented this model (Figure 3).
Other Medical Devices Applications
The addition of copper compounds to polymers and the resulting antimicrobial properties have promising applications in medical devices development 11. These applications can include postoperative prostheses 11,14, wound dressing 15, and surgical instruments (Figure 4) 16.
Wound dressings are external barriers that isolate the injury site from the external environment and provide an optimal environment for the wound to heal. When a wound occurs, the barrier becomes compromised.
A previous investigation15 used zinc, copper, and silver particles incorporated into polycaprolactone to develop patient-specific 3D printed antimicrobial wound dressings. The authors found that wound dressings using 3D printing filament containing silver and copper had the most potent bactericidal properties. These wound dressings showed the most bactericidal properties against methicillin-resistant Staphylococcus aureus (MRSA), a common bacterium that causes skin infections. Copper compounds are preferable over silver due to the lower cost of copper and a lack of the reported side effects, including local skin irritation, discoloration, or staining15.
Antibacterial filament also provides the possibility of developing antibacterial surgical instruments. A previous investigations16 uses a polylactic acid filament to establish a low-cost Army/Navy retractor strong enough to be used in the operating room (75% infill could support 13.6 kg before fracture). PLA is a safe and suitable material for surgical instruments16. 3D Printers extrude PLA at temperatures well above the 121°C recommended for steam sterilization or even the 170° C recommended for dry heat sterilization. However, other sterilization methods, such as autoclaving, compromise polylactic acid’s structural integrity limiting the use of these devices in surgery16. Although lower temperature methods of sterilization such as ethylene oxide “gas” sterilization did not impact polylactic acid strength, high ethylene oxide residue levels are a concern16. PLA is considered hypoallergenic and safe by the FDA and approved as a semi-permanent dermal filler and suture material 16,17.
New Commercial Antimicrobial Materials for 3D Printing Medical Devices
AMultraXTM: The main problem with standard PLA is the lack of durability and low resistance to high temperatures. The AMultraX is an industrial-grade, high-performance bio-based antimicrobial PLA that allows high printing speeds to decrease production time, increased mechanical properties, and resistant to high heat environments. This material is recommended for the manufacturing of custom medical devices, such as prostheses, orthoses, and surgical instruments in austere environments. Currently, AMultraX has been evaluated by the Biomechanics Department at the University of Nebraska at Omaha for the manufacturing of prototypes for medical instruments for astronauts in the International Space Station. The main characteristics of this new antimicrobial PLA are fast printing (up to 150m/s), high heat deflection temperature of 100°, high mechanical performance (Tensile modulus of 4,000 MPa), easy to print, and low shrinkage <1%.
NANOCleanTM (Recycled Post-Industrial PET-G): The main problem with standard Polyethylene terephthalate glycol (PET-G) is warping and deformation material after printing. Most PET-G filaments are made from non-recyclable materials contributing to waste and pollution. The new antimicrobial PIPG is easier to print, keeping the intended shape with no warping or deformation of the printed object. The most important feature of the new antimicrobial PIPG is that it originates from Post Industrial Recycled materials contributing to a circular economy. This unique antimicrobial material can also facilitate “Closed-Loop Recycling,” a recycling process through which a manufactured good is recycled back into a similar product without significant degradation or waste.
Life in space can negatively affect the human body, from decreasing muscle mass to weakening the immune system. Previous findings from spaceflight experiments suggest changes in microbial growth, including increased virulence and increased growth rate in microgravity. In combination with potential host susceptibility due to a dysfunctional immune system, the risk of infection may be much higher in the spaceflight environment than in a typical workplace environment.18 Some crew members also experience chronic allergic reactions due to immune dysregulation, limiting the longevity of space mission18.
There is a critical need for a multipurpose and recyclable antimicrobial material for medical applications. NASA logistics analyses show that the implementation of in-space manufacturing and recycling of a common raw material can create adaptable or reconfigurable systems and mitigate crew risks by providing on-demand spares and enabling adaptation to unforeseen scenarios by using “Closed-Loop Recycling.” Thus, the use of antimicrobial 3D printed filament has promising potential applications for manufacturing a wide range of medical devices associated to bacterial control, such as orthoses, wound dressing, and surgical equipment.10,19
NASA Nebraska Space Grant Office (Federal Award #NNX15AI09H) funded this study. Copper3D donated the antibacterial 3D-printed filament for our laboratory research and antimicrobial testing.
1. FEMA. The Defense Production Act of 1950, as amended (50 U.S.C. App. 2061 et seq.). 1950; https://www.fema.gov/media-library/assets/documents/15666. Accessed March 20, 2020.
2. Zuniga JM, Cortes A. The role of additive manufacturing and antimicrobial polymers in the COVID-19 pandemic. Expert review of medical devices. Jun 2020;17(6):477-481.
3. FDA. Coronavirus (COVID-19) Supply Chain Update. 2020; https://www.fda.gov/news-events/press-announcements/coronavirus-covid-19-supply-chain-update. Accessed March 22, 2020.
4. Gonzalez-Henriquez CM, Sarabia-Vallejos MA, Rodriguez Hernandez J. Antimicrobial Polymers for Additive Manufacturing. International journal of molecular sciences. Mar 10, 2019;20(5).
5. Borkow G, Sidwell RW, Smee DF, et al. Neutralizing viruses in suspensions by copper oxide-based filters. Antimicrobial agents and chemotherapy. Jul 2007;51(7):2605-2607.
6. Borkow G, Zhou SS, Page T, Gabbay J. A novel anti-influenza copper oxide containing a respiratory face mask. PloS one. Jun 25 2010;5(6):e11295.
7. van Doremalen N, Bushmaker T, Morris DH, et al. Aerosol and Surface Stability of SARS-CoV-2 as Compared with SARS-CoV-1. The New England journal of medicine. Mar 17, 2020.
8. Palza H, Nunez M, Bastias R, Delgado K. In situ antimicrobial behavior of materials with copper-based additives in a hospital environment. International journal of antimicrobial agents. Jun 2018;51(6):912-917.
9. Palza H, Quijada R, Delgado K. Antimicrobial polymer composites with copper micro- and nanoparticles: Effect of particle size and polymer matrix. Journal of Bioactive and Compatible Polymers. 2015;30(4):366-380.
10. Zuniga J. 3D Printed Antibacterial Prostheses. Applied Sciences. 2018;8(9):1651.
11. Palza H. Antimicrobial polymers with metal nanoparticles. International journal of molecular sciences. Jan 19 2015;16(1):2099-2116.
12. Council NR. Commodity Polymers from Renewable Resources: Polylactic Acid. 2001; https://www.ncbi.nlm.nih.gov/books/NBK44131/, 2020.
13. FDA. Personal Protective Equipment for Infection Control. 2020; https://www.fda.gov/medical-devices/general-hospital-devices-and-supplies/personal-protective-equipment-infection-control. Accessed March 20, 2020.
14. Zuniga JM, Peck J, Srivastava R, Katsavelis D, Carson A. An Open Source 3D-Printed Transitional Hand Prosthesis for Children. JPO: Journal of Prosthetics and Orthotics. 2016;28(3):103-108.
15. Muwaffak Z, Goyanes A, Clark V, Basit AW, Hilton ST, Gaisford S. Patient-specific 3D scanned and 3D printed antimicrobial polycaprolactone wound dressings. International journal of pharmaceutics. Jul 15 2017;527(1-2):161-170.
16. Rankin TM, Giovinco NA, Cucher DJ, Watts G, Hurwitz B, Armstrong DG. Three-dimensional printing surgical instruments: are we there yet? The Journal of surgical research. Jun 15 2014;189(2):193-197.
17. COHEN JL. Understanding, Avoiding and Managing Dermal Filler Complications. Dermatologic Surgery. 2008;34:S92-S99.
18. Crucian BE, Choukèr A, Simpson RJ, et al. Immune System Dysregulation During Spaceflight: Potential Countermeasures for Deep Space Exploration Missions. Frontiers in immunology. 2018;9:1437-1437.
19. Zuniga JM, Thompson M. Applications of antimicrobial 3D printing materials in space. Journal of 3D Printing in Medicine.0(0): null.
About the Author:
Dr. Jorge M. Zuniga received a Master of Science degree from the University of Nebraska at Omaha and a Ph.D. from the University of Nebraska-Lincoln. Currently, Dr. Zuniga is a faculty at the Department of biomechanics at the University of Nebraska at Omaha (UNO). He is the co-director of the Center for Biomechanical Rehabilitation and Manufacturing at UNO, a member of The Association of Children’s Prosthetic-Orthotic Clinics. Dr. Zuniga’s main research interests include the development of low-cost 3D printed prostheses and 3D printed anatomical models for surgical planning. Dr. Zuniga has been awarded several grants from NASA, The National Institute of Health, and several industry grants. Dr. Zuniga has authored and co-authored over 80 manuscripts published in peer-reviewed scientific journals. Dr. Zuniga developed a 3D printed prosthetic hand for children named Cyborg Beast. The Cyborg Beast was named one of the best 5 inventions of 2014 by MSN.com.
Dr. Zuniga’s active international collaboration and scholarly productivity led to his nomination as the 2018 “Runner Up” for the APEC (Asia-Pacific Economic Cooperation) Science Prize for Innovation, Research, and Education (“ASPIRE”) given by the U.S. Department of State.