Opinion
VIEWPOINT
Mark H. Michalski, MD Investigative Medicine Program, Department of Diagnostic Radiology, Yale University School of Medicine, New Haven, Connecticut. Joseph S. Ross, MD, MHS Robert Wood Johnson Foundation Clinical Scholars Program, Section of General Internal Medicine, Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut; Department of Health Policy and Management, Yale School of Public Health, New Haven, Connecticut; and Center for Outcomes Research and Evaluation, Yale–New Haven Hospital, New Haven, Connecticut.
Video at jama.com
Corresponding Author: Mark H. Michalski, MD, Department of Diagnostic Radiology, Yale University School of Medicine, PO Box 208042, New Haven, CT 06520 (mark [email protected]).
The Shape of Things to Come 3D Printing in Medicine 3D printing—a manufacturing technique by which objects are built from digital data in a way analogous to how computer text is printed on a page—has captured the imagination of many with its potential to offer flexible, inexpensive manufacturing for widespread use. 3D printers have been used to build everything from rockets to houses to guns to other 3D printers, their capabilities limited only by access to a low-cost 3D printer, a set of digital blueprints, and some ingenuity. 3D printing aficionados now include physicians, medical researchers, and patients, many of whom are beginning to explore what this technology might mean for health and health care. While not a panacea, 3D printing is increasingly finding its place in patient care, from its expanding use in surgical planning to the vision of printing whole new organs for transplantation (Video).
sans now create individualized jewelry on demand, and maintenance workers can print replacement parts for household devices. Indeed, 3D printing may serve as a means of distributing manufacturing in the same way that the Internet distributes information.
3D Printing in Today’s (and Tomorrow’s) Medical Practice
Although 3D printing applications in medicine are increasing rapidly, its application in dentistry has been established for more than a decade,2 allowing rapid fabrication of molds for many common dental implants. More recently, head and neck surgeons have used 3D printing to provide preoperative models for complex surgeries. For example, several facial reconstructive surgeries are performed by first harvesting the fibula, which is then fashioned in the operating room into new bony structures. These surgeries can now be augmented using What Is 3D Printing? Once a niche tool for industrial prototyping, 3D print- computer-planning programs to generate surgical plans ing technology is based on the concept of “additive” that determine the ideal way to harvest and incise the manufacturing—that is, 3D printing builds structures by fibula to create a reconstructive graft. 3D-printed moddepositing material layer by layer. This is in contrast to els translate preoperative imaging data into useful tools that may help surgeons both reduce operating room time and potentially improve surgical results.3-5 Indeed, 3D printing may serve as a In addition, using models based on means of distributing manufacturing in imaging of real-world patients, 3D printing can be a useful tool in the instructhe same way that the Internet tion of normal and pathologic anatomy. distributes information. For instance, at our institution, the use of 3D models to educate trainees about standard manufacturing techniques, which often rely on complex traumatic bony fracture patterns is being excreating structures by cutting, molding, or otherwise ma- plored. These models may also be used to communinipulating raw materials. As a consequence, 3D print- cate imaging studies to patients in a tangible, easy-toing is flexible and can create myriad structures in a va- understand format. riety of materials, in nearly any shape or size. 3D printers are now capable of using components as varied as ce- Printing Devices, Cells, and Organs ramics, sandstone, and chocolate. Outside the clinic and operating room, researchers are 3D printers leverage the advantages of computer using 3D printers to reshape health care. The flexibility design by making it simple to translate these designs into of 3D printing allows investigators and manufacturers to tangible objects. In this way, 3D printing serves as a create medical devices with a broad range of biological bridge between digital 3D models and the physical world. and physical properties. When paired with medical Digital models can be widely distributed and modified, imaging, this flexibility may be leveraged to fabricate dedemocratizing manufacturing in a way not previously vices tailored to an individual patient’s anatomy in a way imagined. Large communities with vast and varied in- similar to how “omics” data are applied to create perterests have formed around sharing the digital data used sonalized therapeutics. For example, a customized polyto print models: one site, for example, contains more mer splint has been used to prevent airway collapse in than 100 000 digital models of all kinds, which users can neonatal bronchomalacia.6 This splint was composed of freely download and print.1 a biocompatible polymer, designed to be naturally reThese communities have been empowered by the sorbed within 3 years, and was specifically tailored to the emergence of low-cost consumer-grade machines that neonate’s anatomy using 3D imaging. have made 3D printers broadly available. New applicaBioengineering researchers have begun to expand tions for 3D printing continue to appear every day: arti- the range of printed materials to biological scaffolds
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JAMA December 3, 2014 Volume 312, Number 21
Copyright 2014 American Medical Association. All rights reserved.
Downloaded From: http://jama.jamanetwork.com/ by a Tulane University User on 05/12/2015
2213
Opinion Viewpoint
and cells. Although these “bioprinters” are in their infancy, this technology is advancing quickly to create tools to facilitate drug discovery. Tiny microcosms of organs can be printed onto an in vitro substrate, where they are exposed to potential drugs. Using these “mini organs,” the effects of drugs and drug toxicity on human tissues may be observed without conducting in vivo studies. The “body-on-a-chip” project is combining bioprinting with microfluidics, which, if successful, could lead to extremely highthroughput drug screening.7 In addition, regenerative medicine researchers are exploring the possibility of using 3D printers to build biocompatible scaffolds with porous microstructures embedded with differentiation and growth factors. These scaffolds can then be seeded with stem cells to regenerate organs with the microscopic and macroscopic characteristics of a normal organ. However, many challenges to 3D organ printing remain, including providing appropriate vascularization and inducing robust stem cell growth and differentiation.
Medical 3D Printing in the Garage Far removed from the aspirations of bioprinting, a community of health care professionals, patients, and advocates is emerging to create homegrown, do-it-yourself devices to fill individual medical needs. For example, an inexpensive 3D-printable prosthetic hand was developed for a 5-year-old boy.8 The digital blueprints for this hand, which could be modified as the child grew, have been made freely available for download and can be reproduced by a printer for approximately $10 worth of materials. Homegrown innovation has spawned dozens of medically related startups. For instance, Bespoke Innovations creates 3D-printed ARTICLE INFORMATION Conflict of Interest Disclosures: The authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Dr Michalski is a PhD candidate in the Investigative Medicine Program, which is funded in part by grants from the National Center for Advancing Translational Science, a component of the National Institutes of Health, and reported serving as a consultant to Butterfly Network Inc and Hyperfine Research Inc. Dr Ross reported receiving support from Medtronic Inc and Johnson & Johnson Inc to develop methods of clinical trial data sharing, from the Centers for Medicare & Medicaid Services to develop and maintain performance measures used for public reporting, and from the US Food and Drug Administration to develop methods for postmarket surveillance of medical devices; receiving support from the National Institute on Aging (K08 AG032886) and the American Federation for Aging Research through the Paul B. Beeson Career Development Award Program; and
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prosthetics by tailoring aesthetics and functionality to each patient’s needs and wishes. Similarly, Evill Designs develops 3D-printed casts for broken extremities based on radiographs and 3D laser scans of the limb. These 3D-printed casts are made with a durable lightweight polymer material with holes to allow air to circulate beneath the cast.
Safety and Regulatory Considerations Critical questions accompany the broad application of 3D printers in medicine. Few studies have evaluated the use of 3D-printed models for preoperative planning, education, or patient communication. A similar paucity of data exists for 3D-printed devices. At this early phase, it is unclear what the ultimate value of 3D printing will be for health and how it will specifically affect outcomes. Additionally, the pathway to ensuring the safety of these devices remains unclear. Will previously cleared devices need additional oversight when produced by 3D printing? Many versions of a printable medical device may exist; will they all be subject to oversight as separate devices? How will the spread of design files be regulated? The US Food and Drug Administration has signaled that these difficult issues will need to be addressed soon—and will likely have significant implications for 3D printing in medicine.9 As 3D printing continues to integrate into medical practice, physicians and patients face the challenge of understanding this complex technology, taking advantage of its potential, and weighing its potential risks. Meanwhile, 3D printing is already beginning to reshape medicine. Although clicking the “print” button can be enough to appreciate the promise of 3D printing, its implications for health care may be substantially more complex.
serving as a member of a scientific advisory board for FAIR Health Inc.
tool to assist neurosurgical planning. Stereotact Funct Neurosurg. 2013;91(3):162-169.
1. Thingiverse website. http://www.thingiverse.com/. Accessed July 15, 2014.
6. Zopf DA, Hollister SJ, Nelson ME, Ohye RG, Green GE. Bioresorbable airway splint created with a three-dimensional printer. N Engl J Med. 2013;368 (21):2043-2045.
2. Liu Q, Leu MC, Schmitt SM. Rapid prototyping in dentistry: technology and application. Int J Adv Manuf Technol. 2006;29(3-4):317-335.
7. Wyss Institute. Harvard University. Organs-on -Chips. Wyss Institute website. http://wyss.harvard .edu/viewpage/461/. Accessed May 5, 2014.
3. Zein NN, Hanouneh IA, Bishop PD, et al. Three-dimensional print of a liver for preoperative planning in living donor liver transplantation. Liver Transpl. 2013;19(12):1304-1310.
8. Henn S, Carpien C. 3-D Printer Brings Dexterity to Children With No Fingers. National Public Radio website. http://www.npr.org/blogs/health/2013/06 /18/191279201/3-d-printer-brings-dexterity-to -children-with-no-fingers. June 18, 2013. Accessed July 24, 2014.
REFERENCES
4. Flügge TV, Nelson K, Schmelzeisen R, Metzger MC. Three-dimensional plotting and printing of an implant drilling guide: simplifying guided implant surgery. J Oral Maxillofac Surg. 2013;71(8):1340-1346. 5. Spottiswoode BS, van den Heever DJ, Chang Y, et al. Preoperative three-dimensional model creation of magnetic resonance brain images as a
9. Gaffney A. FDA Plans Meeting to Explore Regulation, Medical Uses of 3D Printing Technology. http://www.raps.org/regulatory-focus/news/2014 /05/19000/FDA-3D-Printing-Guidance-and -Meeting/. 2014. Accessed May 20, 2014.
JAMA December 3, 2014 Volume 312, Number 21
Copyright 2014 American Medical Association. All rights reserved.
Downloaded From: http://jama.jamanetwork.com/ by a Tulane University User on 05/12/2015
jama.com
VIEWPOINT
Mark H. Michalski, MD Investigative Medicine Program, Department of Diagnostic Radiology, Yale University School of Medicine, New Haven, Connecticut. Joseph S. Ross, MD, MHS Robert Wood Johnson Foundation Clinical Scholars Program, Section of General Internal Medicine, Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut; Department of Health Policy and Management, Yale School of Public Health, New Haven, Connecticut; and Center for Outcomes Research and Evaluation, Yale–New Haven Hospital, New Haven, Connecticut.
Video at jama.com
Corresponding Author: Mark H. Michalski, MD, Department of Diagnostic Radiology, Yale University School of Medicine, PO Box 208042, New Haven, CT 06520 (mark [email protected]).
The Shape of Things to Come 3D Printing in Medicine 3D printing—a manufacturing technique by which objects are built from digital data in a way analogous to how computer text is printed on a page—has captured the imagination of many with its potential to offer flexible, inexpensive manufacturing for widespread use. 3D printers have been used to build everything from rockets to houses to guns to other 3D printers, their capabilities limited only by access to a low-cost 3D printer, a set of digital blueprints, and some ingenuity. 3D printing aficionados now include physicians, medical researchers, and patients, many of whom are beginning to explore what this technology might mean for health and health care. While not a panacea, 3D printing is increasingly finding its place in patient care, from its expanding use in surgical planning to the vision of printing whole new organs for transplantation (Video).
sans now create individualized jewelry on demand, and maintenance workers can print replacement parts for household devices. Indeed, 3D printing may serve as a means of distributing manufacturing in the same way that the Internet distributes information.
3D Printing in Today’s (and Tomorrow’s) Medical Practice
Although 3D printing applications in medicine are increasing rapidly, its application in dentistry has been established for more than a decade,2 allowing rapid fabrication of molds for many common dental implants. More recently, head and neck surgeons have used 3D printing to provide preoperative models for complex surgeries. For example, several facial reconstructive surgeries are performed by first harvesting the fibula, which is then fashioned in the operating room into new bony structures. These surgeries can now be augmented using What Is 3D Printing? Once a niche tool for industrial prototyping, 3D print- computer-planning programs to generate surgical plans ing technology is based on the concept of “additive” that determine the ideal way to harvest and incise the manufacturing—that is, 3D printing builds structures by fibula to create a reconstructive graft. 3D-printed moddepositing material layer by layer. This is in contrast to els translate preoperative imaging data into useful tools that may help surgeons both reduce operating room time and potentially improve surgical results.3-5 Indeed, 3D printing may serve as a In addition, using models based on means of distributing manufacturing in imaging of real-world patients, 3D printing can be a useful tool in the instructhe same way that the Internet tion of normal and pathologic anatomy. distributes information. For instance, at our institution, the use of 3D models to educate trainees about standard manufacturing techniques, which often rely on complex traumatic bony fracture patterns is being excreating structures by cutting, molding, or otherwise ma- plored. These models may also be used to communinipulating raw materials. As a consequence, 3D print- cate imaging studies to patients in a tangible, easy-toing is flexible and can create myriad structures in a va- understand format. riety of materials, in nearly any shape or size. 3D printers are now capable of using components as varied as ce- Printing Devices, Cells, and Organs ramics, sandstone, and chocolate. Outside the clinic and operating room, researchers are 3D printers leverage the advantages of computer using 3D printers to reshape health care. The flexibility design by making it simple to translate these designs into of 3D printing allows investigators and manufacturers to tangible objects. In this way, 3D printing serves as a create medical devices with a broad range of biological bridge between digital 3D models and the physical world. and physical properties. When paired with medical Digital models can be widely distributed and modified, imaging, this flexibility may be leveraged to fabricate dedemocratizing manufacturing in a way not previously vices tailored to an individual patient’s anatomy in a way imagined. Large communities with vast and varied in- similar to how “omics” data are applied to create perterests have formed around sharing the digital data used sonalized therapeutics. For example, a customized polyto print models: one site, for example, contains more mer splint has been used to prevent airway collapse in than 100 000 digital models of all kinds, which users can neonatal bronchomalacia.6 This splint was composed of freely download and print.1 a biocompatible polymer, designed to be naturally reThese communities have been empowered by the sorbed within 3 years, and was specifically tailored to the emergence of low-cost consumer-grade machines that neonate’s anatomy using 3D imaging. have made 3D printers broadly available. New applicaBioengineering researchers have begun to expand tions for 3D printing continue to appear every day: arti- the range of printed materials to biological scaffolds
jama.com
JAMA December 3, 2014 Volume 312, Number 21
Copyright 2014 American Medical Association. All rights reserved.
Downloaded From: http://jama.jamanetwork.com/ by a Tulane University User on 05/12/2015
2213
Opinion Viewpoint
and cells. Although these “bioprinters” are in their infancy, this technology is advancing quickly to create tools to facilitate drug discovery. Tiny microcosms of organs can be printed onto an in vitro substrate, where they are exposed to potential drugs. Using these “mini organs,” the effects of drugs and drug toxicity on human tissues may be observed without conducting in vivo studies. The “body-on-a-chip” project is combining bioprinting with microfluidics, which, if successful, could lead to extremely highthroughput drug screening.7 In addition, regenerative medicine researchers are exploring the possibility of using 3D printers to build biocompatible scaffolds with porous microstructures embedded with differentiation and growth factors. These scaffolds can then be seeded with stem cells to regenerate organs with the microscopic and macroscopic characteristics of a normal organ. However, many challenges to 3D organ printing remain, including providing appropriate vascularization and inducing robust stem cell growth and differentiation.
Medical 3D Printing in the Garage Far removed from the aspirations of bioprinting, a community of health care professionals, patients, and advocates is emerging to create homegrown, do-it-yourself devices to fill individual medical needs. For example, an inexpensive 3D-printable prosthetic hand was developed for a 5-year-old boy.8 The digital blueprints for this hand, which could be modified as the child grew, have been made freely available for download and can be reproduced by a printer for approximately $10 worth of materials. Homegrown innovation has spawned dozens of medically related startups. For instance, Bespoke Innovations creates 3D-printed ARTICLE INFORMATION Conflict of Interest Disclosures: The authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Dr Michalski is a PhD candidate in the Investigative Medicine Program, which is funded in part by grants from the National Center for Advancing Translational Science, a component of the National Institutes of Health, and reported serving as a consultant to Butterfly Network Inc and Hyperfine Research Inc. Dr Ross reported receiving support from Medtronic Inc and Johnson & Johnson Inc to develop methods of clinical trial data sharing, from the Centers for Medicare & Medicaid Services to develop and maintain performance measures used for public reporting, and from the US Food and Drug Administration to develop methods for postmarket surveillance of medical devices; receiving support from the National Institute on Aging (K08 AG032886) and the American Federation for Aging Research through the Paul B. Beeson Career Development Award Program; and
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prosthetics by tailoring aesthetics and functionality to each patient’s needs and wishes. Similarly, Evill Designs develops 3D-printed casts for broken extremities based on radiographs and 3D laser scans of the limb. These 3D-printed casts are made with a durable lightweight polymer material with holes to allow air to circulate beneath the cast.
Safety and Regulatory Considerations Critical questions accompany the broad application of 3D printers in medicine. Few studies have evaluated the use of 3D-printed models for preoperative planning, education, or patient communication. A similar paucity of data exists for 3D-printed devices. At this early phase, it is unclear what the ultimate value of 3D printing will be for health and how it will specifically affect outcomes. Additionally, the pathway to ensuring the safety of these devices remains unclear. Will previously cleared devices need additional oversight when produced by 3D printing? Many versions of a printable medical device may exist; will they all be subject to oversight as separate devices? How will the spread of design files be regulated? The US Food and Drug Administration has signaled that these difficult issues will need to be addressed soon—and will likely have significant implications for 3D printing in medicine.9 As 3D printing continues to integrate into medical practice, physicians and patients face the challenge of understanding this complex technology, taking advantage of its potential, and weighing its potential risks. Meanwhile, 3D printing is already beginning to reshape medicine. Although clicking the “print” button can be enough to appreciate the promise of 3D printing, its implications for health care may be substantially more complex.
serving as a member of a scientific advisory board for FAIR Health Inc.
tool to assist neurosurgical planning. Stereotact Funct Neurosurg. 2013;91(3):162-169.
1. Thingiverse website. http://www.thingiverse.com/. Accessed July 15, 2014.
6. Zopf DA, Hollister SJ, Nelson ME, Ohye RG, Green GE. Bioresorbable airway splint created with a three-dimensional printer. N Engl J Med. 2013;368 (21):2043-2045.
2. Liu Q, Leu MC, Schmitt SM. Rapid prototyping in dentistry: technology and application. Int J Adv Manuf Technol. 2006;29(3-4):317-335.
7. Wyss Institute. Harvard University. Organs-on -Chips. Wyss Institute website. http://wyss.harvard .edu/viewpage/461/. Accessed May 5, 2014.
3. Zein NN, Hanouneh IA, Bishop PD, et al. Three-dimensional print of a liver for preoperative planning in living donor liver transplantation. Liver Transpl. 2013;19(12):1304-1310.
8. Henn S, Carpien C. 3-D Printer Brings Dexterity to Children With No Fingers. National Public Radio website. http://www.npr.org/blogs/health/2013/06 /18/191279201/3-d-printer-brings-dexterity-to -children-with-no-fingers. June 18, 2013. Accessed July 24, 2014.
REFERENCES
4. Flügge TV, Nelson K, Schmelzeisen R, Metzger MC. Three-dimensional plotting and printing of an implant drilling guide: simplifying guided implant surgery. J Oral Maxillofac Surg. 2013;71(8):1340-1346. 5. Spottiswoode BS, van den Heever DJ, Chang Y, et al. Preoperative three-dimensional model creation of magnetic resonance brain images as a
9. Gaffney A. FDA Plans Meeting to Explore Regulation, Medical Uses of 3D Printing Technology. http://www.raps.org/regulatory-focus/news/2014 /05/19000/FDA-3D-Printing-Guidance-and -Meeting/. 2014. Accessed May 20, 2014.
JAMA December 3, 2014 Volume 312, Number 21
Copyright 2014 American Medical Association. All rights reserved.
Downloaded From: http://jama.jamanetwork.com/ by a Tulane University User on 05/12/2015
jama.com
