# data[].attributes.attachment_link.readable_text
Posters are an effective way of sharing your research, usually presented at professional conferences, local research events, or educational events. Research posters allow you to communicate information about your work in a concise and visual manner, and engage with viewers in an informal setting. They provide an opportunity for you to share your research, engage your audience, stay up-to-date on developments in your field, and network with experts.

Your poster should be a visual aid to a story you tell about your research.

A typical poster contains the same information as a research paper, but modified for viewing quickly. A poster will have:

less text

shorter sentences, more use of bullets

visual aids such as images, icons or charts

references (even if it's a small font)

# data[].attributes.attachment_link.title
Library Guides: Digital Posters & Infographics: Getting Started

# data[].attributes.attachment_link.description
Posters are an effective way of sharing your research, usually presented at professional conferences, local research events, or educational events. Research posters allow you to communicate information about your work in a concise and visual manner, and engage with viewers in an informal setting.

# data[].attributes.attachment_link.title
Mohawk College Library - Off Campus Login

# data[].attributes.attachment_link.description
This is the login page for off-site access to library eResources such as databases, eBooks, online videos and articles. The login is your 9-digit MohawkID number and password.

# data[].attributes.attachment_link.readable_text
BACKGROUND:Recent advances in 3D printing technology, and biomaterials are revolutionizing medicine. The beneficiaries of this technology are primarily patients, but also students of medical faculties. Taking into account that not all students have full, direct access to the latest advances in additive technologies, we surveyed their opinion on 3D printing and education in this area. The research aimed to determine what knowledge about the use of 3D printing technology in medicine, do students of medical faculties have. METHODS:The research was carried out in the form of a questionnaire among 430 students of the Medical University of Silesia in Katowice (Poland) representing various fields of medicine and health sciences. The questions included in the survey analyzed the knowledge of the respondents for 3D printing technology and the opportunities it creates in medicine. RESULTS:The results indicate that students do have knowledge about 3D printing obtained mainly from the internet. They would be happy to deepen their knowledge at specialized courses in this field. Students appreciated the value of 3D printing in order to obtain accurate anatomical models, helpful in learning. However, they do not consider the possibility of complete abandonment of human cadavers in the anatomy classes. Their knowledge includes basic information about current applications of 3D printing in medicine, but not in all areas. However, they have no ethical doubts regarding the use of 3D printing in any form. The vast majority of students deemed it necessary to incorporate information regarding 3D printing technology into the curriculum of different medical majors. CONCLUSION:This research is the first of its kind, which allows for probing students' knowledge about the additive technologies in medicine. Medical education should be extended to include issues related to the use of 3D printing for medical applications.

Published in PLoS ONE

ISSN

1932-6203 (Online)

Publisher

Public Library of Science (PLoS)

Country of publisher

United States

LCC subjects

Medicine

Science

Website

http://journals.plos.org/plosone/

About the journal

# data[].attributes.attachment_link.description
BACKGROUND:Recent advances in 3D printing technology, and biomaterials are revolutionizing medicine. The beneficiaries of this technology are primarily patients, but also students of medical faculties. Taking into account that not all students have full, direct access to the latest advances in additive technologies, we surveyed their opinion on 3D printing and education in this area.

# data[].attributes.attachment_link.readable_text
Australasian Medical Journal (2016-01-01)

Affiliations

Jon Cornwall

Graduate School of Nursing, Midwifery and Health, Victoria University of Wellington, Wellington, New Zealand

Many emerging technologies have the potential to revolutionise aspects of everyday life. At every turn, new examples of technological advances surround us, from self-driving cars through to gene therapy and genomic medicine. The rapid development and integration of 3D printing is another example of a new technology having a major impact on society. Objects can now be printed as near - perfect reproductions by anyone with a moderately capable computer and enough money to purchase a 3D printer. Everyday items, furniture, household appliances, and even guns can now be reproduced. Even human body parts, from cadavers donated to medical science, are now being 3D printed and used for the purpose of medical education and research.

Keywords

Published in Australasian Medical Journal

ISSN

1836-1935 (Online)

Publisher

Australasian Medical Journal pty ltd.

Country of publisher

Australia

LCC subjects

Medicine: Medicine (General)

Website

https://amj.net.au/index.php/AMJ

About the journal

# data[].attributes.attachment_link.description
Australasian Medical Journal (2016-01-01) Affiliations Jon Cornwall Graduate School of Nursing, Midwifery and Health, Victoria University of Wellington, Wellington, New Zealand Many emerging technologies have the potential to revolutionise aspects of everyday life. At every turn, new examples of technological advances surround us, from self-driving cars through to gene therapy and genomic medicine.

# data[].attributes.attachment_link.readable_text
Three-dimensional (3D) printing refers to a number of manufacturing technologies that generate a physical model from digital information. Medical 3D printing was once an ambitious pipe dream. However, time and investment made it real. Nowadays, the 3D printing technology represents a big opportunity to help pharmaceutical and medical companies to create more specific drugs, enabling a rapid production of medical implants, and changing the way that doctors and surgeons plan procedures. Patient-specific 3D-printed anatomical models are becoming increasingly useful tools in today's practice of precision medicine and for personalized treatments. In the future, 3D-printed implantable organs will probably be available, reducing the waiting lists and increasing the number of lives saved. Additive manufacturing for healthcare is still very much a work in progress, but it is already applied in many different ways in medical field that, already reeling under immense pressure with regards to optimal performance and reduced costs, will stand to gain unprecedented benefits from this good-as-gold technology. The goal of this analysis is to demonstrate by a deep research of the 3D-printing applications in medical field the usefulness and drawbacks and how powerful technology it is.

1. Introduction

Among the different manufacturing processes that are currently adopted by the industry, the 3D printing is an additive technique. It is a process through which a three-dimensional solid object, virtually of any shape, is generated starting from a digital model. Medical 3D printing was once an ambitious pipe dream. However, time and investment made it real. Nowadays, the 3D printing technology represents a big opportunity to help pharmaceutical and medical companies to create more specific drugs, enabling a rapid production of medical implants and changing the way that doctors and surgeons plan procedures [ 1]. This technology has multiple applications, and the fastest growing innovation in the medical field has been represented by the advent of the 3D printing itself [ 2]. Five technical steps are required to finalize a printed model. They include selecting the anatomical target area, the development of the 3D geometry through the processing of the medical images coming from a CT/MRI scan, the optimization of the file for the physical printing, and the appropriate selection of the 3D printer and materials (Figure 1). This file represents the guidance for the subsequent printing, "slicing" that digital design model into cross sections. That "sliced" design is then sent to a 3D printer, which manufactures the object by starting at the base layer and building a series of layers on top until the object is built using the raw materials that are needed for its composition. A patient-specific model with anatomical fidelity created from imaging dataset is finally obtained.

In this way, the 3D printing has the potential to significantly improve the research knowledge and the skills of the new generation of surgeons, the relationship between patient and surgeon [ 3], increasing the level of understanding of the disease involved, and the patient-specific design of implantable devices and surgical tools [ 4- 6] and optimize the surgical process and cost [ 7]. Nowadays, different printing techniques and material are available in order to better reproduce the patient anatomy. Most of the available printing materials are rigid and therefore not optimum for flexibility and elasticity, unlike biological tissue [ 8]. Therefore, there are nowadays materials able to close the gap between the real anatomy and the reproduced one, especially considering the soft tissue [ 9, 10]. In this analysis, an overview of the 3D printing application in medical field is presented, highlighting the usefulness and limitations and how it could be useful for surgeons.

2. Additive Manufacturing Technologies

The 3D-printing techniques have grown in the last decades starting from 1986 when the first stereolithographic (SLA) systems were introduced in practice. Seven are the technical processes related to the 3D printing, each of which is represented by one or more commercial technologies, as shown by the ASTM International [ 11]. All the processes are listed in Table 1 that reported information about the technologies involved, the materials used, and the medical applications related to each process [ 12]. A comparison among all the seven techniques is proposed in the same table showing the advantages and disadvantages related to all the processes. Each process uses specific materials with specific properties that relate to medical applications, which are also summarized in Table 1. This general information helps the users to better choose the right technology depending on the application needed.

These technologies and the related advantages enable the researchers to improve existing medical applications that use 3D-printing technology and to explore new ones. The medical goal that has been already reached is significant and exciting, but some of the more revolutionary applications, such as bio/organ printing, require more time to evolve [ 2].

3. Transformation Process and Materials Used

Materials used in 3D printing are transformed during the production of the specific model by changing their consistency. This process is named cure and can be done in different ways: a melting of a hard filament in order to give the desired form to the model by the material distortion, liquid solidification for the construction of the structure and powder solidification. All these processes require filler or support material in lattice forms avoiding distortion of the model while the material is being cured. The support material can be easily removed by hand with a cutting tool; however, there is the risk to leave impression on the surface requiring an additional polishing in order to obtain a good-quality printing. The risk of damaging the model, losing details, or break the geometry is really high [ 23].

The correct selection of the material is directly linked to the selection of the 3D-printing process and printer, as well as the requirements of the model. Related to medical application, similarly to other applications, different anatomical structures need different mechanical properties of the materials to fulfill the required performance of the printed object [ 8]. The main distinction among the different materials that characterize the human body is between rigid and soft materials. Human bones are an example of rigid tissue and ligaments or articular cartilage are examples of soft materials. Bones are the simplest and easiest biological tissue to be produced by 3D printing as the majority of the materials are rigid. The materials used in 3D printing to model the bone structure are for example acrylonitrile butadiene styrene (ABS) [ 23], powder of plasters [ 24], and hydroquinone [ 8].

Relating to soft tissues, deeper research is still needed in order to decrease the gap between a 3D-printed anatomical model and the human structure. Most of the 3D-printing materials present a lack of realism to mimic adequately a soft human biological tissue. Thus, postprocessing may be necessary in order to soften the printed structures. Some examples are given in the reproduction of cartilaginous tissues [ 25], arteries for practicing valve replacement [ 26], hepatic segment [ 27], and hearts [ 28]. An interesting example is the development of a 3D-printed brain aneurysm using the flexible TangoPlus™ photopolymer [ 29] that represented a useful tool to plan the operative strategy in order to treat congenital heart disease. Furthermore, some of the materials used are urethane and rubber-like material, mixed with a rigid photopolymer, to reasonably mimic the artery structure due to their Shore value and elastic properties similar to the physiological one [ 30, 31].

For a promising future, the multimaterial composites seem to represent a good chance for the 3D printing of human tissues since none of the current available material is able to fully mimic elastic and biological tissues. Multimaterial composites may be designed based on the capacity of the selected biological material to replicate the mechanical properties of human tissue [ 32]. Mechanical testing may represent a necessary tool to analyze the biomechanical response and validate the artificial material.

Moreover, it is also important to mention that 3D printing allows the reproduction of implantable custom device, but still deeper research needs to be done in order to examine the differences between the traditional and additive manufacturing in terms of mechanical and structural properties, especially fatigue limit needs to be examined further [ 33].

4. Role of 3D Printing in Medical Field

Every year, 3D printing offers more and more applications in the healthcare field helping to save and improve lives in ways never imagined up to now. In fact, the 3D printing has been used in a wide range of healthcare settings including, but not limited to cardiothoracic surgery [ 34], cardiology [ 26], gastroenterology [ 35], neurosurgery [ 36], oral and maxillofacial surgery [ 37], ophthalmology [ 38], otolaryngology [ 39], orthopaedic surgery [ 22], plastic surgery [ 40], podiatry [ 41], pulmonology [ 42], radiation oncology [ 43], transplant surgery [ 44], urology [ 45], and vascular surgery [ 46].

Thanks to the different benefits that this technology could induce in the field, the main direct applications of 3D printing in the medical and clinical field are as follows [(i) Used for personalized presurgical/treatment and for preoperative planning. This will lead to a multistep procedure that, integrating clinical and imaging information, will determine the best therapeutic option. Several studies have demonstrated that patient-specific presurgical planning may potentially reduce time spent in the operating room (OR) and result in fewer complications [(ii) Customize surgical tools and prostheses: the 3D printing can be used to manufacture custom implants or surgical guides and instruments. Therefore, the customization of surgical tools and prostheses means a reduction of cost given by the additive manufacturing technique [(iii) Study of osteoporotic conditions: following a pharmacological treatment, 3D printing is useful in validating the results achieved by the patient. This enables a more accurate estimation of patientʼs bone condition and a better decision on the surgical treatment [(iv) Testing different device in specific pathways: a clear example is the reproduction of different vascular patterns to test the effectiveness of a cardiovascular system used to treat peripheral and coronary artery disease [(v) Improving medical education: 3D-printed patient-specific models have demonstrated that they can increase performance and foster rapid learning [(vi) Patient education: patient-centered cares makes patient education one of the top priorities for most healthcare providers. However, communicating imaging reports verbally or by showing patients their CT or MRI scans may not be effective; the patients may not fully understand 2D images representation of a 3D anatomy. On the contrary, 3D printing may improve the doctor-patient communication by showing the anatomic model directly [(vii) Storage of rare cases for educational purposes: this role is closely linked to the previous one. This allows the generation of a large dataset composed by datasets of patients affected by rare pathologies, allowing the training of surgeons in specific applications [(viii) Improve the forensic practice: in the courtroom, a 3D model could be used to easily demonstrate various anatomic abnormalities that may be difficult to jury members to understand using cross-sectional imaging [(ix) Bioprinting: the 3D printing allows also the modelling of implantable tissue. Some examples are the 3D printing of synthetic skin for transplanting to patients, who suffered burn injuries [(x) Personalized drug 3D printing: the 3D printing of drugs consists of the printing out the powdered drug layer to make it dissolve faster than average pills [(xi) Customizing synthetic organs: the 3D printing may represent an opportunity to save life reducing the waiting list of patients that need transplantation [ 47]: 48, 52- 15]. 61]. In this way, the 3D printing enables us to quickly produce prototypes of new design concepts or improvements to existing devices. 62], while significantly ameliorating the knowledge, management, and confidence of the trainees regardless of the area of expertise [ 66, 52- 68]. 69]. It may also be used for testing of cosmetic, chemical, and pharmaceutical products. Another example is the replicating of heart valves using a combination of cells and biomaterials to control the valve's stiffness [ 71]. It allows also personalization of the patient's needed quantity [ 72]. Bioprinted organs may also be used in the future by pharmaceutical industries to replace animal models for analyzing the toxicity of new drugs [ 73]. 2]. 26] or the replicating of human ears using molds filled with a gel containing bovine cartilage cells suspended in collagen [ 70]. 54]. 67]. 8]. The benefits of 3D printing in education are the reproducibility and safety of the 3D-printed model with respect to the cadaver dissection, the possibility to model different physiologic and pathologic anatomy from a huge dataset of images, and the possibility to share 3D models among different institutions, especially with ones that have fewer resources [ 63]. 3D printers that have the capability to print with different densities and colours can be used to accentuate the anatomical details [ 64, 65]. 54, 60]. 49]. Moreover, this may lead to reduced postoperative stays, decreased reintervention rates, and lower healthcare costs. The 3D-printing technology allows to provide to the surgeon a physical 3D model of the desired patient anatomy that could be used to accurately plan the surgical approach along with cross-sectional imaging or, alternatively, modelling custom prosthetics (or surgical tool) based on patient-specific anatomy [ 50- 54]. In this way, a better understanding of a complex anatomy unique to each case is allowed [ 52- 56]. Furthermore, the 3D printing gives the possibility to choose before the implantation the size of the prostheses components with very high accuracy [ 57- 59].

Therefore, these examples clearly demonstrated that 3D printing is one of the most disruptive technologies that have the potential to change significantly the clinical field, improving medicine and healthcare, making care affordable, accessible, and personalized. As printers evolve, printing biomaterials get safety regulated and the general public acquires a common sense about how 3D printing works.

4.1. Lack of Regulation

The biomedical field is one of the areas in which 3D printing has already shown its potentialities and that, in not too distant future, may be one of the key elements for the resolution of important problems related to human health that still exist.

Nowadays, despite the additive manufacturing offers a great potential for the manufacturing, the 3D-printing products do not have a proper legal status that defines them, both for implantable and nonimplantable devices. All the 3D-printed products are categorized as custom-made device under the Regulation (EU) 2017/745 of the European Parliament and of the Council of the 5 April 2017 [ 74]. They are defined as follow: " any device specifically made in accordance with a written prescription of any person authorized by national law by virtue of that person's professional qualifications which gives, under that person's responsibility, specific design characteristics, and is intended for the sole use of a particular patient exclusively to meet their individual conditions and needs". Differently for mass-produced devices " which need to be adapted to meet the specific requirements of any professional user and devices which are mass-produced by means of industrial manufacturing processes in accordance with the written prescriptions of any authorized person shall not be considered to be custom-made devices" [ 75]. Indeed, manufacturers of custom-made devices shall only be guaranteed by an obligation of conformity assessment procedures upon which the device shall be compliant with safety and performance requirements [ 76]. Furthermore, the regulation states that " Devices, other than custom-made or investigational devices, considered to be in conformity with the requirements of this Regulation shall bear the CE marking of conformity" [ 77]. Thus, these medical devices do not require affixation of CE markings: a significant and constraining procedure demonstrating the safety and the performance of the device for the patient. Moreover, the custom-made devices do not require the UDI System (Unique Device Identification system) as reported in the Article 27, Comma 1 of the regulation.

A different approach has to be applied for custom-made implants, such as dental prostheses, that are defined as "(i) (ii) any device, including those that are partially or wholly absorbed, which is intended: to be totally introduced into the human body, or to replace an epithelial surface or the surface of the eye, by clinical intervention and which is intended to remain in place after the procedure.

Any device intended to be partially introduced into the human body by clinical intervention and intended to remain in place after the procedure for at least 30 days shall also be deemed to be an implantable." [ 78]. The custom-made implantable devices require the CE marking in order to guarantee the safety and to be commercialized.

The EU has been working for many years on an update to the Medical Devices Directive. This proposed legislation has many noble attributes in addition to overcoming the gaps of the existing Medical Devices Directive, such as supporting technology and science innovation, while simultaneously strengthening patient safety. However, the current version of the draft Regulation lacks some depth that is mandatory to safeguard safe usage of 3D-printing technology and, thus, enable its increasing prevalence in medicine.

4.2. Examples of Application of 3D Printing in Paediatric Cases

Three-dimensional (3D) modelling and printing greatly supports advances in individualized medicine and surgery. Looking to the field of paediatrics, it is possible to identify four main applications categories: surgical planning, prostheses, tissue construct, and drug printing.

There are many successful cases that demonstrate the potential of the additive manufacturing in surgical planning in paediatric cases. In particular, most of the applications of 3D printing reported in the literature are related to the congenital heart disease [ 29]. This is due to the fact that children have a smaller chest cavity than adults, and the surgical treatment in paediatric cases may be much more difficult. The additive manufacturing helps the surgeons to have more information than the only ones that imaging technologies can afford. It helps the surgeon in the spatial orientation inside the cavities of a small infant heart and in simulating the surgical approach and steps of the operation with high fidelity [ 79]. This leads to shorter intraoperative time that per se has significant impact on complication rate, blood loss, postoperative length-of-stay, and reduced costs [ 80]. An example of the application of the 3D printing in the paediatric congenital heart disease treatment is a study reported in the literature based on the development of a 3D heart model of a 15-years-old boy to improve interventional simulation and planning in patient with aortic arch hypoplasia. The 3D-printed model allowed simulation of the stenting intervention. The assessment of optimal stent position, size, and length was found to be useful for the actual intervention in the patient. This represents one of the most technically challenging surgical procedures which opens the door for potential simulation applications of a 3D model in the field of catheterization and cardiovascular interventions [ 81].

Another study proposed in which the 3D printing had a relevant role consists in a clinical preoperative evaluation on five patients ranged from 7 months to 11 years of age affected by a double outlet right ventricle with two well-developed ventricles and with a remote ventricular septal defect. The three-dimensional printed model based on the data derived from computed tomography (CT) or magnetic resonance (MRI) contributed to a more complete appreciation of the intracardic anatomy, leading to a successful surgical repair for three of the five patients. [ 82] Lastly, CT and MRI data were used to construct 3D digital and anatomical models to plan a heart transplantation surgical procedure of two patients of 2 and 14 years old affected relatively by hypoplastic left heart syndrome and pulmonary atresia with a hypoplastic right ventricle. These physical models allowed the surgeon and the paediatric cardiologist to develop the optimal surgical treatment during the heart transplantation anticipating problems that may arise during the procedure. The specific dimensions and distances can be measured, and heart transplantation can be planned [ 83].

The importance of three-dimensional printing has been demonstrating also in other application. The additive manufacturing in fact has been used to plan surgical treatment of paediatric orthopaedic disorders [ 84]. The 3D model of a 2-year-old male child was produced in order to plan the surgical treatment for his multisutural craniosynostosis with a history of worsening cranial deformity. Other than the turribrachycephalic skull, the child also had greatly raised intracranial pressure with papilledema and copper beaten appearance of the skull. Thorough preoperative planning enabled faster surgery and decreased anesthesia time in a compromised patient [ 85].

Another study, based on 13 cases of multiplane spinal or pelvic deformity, was developed in order to demonstrate that the three-dimensional printing may represent a useful tool in the surgical planning of complex paediatric spinal deformities treatment [ 86].

Changing the final goal of the additive manufacturing, other applications cases are reported in the literature to demonstrate the usefulness in the production of paediatric patient-specific prostheses. An example in the literature is given by the development of a low-cost three-dimensional printed prosthetic hand for children with upper-limb reductions using a fitting methodology that can be performed at a distance [ 87]. This specific case demonstrates that the advancements in computer-aided design (CAD) programs, additive manufacturing, and imaging editing software offer the possibility of designing, printing, and fitting prosthetic hands devices overcoming the costs limitation. As a consequence, the advantages of 3D-printed implants over conventional ones are in terms of customizability and cost as seems to be clear from the previous example. On the contrary, the major adversity is related to the rapid physical growth that makes the customize prostheses outsized frequently. This leads to the production of advanced technological implant that, due to their high complexity and weight, increases cost. The additive manufacturing can be used to fabricate rugged, light-weight, easily replaceable, and very low-cost prostheses for children [ 88]. The major prostheses lack is related to the ability to communicate with the brain in terms of sensibility. With the advent of bioprinting, cellular prostheses could be an interesting area of research, which can lead to integrated prostheses in the brain communication system, and exhibit more biomimicry with tissue and organ functionalities [ 89].

Related to bioprinting, there are few applications nowadays involved in the tissues production in regenerative medicine. Many different tissues have been successfully bioprinted as reported in many journal articles [ 90] including bone, cartilage, skin, and even heart valves. However, the bioprinted tissues and organs are at the laboratory level; a long way needs to be travelled to achieve successful clinical application [ 91].

Last but not the least, the additive manufacturing in terms of drug printing may also represent an innovative technique in the production of patient-specific medicine with regard to the composition and the dose needed by the patients. The drug-printing introduces the concept of tailor-made drugs in order to make drugs safer and more effective. Especially for children, furthermore, drug-printing represents the possibility of choosing colour, shape, and design of the medication, reducing the resistance in taking them. Imagine a paediatrician talking to a four-year-old child who is having trouble adjusting to taking daily doses of steroids after being diagnosed with Duchenne muscular dystrophy the previous month. 3D printing allows us to design in particular shape the drug, making medicine more appealing to the child [ 92]. It is amental to note that changing the shape of a capsule does not have to lead to different dose and drug properties, such as drug release or dissolution rate [ 93].

5. Conclusions

The 3D printing in medical field and design needs to think outside the norm for changing the health care. The three main pillars of this new technology are the ability to treat more people where it previously was not feasible, to obtain outcomes for patients and less time required under the direct case of medical specialists. In few words, 3D printing consists in "enabling doctors to treat more patients, without sacrificing results" [ 94].

Therefore, like any new technology, 3D printing has introduced many advantages and possibilities in the medical field. Each specific case in which 3D printing has found application shown in this analysis is a demonstration of this. However, it must be accompanied by an updated and current legislation in order to guarantee its correct use.

Conflicts of Interest

The authors declare that there are no conflicts of interest regarding the publication of this paper.

Acknowledgments

The publication of the article was funded through the collaboration between Aid4Med S.r.l. and the Universitè Libre de Bruxelles.

References

1. H. Arun, Healthcare 3D Printing Market 2018 Prominent Players-Aprecia Pharmaceuticals, Aspect Biosystems, Bio 3D Technologies, Biobots, Cyfuse Biomedical, Digilab, 3 Dynamics Systems, Envision Tec, Luxexcel, Materialise NV, Nano 3D Biosciences, Oceanz, Organovo Ho, http://www.openpr.com.

2. ASTM, Standard Technology for Additive Manufacturing-General Principles/Terminology, ASTM ISO/ASTM 52900:2015 (E), West Conshohocken, PA, USA, 2015.

3. H. J. Chen and M. Gariel, Aroadmap from Idea to Implementation-3D Printing for Pre-Surgical Applications, CreateSpace Independent Publishing Platform, Scotts Valley, CA, USA, 1st edition, 2012.

4. https://www.sys-uk.com/news/3d-printed-surgical-guides-and-dental-implants/.

5. Medtronic case study, Custom surgical instruments becoming working prototypes using FDM 3D printing technology.

6. Stratasys, Case study, Dante Pazzanese Cardiology Institute uses 3D printed arteries to diagnose and treat diseases.

7. Stratasys, Case study, Shaping Young Hearts. Stratasys Helps a Surgeon Save More Kids.

8. Stratasys, Case study, 3D Printing for Vascular Health. Shaping Breakthroughs in Brain Aneurysm Treatments.

9. Stratasys, Case study, Printing Pathways to Medical Innovation. 3D Printing's Versatility Paves the Way for Medical Advancements by Cardiovascular Systems, Inc..

10. Regulation (EU) 2017/745 of the European Parliament and of the Council of 5 April 2017 on medical devices, amending Directive 2001/83/EC, Regulation (EC) No 178/2002 and regulation (EC) No 1223/2009 and repealing Council Directive 90/985/EEC and 93/42/EEC.

11. Article 2, Comma 3 of the Regulation (EU) 2017/745.

12. Article 20, Comma 1 of the Regulation (EU) 2017/745.

13. Article 10 of the Regulation (EU) 2017/745.

14. Article 2, Comma 5 of the Regulation (EU) 2017/745.

15. Stratasys, Case Study, Skull Reconstruction. CTI Renato Archer 3D Prints Prototypes of an Accident Victim's Skull.

16. S. Dunham, Surgeon's Helper: 3D Printing is Revolutionizing Health Care (Op-Ed), SmarTech Markets, Charlottesville, VA, USA, 2015, https://www.livescience.com/49913-3d-printing-revolutionizing-health-care.html.

# data[].attributes.attachment_link.title
The Role of 3D Printing in Medical Applications: A State of the Art

# data[].attributes.attachment_link.description
Three-dimensional (3D) printing refers to a number of manufacturing technologies that generate a physical model from digital information. Medical 3D printing was once an ambitious pipe dream. However, time and investment made it real.

# data[].attributes.attachment_link.readable_text
3D printing is creating an enormous opportunity for the medical industry. According to a report by market research firm, SmarTech Analysis, the market for medical 3D printing is currently estimated to be worth $1.25 billion. By 2027, the market value is set to grow to $6.08 billion. Clearly, the potential for 3D printing within healthcare is huge.

Multiple sectors within the medical industry are benefiting from 3D printing, including orthopaedics and dental. The technology is offering exciting new ways to provide personalised care and create better-performing medical devices.

In today's article, we'll be exploring the key uses of 3D printing in medicine and how they will evolve, the challenges to wider adoption and what the future looks like for medical 3D printing.

3 key applications of 3D printing in healthcare

1. 3D-printed orthopaedic implants

Orthopaedic implants - medical devices used to surgically replace a missing joint or bone - are one of the applications that benefit the most from 3D printing. The technology enables medical professionals to create better-fitting, longer-lasting and higher-performing implants.

The first use of 3D printing for orthopaedic implants dates back over a decade, with the first 3D-printed implants manufactured around 2007. In 2010, Adler Ortho Group, an early adopter of Arcam's Electron Beam Melting (EBM) metal 3D printing technology, received the first FDA approvals for implants created by 3D printing.

Today, the technology can be used to make a wide range of implants, including spinal, hip, knee and skull implants. By the end of 2019, it's estimated that over 600,000 implants will have been produced with 3D printing. By 2027, this number could increase to four million.

In addition to EBM, Selective Laser Melting is another metal 3D printing technology used by orthopaedic manufacturers. Both technologies are optimised to work with biocompatible metals like titanium, and can produce many complex implants in one batch.

For example, US-based manufacturing company, Slice Mfg. Studios, says that each of its Arcam Q10 EBM machines can produce around 70 acetabular hip cups every five days .

One of the factors driving the demand for 3D-printed implants is the potential for enhanced implant performance. Thanks to the design flexibility offered by 3D printing, implants can be designed with porous surface structures, facilitating faster integration between a living bone and the artificial implant.

The orthopaedic medical device industry is dominated by a small number of multi-billion dollar medical companies, notably Stryker, DePuy Synthes, Medtronic and Smith & Nephew, all of whom are actively exploring AM for a range of innovative medical devices.

For example, Stryker has recently launched 3D-printed implants, including the 3D-printed Tritanium TL Curved Posterior Lumbar Cage. This hollow-bodied spinal implant received FDA approval in March 2018.

3D printing in the orthopaedic sector is largely being used to enhance the design of standard implants to improve their performance. The biggest potential, however, lies in the production of patient-specific implants, which remains largely untapped due to regulatory issues that we'll be discussing below.

Despite current challenges, 3D printing individualised implants represents a key opportunity for the orthopaedic segment, and one that will see tremendous growth in the years ahead.

2. Personalised surgery

3D printing technologies are increasingly being used to develop patient-specific models of organs and surgical tools, using patient's own medical imaging.

Patient-specific anatomical models

Anatomical models are currently one of the most widely adopted applications of 3D printing in the medical industry. The accessibility of medical CAD/CAM software and lower-cost desktop 3D printers is increasing, enabling more hospitals to establish 3D printing labs.

In such labs, medical professionals can produce high-accuracy 3D-printed models to assist in presurgical planning. 3D-printed anatomical models help surgeons evaluate better treatment decisions and plan their surgeries more accurately.

The process begins by taking CT or MRI scans. The scans are then analysed and modified to remove undesired areas and keep the regions of interest (a process known as segmentation). Bones, vessels and solid organs all need to be modelled in different ways. Once the digital model is created, it is converted into an STL file format, prepared for printing and sent to a 3D printer.

Rady Children's Hospital in the US, for example, has established a 3D Innovations Lab , where medical engineers 3D print dozens of models per week.

"We actually sit and analyse the models and that helps us understand what is the optimal approach to repairing the defect," said John Nigro, M.D., chief of Rady Children's cardiac surgery, speaking in an interview with KPBS News .

By preparing for surgery using a 3D-printed model, surgeons can reduce the time a patient spends in the operating room. Ultimately, this leads to fewer complications and a better long-term outcome for the patient.

Beyond surgery, 3D printers that can replicate patient organs are excellent tools for medical research, education and training. For example, holding a model and viewing the pathology from different angles helps students understand the steps involved in surgery more clearly.

Enhanced surgical tools

Another area where 3D printing is making an impact is personalised surgical tools. Surgical instruments, like forceps, hemostats, scalpel handles and clamps can be produced using 3D printers. Creating personalised surgical instruments offers many benefits. They facilitate faster and less traumatic procedures, increase a surgeon's dexterity and support better surgery outcomes.

For such applications, 3D printing companies have developed biocompatible materials that can withstand sterilisation, including high-performance thermoplastics like Ultem, PEEK, nylon and also metals like stainless steel, nickel and titanium alloys.

German medical device company, endocon GmbH, has used metal 3D printing and stainless steel alloy (17-4 PH) to develop a surgical tool for hip cup removal. The goal was to make the process of removing hip cups easier and faster.

Typically, the procedure lasts around 30 minutes and is carried out with a chisel, which risks damaging bone and tissue. This, in turn, can make the surface of a bone uneven and the insertion of a new implant even more difficult.

The new tool features additively manufactured blades, which enable more precise cutting along the edge of the acetabular cup, allowing surgeons to remove the cup within three minutes.

In terms of biocompatibility, the 3D-printed blades are said to lead to a more consistent outcome of hip cup replacement, with the rejection rate reduced from 30% to less than 3%. Furthermore, the production and finishing of 3D-printed blades take just three weeks, while the costs are reduced by 45%.

As advantages of 3D printing for surgical devices become more widely recognised, stories like this will become much more common in the future.

3. Medical & Dental devices

Medical and dental devices like prosthetics, braces, dentures, restorations and clear aligners can significantly benefit from 3D printing. According to a report, the global 3D printing medical devices market was valued at approximately $890 million in 2017. The market is expected to generate around $2.34 billion of revenue by the end of 2024, pointing to a significant growth opportunity.

Low-cost personalisation is a key benefit, driving the adoption of 3D printing for medical & dental devices. A 3D printer requires only a digital file to produce a device, which makes it possible to customise a design more easily and produce many different devices in one batch.

With traditional manufacturing like moulding, each customised device would require special tooling, making customised production economically unviable.

With 3D printing, prosthetic limbs are becoming much more affordable and faster to produce. Furthermore, the technology can be used to create prosthetics tailored to the patient's anatomy, thereby improving the fit of the prosthetic.

Increasingly, 3D printing is being used to create prostheses for children. Children's rapid growth means that they can quickly outgrow traditional prostheses. As a result, it's necessary to replace them with a larger size version every couple of years. The lower costs associated with 3D printing make this a far better-suited manufacturing option.

Nonprofit Limbitless Solutions, for example, provides children with an opportunity to customise their prosthetic limbs by choosing from a collection of colour palettes and designs, which reflect their personality.

The designs are then 3D-printed using FDM technology from Stratasys and durable plastics like ABS. In addition to the ability to create complex prosthetic designs, 3D printing reduces the cost of production. In some cases, Limbitless' prosthetics cost 40 times less than a traditional prosthetic limb.

Dental 3D printing

3D printing is to make a huge impact in the dental sector. A report by SmarTech Analysis suggests that revenues for 3D-printed dentistry will grow to $3.7 billion by 2021, and the technology will become the leading production method for dental restorations and devices worldwide by 2027.

"We're seeing that 3D printing is becoming one of the key tools in areas like dental care and dental restoration. The digital thread there has been largely developed all the way from intraoral scanning to the workflows and the planning - not just in the lab, but also in the dental clinic. So there you can see a market that is ready for mass adoption, " says Avi Reichental, Founder of XponentialWorks, speaking in an interview with AMFG.

Clear aligners - invisible teeth straightening devices - are perhaps the biggest use case of 3D printing in dental today. Major clear aligner companies like Align Technology and NextDent use 3D printing to create hundreds of thousands of moulds for clear aligners.

Over the next five years, 3D printing is predicted to evolve to the point where it can be used to create clear aligners directly.

3D printing in healthcare: regulatory perspectives

However, unlocking the full potential of 3D printing for healthcare is not without challenges. Currently, the lack of a comprehensive regulatory framework for 3D-printed medical and dental products is one of the industry's biggest barriers.

Several regulatory bodies are working on developing standards for 3D printing in healthcare. The U.S. Food and Drug Administration (FDA), for example, issued a guidance "Technical Considerations for Additive Manufactured Devices" in December 2017. The guidance highlights the technical considerations and recommendations for design, manufacturing and testing of 3D-printed medical devices.

Standardising medical devices

There are three major classes of medical devices, based on the level of harm they may pose to a patient.

Class I: Devices represent a low risk to the patient. Examples include nasal oxygen cannulas, manual stethoscopes and hand splints.

Class II: These devices are more invasive and represent a moderate risk to the patient.The majority of medical devices are class II, with examples including tracheal tubes, bone plates and elbow joint radial prostheses.

Class III: These are devices that represent the highest risk to the patient and include aortic valves, constrained metal hip prostheses and coronary stents.

While a 3D-printed prosthetic may be classified as Class I, or low risk, the technology has progressed to enable more advanced implants and tools to be produced that encompass Class III, or high risk, medical devices.

To certify devices under Class I, manufacturers have to prove that the final product is largely the same as a device that is already on the market.

For Class II and III medical devices, FDA and other regulatory bodies have yet to issue guidelines on pre-market approval of 3D-printed medical devices. These are innovative products, and would likely require modifications to an existing medical regulatory framework.

To date, more than 100 medical devices have been approved by the FDA, most of which fall under Class I medical devices.

Patient-specific devices are the most complicated case to regulate. Traditionally manufactured medical devices are standard, one-size-fits-all. However, with a product that is customised, it can be challenging to test each and every single device that is custom-made.

Going forward, to create more opportunities for personalisation, regulatory bodies should find ways of how to pre-approve custom devices.

Currently, it's challenging because the requirements for approval are developed to certify off the shelf implants and instruments. Therefore, regulatory bodies need to focus on how they can address the differences between people rather than only similarities to enable this level of personalised care.

Organisations like the FDA are trying to overcome this issue by setting maximum and minimum sizes or features for custom-created devices.

Reimbursement challenges

Lack of reimbursement can be a major barrier for hospitals thinking about establishing a 3D printing lab.

Within the healthcare industry, reimbursement describes the payment that a hospital, doctor, diagnostic facility or other healthcare providers receive for providing a medical service. Often, a health insurer or a government payer covers the cost of all or part of a provided care.

While an FDA-approved 3D-printed joint implant or bone fixator may be reimbursed, 3D models of a patient's anatomy and professional fees often are not.

Fortunately, healthcare organisations are actively working to change that. For example, the American Medical Association (AMA) has recently approved four Category III Current Procedural Terminology (CPT) codes for 3D-printed anatomical models and personalised 3D-printed cutting or drilling tools.

The four new codes will allow radiologists and other clinicians to seek reimbursement for 3D printing services. Another driver for using CPT codes is to ensure all of the production steps of a 3D-printed medical device are recorded. The data collected through the codes will be used to support the FDA approval processes.

For medical 3D printing, the introduction of the codes represents a key milestone on the way towards widespread adoption of 3D printing in healthcare.

The future of 3D printing in healthcare

3D printing is set to hold a fundamental position in the future of healthcare. Today, the technology is facilitating surgical teams both inside (surgical tools) and outside (anatomical models) the operating room. Furthermore, it creates dental products cheaper and faster and enables personalised care through custom-produced instruments and implants.

In 2019, leading hospitals and labs are adopting 3D printing as part of their medical practices and research efforts. This serves as yet another validation of the technology's value for medical applications.

Supporting the technology's evolution within the medical industry is the collaborative effort to create a single, cohesive set of standards and test methods for 3D-printed medical products. Overcoming current regulatory and legal challenges will certainly help to guide the technology going forward.

Looking beyond the applications discussed in this article, the potential of 3D printing is expanding to other healthcare sectors. Among them are bioprinting and regenerative medicine, ophthalmology and pharmaceuticals. Here, 3D printing is still very much in its early stages, but its potential is significant.

All in all, the future of healthcare will look very different from the healthcare of today - and 3D printing will be one of the key technologies to drive forward this exciting and meaningful transformation.

# data[].attributes.attachment_link.title
3D Printing In Healthcare: Where Are We In 2019? - AMFG

# data[].attributes.attachment_link.description
3D printing is creating an enormous opportunity for the medical industry. According to a report by market research firm, SmarTech Analysis, the market for medical 3D printing is currently estimated to be worth $1.25 billion. By 2027, the market value is set to grow to $6.08 billion.

# data[].attributes.attachment_link.readable_text
Spotlight on 3D Printing for Medical Applications

On November 15th 2017, Cogeco TV visited Javelin Technologies' Oakville headquarters for a tour of the 3D Printing lab. Accompanied by Cogeco TV 's Kristin Demeny, John Brown of Javelin discussed the benefits of 3D printing and the major role it plays in Canada's health care industry. Watch the full interview below.

3D Printing in Health Care

3D printing is an additive manufacturing technology with a wide range of materials to create precision prototypes. Stratasys offers the world's most advanced 3D printing solutions, allowing medical manufacturers, doctors, and researchers to create parts for patient care and advanced experimental work. Stratasys FDM and PolyJet 3D Printers offer bio-compatible materials for rapid prototyping of medical and dental products including dental delivery devices, surgical orthopedic guides and hearing aids. These medical-grade materials offer excellent visualization and great dimensional stability.

Interested in 3D Printing?

Contact us to learn how a Stratasys 3D Printer can improve your business processes.

# data[].attributes.attachment_link.title
The Impact of 3D Printing on Canada's Health Care Industry [VIDEO]

# data[].attributes.attachment_link.description
On November 15th 2017, Cogeco TV visited Javelin Technologies' Oakville headquarters for a tour of the 3D Printing lab. Accompanied by Cogeco TV 's Kristin Demeny, John Brown of Javelin discussed the benefits of 3D printing and the major role it plays in Canada's health care industry. Watch the full interview below.

# data[].attributes.body
April 2019

# data[].attributes.attachment_link.readable_text
Background

In the 1980s, the first 3-D printing (3-DP) patent was filed by Charles Hull. ¹ Since then, substantial hype and growing demand has developed around a technology class that some anticipate will fundamentally change manufacturing across industries. ²⁻⁵ Promising medical solutions such as bionic limbs, replacement organs, and advanced pharmaceutical delivery systems have been conceived, yet technical, scientific, and regulatory challenges persist. While some medical applications of 3-DP are diffusing into practice, many remain in the exploratory research and development phase. ⁶ This bulletin provides an overview of clinical applications of 3-DP and bioprinting, including the current context in Canada and other countries, emerging technology developments, potential implementation issues, and challenges for the assessment and evaluation of 3-DP technologies.

What is 3-D Printing?

In health care, there is great interest in 3-DP as a tool that may help clinicians, health care administrators, and device manufacturers to: ¹²⁻¹⁶

visualize and plan complex interventions

create personalized or patient-specific devices

build devices of complex internal and external shape and structure from biocompatible materials

produce devices or supplies on-site, as needed

streamline supply chains

reduce inventory needs

reduce labour costs.

3-DP may also appeal to health care providers who regularly use small parts suitable for printing (e.g., dental crowns) ¹⁵ and promises to help move health care from its current one-size-fits-all approach to small-batch or even patient-specific medical devices. ¹⁶

What is Bioprinting?

Part of a complex process known as biofabrication, bioprinting is a 3-DP technique that combines living cells (e.g., stem cells) and supportive biomaterials (e.g., scaffolds on which cells can grow) into so-called bioinks. 13,20,21 These bioinks are printed into pre-specified computer-generated designs with the goal of eventually maturing into specific tissues. 13,20,21

Driven in part by a lack of donor tissues and organs, ²² advances in "bioprinting instrument capabilities; printing speed and precision; better preservation of living cells pre- and post-printing; printing multiple bioinks together; and innovations in bioink and support material formulations allowing printing of soft flexible tissue materials" ²³ are helping the progress of research and development in the field.

While in vivo work in regenerative medicine is still in the very early stages of research - with full organ transplant seen as the long-term goal ²³ - a number of companies around the world are actively working to improve bioprinting by expanding the types of materials and optimizing technological approaches. ²⁴

Scope

In 2016, CADTH produced a brief horizon scan on 3-DP applications in health care. ²⁵ This bulletin expands on this work, focusing primarily on the clinical applications of 3-D printing and bioprinting. Other health care applications of 3-D printing and bioprinting, including 3-DP of pharmaceuticals, are also discussed.

Methods

CADTH Horizon Scanning bulletins are not systematic reviews and do not involve critical appraisal or include a detailed summary of study findings. Rather, they present an overview of the technology and available evidence. They are not intended to provide recommendations for or against a particular technology.

Literature Search Strategy

A series of limited literature searches were conducted using the following bibliographic databases: MEDLINE, Embase, and the Cochrane Library. Grey literature was identified by searching relevant sections of the Grey Matters checklist ( https://www.cadth.ca/grey-matters). The searches were completed on October 2018 and limited to English-language documents published after January 1, 2008. Regular alerts updated the search until project completion. Conference abstracts were excluded from the search results.

Study Selection

One author screened the literature search results and reviewed the full text of all potentially relevant studies. Studies were considered for inclusion if the intervention was a clinical application of 3-D printing or bioprinting. The final selection focused primarily on existing evidence syntheses including systematic reviews and meta-analyses. Studies providing direct cost data, narrative reviews, and expert commentaries were also included. Grey literature was included when it provided additional information not available in the published studies selected.

Peer Review

A draft version of this bulletin was peer-reviewed by a clinical expert.

Stakeholder Review

A draft version of this bulletin was posted publicly for stakeholder review.

The Technology

3-DP objects and bioprinted objects can be created using a number of different production techniques that, in general, share the following common components: 7,14,26

data (e.g., images) for the design software to use

computer software for modelling, designing, and translating digital models into printer instructions

a computer-controlled printer

appropriate layering materials for producing the desired object.

Common production techniques for 3-DP and bioprinting used in clinical applications are described in Table 1.
Table 1: Description of Common Production Techniques for 3-D Printing and Bioprinting

3-DP Techniquesa

Description and Considerations7,21,26-31

Vat Photopolymerization

Powder-Bed Fusion

Material Extrusion

Fused filament fabrication (FFF) ²⁸ b

Forms an object using a computer-controlled extrusion nozzle to deposit layers of heat-softened polymer melted from a filament.

Material Jetting

Bioprinting Techniques

Description and Considerations7,21,26-31

2-D = two-dimensional; 3-D = three dimensional; 3-DP = 3-dimensional printing.
a This is not a comprehensive list of 3-D printing technologies; rather, some examples of approaches used in clinical applications.
b Also referred to as fused deposition modelling (FDM).

Regardless of the technique used for printing, the production of 3-DP objects (including medical devices) involves three general steps: pre-processing, printing, and post-processing. 7,26,33 Bioprinting follows a similar production path but with some notable differences throughout the process. 21,23 These production steps (with additional considerations for bioprinting) are described in more detail in Table 2.

Other factors that may also be taken into consideration when producing a 3-DP object include:

material selection, which depends on both the needs of the object being printed and the requirements of the printing process and equipment being used²⁶

design considerations beyond the object itself, such as the support structures and the thickness of layered materials.26,33

Table 2: A General Approach to the Production of 3-D Printed Objects and Considerations for Bioprinting

Production Step

3-D Printing

Bioprinting Considerations

Pre-processing

Acquire images (e.g., from MRI or CT).7,33

Convert images into files the printer can use (e.g., computer-aided design filesa or additive manufacturing files).26,33

Select design inputs (e.g., "surface characteristics, object rigidity...reaction to external forces applied during use").²⁶

May include:

collection of tissue samples (for a source of autologous cells)

work with stem cell lines

developing processes for biomimicry (to allow for cell growth)²¹

Printing

Select the layering material(s)7,26 (e.g., metal, plastic, ceramic, glass, liquid, and living cells [used for bioprinting]).

Select an approach to printing.7,26-28

Select the software to prepare design files for printing.²⁶

Printing materials are bioinks:21,23 a mixture of cells, growth matrix, and nutrients loaded into printing cartridges.²³

Certain methods can impede cellular growth and should be considered when selecting a bioprinting method.21,23

The speed of printing is also important because cells cannot survive outside an incubator for long.²³

Cell material needs to interact and printing at a high resolution can facilitate this.²¹

Post-processing

Remove any remaining support structures and residues.²⁶

Final quality assurance testing.²⁶

This is focused on continued growth and development of the cells.²¹

Structures must be loaded into an incubator and provided with appropriate biological conditions to grow into mature tissue.²³

CT = computed tomography; MRI = magnetic resonance imaging.
a Note: Design files can also be informed using lessons learned from previous product design. ¹⁶

While the aforementioned production steps describe a typical approach to building a 3-DP object itself, manufacturers can use 3-DP to build "negative" structures for use as casts or molds. ¹³

Emergence of 3-D Printing and Bioprinting in Canada

A 2017 report from Canada's Standing Senate Committee on Social Affairs, Science and Technology identified 3-DP as one of three areas anticipated to present challenges to the Canadian health care system. ³⁴ Presentations from Health Canada to the committee indicated that devices produced using 3-DP have already been approved for use in Canada. ³⁴

Our search of the grey literature identified many examples of research, development, and production in 3-DP for health in Canada. ³⁵⁻⁴⁵ Examples of Canadian activities include hospital scale printing, 40,46,47 academic initiatives and collaborations, 37-39,44,48 not-for-profit initiatives, 35,49 and for-profit start-ups and organizations. 36,41-43,45,50-52 A network of private, public, academic, and not-for-profit organizations, Canada Makes - "dedicated to promoting the adoption and development of advanced and additive manufacturing (AM) in Canada" - includes a section dedicated to 3-DP in medicine and dentistry on its website. ⁵³

Regulatory Considerations

As emerging and potentially disruptive health technologies, 3-DP and bioprinting present challenges to existing regulatory frameworks. Decisions around these frameworks could affect the adoption of 3-DP within the health system. ⁵⁴ This section discusses approaches to 3-DP and bioprinting in Canada and around the world.

Canada

In Canada, medical devices produced using 3-DP are subject to the Medical Devices Regulations. ⁵⁵ In August 2018, Health Canada announced it was beginning to develop guidance for manufacturers wishing to obtain licences for 3-DP medical devices. ⁵⁴ A draft guidance document was released for comment in October 2018 and final guidance is expected in the spring of 2019. ⁵⁵ Feedback on the guidance issued has been posted publicly by some stakeholder groups. ⁵⁶ The guidance is intended for manufacturers (including hospitals producing 3-DP devices for distribution outside their organizations) of 3-DP Class III and Class IV implantable medical devices and is supplementary to existing evidence requirements for all Class III and Class IV devices. ⁵⁵ It does "not provide guidance on third-party software, custom-made devices, patient-specific anatomical models, devices manufactured at point-of-care, and devices with biological components." ⁵⁵ The draft guidance is considered a first step for 3-DP policy in Canada and is intended to evolve, along with the technology. ⁵⁵

Health Canada's draft guidance notes that the production of 3-DP devices presents some unique considerations for manufacturers and that, in addition to the data required for the approval of all Class III and Class IV medical devices, additional information may be required for the approval of 3-DP medical devices. ⁵⁵ For example:

Manufacturers should specify the starting materials, any additives, and the 3-DP technique used for production.

Manufacturers should indicate if all or part of the device is 3-D printed.

Submissions should include a design philosophy explaining why 3-DP was the appropriate manufacturing approach.

Records of printer maintenance and cleaning, validation of consistent performance, the accuracy of reproduction of patient-specific images, and the validation of printer-material combinations should be retained.

The processes for removal and possible reuse or recycling of layering materials should be validated.

Verification and validation of the software for design and printing is required.

Biocompatibility testing should be conducted on finished devices.

Processes for the post-processing removal of residues, and excess layering material and sterilization of 3-DP devices, should demonstrate that the bioburden is minimized and consider how sterilization may affect the final product.

United States

In recognition of the wide range of 3-DP applications, the FDA regulates technologies as either medical devices, biologics, or drugs. ⁹ As of December 2017, more than one hundred 3-DP devices currently on the market had been reviewed by the FDA. ⁵⁷

Europe

Australia

In Australia, consultations are underway on proposed changes to the regulation of medical devices to better address the introduction of personalized medical devices, including 3-DP devices. ⁵⁹ The proposed changes include:

adopting international definitions (e.g., custom-made, patient-matched) developed by the International Medical Device Regulators Forum (IMDRF)⁶⁰

creating a framework to allow clinicians to produce low-risk devices without manufacturing certification

regulating anatomic models in a way similar to diagnostic images

regulating "medical devices with a human origin component" (e.g., bioprinted patient-specific implants) as medical devices and not as biologics.⁵⁹

Lack of Fit-for-Purpose Regulatory Frameworks for Bioprinting

Other Considerations

Our literature search identified a number of other possible questions and considerations for the regulation of 3-DP medical devices; for example:

What are the biocompatibility needs for materials used for 3-DP medical instruments (e.g., surgical guides)? If 3-DP medical instruments have less biocompatibility requirements than 3-DP implantable devices, does this open up the possibility of using different products and materials?¹³

A 2016 systematic review of surgical applications of 3-DP noted that, for hospitals wishing to produce their own devices and equipment, regulatory requirements are a concern and might prevent 3-DP from being adopted.⁶³

If there are requirements to label and be able to track medical devices, how does this work for custom 3-DP devices?¹⁴

Who Might Benefit?

It has been suggested that 3-DP will bring advantages to many aspects of health care such as diagnostics (using medical imaging to create models that aid in visualization), surgical planning, and personalized medicine. ⁷ Applications of bioprinting may disrupt existing models of organ and tissue donation, although these applications are likely further in the future than other 3-DP applications. ⁷ Many clinical areas are currently using, or investigating the use of, 3-DP. Because of this, 3-DP has the potential to affect Canadians living with many different health conditions.

Clinical Applications of 3-D Printing

Initially reserved for complex cases, 3-DP is becoming more common or routine in some clinical areas. ⁶⁴ A 2018 narrative review of registered clinical trials found orthopedics, dentistry, and maxillofacial surgery to be the most active areas of ongoing research. ⁶⁵

3-DP health care applications are generally categorized in the literature into the following applications: 8,13,14,26,28,66,67

anatomical models (e.g., for surgical preparation, planning, or to aid diagnosis)

surgical guides

tools and instruments

implants and therapeutic devices

prosthetics

tissues and organs

dental applications.

3-DP medical devices can be further classified into three types, based on their degree of customization: ¹⁴

custom-made medical devices (i.e., devices unique to an individual)

customizable medical devices (i.e., mass produced using a standard process and individualized to specific patients)

standard medical devices (i.e., mass produced using 3-DP because of device complexity or to lower costs).

Information on applications of 3-DP in dentistry; prosthetics, orthotics, and assistive devices; and surgery are summarized. Because of overlap between clinical specialties (e.g., oral surgery and dentistry), some applications are discussed in more than one section of this report.

Dentistry

Advances in dental imaging (such as cone beam computed tomography [CT]) have resulted in increased interest in 3-DP for dentistry. ⁶⁸ 3-DP applications in dentistry include :

orthodontics7,69 (for making and positioning brackets, as well as aligners)

dental crowns and partial dentures27,70

removable complete dentures70,71

oral surgery:⁶⁹

surgical guides placed over teeth to align drills27,68

access guides for root canals⁶⁸

replica teeth to prepare autotransplantation sites⁶⁸

dental implants.⁶⁹

Prosthetics, Orthotics, and Assistive Devices

The use of 3-DP in both prosthetics (devices that replace missing body parts) and orthotics (the design of external devices that modify the structure and function of the body) may be beneficial because of: 13,64,72

customization to offer a better fit and ability to adjust or increase device functionality

lighter weight

lower costs to make the devices available to a broader market.

These potential benefits are of particular interest for children who can quickly outgrow expensive devices. ⁶⁴

Other examples include using 3-DP to produce customized ear shells (devices that connect hearing instruments to a person's ear canal) for hearing aids; ¹⁵ and the printing of assistive devices, such as straw holders and key turners in occupational therapy. ⁷³

Surgery

In surgery, 3-DP may provide surgeons with a better understanding of complex anatomy when planning surgeries, allow for customized or patient-specific implants and surgical guides, and ultimately reduce operating room time. 63,74 Advantages may include shorter operative time and reduced costs, while disadvantages to 3-DP may include reactions to the material used and added planning time.

Surgical applications of 3-DP have been grouped into the following categories: ²⁸

anatomic models⁶⁷ (for preoperative planning)

surgical instruments

implants and prostheses, splints and external fixators.⁶⁷

Imaging in surgical applications of 3-DP is conducted using CT and magnetic resonance imaging (MRI). As well, "a number of other 3D imaging options have been used in 3D printing, such as: cone beam CT, CTA [CT angiography], MRA [magnetic resonance angiography], PET [positron emission tomography], MRCP [magnetic resonance cholangiopancreatography], 3D echocardiography, 3D laser scanning systems, and even images captured on an iPhone." ⁶⁷

Areas of research in surgical applications include surgical guides, models for surgical planning, or custom implants. ⁷⁴ Areas in development within surgical applications include orthopedics (particularly knee surgery), maxillofacial surgery (cranial and spinal surgery), dental surgery, cardiovascular surgery, cerebrovascular surgery, otolaryngology, and general surgery. ⁷⁴

Examples of surgical applications of 3-DP are discussed, by subspecialty, in the following sections.

Neurosurgery

The use of 3-DP in neurosurgery ⁷⁵ includes the development of patient-specific anatomical models, the design of devices to assess and treat neurosurgical conditions, and biological tissue-engineered implants. In addition, subspecialty 3-D printing applications in neurosurgery are listed in Table 3. 75,76

Table 3: Subspecialty Applications of 3-DP in Neurosurgery ⁷⁵

Cerebrovascular⁷⁵

Surgical planning and modelling

Cerebral aneurysm surgery

Neuro-oncology⁷⁵

Surgical planning and modelling

Visualization of the relationship between skull, tissue, and tumour for resection - including incorporating information from fMRI

Neurosurgical devices

Proton range compensator - creates a conformal dose distribution to protect tissues surrounding the tumour

Functional⁷⁵

Surgical planning and modelling

Placement of intracranial electrodes for treatment-resistant epilepsy

Neurosurgical devices

Patient-specific head casts to reduce movement when monitoring brain activity

Spinal75,76

Neurosurgical devices 75,76

Patient-specific screw guides for optimizing the trajectory of pedicle screws used for spinal fixation

Custom implants

Used in complex cases (e.g., for congenital malformations or the replacement of whole vertebrae), where an individualized approach is important for the prognosis

Orthopedics

3-DP has also been used in limb and pelvic injuries to help repair damage to many bones of both the upper and lower extremities, including those of the hands and feet. ⁶⁴

Vascular and Endovascular Surgery

In vascular and endovascular surgery, 3-DP applications focus on the visualization of anatomical structures.

3-DP models have been developed for infrarenal and juxtarenal arteries, abdominal aortic aneurysm, and thoracic aorta pathology and 3-DP of vessel pathologies have been used to better understand anatomy and post-surgical complications. ⁷⁸

Plastic and Reconstructive Surgery

3-DP is being studied and used in plastic and reconstructive surgery for procedural planning, the creation of surgical tools, and the customization of implants.

3-DP has been studied or used in maxillofacial surgery, dental implant surgery, mandibular reconstruction, orthognathic surgery, and midface reconstruction. ⁷⁹ Common applications include anatomic models, surgical guides (most common application), occlusal splints, patient-specific implants, and facial epithesis. 79,80

Hepatobiliary Surgery

Applications of 3-DP in hepatobiliary surgery include models for surgical planning for liver surgery, including as a supplement to medical imaging. The clinical value and application of 3-DP in liver surgery may be in printing models to plan for surgery. ⁸³ It has been reported that printing time varies from 11 hours to 100 hours, and that some models take weeks to be printed and delivered. ⁸³

The production of models can be used as an adjunct or alternative to imaging because of the complex, unique anatomy involved in procedures such as liver transplant or cancer resection. ⁸⁴

Urology and Renal Surgery

In urology and renal surgery, 3-DP models are used for visualization to assist diagnosis; and in structural visualization to plan for surgery, transplantation, and other procedures.

In renal surgery, 3-DP is used to visualize renal tumours for removal. ⁸⁵

In urology surgery, 3-DP applications include pre-surgical planning to remove renal masses, building molds to visualize the renal collection system for patients with kidney stones (to facilitate novel treatments), and producing models of a donor's kidney and pelvic cavity to plan a kidney transplant. ⁸⁶ For prostate conditions, 3-DP models have been used alongside MRI to diagnose prostate cancers, to help plan prostate surgery, and to plan complex urologic surgeries. ⁸⁶

In urologic cancer, 3-DP has been applied to generate anatomical models for planning and surgical simulation. ⁸⁷

Cardiac Surgery

Surgical planning is noted as a potential application of 3-DP in cardiac surgery. The use of 3-DP heart models for surgical planning for people with congenital heart defects has been reported. ⁸⁸

Anesthesiology

3-DP has been used to produce anatomical models to preoperatively size airway devices and plan for airway management. ⁸⁹ Bioabsorbable airway splints have also been produced using 3-DP. ⁸⁹

Clinical Applications of Bioprinting

The development in the field of bioprinting is being driven largely by "[the medical needs of] aging populations; increasing unmet demand for organ donors; trends towards non-animal testing on therapeutics using 3-D cell culture platforms; clinical needs in wound care; and joint repair and replacement surgeries." ²³

Bioprinting is being explored for the purposes of repair, replacement, or regeneration to develop an assortment of tissues including cartilage, bone, skin and periodontal tissues; other vascularized tissues; and cardiovascular tissues. 13,90,91 Bioprinted tissues are being investigated as analogues for toxicity testing, disease modelling, and for patient-specific drug screening, with the potential to eliminate testing on animals. ¹³

Bioprinting applications noted the following areas of inquiry in descending order of most to least developed and validated: ²³

tissue modelling (drug discovery and development)

toxicology testing (drug screening and cosmetics)

engineered tissues (regenerative medicine, prosthetics, and dental applications)

transplantation (full or partial organs as part of regenerative medicine).

3-D Printed Medications

The potential benefits of using 3-DP techniques for producing medications include the ability to personalize a medication dose, combine the delivery of medications, and avoid the use of bulking agents or fillers that a person may be intolerant to (such as lactose). ¹⁶

One example is levetiracetam (a treatment for epilepsy), approved by FDA in 2015. ⁷ This product is produced using a 3-DP technique called ZipDose that combines power and liquid printing to produce high-dose, quick-dissolving pills. ⁹²

A structured review of 3-DP of medications was published in 2013. ⁹³

Clinician Education and Training

Examples of using 3-DP models to educate and train clinicians are common in the literature. Clinical areas where 3-DP training and education models are in use include pathology, urology, neurosurgery, vascular and endovascular surgery, congenital heart disease, and anesthesia. 67,75,78,86-89,94

In vascular and endovascular surgery, the use of 3-D printing has been discussed regarding the potential of moving from a traditional learning model of "see-one, do-one, teach one" to an approach that includes simulation using 3-DP models. ⁷⁸

While experienced clinicians may be able to clearly visualize internal structures, it is possible they could benefit from training using 3-DP anatomical models when preparing for complex interventions. ¹³

Patient Education

Other Applications

3-DP is also used to produce phantoms - objects that are specially designed to be scanned or imaged - for testing imaging systems. ⁹⁵

Implementation Issues

The integration of 3-DP into routine clinical practice goes beyond the effectiveness and safety of individual technologies. There are several potential implementation considerations related to technical features, cost, legal and ethical issues, and patient-related factors.

Technical Considerations

There are a range of important considerations in the implementation of 3-DP related to factors such as the technological and manufacturing process, the materials used, and technical limitations of the technology.

Cost and Administration

3-D Printing

The literature search aimed to identify cost-related information about 3-DP in health care. Few studies were identified that directly evaluated costs; however, many studies and reports discuss them indirectly.

A number of articles identified reported direct cost information and considerations. These examples are summarized in Table 4.
Table 4: Examples of Reported Costs of 3-DP Clinical Applications

Clinical Specialty

Application

Reported Cost

Considerations

Spinal surgery ⁷⁶

Anatomic models

US$300 to more than US$1,000

Cost of printing models would be in addition to standard surgical planning

The authors also reported time costs associated with the two to five hours required for printing but noted that these up-front costs to 3-DP may be offset by time savings in actual procedures

Printers

US$2,210 to US$50,000

One high-end industrial printer had a reported cost of €230,000

3-DP = three dimensional printing; N/A = not applicable.

Moving away from costs, a 2017 systematic review of 3-DP in liver surgery noted that 3-D modelling use is not widespread because of a lack of technicians with specialist knowledge in interpreting medical imaging. ⁸⁴ Specialized knowledge needed by both radiologists and technicians includes: "anatomical structure segmentation (automatic, semiautomatic, or manual), virtual modeling, preparation for 3D printing, the printing process itself, and post-processing." ⁸⁴

Bioprinting

A 2018 review of the bioprinting process discusses affordability as a concern throughout production. The cost of bioinks depends on the materials used in their composition. ²¹ For example, as the concentration of cells increases, so does the overall cost of bioinks. ²¹ The high cost of current bioprinters may also be a barrier to the wider adoption of bioprinting in clinical use. ²¹ The processes required for successful bioprinting - for example, sterility - may also contribute to the expensive cost. ²¹ A 2018 review of bioprinting skin noted that costs included cells, scaffolds, and printers. ⁹¹ Other costs associated with bioprinting include post-processing (e.g., the need for bioreactors to grow the tissues). ²¹ Reported costs of bioprinters range from US$500 to US$200,000. ²¹

Legal Considerations

Data Ownership and Privacy

3-DP (particularly for custom or patient-specific devices) requires individual patient data. ¹⁴ The method of data collection and use must be taken into account when considering 3-DP as part of a patient's care plan. ¹⁴ The use of computer-aided design files may lead to intellectual property disputes and privacy concerns, ⁹⁸ and questions about a patient's right to access and own their own data. ¹⁴ It is not yet clear who will own the computer-aided designs, medical images, and final products, particularly when biological material is utilized. ⁹⁸ To ensure patient data are kept private, 3-DP systems must also have adequate cybersecurity protocols in place. ²⁶

Liability

3-DP deviates from standard chains of production, distribution, and use, making the question of who is the producer or manufacturer difficult to answer. ¹⁴ It is unclear whether responsibility for custom-designed implant failure could fall to, for example, the surgeon who designed the implant, the software engineer who built the design software, the printer manufacturer, the manufacturer of the materials used for the final product, or a combination of those involved in its creation. ¹⁴

Ethical Considerations

Bioprinting

Ethical considerations, specifically related to the introduction of bioprinting, have been summarized in a review by Gilbert et al. ²⁰ The authors raise questions on several key topics including: ²⁰

whether there should be restrictions on what (i.e., material and products) can be bioprinted

the risks and challenges associated with testing bioprinted technologies in humans

ethical questions about treatment irreversibility, loss of treatment opportunity, and treatment replicability

the lack of guidance frameworks for the testing and regulation of bioprinting in humans.

Additional relevant ethical issues in bioprinting have been reviewed by others. 101,102

Restrictions to Bioprinting Materials and Products

Bioprinting has generated interest for its potential role in reducing disease burden and health care costs, ¹⁰³ but there is also the potential for bioterrorism ¹⁰⁴ and unauthorized use by those with access to printing equipment. ²⁰ Gilbert et al. noted the conflicting desire to provide access to potentially lifesaving treatments while avoiding doing harm in the face of uncertainty. ²⁰ Further, the risks may differ depending on the product being printed and the bioink used for its creation. ²⁰ There may be ethical concerns with administering bioprinted treatments of animal or embryonic origin to those with religious or other ethical conflicts. ²⁰ The potential for donor coercion to supply biological materials was also noted. ²⁰ The authors also touched on the potential implications of the origin of the material and the possibility that certain materials may carry a higher risk of harm, such as disease transmission, than others. General ethical concerns with tissue engineering may also apply in the case of bioprinting. ²⁰

Risk of Testing Bioprinting in Humans

To help patients make informed decisions about 3-DP technologies, KCE Belgium recommended "giving the patient complete information on the existing alternatives and, as necessary, on the scientific uncertainty that the 3D-printed medical device concerned would be safer or more effective than the existing alternative." ¹⁴

Irreversibility, Loss of Opportunity for Future Treatment, and Limited Replicability of Treatment

Patients may not have the same opportunity to withdraw from a trial after the implantation of a bioprinted product. ²⁰ Procedures may have limited reversibility, particularly when cells are inserted into an existing biological structure. ²⁰ The inability to withdraw from a trial may limit the opportunity for access to future treatment, restricting patient autonomy. 20,106 Gilbert et al. (also citing others) raised the question of whether it is morally appropriate to implant bioprinted materials for safety testing given the uncertainty regarding the risk-benefit profile. 20,107-109 This is a concern given the current climate of extending experimental therapy opportunities in the regulatory context. ²⁰ Further, treatment effects may not be replicable from patient to patient, as the intervention will elicit a genetically, structurally, and phenotypically unique response. ²⁰

Considerations for Evaluation and Assessment of 3-D Printing and Bioprinting Technologies

Organizations conducting secondary research and evaluations of 3-DP technologies may encounter certain challenges and opportunities. Among these are the quality and maturity of the evidence, unique features of 3-DP that may warrant alternative study designs and data collection measures, challenges associated with the customized nature of the technology, and a lack of consensus on nomenclature.

Authors of literature reviewed for this bulletin often expressed concern with both the quality and quantity of available evidence (e.g., the lack of randomized controlled trials) for 3-DP in health, as well as a need for evaluation of relevant outcomes measures (e.g., the impact of 3-DP on surgical time and precision). 8,14,76,79,84,97,110,111

The current quantity and quality of evidence, and unique features of 3-DP, may present challenges in conducting comprehensive evaluations of the technology. Specific challenges may exist for conducting health technology assessments. In a project description and planning document for a health technology assessment on a 3-DP topic, EUnetHTA made note of several relevant considerations. These included but were not limited to inconsistency in regulatory and market access requirements, questions around the type of data collection needed to monitor long-term safety outcomes, challenges identifying specific manufacturers and low manufacturer engagement, lack of standardization of the device due to customization, and the need for a technical expertise (in addition to clinical expertise) on the project. ¹¹²

A 2017 review of taxonomy and terminology used in 3-DP research found that a wide range of terms are being used to describe these applications. ¹¹ The authors noted that a consistent, common set of language is necessary for collaborative research and eventually for reimbursement of 3-DP technologies, and proposed that "3D Printing" be adopted as the common term. ¹¹ The lack of consensus on terminology could present challenges when evaluating 3-DP technologies using epidemiological methods that rely on literature searching and review strategies, such as health technology assessments and systematic reviews.

Final Remarks

Research on clinical applications of 3-DP and bioprinting has progressed, in both volume and stage of inquiry, with some applications exiting the exploratory phase and undergoing concrete clinical evaluation. 8,65 In parallel, there has been growth in Canadian and international initiatives in 3-DP. ³⁵⁻⁴⁵

Concepts that could help foster research and development in bioprinting include open sourcing of hardware and software, open innovation (greater use of external ideas and technologies for internal business, and greater sharing of internal ideas with external businesses), ¹¹³ and developing a greater understanding of customer and market needs. ²³

Looking beyond the current state of 3-DP, 4-D printing - an approach that "adds a dimension of transformation over time, where printed products are sensitive to parameters like temperature, humidity, time etc." - may offer additional advantages in the medical field as smart implants, tools, and devices become more common. ¹¹⁴

References

1. Hull CW, Inventor; US Patent US4,575,330, assignee. Apparatus for production of three-dimensional objects by stereolithography. 1986 Mar 11.

2. Basiliere P, Shanler M. Hype cycle for 3D printing, 2018. Stamford (CT): Gartner; 2018: https://www.gartner.com/doc/3881825/hype-cycle-d-printing-. Accessed 2019 Jan 21.

3. d'Aveni R. The 3-D printing revolution. Harv Bus Rev. 2015;93(5):40-48.

4. Petrick IJ, Simpson TW. 3D printing disrupts manufacturing: how economies of one create new rules of competition. Res Technol Manag. 2013;56(6):12-16.

5. Jamroz W, Szafraniec J, Kurek M, Jachowicz R. 3D printing in pharmaceutical and medical applications - Recent achievements and challenges. Pharm Res. 2018;35(9):176.

6. Combellack E, Jessop ZM, Whitaker IS. The commercial 3D bioprinting industry. In: Thomas DJ, Jessop ZM, Whitaker IS, eds. 3D Bioprinting for Reconstructive Surgery. Cambridge (GB): Woodhead Publishing; 2018:413-421.

7. Jagadeesh V. Medical applications of 3D printing. Pharma Times. 2018;50(5):9-17.

8. Diment LE, Thompson MS, Bergmann JHM. Clinical efficacy and effectiveness of 3D printing: A systematic review. BMJ Open. 2017;7(12):e016891.

9. 3D printing of medical devices. Silver Spring (MD): U.S. Food & Drug Administration; 2018: https://www.fda.gov/MedicalDevices/ProductsandMedicalProcedures/3DPrintingofMedicalDevices/default.htm. Accessed 2018 Dec 21.

10. Technical considerations for additive manufactured medical devices: guidance for industry and Food and Drug Administration staff. Silver Spring (MD): U.S. Food & Drug Administration; 2017: https://www.fda.gov/downloads/MedicalDevices/DeviceRegulationandGuidance/GuidanceDocuments/UCM499809.pdf. Accessed 2019 Jan 04.

11. Chepelev L, Giannopoulos A, Tang A, Mitsouras D, Rybicki FJ. Medical 3D printing: methods to standardize terminology and report trends. 3D Print Med. 2017;3(1):4.

12. The 3Rs of 3D printing: FDA's role. Silver Spring (MD): U.S. Food & Drug Administration; 2016: https://www.fda.gov/ForConsumers/ConsumerUpdates/ucm533992.htm. Accessed 2019 Jan 04.

13. Zadpoor AA, Malda J. Additive manufacturing of biomaterials, tissues, and organs. Ann Biomed Eng. 2017;45(1):1-11.

14. Vinck I, Vijverman A, Vollebregt E, et al. Responsible use of high-risk medical devices: the example of 3D printed medical devices. Brussels: Belgian Health Care Knowledge Centre (KCE); 2018.

15. Snyder GH, Cotteleer M, Kotrek B. 3D opportunity in medical technology : additive manufacturing comes to life. San Francisco (CA): Deloitte Touche Tohmatsu Limited; 2014: https://www2.deloitte.com/insights/us/en/focus/3d-opportunity/additive-manufacturing-3d-opportunity-in-medtech.html. Accessed 2019 Mar 14.

16. Zema L, Melocchi A, Maroni A, Gazzaniga A. Three-dimensional printing of medicinal products and the challenge of personalized therapy. J Pharm Sci. 2017;106(7):1697-1705.

17. International clinical trials registry platform search portal. http://apps.who.int/trialsearch/: Accessed 2019 Feb 04.

18. Clinicaltrials.gov. https://clinicaltrials.gov/: Accessed 2019 Feb 04.

19. PROSPERO: International prospective register of systematic reciews. https://www.crd.york.ac.uk/prospero/: Accessed 2019 Feb 03.

20. Gilbert F, O'Connell CD, Mladenovska T, Dodds S. Print me an organ? Ethical and regulatory issues emerging from 3D bioprinting in medicine. Sci Eng Ethics. 2018;24(1):73-91.

21. Datta P, Barui A, Wu Y, Ozbolat V, Moncal KK, Ozbolat IT. Essential steps in bioprinting: from pre- to post-bioprinting. Biotechnol Adv. 2018;36(5):1481-1504.

22. Lieben L. Regenerative medicine: the future of 3D printing of human tissues is taking shape.[Erratum appears in Nat Rev Rheumatol. 2016 Apr;12(4):191]. Nat Rev Rheumatol. 2016;12(4):191.

23. Thakur PC, Cabrera DD, DeCarolis N, Boni AA. Innovation and commercialization strategies for three-dimensional-bioprinting technology: a lean business model perspective. J Commer Biotechnol. 2018;24(1):78-87.

24. Fraser A. 3D printing humans: a quick review of 3D bioprinters. 2018; http://bionics.ubc.ca/2018/08/03/3d-printing-humans-a-quick-review-of-3d-bioprinters/: Accessed 2019 Mar 13.

25. Mason J. Focus on: 3-D printing. Health Technol Update. 2016(17).

26. ECRI Institute. 3-D printing in medicine: an introduction. Health Devices. 2018.

27. Dawood A, Marti Marti B, Sauret-Jackson V, Darwood A. 3D printing in dentistry. Br Dent J. 2015;219(11):521-529.

28. Malik HH, Darwood AR, Shaunak S, et al. Three-dimensional printing in surgery: a review of current surgical applications. J Surg Res. 2015;199(2):512-522.

29. Gokuldoss PK, Kolla S, Eckert J. Additive manufacturing processes: selective laser melting, electron beam melting and binder jetting-selection guidelines. Materials (Basel). 2017;10(6):672.

30. Wong KV, Hernandez A. A review of additive manufacturing. ISRN Mechanical Eng. 2012.

31. Turksen K. Bioprinting in regenerative medicine. Switzerland: Springer; 2015.

32. Baumers M, Tuck C, Hague R. Selective heat sintering versus laser sintering: comparison of deposition rate, process energy consumption and cost performance. Paper presented at: Sold Freeform Fabrication Symposium, 2015; Austin (TX).

33. Ripley B, Levin D, Kelil T, et al. 3D printing from MRI Data: harnessing strengths and minimizing weaknesses. J Magn Reson Imaging. 2017;45(3):635-645.

34. Standing Senate Committee on Social Affairs, Science and Technology. Challenge ahead : integrating robotics, artificial intelligence and 3D printing technologies into Canada's healthcare systems. Ottawa (ON): Canada Senate; 2017: http://publications.gc.ca/site/eng/9.846477/publication.html. Accessed 2018 May 24.

35. The Victoria Hand Project. The Victoria hand project: prosthetics within reach. 2019; https://www.victoriahandproject.com/: Accessed 2019 Mar 13.

36. Precision ADM. Advanced digital manufacturing. 2019; https://www.precisionadm.com/: Accessed 2019 Mar 13.

37. Living Cell Imaging Resource Lab. Living cell imaging resource laboratory. 2019; https://snyder.ucalgary.ca/imaging/: Accessed 2019 Mar 13.

38. Kinsella Lab. Kinsella lab. 2018; http://kinsella.lab.mcgill.ca/: Accessed 2019 Mar 13.

39. Institute for Reconstructive Sciences in Medicine. Institute for Reconstructive Sciences in Medicine (iRSM). 2016; https://www.covenanthealth.ca/media/122141/research-excellence-irsm-2016jan07.pdf: Accessed 2019 Mar 13.

40. CBC News. Ottawa Hospital opens 1st medical 3D printing program of its kind in Canada. 2017; https://www.cbc.ca/news/canada/ottawa/ottawa-hospital-medical-3d-printing-1.3967350: Accessed 2019 Mar 13.

41. Aspect Biosystems Ltd. 3D bioprinting and tissue engineering: creating human tissues on demand. 2019; https://www.aspectbiosystems.com/: Accessed 2019 Mar 13.

42. Additive Design in Surgical Solutions Centre (ADEISS). Advanced medical and dental 3D metal printing solutions. 2019; http://adeiss.ca/: Accessed 2019 Mar 13.

43. Adaptiiv. Adaptiiv: the key to any fight is a strong ally. 2019; https://www.adaptiiv.com/: Accessed 2019 Mar 13.

44. Canada Makes. Quebec to open its frst medical 3D printing center. 2017; http://canadamakes.ca/quebec-open-first-medical-3d-printing-center/: Accessed 2019 Mar 13.

45. Javelin Technologies Inc. Welcome to Javelin, Canada's largest 3D solution provider. 2019; https://www.javelin-tech.com/3d/: Accessed 2019 Mar 13.

46. The Lynn and Arnold Irwin Advanced Perioperative Imaging Laboratory. The Lynn and Arnold Irwin advanced perioperative imaging laboratory. 2019; http://apil.ca/: Accessed 2019 Feb 22.

47. Hospital SMs. 3D Printing. 2019; http://stmichaelshospitalresearch.ca/staff-services/research-facilities/facilities/microfabrication/3d-printing/: Accessed 2019 Feb 22.

48. MED 3D Network. MED 3D network. 2019; https://www.munmed3dnetwork.ca/: Accessed 2019 Feb 22.

49. Nia Technologies Inc. Nia. 2018; https://niatech.org/: Accessed 2019 Feb 22.

50. 3D4MD Inc. Medical supplies made on-site: improving efficiency in healthcare. 2019; http://www.3d4md.com/: Accessed 2019 Feb 22.

51. Medical Makers. Medical Makers: make healthcare better. 2019; https://www.medicalmakers.org/: Accessed 2019 Feb 22.

52. TDL Systems Inc. O.L.T. footcare: 3D printed foot orthotics, AFO, orthotic sandals. 2019; https://www.oltfoot.com/: Accessed 2019 Feb 22.

53. Canada Makes. About Canada Makes. 2019; http://canadamakes.ca/about/: Accessed 2019 Mar 14.

54. Health Canada. Notice: upcoming guidance development on the licensing requirements for 3D-printed devices. 2018; https://www.canada.ca/en/health-canada/services/drugs-health-products/medical-devices/activities/announcements/3d-printing-notice.html: Accessed 2018 Aug 29.

55. Health Canada. Draft guidance document - licensing requirements for implantable medical devices manufactured by 3D printing. 2018; https://www.canada.ca/en/health-canada/services/drugs-health-products/medical-devices/activities/announcements/notice-licensing-requirements-implantable-3d-printing/draft-guidance-document.html: Accessed 2019 Mar 14.

56. Mulero A. AdvaMed calls for revisions to Health Canada guidance on 3D-printed implantable devices. Reg Focus. 2019;1.

57. U.S. Food and Drug Administration. Statement by FDA Commissioner Scott Gottlieb, M.D., on FDA ushering in new era of 3D printing of medical products; provides guidance to manufacturers of medical devices. 2017; https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm587547.htm: Accessed 2019 Mar 14.

58. U.S. Food and Drug Administration. About FDA: Emerging Technology Program. 2018; https://www.fda.gov/aboutfda/centersoffices/officeofmedicalproductsandtobacco/cder/ucm523228.htm: Accessed 2019 Jan 04.

59. Therapeutics Goods Administration. Consultation: proposed regulatory scheme for personalised medical devices, including 3D-printed devices. 2019; https://www.tga.gov.au/consultation/consultation-proposed-regulatory-scheme-personalised-medical-devices-including-3d-printed-devices: Accessed 2019 Feb 25.

60. IMDRF Personalized Medical Devices. Definitions for personalized medical devices. Canberra, Australia: Therapeutic Goods Administration; 2018: http://imdrf.org/docs/imdrf/final/technical/imdrf-tech-181018-pmd-definitions-n49.pdf. Accessed 2019 Mar 14.

61. Davies C, Baird L, Jacobson M, et al. 3D printing of medical devices: when a novel technology meets traditional legal principles. New York (NY): Reed Smith, LLP; 2015.

62. van Schothorst M, Weeda J, Schiffers K, et al. Study on the regulation of advanced therapies in selected jurisdictions. London, England: European Union; 2016: https://ec.europa.eu/health/sites/health/files/human-use/docs/20147306_rfs_chafea_2014_health_24_060516.pdf: Accessed 2019 Mar 14.

63. Martelli N, Serrano C, van den Brink H, et al. Advantages and disadvantages of 3-dimensional printing in surgery: a systematic review. Surgery. 2016;159(6):1485-1500.

64. Lal H, Patralekh MK. 3D printing and its applications in orthopaedic trauma: a technological marvel. J Clin Orthop Trauma. 2018;9(3):260-268.

65. Witowski J, Sitkowski M, Zuzak T, et al. From ideas to long-term studies: 3D printing clinical trials review. Int J Comput Assist Radiol Surg. 2018;13(9):1473-1478.

66. Trenfield SJ, Madla CM, Basit AW, Gaisford S. The shape of things to come: emerging applications of 3D printing in healthcare. In: Basit AW, Gaisford S, eds. 3D Printing of Pharmaceuticals. Switzerland: Springer; 2018:1-19.

67. Hoang D, Perrault D, Stevanovic M, Ghiassi A. Surgical applications of three-dimensional printing: a review of the current literature & how to get started. Ann Transl Med. 2016;4(23):456.

68. Anderson J, Wealleans J, Ray J. Endodontic applications of 3D printing. Int Endod J. 2018;51(9):1005-1018.

69. Nayar S, Bhuminathan S, Bhat WM. Rapid prototyping and stereolithography in dentistry. J Pharm Bioallied Sci. 2015;7(Suppl 1):S216-219.

70. Alharbi N, Wismeijer D, Osman RB. Additive manufacturing techniques in prosthodontics: where do we currently stand? A critical review. Int J Prosthodont,. 2017;30(5):474-484.

71. Bilgin MS, Baytaroglu EN, Erdem A, Dilber E. A review of computer-aided design/computer-aided manufacture techniques for removable denture fabrication. Eur J Dent. 2016;10(2):286-291.

72. Diment LE, Thompson MS, Bergmann JH. Three-dimensional printed upper-limb prostheses lack randomised controlled trials: a systematic review. Prosthet Orthot Int. 2018;42(1):7-13.

73. Wagner JB, Scheinfeld L, Leeman B, Pardini K, Saragossi J, Flood K. Three professions come together for an interdisciplinary approach to 3D printing: occupational therapy, biomedical engineering, and medical librarianship. J Med Libr Assoc. 2018;106(3):370-376.

74. Tack P, Victor J, Gemmel P, Annemans L. 3D-printing techniques in a medical setting: a systematic literature review. Biomed Eng Online. 2016;15(1).

75. Randazzo M, Pisapia JM, Singh N, Thawani JP. 3D printing in neurosurgery: a systematic review. Surg Neurol Int. 2016;7(Suppl 33):S801-S809.

76. Wilcox B, Mobbs RJ, Wu AM, Phan K. Systematic review of 3D printing in spinal surgery: the current state of play. J Spine Surg. 2017;3(3):433-443.

77. Xie L, Chen C, Zhang Y, Zheng W, Chen H, Cai L. Three-dimensional printing assisted ORIF versus conventional ORIF for tibial plateau fractures: a systematic review and meta-analysis. Int J Surg. 2018;57:35-44.

78. Tam CHA, Chan YC, Law Y, Cheng SWK. The Role of three-dimensional printing in contemporary vascular and endovascular surgery: a systematic review. Ann Vasc Surg. 2018;53:243-254.

79. Louvrier A, Marty P, Barrabe A, et al. How useful is 3D printing in maxillofacial surgery? J Stomatol Oral Maxillofac Surg. 2017;118(4):206-212.

80. Lin HH, Lonic D, Lo LJ. 3D printing in orthognathic surgery - a literature review. J Formos Med Assoc. 2018;02:02.

81. Bauermeister AJ, Zuriarrain A, Newman MI. Three-dimensional printing in plastic and reconstructive surgery: a systematic review. Ann Plast Surg. 2016;77(5):569-576.

82. Choi JW, Kim N. Clinical application of three-dimensional printing technology in craniofacial plastic surgery. Arch Plast Surg. 2015;42(3):267-277.

83. Perica ER, Sun Z. A systematic review of three-dimensional printing in liver disease. J Digit Imaging. 2018;31(5):692-701.

84. Witowski JS, Coles-Black J, Zuzak TZ, et al. 3D Printing in liver surgery: a systematic review. Telemed J E Health. 2017;23(12):943-947.

85. Sun Z, Liu D. A systematic review of clinical value of three-dimensional printing in renal disease. Quant Imaging Med Surg. 2018;8(3):311-325.

86. Parikh N, Sharma P. Three-dimensional printing in urology: history, current applications, and future directions. Urology. 2018;121:3-10.

87. Manning TG, O'Brien JS, Christidis D, et al. Three dimensional models in uro-oncology: a future built with additive fabrication. World J Urol. 2018;36(4):557-563.

88. Lau I, Sun Z. Three-dimensional printing in congenital heart disease: a systematic review. J Med Radiat Sci. 2018;65(3):226-236.

89. Chao I, Young J, Coles-Black J, Chuen J, Weinberg L, Rachbuch C. The application of three-dimensional printing technology in anaesthesia: a systematic review. Anaesthesia. 2017;72(5):641-650.

90. Trombetta R, Inzana JA, Schwarz EM, Kates SL, Awad HA. 3D printing of calcium phosphate ceramics for bone tissue engineering and drug delivery. Ann Biomed Eng. 2017;45(1):23-44.

91. Tarassoli SP, Jessop ZM, Al-Sabah A, et al. Skin tissue engineering using 3D bioprinting: an evolving research field. J Plast Reconstr Aesthet Surg. 2018;71(5):615-623.

92. Aprecia Pharmaceuticals LLC. Zipdose technology: the world's first 3DP dosage form. 2018; https://www.aprecia.com/technology/zipdose: Accessed 2019 Jan 08.

93. Ursan ID, Chiu L, Pierce A. Three-dimensional drug printing: a structured review. J Am Pharm Assoc. 2013;53(2):136-144.

94. Vakharia VN, Vakharia NN, Hill CS. Review of 3-dimensional printing on cranial neurosurgery simulation training. World Neurosurg. 2016;88:188-198.

95. Filippou V, Tsoumpas C. Recent advances on the development of phantoms using 3D printing for imaging with CT, MRI, PET, SPECT, and ultrasound. Med Phys. 2018;22.

96. Chen J, Gariel M. A roadmap from idea to implementation: 3D printing for pre-surgical application: operational management for 3D printing in surgery. 2016: https://www.sec.gov/Archives/edgar/data/1703997/000167025418000347/document_14.pdf: Accessed 2019 Mar 14.

97. Rogers-Vizena CR, Sporn SF, Daniels KM, Padwa BL, Weinstock P. Cost-benefit analysis of three-dimensional craniofacial models for midfacial distraction: a pilot study. Cleft Palate Craniofac J. 2017;54(5):612-617.

98. Mendis D, Lemley M, Rimmer M. The future of printcrime: intellectual property, innovation law, and 3D printing. 3D Printing and Beyond: The Intellectual Property and Legal Implications Surrounding 3D Printing and Emerging Technology. Cheltenham Glos (UK): Edward Elgar Publishing; 2019.

99. Haddow G, Vermeulen N. So, what is not to like about 3D bioprinting? Journal of Medical Ethics Blog 2017; https://blogs.bmj.com/medical-ethics/2017/03/21/so-what-is-not-to-like-about-3d-bioprinting/: Accessed 2019 Mar 14.

100. Gilbert F, Viana JNM, O'Connell CD, Dodds S. Enthusiastic portrayal of 3D bioprinting in the media: ethical side effects. Bioethics. 2018;32(2):94-102.

101. Neely EL. The risks of revolution: ethical dilemmas in 3D printing from a US perspective. Sci Eng Ethics. 2016;22(5):1285-1297.

102. Vermeulen N, Haddow G, Seymour T, Faulkner-Jones A, Shu W. 3D bioprint me: a socioethical view of bioprinting human organs and tissues. J Med Ethics. 2017;43(9):618-624.

103. Marchioli G, van Gurp L, Van Krieken P, et al. Fabrication of three-dimensional bioplotted hydrogel scaffolds for islets of Langerhans transplantation. Biofabrication. 2015;7(2):025009.

104. Wolinsky H. Printing organs cell‐by‐cell: 3‐D printing is growing in popularity, but how should we regulate the application of this new technology to health care? EMBO Rep. 2014;15(8):836-838.

105. Munsie M, Hyun I. A question of ethics: selling autologous stem cell therapies flaunts professional standards. Stem Cell Res. 2014;13(3 Pt B):647-653.

106. Gilbert F. A threat to autonomy? The intrusion of predictive brain implants. AJOB Neurosci. 2015;6(4):4-11.

107. Gilbert F. The burden of normality: from 'chronically ill'to 'symptom free'. New ethical challenges for deep brain stimulation postoperative treatment. J Med Ethics. 2012;38(7):408-412.

108. Bretzner F, Gilbert F, Baylis F, Brownstone RM. Target populations for first-in-human embryonic stem cell research in spinal cord injury. Cell Stem Cell. 2011;8(5):468-475.

109. Hess P. Intracranial stem cell-based transplantation: reconsidering the ethics of phase 1 clinical trials in light of irreversible interventions in the brain. AJOB Neurosci. 2012;3(2):3-13.

110. ECRI Institute. Use of three-dimensional printed anatomic models for cardiovascular and neurologic surgical planning. Plymouth Meeting (PA): ECRI Institute; 2018.

111. AETNA. Stereolithography 2017; http://www.aetna.com/cpb/medical/data/600_699/0613.html: Acccessed 2019 Mar 14.

112. EUnetHTA. Custom-made or customisable 3D printed implants and cutting guides versus non-3D printed standard implants and cutting guides for improving outcome in patients undergoing knee, maxillofacial, or cranial surgery. Netherlands: EUnetHTA; 2018: https://www.eunethta.eu/wp-content/uploads/2018/11/OTCA11_Final-Project-Plan_3D_printing.pdf: Accessed 2019 Mar 14.

113. Chesbrough HW. Bringing open innovation to services. MIT Sloan Manag Rev 2011; https://sloanreview.mit.edu/article/bringing-open-innovation-to-services/: Accessed 2019 Mar 14.

114. Javaid M, Haleem A. 4D printing applications in medical field: a brief review. Clin Epidemiol Global Health. 2018.

About this Document

Authors: Jeff Mason, Sarah Visintini, Teo Quay

Acknowledgments: Caitlyn Ford, Lesley Dunfield, Iryna Magega, Kinneret Globerman, Taralyn Carver, Glenda Proctor, and Charlene Argaez. CADTH thanks the external reviewers who kindly provided comments on an earlier draft of this bulletin.

Cite as: An Overview of Clinical Applications of 3-D Printing and Bioprinting. Ottawa: CADTH; 2019 Apr. (CADTH Issues in Emerging Health Technologies; Issue 175).

ISSN: 1488-6324

Disclaimer: The information in this document is intended to help Canadian health care decision-makers, health care professionals, health systems leaders, and policymakers make well-informed decisions and thereby improve the quality of health care services. While patients and others may access this document, the document is made available for informational purposes only and no representations or warranties are made with respect to its fitness for any particular purpose. The information in this document should not be used as a substitute for professional medical advice or as a substitute for the application of clinical judgment in respect of the care of a particular patient or other professional judgment in any decision-making process. The Canadian Agency for Drugs and Technologies in Health (CADTH) does not endorse any information, drugs, therapies, treatments, products, processes, or services.

While care has been taken to ensure that the information prepared by CADTH in this document is accurate, complete, and up-to-date as at the applicable date the material was first published by CADTH, CADTH does not make any guarantees to that effect. CADTH does not guarantee and is not responsible for the quality, currency, propriety, accuracy, or reasonableness of any statements, information, or conclusions contained in any third-party materials used in preparing this document. The views and opinions of third parties published in this document do not necessarily state or reflect those of CADTH.

CADTH is not responsible for any errors, omissions, injury, loss, or damage arising from or relating to the use (or misuse) of any information, statements, or conclusions contained in or implied by the contents of this document or any of the source materials.

This document may contain links to third-party websites. CADTH does not have control over the content of such sites. Use of third-party sites is governed by the third-party website owners' own terms and conditions set out for such sites. CADTH does not make any guarantee with respect to any information contained on such third-party sites and CADTH is not responsible for any injury, loss, or damage suffered as a result of using such third-party sites. CADTH has no responsibility for the collection, use, and disclosure of personal information by third-party sites.

Subject to the aforementioned limitations, the views expressed herein do not necessarily reflect the views of Health Canada, Canada's provincial or territorial governments, other CADTH funders, or any third-party supplier of information.

This document is prepared and intended for use in the context of the Canadian health care system. The use of this document outside of Canada is done so at the user's own risk.

This disclaimer and any questions or matters of any nature arising from or relating to the content or use (or misuse) of this document will be governed by and interpreted in accordance with the laws of the Province of Ontario and the laws of Canada applicable therein, and all proceedings shall be subject to the exclusive jurisdiction of the courts of the Province of Ontario, Canada.

The copyright and other intellectual property rights in this document are owned by CADTH and its licensors. These rights are protected by the Canadian Copyright Act and other national and international laws and agreements. Users are permitted to make copies of this document for non-commercial purposes only, provided it is not modified when reproduced and appropriate credit is given to CADTH and its licensors.

About CADTH: CADTH is an independent, not-for-profit organization responsible for providing Canada's health care decision-makers with objective evidence to help make informed decisions about the optimal use of drugs, medical devices, diagnostics, and procedures in our health care system.

Funding: CADTH receives funding from Canada's federal, provincial, and territorial governments, with the exception of Quebec.

Contact requests@cadth.ca with inquiries about this notice or legal matters relating to CADTH services.

# data[].attributes.attachment_link.title
An Overview of Clinical Applications of 3-D Printing and Bioprinting

# data[].attributes.attachment_link.description
In the 1980s, the first 3-D printing (3-DP) patent was filed by Charles Hull. 1 Since then, substantial hype and growing demand has developed around a technology class that some anticipate will fundamentally change manufacturing across industries. 2-5 Promising medical solutions such as bionic limbs, replacement organs, and advanced pharmaceutical delivery systems have been conceived, yet technical, scientific, and regulatory challenges persist.

# data[].attributes.attachment_link.readable_text
3D printed anatomical models from patient scan data are becoming increasingly useful tools in today's practice of personalized, precision medicine. As cases become more complex and operating room efficiency becomes more important for routine cases, visual and tactile reference models can enhance understanding and communication within OR teams and with patients.

Healthcare professionals, hospitals, and research organizations across the globe are using 3D printed anatomical models as reference tools for preoperative planning, intraoperative visualization, and sizing or pre-fitting medical equipment for both routine and highly complex procedures that have been documented in hundreds of publications.

Producing patient-specific, tactile reference models from CT and MRI scans is affordable and straightforward with 3D printing. Peer-reviewed literature shows that they provide an additional view that helps physicians prepare better for surgeries, leading to drastically reduced time and cost in the operating room while improving patient satisfaction, lowering anxiety, and reducing recovery time.

Physicians can use patient-specific surgical models to explain the procedure beforehand, improving patient consent and lowering anxiety.

Learning from preoperative models can influence the course of treatment as well. This was true of the experience of Dr. Michael Eames. After replicating a young patient's forearm bones, Dr. Eames realized the injury differed from what he'd previously thought.

Dr. Eames settled on a new, soft-tissue procedure-one that was much less invasive, decreased rehabilitation time, and produced far less scarring. Using the printed bone replica, Dr. Eames walked the young patient and his parents through the procedure and obtained their consent.

The result? A surgery time of less than 30 minutes, instead of the initially planned surgery of three hours. This difference in surgery time led to an estimated $5,500 in cost avoidance for the hospital and meant the patient would need to spend less recovery time in postoperative care.

In the words of Dr. Alexis Dang, an orthopedic surgeon at the University of California San Francisco (UCSF) and the San Francisco Veteran's Affairs Medical Center: "Every one of our full-time orthopedic surgeons and nearly all of our part-time surgeons have utilized 3D printed models for care of patients at the San Francisco VA. We've all seen that 3D printing improves performance on game day."

New biocompatible medical 3D printing materials have also enabled new surgical tools and techniques to be developed for the express purpose of further improving clinical experience during surgery. These include sterilizable fixation trays, contouring templates, and implant sizing models that can be used to size implants in the OR before the first cut, helping surgeons reduce time and increase accuracy of complex procedures.

Anatomical model of a hand, including the 'skin' made out of an elastic 3D printing material.

Todd Goldstein, PhD, Instructor at the Feinstein Institute for Medical Research, is unequivocal in his estimation of how central 3D printing technology has become to his department. He estimates that if Northwell uses 3D printed models in 10-15% of its cases, it could save $1,750,000 a year.

"From medical device prototypes, complicated anatomical models for our children's hospital, to creating training systems, and finally entering the dental clinic with implant surgical guides, [3D printing technology] has increased our capabilities and decreased our costs, all while allowing us to provide tools to treat patients that would be next to impossible to replicate without our go-to SLA 3D printer," said Goldstein.

3D printing has virtually become a synonym for rapid prototyping. The ease of use and low cost of in-house 3D printing has also revolutionized product development and many manufacturers of medical tools have adopted the technology to produce brand new medical devices and surgical instruments.

Over 90 percent of the top 50 medical device companies use 3D printing to create accurate prototypes of medical devices, as well as jigs and fixtures to simplify testing.

In the words of Alex Drew, a mechanical project engineer at DJO Surgical, a global provider of medical devices. "Before DJO Surgical brought the [Formlabs 3D printer] on board, we relied almost exclusively on outside print vendors for prototypes. Today, we are running four Formlabs machines, and the impact has been profound. Our rate of 3D printing has doubled, cost has been reduced by 70 percent, and the level of print detail allows for clear communication of designs with orthopedic surgeons."

Medical device companies like Coalesce use 3D printing to create accurate prototypes of medical devices.

3D printing can accelerate the design process by iterating complex designs in days instead of weeks. When Coalesce was tasked to create an inhaler device that can digitally assess an asthma patient's inspiratory flow profile outsourcing to service providers would have resulted in lengthy lead times for each prototype. Design files would have had to be painstakingly refined through various iterations before being sent off-site to be built.

Instead, desktop SLA 3D printing allowed Coalesce to keep the entire prototyping process in-house. The prototypes were fit for use in clinical studies and looked just like a finished product. In fact, when they showcased the device, their clients mistook the prototype for the final product.

Overall, in-house represented an enormous 80-90% reduction in lead time for prototypes. What's more, the parts took only eight hours to print and could be finished and painted within a few days, while the same process would have taken a week or two through an external contractor.

Each year hundreds of thousands of people lose a limb, but only a subset of them get access to a prosthesis to recover its function.

Simple prostheses are only available in a few sizes, so patients must make do with what fits best, while custom-fit bionic devices designed to mimic the motions and grips of real limbs that rely on muscles in a person's residual limb to control their functions are so expensive that they're only accessible to patients with the best health insurance in developed countries. This particularly affects prostheses for children. As children grow and get into adventures, they inevitably outgrow their prostheses and require expensive repairs.

The difficulty is the lack of manufacturing processes that can produce custom parts affordably. But increasingly, prosthetists can take advantage of 3D printing's much-noted design freedom to mitigate these high financial barriers to treatment.

Initiatives such as e-NABLE allow entire communities around the world to form around 3D printed prostheses. They're driving an independent movement in prosthetic production by sharing information and open-source designs freely online, so patients can get a custom-designed prosthesis that is well-adapted for them for as little as $50.

Other inventors likeLyman Connor, take this one step further. With only a small facility of four desktop 3D printers, Lyman was able to complete and fit his first production prostheses. His ultimate objective? To create a customizable, fully bionic hand to be sold at a fraction of the current tens of thousands of dollars retail price tag for such advanced prostheses.

Elsewhere, researchers at MIT have also identified 3D printing as an optimal means of producing more comfortable prosthesis sockets.

Needless to say, the low cost of producing these prostheses, along with the freedom that comes with custom designs, has proved revelatory. Prostheses made with 3D printing can be turned around in as little as two weeks and then can be trialed and maintained at a much lower cost than their traditional counterparts.

As the costs continue to decrease and material properties improve, 3D printing will undoubtedly play an increasing role in this department of healthcare.

Many of the same high financial barriers to treatment seen in prosthetics are also native to fields such as orthoses and insoles. Like many other patient-specific medical devices, custom orthoses are often inaccessible due to their high cost and take weeks or months to get manufactured. With 3D printing, that no longer needs to be the case.

The example of Matej and his son Nik springs to our mind. Born prematurely in 2011, difficulties during childbirth caused Nik to have cerebral palsy, a condition that affects almost twenty million people worldwide. Matej was inspired by his son's unwavering will to transcend the limitations of his condition, but he was faced with a choice between a standard, pre-made orthosis that would have been inadequate and uncomfortable for his son, or an expensive custom solution that would take weeks or months to be delivered, only to be made quickly obsolete by a growing child.

He decided to take matters into his own hands and sought out new solutions to achieve this goal. With the freedom offered by digital technologies including 3D scanning and 3D printing, Matej and Nik's physical therapists were able to experiment liberally and develop an entirely new innovative workflow for ankle foot orthoses (AFOs).

The resulting custom-made, 3D printed orthosis provided Nik with support, comfort, and correction precisely where it was needed, helping Nik to at last take his first independent steps. This custom orthotic device reprised the highly-adjusted finish of high-end orthotics, at a fraction of the price, and with no further adjustments required.

Professionals around the world are using 3D printing to reinvent patient- and customer-specific insoles and orthoses, as well as a range of other tools for improving physical therapy. In the past, the course of physical therapy using customized tools had proved difficult. Patients often faced long wait times and finished pieces that led to discomfort. 3D printing is on the path to change this status quo. 3D printed insoles and orthoses have proved to be a better fit, led to better therapeutic outcomes, and provided a greater degree of comfort and use for patients.

The conventional means of treating patients with grave organ failures currently involve using autografts, a graft of tissue from one point to another of the same individual's body, or organ transplants from a donor. Researchers in the fields of bioprinting and tissue engineering are hoping to soon change that and be able to create tissues, blood vessels, and organs on demand.

3D bioprinting refers to the use of additive manufacturing processes to deposit materials known as bioinks to create tissue-like structures that can be used in medical fields. Tissue engineering refers to the various evolving technologies, including bioprinting, to grow replacement tissues and organs in the laboratory for use in treating injury and disease.

With the help of high-precision 3D printing, researchers like Dr. Sam Pashneh-Tala from the University of Sheffield have brought new possibilities to tissue engineering.

To direct cellular growth so that the required tissue is formed, Dr. Pashneh-Tala grows living cells on a scaffold in the lab, that provides a template of the required shape, size, and geometry. For example, a tubular structure is needed to create a blood vessel for a cardiovascular patient. The cells will multiply and cover the scaffold, taking on its shape. The scaffold then gradually breaks down, leaving the living cells arranged into the shape of the target tissue, that is cultured in a bioreactor, a chamber that contains the developing tissue and can reproduce the internal environment of the body, to acquire mechanical and biological performance of organic tissue.

A 3D printed bioreactor chamber with a tissue-engineered miniature aorta growing inside. The tissue is cultured in the bioreactor to acquire the mechanical and biological performance of organic tissue.

This will empower scientists to create patient-specific vascular graft designs, improved surgical options and provides a unique testing platform for new vascular medical devices for those suffering from cardiovascular disease, that is currently the number one cause of death worldwide. Following that, the ultimate goal is to create blood vessels that are ready to be implanted into the patients. As tissue engineering uses cells that are taken from the patient requiring the treatment, it eliminates the possibility of rejection by the immune system-a major issue in conventional organ transplant procedures today.

3D printing has proven capable of responding to the challenges of producing synthetic blood vessels by solving the difficulties of recreating the precise shapes, sizes and geometries of the vessel required. Being able to closely match printed solutions to the specific needs of patients has proved revelatory.

In Dr. Pashneh-Tala's words: "[Creating blood vessels through 3D printing] offers the potential for improved surgical options and even patient-matched blood vessel designs. Without access to high-precision, affordable 3D printing, creating these shapes would not be possible."

We have seen exciting breakthroughs in biological materials suitable for use in 3D printers. Scientists are developing new hydrogel materials that have the same consistency as organ tissue that can be found in the human brain and lungs and can be compatible with various 3D printing processes. Scientists are hoping to be able to implant them onto an organ, to act as 'scaffold' onto which cells would be encouraged to grow.

While bioprinting fully functional internal organs such as hearts, kidneys, and livers still sounds futuristic, advancements with hybrid 3D printing techniques are happening at a very rapid rate.

Sooner or later, building biological matter in laboratory printers is expected to lead to the ability to generate new, fully functional 3D printed organs. In April 2019, scientists created the first 3D heart using a patient's biological materials at Tel Aviv University. The tiny replica was created using the patient's own biological materials, engendering a complete match of the patient's immunological, cellular, biochemical, and anatomical profile.

"At this stage, our 3D heart is small, the size of a rabbit's heart, but larger human hearts require the same technology," said Professor Tal Dvir.

The first 3D bioprinted heart, created at the University of Tel Aviv.

Precise and affordable 3D printing processes like desktop stereolithography are democratizing access to the technology, empowering healthcare professionals to develop new clinical solutions and quickly manufacture custom devices, and allowing physicians to deliver new treatments across the globe.

As 3D printing technologies and materials continue to improve, they will pave the path for personalized care and high-impact medical applications.
Learn More About 3D Printing in Healthcare

# data[].attributes.attachment_link.title
5 Innovative Use Cases for 3D Printing in Medicine

# data[].attributes.attachment_link.description
3D printed anatomical models from patient scan data are becoming increasingly useful tools in today's practice of personalized, precision medicine. As cases become more complex and operating room efficiency becomes more important for routine cases, visual and tactile reference models can enhance understanding and communication within OR teams and with patients.

# data[].attributes.attachment_link.readable_text
Highlights

*

The contributions of Three-dimensional Printing in Healthcare and Medicine.

*

A comprehensive review of technologies types used in 3D printing.

*

Discussing the foremost applications and approaches to Bio-materials-based Additive Manufacturing technology.

*

Addressing the advantages of three-dimensional printing in relation to medical implants.

Abstract

Different three-dimensional (3D) printing techniques are being increasingly used to produce medical apparatus due to their ability to print intended designs with high dimensional accuracy. Indeed, the major credit for the broad use of 3D printing techniques in medical fields stems from the ability of this method to prepare patient-matched devices due to the conventional manufacturing methods limitations such as economically inefficiency and multiple steps processing for complex geometries. This review manuscript aims to present brief insights of various 3D printing concepts and technologies used in the medical field. Biomaterials and bioprinting are pinpointed. Finally, the pharmaceutical potentials of 3D printing are discussed.

View Abstract

# data[].attributes.attachment_link.title
The role of three-dimensional printing in healthcare and medicine

# data[].attributes.attachment_link.description
The contributions of Three-dimensional Printing in Healthcare and Medicine. * A comprehensive review of technologies types used in 3D printing. * Discussing the foremost applications and approaches to Bio-materials-based Additive Manufacturing technology. * Addressing the advantages of three-dimensional printing in relation to medical implants.

# data[].attributes.attachment_link.readable_text
Background: Three-dimensional (3D) printing is becoming increasingly important in medicine and especially in surgery. The aim of the present work was to identify the advantages and disadvantages of 3D printing applied in surgery. Methods: We conducted a systematic review of articles on 3D printing applications in surgery published between 2005 and 2015 and identified using a PubMed and EMBASE search. Studies dealing with bioprinting, dentistry, and limb prosthesis or those not conducted in a hospital setting were excluded. Results: A total of 158 studies met the inclusion criteria. Three-dimensional printing was used to produce anatomic models (n = 113, 71.5%), surgical guides and templates (n = 40, 25.3%), implants (n = 15, 9.5%) and molds (n = 10, 6.3%), and primarily in maxillofacial (n = 79, 50.0%) and orthopedic (n = 39, 24.7%) operations. The main advantages reported were the possibilities for preoperative planning (n = 77, 48.7%), the accuracy of the process used (n = 53, 33.5%), and the time saved in the operating room (n = 52, 32.9%); 34 studies (21.5%) stressed that the accuracy was not satisfactory. The time needed to prepare the object (n = 31, 19.6%) and the additional costs (n = 30, 19.0%) were also seen as important limitations for routine use of 3D printing. Conclusion: The additional cost and the time needed to produce devices by current 3D technology still its widespread use in hospitals. The development of guidelines to improve the reporting of experience with 3D printing in surgery is highly desirable.

Figures - uploaded by Isabelle Borget

Author content

All figure content in this area was uploaded by Isabelle Borget

Content may be subject to copyright.

# data[].attributes.attachment_link.title
(PDF) Advantages and disadvantages of 3-dimensional printing in surgery: A systematic review

# data[].attributes.attachment_link.description
Background: Three-dimensional (3D) printing is becoming increasingly important in medicine and especially in surgery. The aim of the present work was to identify the advantages and disadvantages of 3D printing applied in surgery. Methods: We conducted a systematic review of articles on 3D printing applications in surgery published between 2005 and 2015 and identified using a PubMed and EMBASE search.

# data[].attributes.attachment_link.readable_text
Abstract

Donor shortages for organ transplantations are a major clinical challenge worldwide. Potential risks that are inevitably encountered with traditional methods include complications, secondary injuries, and limited source donors. Three-dimensional (3D) printing technology holds the potential to solve these limitations; it can be used to rapidly manufacture personalized tissue engineering scaffolds, repair tissue defects in situ with cells, and even directly print tissue and organs. Such printed implants and organs not only perfectly match the patient's damaged tissue, but can also have engineered material microstructures and cell arrangements to promote cell growth and differentiation. Thus, such implants allow the desired tissue repair to be achieved, and could eventually solve the donor-shortage problem. This review summarizes relevant studies and recent progress on four levels, introduces different types of biomedical materials, and discusses existing problems and development issues with 3D printing that are related to materials and to the construction of extracellular matrix in vitro for medical applications.

# data[].attributes.attachment_link.title
A Review of 3D Printing Technology for Medical Applications

# data[].attributes.attachment_link.description
Donor shortages for organ transplantations are a major clinical challenge worldwide. Potential risks that are inevitably encountered with traditional methods include complications, secondary injuries, and limited source donors. Three-dimensional (3D) printing technology holds the potential to solve these limitations; it can be used to rapidly manufacture personalized tissue engineering scaffolds, repair tissue defects in situ with cells, and even directly print tissue and organs.

# data[].attributes.attachment_link.readable_text
Since the invention of 3D printing way back in the early 1980s, this technology has been utilised to create almost everything including construction materials, automobile parts and even food and snacks.

One notable application of the 3d printing technology is in the field of pharmaceuticals. The technology also has benefits for pharmacists and medical practitioners. As of today, 3D printing has been a growing demand in the pharmaceutical industry.

However, the used and abused of 3D printed medicines has also been the subject of discussion nowadays. This is because it can also have some downsides. This blog post will discuss the benefits and drawbacks of 3D printing in the pharmaceutical industry. Read on below.

Benefits of 3D printing in the pharmaceutical field

3D printing has brought innovations in the pharmaceutical field. Here is a list of the few benefits offered by 3D printing.

Quicker pre-medical assessment of new drugs

3D printing has given pharmacists and medical engineers the ability to customised drugs by modifying the design straight to its CAD file. In this way, iterations can be made more quickly. These iterations are also a lot cheaper than the traditional way of manufacturing medicines.

For instance, tweaks or adjustments in the excipients, salt forms and dosages of the medicines can be made easily.

Chance for personalised medication

For patients with multiple diseases, a 3D printed pill such as a "polypill" can be used. Polypill contains multiple active ingredients that are combined into a single pill. This is used to treat different diseases.

Some pills are also designed to treat the disease of some particular patient. However, the patient's age, weight or organ function must also be considered.

New formulations for improved drug

With the conventional method of producing medicines, some pills are difficult to swallow. But with 3D printing, pills can be designed according to a patient's preferences.

For example, medical engineers can create a pill that can disintegrate rapidly in a patient's mouth, thus, making it easier to take.
Spritam: First 3D printed drug
In 2015, Aprecia was the first pharmaceutical brand to use 3D printing technology to produce a drug called Spritam. This drug is meant to treat symptoms of epilepsy such as onset seizures and myoclonic seizures.

When it was released, Spritam also received the necessary US FDA approval. The drug has a unique structure that dissolves significantly faster than the average pill.

On-demand pharmaceutical manufacturing

3D printing allows pharmacies and healthcare providers to print medicines on-demand instead of mass producing them. In this way, the pharmaceutical industries can revolutionise the supply chain. Therefore, lowering distribution costs.

Drawbacks of 3D printing in the pharmaceutical field

Though 3D printing technology has some benefits in the field of medicine, it also brings with it a few disadvantages. There are still many downsides that are not on this list. Nevertheless, here are some major drawbacks that pharmacies and medical practitioners should know about 3D printing.

Product liability risk

With 3D printing, pharmaceutical companies can authorise their blueprints to pharmacies and healthcare providers. Thus, they can now easily print drugs locally.

However, pharmaceutical companies cannot possibly oversee the efficiency of every 3D printing operation. Moreover, they need to consider the potential product liability implications.

According to the pharmaceutical companies' role in providing their product blueprint, they may be partially responsible for any undesirable incidents or product defect claims.

Other parties involved such as the printer manufacturer, material supplier, software designer, and product manufacturer may also be liable for this fallout.

For pharmaceutical companies who are planning to venture into 3D printing, they should develop a policy for certifying their blueprints. In this way, they will ensure that they are financially and legally protected.

Cyber risk

The rapid increase in reproducing fake pills is one of the greatest concerns with 3D printing. Furthermore, 3D printers are now being used by hackers to produce counterfeit medicines faster than the traditional manufacturing method.

As an illustration, hackers who gain access to a medicine's blueprint can mass-produce the drug overseas. This can exploit the intellectual property of the pharmaceutical company. Moreover, if the drug is improperly produced, it can cause harm to the patients. Thus, hitting the pharmaceutical company's reputation and financial status.

Apart from that, hackers can also make modifications to the medicine's ingredients or doses. This may lead to severe health consequences for the patients.

Safety and efficiency of 3D printers

The traditional way of mass-producing medicines is subject to intense supervision from authorised agencies such as FDA. This guarantees the company and the consumers that the products are manufactured carefully.

However, with 3D printing, the FDA cannot regulate every printing operation. Thus, determining how the product is developed may be questioned. Furthermore, with 3D printing, there is still a possibility of defective 3D printer and unnecessary printing failures.

Conclusion

3D printing has been an advanced technology in the field of medicine. It has the potential to open new doors in product development, manufacturing and product distribution. Aside from that, it allows the personalisation of medicine to be more accessible.

Apart from the benefits that are mentioned above, the downsides of 3D printing in this industry must also be considered. Nonetheless, for pharmaceutical companies who are considering 3D printing in the future, understanding the drawbacks that are listed above must be the priority.

If you are interested in 3D printing, don't hesitate to ask for help from the experts. There is a 3D printing service provider in Sydney that can provide outstanding 3D printing services. These include custom 3D printing, 3D design and modelling, industrial 3D printing and many more.

# data[].attributes.attachment_link.title
Benefits vs drawbacks of 3D printing in the Pharmaceutical industry

# data[].attributes.attachment_link.description
Since the invention of 3D printing way back in the early 1980s, this technology has been utilised to create almost everything including construction materials, automobile parts and even food and snacks. One notable application of the 3d printing technology is in the field of pharmaceuticals. The technology also has benefits for pharmacists and medical practitioners.

# data[].attributes.attachment_link.readable_text
DUBLIN--()--The "3D Printing in Healthcare - Thematic Research" report has been added to ResearchAndMarkets.com's offering.

In healthcare, 3D bioprinting is used to create living human cells or tissue for use in regenerative medicine and tissue engineering. 3D printing is also used to manufacture precision and personalized pharmaceuticals. Additionally, 3D printing technology is widely used in the manufacturing of medical devices, such as prosthetic limbs, orthopedic and dental implants, surgical instruments, and medical education models. The main focus of this report is 3D bioprinting and the manufacturing of 3D printed pharmaceuticals.

3D bioprinting of human tissue and cells has the potential to solve many critical unmet needs in healthcare, including regenerative medicine, functional organ replacement, and drug discovery. The growing aging population has driven the demand for donor organs, while regenerative medicine using bioprinted, patient-derived stem cells allows for personalized treatment of certain diseases. Use of bioprinted human tissue in drug discovery allows for quicker and more efficient processes, with better outcomes compared to using animal tissue. It also removes the need for animal testing, both in drug and cosmetic development. 3D printing of personalized drugs has the potential to revolutionize the pharmaceutical market. These drugs can be adapted to specific patient requirements, such as age, weight, and comorbidities. This ability to print therapies on demand not only has the potential to make medicine personal to patients, but would equally save millions in costs, resources, and, waste.

Recently, the rapid proliferation of COVID-19 has put an enormous strain on global healthcare systems, with demand for critical medical equipment and supplies mounting. The 3D printing community, from major manufacturers to start-ups and individuals, has responded to the COVID-19 crisis by pledging to support the production of vital medical equipment such as ventilators and personal protective equipment (PPE) for hospitals tackling the pandemic.

Scope of the report:

Key Industry Players - the leading companies in the 3D printing space in healthcare and where they sit in the value chain.

Industry Trends - key trends impacting the 3D Printing industry classified into healthcare, technology, macroeconomic, and regulatory themes.

Industry Analysis - market value of the entire 3D printing industry to 2025 and 2030, as well as key M&A, funding and partnerships in healthcare. There are also a number of case studies highlighting the different applications of 3D printing in healthcare, including how the 3D printing industry has rallied to provide medical equipment and supplies to healthcare systems fighting the current COVID-19 crisis.

Value Chain - Detailed overview of 3D bioprinting and 3D printing of pharmaceuticals by hardware and materials, including leading companies and challengers

Key report benefits:

Develop business strategies by understanding how 3D printing is being used in the healthcare industry today and how the technology is expected to affect the healthcare sector in the future.

Stay up to date on the industry's big players in 3D printing and where they sit in the value chain.

Identify emerging industry trends to gain a competitive advantage.

Key Topics Covered:

1 Table of Contents

1.1 List of Tables

1.2 List of Figures

2 Industry Players

3 Industry Trends

3.1 Healthcare Trends

3.2 Technology Trends

3.3 Macroeconomic Trends

3.4 Regulatory Trends

3.5 Expected Impact of 3D Printing on the Healthcare Industry

3.5.1 Impact on the Biopharmaceutical Industry

3.5.2 Impact on the Medical Device Industry

4 Industry Analysis

4.1 Market Size and Growth Forecasts

4.2 Cost of Different Types of 3D Printing Technology

4.3 Deals in 3D Printing in Healthcare

4.4 Timeline of 3D Printing in Healthcare

4.5 3D Printing in Healthcare Case Studies

4.5.1 Use of 3D Printing in the Fight Against COVID-19

4.5.2 3D Bioprinting and Regenerative Medicine

4.5.3 Use of 3D Printing in Precision and Personalized Medicines

4.5.4 Use of 3D Printing for Medical Education and Training

5 Value Chain

5.1 3D Bioprinting

5.1.1 3D Bioprinting Hardware

5.1.2 3D Bioprinting Materials

5.2 3D Printing of Pharmaceuticals

6 Companies

6.1 3D Bioprinting Companies

6.2 3D Printing Companies

7 Glossary

8 Appendix

For more information about this report visit https://www.researchandmarkets.com/r/vtnbjg

About ResearchAndMarkets.com

ResearchAndMarkets.com is the world's leading source for international market research reports and market data. We provide you with the latest data on international and regional markets, key industries, the top companies, new products and the latest trends.

# data[].attributes.attachment_link.title
3D Printing in Healthcare 2020 - Use of 3D Printing in the Fight Against COVID-19 - ResearchAndMarkets.com

# data[].attributes.attachment_link.description
DUBLIN--()--The "3D Printing in Healthcare - Thematic Research" report has been added to ResearchAndMarkets.com's offering. In healthcare, 3D bioprinting is used to create living human cells or tissue for use in regenerative medicine and tissue engineering. 3D printing is also used to manufacture precision and personalized pharmaceuticals.

# data[].attributes.body
https://www.livescience.com/65257-3d-printed-heart-human-tissue.html