|Year : 2018 | Volume
| Issue : 3 | Page : 252-265
Medical applications of stereolithography: An overview
Anish Kaza1, Julia Rembalsky1, Nicholas Roma2, Vikas Yellapu3, William G Delong4, Stanislaw P Stawicki1
1 Department of Research and Innovation, St. Luke's University Health Network, Bethlehem, Pennsylvania, USA
2 Temple/St. Luke's School of Medicine, Bethlehem, Pennsylvania, USA
3 Department of Research and Innovation; Department of Orthopaedics, St. Luke's University Health Network, Bethlehem, Pennsylvania, USA
4 Department of Orthopaedics, St. Luke's University Health Network, Bethlehem, Pennsylvania, USA
|Date of Submission||11-Nov-2018|
|Date of Acceptance||19-Nov-2018|
|Date of Web Publication||24-Dec-2018|
Dr. Stanislaw P Stawicki
Department of Research and Innovation, St. Luke's University Health Network, Bethlehem, Pennsylvania
Source of Support: None, Conflict of Interest: None
Stereolithography or three-dimensional printing (3DP) is a fast-growing field, with increasing number of health-care applications. As an industry, stereolithography is expected to grow from an estimated $700 million to nearly $9 billion in revenue over the next few years, mainly due to continued advancements and practical implementations of the technology. More established applications of 3DP in medicine involve the creation of wearable assist devices, prosthetics, and orthotics. Research is ongoing in the area of incorporating biologic (including genetic) implementations of 3DP technology, with the long-term goal of three-dimensional printing of organs and tissues that can be subsequently implanted into human body. Given that applications of 3DP in health-care have only recently begun to proliferate, there continues to be paucity of literature in this important and rapidly evolving area of research. In the current review, we sought to present a comprehensive and most current high-level overview of 3DP, with the goal of catalyzing better general understanding and promoting research in 3DP for biomedical applications.
The following core competencies are addressed in this article: Medical knowledge, Systems-Based Practice.
Keywords: Bioprinting, innovation, intellectual property, medical applications, stereolithography, technology, three-dimensional printing
|How to cite this article:|
Kaza A, Rembalsky J, Roma N, Yellapu V, Delong WG, Stawicki SP. Medical applications of stereolithography: An overview. Int J Acad Med 2018;4:252-65
|How to cite this URL:|
Kaza A, Rembalsky J, Roma N, Yellapu V, Delong WG, Stawicki SP. Medical applications of stereolithography: An overview. Int J Acad Med [serial online] 2018 [cited 2019 Mar 22];4:252-65. Available from: http://www.ijam-web.org/text.asp?2018/4/3/252/248331
| Introduction and Definitions|| |
During the past two decades, three-dimensional printing (3DP) technologies have seen rapid growth and increasing number of practical implementations., From its humble beginnings in “rapid prototyping,” 3DP gradually evolved into a multi-billion dollar industry, with an ever-expanding repertoire of health-care applications., Actual and potential uses of 3DP include the ability to create patient-specific models for pre-operative planning; customized implantable devices, grafts, and prostheses; personalized organs for implantations; and improved drug delivery methods and platforms.,,,,, In addition to enhanced personalization and greater degree of precision, benefits of 3DP technology include the ability to optimize medical supply chains and reduce costs currently associated with high degree of medical device/implant customization.,,,
At its core, 3DP is an important component of a much larger trend, “health industrialization”., Furthermore, it is important to emphasize that 3DP is truly an “umbrella term” which encompasses a wide array of techniques (e.g., medical modeling, rapid prototyping) that are used to create three-dimensional products., In health-care, the primary approaches utilizing 3DP include stereolithography, selective laser sintering (SLS), electrospinning, and bioprinting [Table 1]., These methods facilitate the degree of precision and control needed to handle structurally fragile cellular materials, and require computer-aided design (CAD) software that uses computed tomography (CT), micro-CT, and magnetic resonance imaging (MRI) information to create 3D models that are eventually converted into a “printable” 3D data matrix.,,
|Table 1: List of three-dimensional printing approaches and possible applications|
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Bioprinting, or an extension of traditional 3DP that combines cells and other biomaterials to fabricate tissue-like constructs, has seen significant progress during the past few years., Bioprinting utilizes bioinks or hydrogels (various natural and synthetic polymers) loaded into a printer that uses high pressures to expel these materials in a controlled fashion to create the intended object/structure in a pre-determined configuration [Figure 1].,, Important work is currently ongoing, involving collaborations between industry and academic institutions, to create and test the feasibility and potential applications of bioprinted tissues and organs., Researchers are focusing on creating hollow monolayer tissues, such as endothelial cells that can form “micro vessels”; successful creation of such vessel-like structures will be critical to subsequent implementations, up to and including the creation of synthetic organ transplants.,,
|Figure 1: Different types of three-dimensional printers/approaches: (a) Bioprinter; (b) selective laser sintering; (c) electrospinning; and (d) stereolithography; Source: Wikimedia commons|
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In the area of orthodontics, stereolithography has been used to create highly customized dental implants and other prosthetic constructs applicable to oral-maxillofacial surgery.,, Within this important area of practical clinical application, 3DP uses high-energy lasers to shape and to harden a polymer into the intended configuration. SLS is another method of manufacturing computer-aided structural models, utilizing serial applications of powdered substrate material exposed to focused laser energy [Figure 1].,
Electrospinning is a relatively new 3DP method, currently subject to significant research efforts.,, This approach enables researchers to generate ultrathin fibers from a diverse number of materials (e.g., ceramics, composites, polymers). In brief, an electric field is used to generate a charged jet of polymer solution. As the jet travels through air, evaporation of the solvent leaves behind a charged fiber that can be electrically deflected or collected on a specialized screen. Electrospinning is used to create fibers and scaffolds at the nanometer level that can withstand a significant amount of stress, providing a potentially useful platform for creating matrices for cartilage regeneration or bone repair [Figure 1]., With different methods of 3DP, continuous improvement and technological evolution will help facilitate increasing number of health-care applications becoming practically feasible.
The goal of this manuscript is to provide an up-to-date, high-level overview of the fast-growing area of 3D bioprinting. Content included in this review is intended to give the reader a general understanding of the current status of 3DP, the growing number of actual and potential applications of 3DP in biomedical sciences and finally to present an overview of future trends and regulatory considerations related to broader implementation of stereolithography.
| History of Three-Dimensional Printing|| |
It is generally accepted that stereolithography (a.k.a., three-dimensional printing or 3DP) as we know it today has been first described by Charles Hull in the early 1980's. Hull and his business partner Raymond Freed initially worked on creating various plastic objects from photopolymers, and after initial efforts and successful proof-of-concept demonstrations, they founded a company called 3D Systems in 1986 and developed the first 3D printer.,, The printer was known as “stereolithography apparatus” and converted liquid plastic into solid objects. Hull developed the process to the point of becoming a viable and reliable option for rapid prototyping. In 1988, the company made the first 3DP, the “SLA-250,” commercially available. Researchers quickly made use of this emerging technology, creating applications across diverse scientific fields from engineering to medicine. Medical applications of 3DP began appearing in the mid-1990s, opening the path to many subsequent biomedical uses.,,
| Stereolithography: Materials, Methods, and Challenges|| |
Rapid technological progress is one of the defining characteristics of stereolighography. Since its inception, 3DP has improved markedly through the use of advanced equipment and better quality of materials utilized in the process., The precision and resolution of the printing process has increased, at times exceeding the resolution of 3D scans or digital templates designed using a CAD system. Similar to other types of specialized computerized applications, a customized “standard tessellation language” (or STL) format has been devised as a 3DP industry reference standard., Consequently, information saved in STL files is interpreted by the computer and sent to the 3DP, where the data conversion into a materialized 3D structure takes place. The overall 3DP resolution is based on the density of “triangles” within a specified area; therefore, the more “triangles”, the higher the quality of the object being printed. The intermediary data format between the STL file and the 3D printer is the so-called “g-file” which breaks down the information further for interpretation by the printer. In brief, the “g-file” facilitates the conversion of information into a two-dimensional horizontal field which is required to initiate the process of printing., As a result, the 3DP effectively “prints” consecutive cross-sectional areas of the intended object, gradually “building up” the final three-dimensional structure one layer at a time.,
With continued technological and methodological advances, it is hoped that biomedical applications of 3DP will expand to include bioprinting of human organs., Currently available 3DP devices are not yet capable of fulfilling this exciting promise, at least not to a degree sufficient for practical use in medicine or surgery. To accomplish the latter, greater 3DP resolution and process precision will be required, including better integration of different high-resolution body imaging systems (e.g., MRI, CT) to help create and map 3D models with the level of fidelity approximating that of actual human tissues and organs.,,, MRI and CT scans are accurate when it comes to mapping anatomic features, with digitized data transformed into a 3D-printed object using scaffolding to create the structural support during the process. When bioprinting, scaffolding is critical to ensuring the maintenance of the correct structural shape; achieving the desired nutrient levels (including the nutrient absorption and transport); and creating a specialized matrix for protection and support of the cell.,, There are three key considerations needed to ensure that the organ is printed in the most precise detail possible. First, CT and MRI scan data are used to outline the overall shape and anatomy of the organ. Second, more granular details pertinent to proper organ function are recreated, including features such as the thickness and size of cells (or layers of cells), dimensions of any pores, and the corresponding interconnections between cells. Third, the nanoarchitecture is mapped out, with focus on cell differentiation, cell proliferation, and cell adhesion. Finally, issues related to 3D printed organ viability and function will need to be addressed, ensuring that tissue compatibility mismatch does not result in organ rejection. Subsequent sections of this manuscript will discuss the status of research pertaining to individual organs/organ systems.
| Kidneys and Urinary System|| |
The renal system is critical to human physiological homeostasis. It regulates serum pH, electrolyte levels, and is vital for eliminating metabolic/nitrogenous waste from the body. Renal dysfunction may progress to chronic kidney failure, resulting in the patient becoming dependent on hemodialysis as the primary management approach. The only proven method of liberating patients from dialysis dependence is the performance of renal transplantation. With average life expectancy on dialysis being 5–10 years, and the waiting period for kidney transplantation being >7 years, the urgency related to limited organ availability becomes apparent.,,, Moreover, the cost of dialysis can become a significant burden on patients, their families, and the overall health-care system.
For more than two decades researchers have also been trying to remedy this situation, both by advancing the understanding of xenotransplantation and by exploring potential ways to design an “artificial kidney”; however, neither of these approaches have yet materialized due to the associated complexities., Given the recent advances in stereolithography, researchers began to examine innovative ways to bioprint various parts of individual organs., Early successes included the development of techniques to print complex structures found in different types of human tissue including the ability to maintain the resultant bio-constructs alive., Using multiple gel-like inks; the researchers can print hollow tubes, to which cells can be added that subsequently mature into the intended tissue.,, With trial/error and time, small, complex tubes that work much like the major components of kidneys have been developed through 3DP technology.,, Although much work remains to be done, these early results represent an excellent proof-of-concept demonstration.
Hollow organs, such as the bladder, are not as complex as the kidneys, and therefore may be somewhat less challenging when it comes to 3DP attempts., Researchers at The Wake Forest Institute of Regenerative Medicine developed a bioengineered urinary bladder that was successfully implanted into a patient., A urethral injury bioprinting model has also been studied, with the intent to use 3DP to replace an injured urethra using various cell blends., Theoretically, similar concepts and approaches could be applied to other tubular structures such as the bile ducts and blood vessels., Despite the above progress, the most practical current uses for 3DP in the context of the renal-urinary system are in the areas of research, education, and surgical planning.,, Other potential applications of bioprinting involving the renal system include the testing of tissue response to radiation and drug dosing (e. g., in patients with chronic renal disease)., The latter application may be especially relevant in the setting of pharmaceutical trials, where bioprinted kidney models could be used to determine the toxicity of a new drug without placing patients at risk.,,
| The Pancreas|| |
The pancreas plays a major role in both digestive and endocrine systems, with pancreatic dysfunction leading to diverse number of potentially life-threatening conditions such as diabetes type I and II, pancreatitis, and pancreatic cancer.,,, In a quest toward a 3D-printed pancreas, researchers were able to successfully create a polylactic acid (PLA) scaffold, to which extracellular matrix protein and two types of adult, human pancreatic stem cells were introduced. Due to the flexibility of the PLA model, the seeded cells were able to differentiate and assume some characteristics of the adult pancreas. However, the synthesis of a fully (or at least sufficiently) functioning bioprinted pancreas that could be implanted into a human is not yet feasible. Other potential applications of 3DP in the context of management of pancreatic conditions include the creation of 3D models of tumorous growths for surgical planning and testing of novel drug delivery systems for pancreatic malignancies. It is hoped that the above developments may help improve our understanding and ability to effectively manage pancreatic cancer.
| The Liver|| |
The liver serves as the body's detoxification system, playing critical role in multitude of metabolic processes, including bile acid, cholesterol, glucose, and drug metabolism.,, Consequently, a reliable, working 3D bioprinted model of the liver can provide a versatile platform for the study of diseases such as diabetes, hepatitis, obesity, and nonalcoholic steatohepatitis, as well as the effects of newly developed drugs.,
In the past, there have been studies examining 3D hepatocyte cell cultures, with limited ability to sustain function for long periods of time., Gradually, the ability to construct structural scaffolds has evolved, thus allowing researchers to approximate the 3D structure of liver tissue; however, the early accuracy of this approach seems insufficient for wider implementations., In one recent report, scaffold-free 3D-printed liver tissue was created that can maintain metabolic function for longer periods of time. In addition to facilitating clinical research and other important scientific applications, 3D bioprinted hepatic tissue promises to become a platform for the development of long-term, implantable clinical management solutions designed to treat/cure various diseases.,, As with other areas of 3DP applications, surgeons have utilized 3DP models in operative planning for complex hepatic procedures.,
| Cardiovascular System|| |
The cardiovascular system is responsible for transporting oxygen, nutrients, and various metabolites throughout the human body., There are many common pathological conditions that can affect the heart and vasculature, including hypertension, thromboembolic phenomena, and structural diseases (e.g., cardiac valves, vascular aneurysms). The incorporation of 3DP into the management of cardiovascular diseases promises to bring about some unique clinically-relevant benefits. For example, the ability to employ 3D models of cardiovascular structures can help facilitate complex surgical and interventional procedures, including pre-operative planning of transcatheter aortic valve replacement approaches.,,,
Creating custom implantable 3D-printed cardiac valves represents an important area of development in the clinical application of stereolithography in the management of cardiovascular disease., Aortic valves were successfully printed using polyethylene glycol-diacrylate hydrogels supplemented with alginate.,,, In one technical report, the authors outlined that 3D printing of cardiac valves, customized through the use of micro CT scans, took between 14 and 45 min. Of note, the resultant valves were shown to be functional after 21 days, suggesting that long-term durability may be possible. Further clinical implementation of cardiac valve bioprinting will require perfect anatomic fit of the device, with focus on refining MRI and CT scan data to map out the corresponding anatomic geometry., As with other implantable devices, potential problems involving 3DP heart valves may include temporal changes within the bioprinted material and the risk of host immune response directed against the implant. For patients with congenital heart disease, 3D printing of aberrant cardiac anatomy based on MRI, CT scans, and echocardiograms allows for accurate and more realistic depiction of congenital defects,,, facilitating preoperative planning for procedures ranging from stent placement to cardiac transplantation.,,
Benefits of the ability to quickly and accurately bioprint a heart (or its segments/tissues) would be significant, including better understanding of a patient's cardiac function (and dysfunction). Although much work remains to be done in this area, some preliminary data are promising. For example, a “heart-on-a-chip” that is based on individualized information from a specific patient allows researchers to closely observe changes within the bioprinted heart or cardiac tissue, and similarly to 3D-printed kidney or liver, may help characterize the effect of drugs and other therapeutic interventions without putting the patient at risk., Although somewhat expensive and time-consuming, this “organ-on-a-chip” approach may well represent the future of heart disease investigation, management, and prevention. Being able to superimpose the true anatomy of the individual's heart on his/her disease process can lead to better treatments and clinical outcomes [Figure 2]. It has been projected that fully functional bioprinted hearts may be feasible within the next two decades.
|Figure 2: The above figure shows examples of three-dimensional printed heart (a-c) and aortic arch (d) including carotid arteries. Three-dimensional printing allows for accurate visualization of patient-specific pathologies. Source: Wikimedia commons|
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| Pulmonary System|| |
The pulmonary system's primary function is an exchange of gases through respiration, with secondary roles including regulation of acid-base homeostasis., The pulmonary system can be affected by a range of significant disease states, from emphysema to malignancy. It is predicted that chronic obstructive pulmonary disease may become one of the top three leading causes of death in the U.S. by 2020., Consequently, the ability to create reliable 3D models of the pulmonary system will be critically important to our understanding of structural and functional lung pathology and will be instrumental to better treatments and clinical outcomes., Researchers from the Czech Republic have developed a plastic-based, experimental model of a 3DP human lung, and although our ability to generate and successfully implant a working a bioprinted lung into a human body is still remote, this model has been successful in demonstrating the effectiveness of inhaled drugs for respiratory conditions and may play a role in health-care education/clinical simulation. Similar models can be beneficial to medical students, clinical trainees, and surgeons to help enhance the understanding of the pulmonary anatomy and the progression of lung disease.,
Although stereolithography of the pulmonary system is among the most complex and thus practically challenging applications of 3DP, the impact of a successfully bioprinted, functional lung would be profound. Such development would revolutionize physiological models (e.g., better understanding of physical triggers of asthma, improved knowledge of pulmonary hypertension, or greater insight into triggers of pulmonary fibrosis); treatment options (e.g., using bioprinted lung in early-phase pharmaceutical trials of safety and efficacy); and personalized clinical care (e.g., the ability to design patient-specific treatments and treatment plans).,
| Trachea and Other Tubular Structures|| |
Among the most advanced applications of 3DP is the area of bioprinting of tubular structures, from large vessel grafts to the trachea., In fact, 3D printing has been used to create tracheal scaffolds that are suitable for human implantation., In the area of bioprinted tracheal implants, further work is being conducted to better approximate in vivo tissue behavior, and tissue-tissue interactions., In the field of vascular surgery, and especially endovascular large-vessel interventions, 3DP models have provided an important platform for preoperative planning in complex/challenging cases.,, Finally, one would be remiss not to mention some of the previously discussed areas in the context of the current section, including the potential for progress in the use of stereolithography for bile ducts,, bowel, and hollow urinary structures., It is hoped that with further evolution of bioprinting capabilities, the applicability of 3DP in this general area will continue to expand, up to and including the development of long-term implantable solutions.
| Musculoskeletal System|| |
Stereolithography has made tremendous strides in the area of orthopedic surgery, from rapid prototyping and anatomical modeling to 3D-printed instruments and implants.,, The incorporation of 3DP has already made impact on clinical areas of great importance, such as the development of prosthetics and joint replacements [Figure 3].,, Specialized polymer-based printing technologies are now able to generate accurate surgical guides and anatomical replicas to help orthopedic surgeons in preoperative planning of complex cases, providing previously unprecedented levels of detail and unique anatomical perspectives.,,
|Figure 3: The above figure shows examples of three-dimensional printed skull flap. One can see that using magnetic resonance imaging and computed tomography data, a three-dimensional cranial prosthesis can be designed and subsequently printed using stereolithography. Source: Wikimedia commons|
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Reconstructive surgery represents an area of active growth for 3DP applications. Stereolithography of metal-based implants is now also possible using templates created with imaging methods such as MRI and CT scans. Since the human anatomy is symmetrical, researchers can “reverse” 3D images using human anatomy data to reconstruct tailored prosthetics.,, One practical example of the latter includes the report of the successful creation of customized implants for acetabular reconstructive surgery. In another example, spinal reconstruction was determined to be plausible using 3D printed material. Finally, porous 3D-printed titanium femoral stems may help facilitate better tissue healing following total hip arthroplasty.
The development of high-fidelity implants and scaffolds is central to the success of 3DP applications in orthopedics. Among many factors, the bioprinting of specialized orthopedic implants is especially relevant to our discussion, primarily due to the considerations of anatomic customization, ease of creation and implantation, and timing-related issues. More specifically, bioprinted structures can be synthesized and applied relatively quickly, especially when cartilage-based.,,, If sufficient reproducibility and reliability can be achieved, the number of patients who require large joint replacements may be reduced.,, Should more extensive tissue replacements be ultimately required, the goal would be to fabricate bioprinted joints that promote more effective bone growth, minimize postoperative infection, and provide enhanced structural support.
| Pharmacological Applications of Stereolithography|| |
As outlined throughout this review, pharmacological testing – including drug metabolism and toxicity– has benefited significantly from 3DP applications., Novel methods of drug delivery are being designed using stereolithography, from microneedles to innovative capsule designs.,, Collectively, such advances would not be possible without the tremendous progress in 3DP outlined herein. Stereolithography promises to be one of the key elements of personalizing and customizing medication administration. In fact, it has been postulated by some that traditional fabrication of medications may well be transformed into “drug printing”– a process that will help optimize the release, uptake, and potentially even the metabolism of the drug– all while minimizing the potential for adverse events.
| Stereolithography: Other Applications, Challenges, and Miscellaneous Topics|| |
Due to the limited scope of the current review, the authors are unable to comprehensively discuss all of the known/reported applications of 3DP in biomedical sciences [Table 2]. Topics not outlined in this manuscript, but worthy of mention include applications of stereolithography in dentistry, oral and maxillofacial surgery, neurosurgery,, plastic and reconstructive surgery [Figure 3],,, spine surgery, and traumatology.
|Table 2: List of three-dimensional printing applications, including current uses and potential future uses|
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Customization and the ability to quickly create high-fidelity, point-of-care 3D bioprinted structures are among the key advantages of stereolithography. The availability of highly customized and personalized 3DP tissues, organs, implants, prosthetics, and drugs promises to revolutionize existing health-care paradigms.,, Although the procedure required to successfully bioprint a fully functioning, three-dimensional organ is complex and intricate, significant progress is being made by tissue regeneration researchers to streamline and simplify this multi-step procedure. In one reported experience, the process of preparing necessary cell lines/types and printing the organ takes up to 8 weeks. The overall task begins with required cells being taken from the specific organ that is to be “3D synthesized”, followed by an incubation of cells for approximately 6–8 weeks, and finally the printing of the organ, which typically takes between 6 and 12 h.,,,
| Challenges and Special Considerations|| |
Despite tremendous progress over the past decade, significant challenges remain before 3D bioprinting can become the mainstream reality of modern healthcare. The primary difficulty revolves around printing structurally sound, biologically compatible, and durable constructs featuring appropriately differentiated living tissues., Other challenges involve finding the best biomaterials that will help optimize the process of printing and maturing the bioprinted tissues and organs.,, The process of printing an organ requires significant amount of preparatory work, the proper equipment and materials to print each layer of the 3D construct, and finally the actual printing of the intended structure. It may be challenging for all three of these events to be sequenced correctly, and problems may arise at any stage of the process., Moreover, once the organ is successfully printed, it requires a maturation period where it continues to grow and function as it would in the body until it is ready for implantation. Finally, it can be difficult to maintain the function and shape of the organ as it goes through this process.
Among important technical limitations, one must remember that the STL format for 3D bioprinting is designed to “translate” imaging data into a pre-defined 3D structure, with each layer of said structure created sequentially in stages., Problems may arise when scaling of the mapped-out organ on the computer screen does not exactly match the structure that is actually printed. When this occurs, the resultant size mismatch may potentially affect the suitability of the organ for in vivo implantation. One proposed solution to this is to perform appropriate adjustments to the final size of the bioprinted organ; however, this may lead to significant shape alterations.
Another area where challenges continue to exist is the need for the creation of more reliable cartridges for bioink, as well as the fabrication of hydrogels that serve as “bio-paper”. Beyond these fundamental considerations, more advanced bioreactors (e.g., devices that facilitate the process of printing and maturation by helping sustain the organ while it is being prepared for implantation) will be needed to increase the reliability of bioprinting, especially given the fact that cells used in 3D printing are very fragile, and any unforeseen disruptions can endanger the entire process (and thus the organ)., The cost of the bioprinting of organs will be considerable, although economically justifiable if eventual implantations lead to lower long-term health-care costs. The size and complexity of the project correlate with its costs. For instance, a tracheal graft may cost around $100; 3D bioprinting of a nose could cost approximately $40,000; while the expenditures required to synthesize a more complex organ (e. g., liver or heart) could exceed $300,000. Finally, it is possible that point-of-care 3D bioprinting will eventually become a reality. Such development could revolutionize how surgical/procedural care is delivered.
Regulatory considerations regarding 3DP constitute another area of active development and special concern. Due to the inherent variability of bioprinted products, strict regulations will be required to guarantee consistent quality and clinical safety of any 3DP implementations. In addition, some degree of controversy continues around the use of stem cells in biomedical application and experimentation. Due to limited integration of 3D bioprinting into the realm of mainstream healthcare, numerous other issues of varying complexity (e.g., insurance coverage, product quality and consistency, long-term durability, and access to the technology) need to be fully addressed.
| Conclusion|| |
Health-care applications of stereolithography represent a rapidly growing and highly dynamic area. The breadth of the 3DP offering continues to expand in parallel with technological and software advances. The associated near-term growth within this sector is expected to increase by an order of magnitude. The promise of stereolithography in medicine is great– from better, more customizable implants to the development of fully functional, immunocompatible 3D-printed tissues and organs suitable for human implantation. This manuscript provides the reader with a high-level, up-to-date overview of essential topics associated with stereolithography for biomedical applications. It is hoped that our work will help stimulate further discussion and research in this rapidly evolving area of health-care.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
Ethical conduct of research
This manuscript represents a literature review. Because this project involved no experimental design, the Institutional Review Board approval was not required.
| References|| |
Dimitrov D, Schreve K, de Beer N. Advances in three dimensional printing–state of the art and future perspectives. Rapid Prototyp J 2006;12:136-47.
Melchels FP, Feijen J, Grijpma DW. A review on stereolithography and its applications in biomedical engineering. Biomaterials 2010;31:6121-30.
Chua CK, Leong KF, Lim CS. Rapid Prototyping: Principles and Applications. Vol. 1. Singapore: World Scientific; 2003.
Giannopoulos AA, Steigner ML, George E, Barile M, Hunsaker AR, Rybicki FJ, et al.
Cardiothoracic applications of 3-dimensional printing. J Thorac Imaging 2016;31:253-72.
Nyberg EL, Farris AL, Hung BP, Dias M, Garcia JR, Dorafshar AH, et al.
3D-printing technologies for craniofacial rehabilitation, reconstruction, and regeneration. Ann Biomed Eng 2017;45:45-57.
Goole J, Amighi K. 3D printing in pharmaceutics: A new tool for designing customized drug delivery systems. Int J Pharm 2016;499:376-94.
Prasad LK, Smyth H. 3D printing technologies for drug delivery: A review. Drug Dev Ind Pharm 2016;42:1019-31.
Stansbury JW, Idacavage MJ. 3D printing with polymers: Challenges among expanding options and opportunities. Dent Mater 2016;32:54-64.
Harris J, Rimell J. Can rapid prototyping ever become a routine feature in general dental practice? Dent Update 2002;29:482-6.
Michalski MH, Ross JS. The shape of things to come: 3D printing in medicine. JAMA 2014;312:2213-4.
Ventola CL. Medical applications for 3D printing: Current and projected uses.P T 2014;39:704-11.
Ruiwale VV, Sambhe RU. Application of additive manufacturing technology for manufacturing medical implants: A review. J Impact Factor 2015;6:45-55.
Birtchnell T, Urry J. A new industrial future? 3D printing and the reconfiguring of production, distribution, and consumption. London, England: Routledge; 2016.
Salgues B. Health Industrialization. London, England: Elsevier; 2016.
Bibb R, Eggbeer D, Paterson A. Medical Modelling: The Application of Advanced Design and Rapid Prototyping Techniques in Medicine. Waltham, Massachusetts: Woodhead Publishing; 2014.
Mota C, Puppi D, Chiellini F, Chiellini E. Additive manufacturing techniques for the production of tissue engineering constructs. J Tissue Eng Regen Med 2015;9:174-90.
An J, Teoh JE, Suntornnond R, Chua CK. Design and 3D printing of scaffolds and tissues. Engineering 2015;1:261-8.
Tappa K, Jammalamadaka U. Novel biomaterials used in medical 3D printing techniques. J Funct Biomater 2018;9. pii: E17.
Tack P, Victor J, Gemmel P, Annemans L. 3D-printing techniques in a medical setting: A systematic literature review. Biomed Eng Online 2016;15:115.
Hockaday LA, Kang KH, Colangelo NW, Cheung PY, Duan B, Malone E, et al.
Rapid 3D printing of anatomically accurate and mechanically heterogeneous aortic valve hydrogel scaffolds. Biofabrication 2012;4:035005.
Pati F, Gantelius J, Svahn HA. 3D bioprinting of tissue/organ models. Angew Chem Int Ed Engl 2016;55:4650-65.
Guvendiren M, Molde J, Soares RM, Kohn J. Designing biomaterials for 3D printing. ACS Biomater Sci Eng 2016;2:1679-93.
Zhang YS, Yue K, Aleman J, Moghaddam KM, Bakht SM, Yang J, et al.
3D bioprinting for tissue and organ fabrication. Ann Biomed Eng 2017;45:148-63.
Williams D, Thayer P, Martinez H, Gatenholm E, Khademhosseini A. A perspective on the physical, mechanical and biological specifications of bioinks and the development of functional tissues in 3D bioprinting. Bioprinting 2018; 9:19-36.
Ouyang L, Highley CB, Sun W, Burdick JA. A generalizable strategy for the 3D bioprinting of hydrogels from nonviscous photo-crosslinkable inks. Adv Mater 2017; 29(8):1604983.
Hewes S, Wong AD, Searson PC. Bioprinting microvessels using an inkjet printer. Bioprinting; 2017;7:14-8.
Thomas DJ. 3-D bioprinting transplantable tissue structures: A perspective for future reconstructive surgical transplantation. Bioprinting 2016;1-2:36-7.
Hasan A, Paul A, Vrana NE, Zhao X, Memic A, Hwang YS, et al.
Microfluidic techniques for development of 3D vascularized tissue. Biomaterials 2014;35:7308-25.
Petzold R, Zeilhofer HF, Kalender WA. Rapid protyping technology in medicine – Basics and applications. Comput Med Imaging Graph 1999;23:277-84.
Nayar S, Bhuminathan S, Bhat WM. Rapid prototyping and stereolithography in dentistry. J Pharm Bioallied Sci 2015;7:S216-9.
Liaw CY, Guvendiren M. Current and emerging applications of 3D printing in medicine. Biofabrication 2017;9:024102.
Liu T, Guessasma S, Zhu J, Zhang W, Nouri H, Belhabib S. Microstructural defects induced by stereolithography and related compressive behaviour of polymers. J Mater Process Technol 2018;251:37-46.
Ligon SC, Liska R, Stampfl J, Gurr M, Mülhaupt R. Polymers for 3D printing and customized additive manufacturing. Chem Rev 2017;117:10212-90.
Mazzoli A. Selective laser sintering in biomedical engineering. Med Biol Eng Comput 2013;51:245-56.
Huang ZM, Zhang YZ, Kotaki M, Ramakrishna S. A review on polymer nanofibers by electrospinning and their applications in nanocomposites. Compos Sci Technol 2003;63:2223-53.
Doshi J, Reneker DH, Electrospinning process and applications of electrospun fibers. J Electrostat 1995;35:151-60.
Li D, Xia Y. Electrospinning of nanofibers: Reinventing the wheel? Adv Mat 2004;16:1151-70.
Agarwal S, Wendorff JH, Greiner A. Use of electrospinning technique for biomedical applications. Polymer 2008;49:5603-21.
Chow LW. Electrospinning Functionalized Polymers for Use as Tissue Engineering Scaffolds, in Biomaterials for Tissue Engineering. New York: Humana Press/Springer; 2018. p. 27-39.
Kocovic P. 3D Printing and Its Impact on the Production of Fully Functional Components: Emerging Research and Opportunities: Emerging Research and Opportunities. Hershey, Pennsylvania: IGI Global; 2017.
Niaki MK, Nonino F. What is additive manufacturing? Additive systems, processes and materials. In: The Management of Additive Manufacturing. Cham, Switzerland: Springer; 2018. p. 1-35.
Niaki MK, Nonino F. The Management of Additive Manufacturing: Enhancing Business Value. Cham, Switzerland: Springer; 2017.
Chua CK, Leong KF, Lim CS. Rapid Prototyping: Principles and Applications (with Companion CD-ROM). Singapore: World Scientific Publishing Company; 2010.
Mitsouras D, Liacouras PC. 3D printing technologies. In: 3D Printing in Medicine. Cham, Switzerland: Springer; 2017. p. 5-22.
Srivatsan T, Sudarshan T. Additive manufacturing: Innovations, advances, and applications. Boca Raton, Florida:CRC Press; 2015.
Berman B. 3D printing: The new industrial revolution. Bus Horiz 2012;55:155-62.
McMenamin PG, Quayle MR, McHenry CR, Adams JW. The production of anatomical teaching resources using three-dimensional (3D) printing technology. Anat Sci Educ 2014;7:479-86.
Lewental A. Print Your Own Pandora's Box: 3D Printing, Intellectual Property Law, and The Internet for Lay-Lawyers. Bus. Entrepreneurship & Tax L. Rev., 2017. 1: p. 104.
Ripley B, Kelil T, Cheezum MK, Goncalves A, Di Carli MF, Rybicki FJ, et al.
3D printing based on cardiac CT assists anatomic visualization prior to transcatheter aortic valve replacement. J Cardiovasc Comput Tomogr 2016;10:28-36.
Gross BC, Erkal JL, Lockwood SY, Chen C, Spence DM. Evaluation of 3D printing and its potential impact on biotechnology and the chemical sciences. Analytical Chemistry 2014;86:3240-3253.
Ciobota ND. Standard tessellation language in rapid prototyping technology. Sci Bull Valahia Univ 2012;7:81-5.
Bentz BZ, Webb KJ. Methods for Forming Optically Heterogeneous Phantom Structures and Phantom Structures Formed Thereby. Google Patents; 2018.
Snyder RM. An overview of the Past, Present, and Future of 3D Printing Technology with an Emphasis on the Present. Association Supporting Computer Users in Education; 2014.
Mironov V, Boland T, Trusk T, Forgacs G, Markwald RR. Organ printing: Computer-aided jet-based 3D tissue engineering. Trends Biotechnol 2003;21:157-61.
Kim GB, Lee S, Kim H, Yang DH, Kim YH, Kyung YS, et al.
Three-dimensional printing: Basic principles and applications in medicine and radiology. Korean J Radiol 2016;17:182-97.
Murphy SV, Atala A. 3D bioprinting of tissues and organs. Nat Biotechnol 2014;32:773-85.
Melchels FP, Domingos MA, Klein TJ, Malda J, Bartolo PJ, Hutmacher DW. Additive manufacturing of tissues and organs. Prog Polym Sci 2012;37:1079-104.
Mitsouras D, Liacouras P, Imanzadeh A, Giannopoulos AA, Cai T, Kumamaru KK, et al.
Medical 3D printing for the radiologist. Radiographics 2015;35:1965-88.
Sun W, Starly B, Nam J, Darling A. Bio-CAD modeling and its applications in computer-aided tissue engineering. Comput Aided Des 2005;37:1097-114.
Lee J, Cuddihy MJ, Kotov NA. Three-dimensional cell culture matrices: State of the art. Tissue Eng Part B Rev 2008;14:61-86.
Chia HN, Wu BM. Recent advances in 3D printing of biomaterials. J Biol Eng 2015;9:4.
Sherwood L. Human Physiology: From Cells to Systems. Boston, Massachusetts: Cengage Learning; 2015.
Arnold-Chamney M, Latimer S, Barton M, Kelly J. Acute renal conditions. Acute Care Nursing; 2018. p. 123.
Webster AC, Nagler EV, Morton RL, MassonP. Chronic kidney disease. Lancet 2017;389:1238-52.
Matas AJ, Smith JM, Skeans MA, Thompson B, Gustafson SK, Stewart DE, et al.
OPTN/SRTR 2013 annual data report: Kidney. Am J Transplant 2015;15 Suppl 2:1-34.
Turin TC, Tonelli M, Manns BJ, Ravani P, Ahmed SB, Hemmelgarn BR. Chronic kidney disease and life expectancy. Nephrol Dial Transplant 2012;27:3182-6.
Stokes JB. Consequences of frequent hemodialysis: Comparison to conventional hemodialysis and transplantation. Trans Am Clin Climatol Assoc 2011;122:124-36.
Tonelli M, Wiebe N, Knoll G, Bello A, Browne S, Jadhav D, et al.
Systematic review: Kidney transplantation compared with dialysis in clinically relevant outcomes. Am J Transplant 2011;11:2093-109.
Ravelingien A. Pig tales, human chimeras and man-made public health hazards: An ethical analysis of xenotransplant benefits and risks. Ghent, Belgium: Ghent University; 2006.
Ronco C, Davenport A, Gura V. The future of the artificial kidney: Moving towards wearable and miniaturized devices. Nefrologia 2011;31:9-16.
Kolesky DB, Truby RL, Gladman AS, Busbee TA, Homan KA, Lewis JA, et al.
3D bioprinting of vascularized, heterogeneous cell-laden tissue constructs. Adv Mater 2014;26:3124-30.
Homan KA, Kolesky DB, Skylar-Scott MA, Herrmann J, Obuobi H, Moisan A, et al.
Bioprinting of 3D convoluted renal proximal tubules on perfusable chips. Sci Rep 2016;6:34845.
Yandell K. Organs on demand. Scientist 2013;27:38-45.
Groopman J. Print thyself. New Yorker 2014; Nov 24;24.
Yeong WY, Chua CK, Leong KF, Chandrasekaran M. Rapid prototyping in tissue engineering: Challenges and potential. Trends Biotechnol 2004;22:643-52.
Boland T, Wilson WC Jr., Xu T. Ink-Jet Printing of Viable Cells. Google Patents; 2006.
Gatenholm P, Backdahl H, Tzavaras TJ, Davalos RV, Sano MB. Three-Dimensional Bioprinting of Biosynthetic Cellulose (BC) Implants and Scaffolds for Tissue Engineering. Google Patents; 2014.
Mironov V, Kasyanov V, Drake C, Markwald RR. Organ printing: Promises and challenges. Regen Med 2008;3:93-103.
Mironov V, Visconti RP, Kasyanov V, Forgacs G, Drake CJ, Markwald RR, et al.
Organ printing: Tissue spheroids as building blocks. Biomaterials 2009;30:2164-74.
Atala A, Kasper FK, Mikos AG. Engineering complex tissues. Sci Transl Med 2012;4:160rv12.
Stock UA, Vacanti JP. Tissue engineering: Current state and prospects. Annu Rev Med 2001;52:443-51.
Orlando G, Wood KJ, Stratta RJ, Yoo JJ, Atala A, Soker S, et al.
Regenerative medicine and organ transplantation: Past, present, and future. Transplantation 2011;91:1310-7.
Zhang K, Fu Q, Yoo J, Chen X, Chandra P, Mo X, et al.
3D bioprinting of urethra with PCL/PLCL blend and dual autologous cells in fibrin hydrogel: An in vitro
evaluation of biomimetic mechanical property and cell growth environment. Acta Biomater 2017;50:154-64.
Soliman Y, Feibus AH, Baum N. 3D printing and its urologic applications. Rev Urol 2015;17:20-4.
Dhir V, Itoi T, Fockens P, Perez-Miranda M, Khashab MA, Seo DW, et al.
Novel ex vivo
model for hands-on teaching of and training in EUS-guided biliary drainage: Creation of “Mumbai EUS” stereolithography/3D printing bile duct prototype (with videos). Gastrointest Endosc 2015;81:440-6.
Koike N, Fukumura D, Gralla O, Au P, Schechner JS, Jain RK, et al.
Tissue engineering: Creation of long-lasting blood vessels. Nature 2004;428:138-9.
Yang T, Lin S, Tan T, Yang J, Pan J, Hu C, et al.
Impact of 3D printing technology on comprehension of surgical anatomy of retroperitoneal tumor. World J Surg 2018;42:2339-43.
Silberstein JL, Maddox MM, Dorsey P, Feibus A, Thomas R, Lee BR, et al.
Physical models of renal malignancies using standard cross-sectional imaging and 3-dimensional printers: A pilot study. Urology 2014;84:268-72.
Torres K, Staśkiewicz G, Śnieżyński M, Drop A, Maciejewski R. Application of rapid prototyping techniques for modelling of anatomical structures in medical training and education. Folia Morphol (Warsz) 2011;70:1-4.
Tran-Gia J, Schlögl S, Lassmann M. Design and fabrication of kidney phantoms for internal radiation dosimetry using 3D printing technology. J Nucl Med 2016;57:1998-2005.
Peloso A, Katari R, Murphy SV, Zambon JP, DeFrancesco A, Farney AC, et al.
Prospect for kidney bioengineering: Shortcomings of the status quo. Expert Opin Biol Ther 2015;15:547-58.
Oerlemans AJ. From lab to Clinic Ethical Aspects of Soft Tissue Engineering. Nijmegen, The Netherlands: Radboud University; 2013. p. 25-7.
Leaf DE, Waikar SS. End points for clinical trials in acute kidney injury. Am J Kidney Dis 2017;69:108-16.
Palevsky PM. Endpoints for clinical trials of acute kidney injury. Nephron 2018;140:111-5.
Wilmer MJ, Ng CP, Lanz HL, Vulto P, Suter-Dick L, Masereeuw R, et al.
Kidney-on-a-chip technology for drug-induced nephrotoxicity screening. Trends Biotechnol 2016;34:156-70.
Gong Z, Muzumdar RH. Pancreatic function, type 2 diabetes, and metabolism in aging. Int J Endocrinol 2012;2012:320482.
Henderson JR, Daniel PM, Fraser PA. The pancreas as a single organ: The influence of the endocrine upon the exocrine part of the gland. Gut 1981;22:158-67.
Gromada J, Franklin I, Wollheim CB. α-Cells of the endocrine pancreas: 35 years of research but the enigma remains. Endocr Rev 2007;28:84-116.
Bardeesy N, DePinho RA. Pancreatic cancer biology and genetics. Nat Rev Cancer 2002;2:897-909.
Marconi S, Pugliese L, Del Chiaro M, Pozzi Mucelli R, Auricchio F, Pietrabissa A, et al.
An innovative strategy for the identification and 3D reconstruction of pancreatic cancer from CT images. Updates Surg 2016;68:273-8.
Yi HG, Choi YJ, Kang KS, Hong JM, Pati RG, Park MN, et al.
A3D-printed local drug delivery patch for pancreatic cancer growth suppression. J Control Release 2016;238:231-41.
American Cancer Society. Cancer Facts & Figures 2008. Atlanta, Georgia: American Cancer Society; 2009.
Corless JK, Middleton HM 3rd
. Normal liver function. A basis for understanding hepatic disease. Arch Intern Med 1983;143:2291-4.
Wilkinson GR, Shand DG. Commentary: A physiological approach to hepatic drug clearance. Clin Pharmacol Ther 1975;18:377-90.
Farrell GC, Cooksley WG, Powell LW. Drug metabolism in liver disease: Activity of hepatic microsomal metabolizing enzymes. Clin Pharmacol Ther 1979;26:483-92.
Lauschke VM, Hendriks DF, Bell CC, Andersson TB, Ingelman-Sundberg M. Novel 3D culture systems for studies of human liver function and assessments of the hepatotoxicity of drugs and drug candidates. Chem Res Toxicol 2016;29:1936-55.
Nguyen DG, Funk J, Robbins JB, Crogan-Grundy C, Presnell SC, Singer T, et al.
Bioprinted 3D primary liver tissues allow assessment of organ-level response to clinical drug induced toxicity in vitro
. PLoS One 2016;11:e0158674.
Soldatow VY, LeCluyse EL, Griffith LG, Rusyn I. In vitro
models for liver toxicity testing. Toxicol Res (Camb) 2013;2:23-39.
Elliott NT, Yuan F. A review of three-dimensional in vitro
tissue models for drug discovery and transport studies. J Pharm Sci 2011;100:59-74.
Sun W, Lal P. Recent development on computer aided tissue engineering – A review. Comput Methods Programs Biomed 2002;67:85-103.
Haycock JW. 3D cell culture: A review of current approaches and techniques. Methods Mol Biol 2011;695:1-5.
Kizawa H, Nagao E, Shimamura M, Zhang G, Torii H. Scaffold-free 3D bio-printed human liver tissue stably maintains metabolic functions useful for drug discovery. Biochem Biophys Rep 2017;10:186-91.
Wang JZ, Xiong NY, Zhao LZ, Hu JT, Kong DC, Yuan JY, et al.
Review fantastic medical implications of 3D-printing in liver surgeries, liver regeneration, liver transplantation and drug hepatotoxicity testing: A review. Int J Surg 2018;56:1-6.
Moldovan NI, Hibino N, Nakayama K. Principles of the kenzan method for robotic cell spheroid-based three-dimensional bioprinting. Tissue Eng Part B Rev 2017;23:237-44.
Moldovan L, Barnard A, Gil CH, Lin Y, Grant MB, Yoder MC, et al.
IPSC-derived vascular cell spheroids as building blocks for scaffold-free biofabrication. Biotechnol J 2017;12: 1700444.
Witowski JS, Coles-Black J, Zuzak TZ, Pędziwiatr M, Chuen J, Major P, et al.
3D printing in liver surgery: A systematic review. Telemed J E Health 2017;23:943-7.
Zein NN, Hanouneh IA, Bishop PD, Samaan M, Eghtesad B, Quintini C, et al.
Three-dimensional print of a liver for preoperative planning in living donor liver transplantation. Liver Transpl 2013;19:1304-10.
Hall JE. Guyton and Hall Textbook of Medical Physiology. 13th
ed. Philadelphia, PA: Elsevier; 2016. p. 1145.
Martini F, Nath JL, Bartholomew EF. Fundamentals of Anatomy and Physiology. 11th
ed., Vol. 1. New York: Pearson Education, Inc.; 2018.
Goldman L, Schafer AI. Goldman-Cecil Medicine. 25th
ed., Vol. 2. Philadelphia, PA: Elsevier/Saunders; 2016.
Giannopoulos AA, Mitsouras D, Yoo SJ, Liu PP, Chatzizisis YS, Rybicki FJ, et al.
Applications of 3D printing in cardiovascular diseases. Nat Rev Cardiol 2016;13:701-18.
Qian Z, Wang K, Liu S, Zhou X, Rajagopal V, Meduri C, et al.
Quantitative prediction of paravalvular leak in transcatheter aortic valve replacement based on tissue-mimicking 3D printing. JACC Cardiovasc Imaging 2017;10:719-31.
Alkhouli M, Sengupta PP. 3-dimensional-printed models for TAVR Planning: Why guess when you can see? JACC Cardiovasc Imaging 2017;10:732-4.
Vukicevic M, Mosadegh B, Min JK, Little SH. Cardiac 3D printing and its future directions. JACC Cardiovasc Imaging 2017;10:171-84.
Billiet T, Vandenhaute M, Schelfhout J, Van Vlierberghe S, Dubruel P. A review of trends and limitations in hydrogel-rapid prototyping for tissue engineering. Biomaterials 2012;33:6020-41.
Kucukgul C, Ozler SB, Inci I, Karakas E, Irmak S, Gozuacik D, et al.
3D bioprinting of biomimetic aortic vascular constructs with self-supporting cells. Biotechnol Bioeng 2015;112:811-21.
Hong S, Sycks D, Chan HF, Lin S, Lopez GP, Guilak F, et al.
3D printing of highly stretchable and tough hydrogels into complex, cellularized structures. Adv Mater 2015;27:4035-40.
Hockaday LA, Kang KH, Colangelo NW, Cheung PY, Duan B, Malone E, et al
. Rapid 3D printing of anatomically accurate and mechanically heterogeneous aortic valve hydrogel scaffolds. Biofabrication 2009;6:247-53.
Zakerzadeh R, Hsu MC, Sacks MS. Computational methods for the aortic heart valve and its replacements. Expert Rev Med Devices 2017;14:849-66.
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; 45(9):e740-60.
Lee VK, Dai G. Printing of three-dimensional tissue analogs for regenerative medicine. Ann Biomed Eng 2017;45:115-31.
Chen SA, Ong CS, Hibino N, Baschat AA, Garcia JR, Miller JL, et al.
3D printing of the fetal heart using 3D ultrasound imaging data. Ultrasound Obstet Gynecol 2018; 26 June 2018 [Epub ahead of print].
Parimi M, Buelter J, Thanugundla V, Condoor S, Parkar N, Danon S, et al.
Feasibility and validity of printing 3D heart models from rotational angiography. Pediatr Cardiol 2018;39:653-8.
Gosnell J, Pietila T, Samuel BP, Kurup HK, Haw MP, Vettukattil JJ, et al.
Integration of computed tomography and three-dimensional echocardiography for hybrid three-dimensional printing in congenital heart disease. J Digit Imaging 2016;29:665-9.
Liu K, Lu B, Zheng Z, Wang E, Shi Y, Gao Y, et al
. GW26-e5394 3D heart model printing of complex congenital heart disease based on the low dose cardiac CT images: Initial experience in China. J Am Coll Cardiol 2015;66:C72.
O'Neill B, Wang DD, Pantelic M, Song T, Guerrero M, Greenbaum A, et al.
Transcatheter caval valve implantation using multimodality imaging: Roles of TEE, CT, and 3D printing. JACC Cardiovasc Imaging 2015;8:221-5.
Smith ML, McGuinness J, O'Reilly MK, Nolke L, Murray JG, Jones JF, et al.
The role of 3D printing in preoperative planning for heart transplantation in complex congenital heart disease. Ir J Med Sci 2017;186:753-6.
Ronaldson-Bouchard K, Vunjak-Novakovic G. Organs-on-a-chip: A Fast track for engineered human tissues in drug development. Cell Stem Cell 2018;22:310-24.
Sherwood L. Human Physiology: From Cells to Systems. 9th
ed., Vol. 1. Boston, MA, USA: Cengage Learning; 2016.
Tortora GJ, Nielsen MT. Principles of Human Anatomy. 13th
ed. Hoboken, NJ: Wiley; 2014..
Murray CJ, Lopez AD, Black R, Mathers CD, Shibuya K, Ezzati M, et al.
Global burden of disease 2005: Call for collaborators. Lancet 2007;370:109-10.
Murray CJ, Lopez AD. Alternative projections of mortality and disability by cause 1990-2020: Global burden of disease study. Lancet 1997;349:1498-504.
Javan R, Herrin D, Tangestanipoor A. Understanding spatially complex segmental and branch anatomy using 3D printing: Liver, lung, prostate, coronary arteries, and circle of willis. Acad Radiol 2016;23:1183-9.
Li X, Cai H, Cui X, Cao P, Zhang J, Li G, et al.
Prevention of late postpneumonectomy complications using a 3D printed lung in dog models. Eur J Cardiothorac Surg 2014;46:e67-73.
Cheng GZ, San Jose Estepar R, Folch E, Onieva J, Gangadharan S, Majid A, et al.
Three-dimensional printing and 3D slicer: Powerful tools in understanding and treating structural lung disease. Chest 2016;149:1136-42.
Hasan A. Tissue Engineering for Artificial Organs: Regenerative Medicine, Smart Diagnostics and Personalized Medicine. Weinheim, Germany: Wiley-VCH; 2017.
Valverde I, Gomez G, Coserria JF, Suarez-Mejias C, Uribe S, Sotelo J, et al.
3D printed models for planning endovascular stenting in transverse aortic arch hypoplasia. Catheter Cardiovasc Interv 2015;85:1006-12.
Lipson H. New world of 3-D printing offers “completely new ways of thinking”: Q and A with author, engineer, and 3-D printing expert hod lipson. IEEE Pulse 2013;4:12-4.
Taniguchi D, Matsumoto K, Tsuchiya T, Machino R, Takeoka Y, Elgalad A, et al.
Scaffold-free trachea regeneration by tissue engineering with bio-3D printing. Interact Cardiovasc Thorac Surg 2018;26:745-52.
Park JH, Hong JM, Ju YM, Jung JW, Kang HW, Lee SJ, et al.
Anovel tissue-engineered trachea with a mechanical behavior similar to native trachea. Biomaterials 2015;62:106-15.
L. Melgoza E, Vallicrosa G, Serenó L, Ciurana J, A. Rodríguez C. Rapid tooling using 3D printing system for manufacturing of customized tracheal stent. Rapid Prototyp J 2014;20:2-12.
Rengier F, Mehndiratta A, von Tengg-Kobligk H, Zechmann CM, Unterhinninghofen R, Kauczor HU, et al.
3D printing based on imaging data: Review of medical applications. Int J Comput Assist Radiol Surg 2010;5:335-41.
Melchiorri AJ, Hibino N, Best CA, Yi T, Lee YU, Kraynak CA, et al.
3D-printed biodegradable polymeric vascular grafts. Adv Healthc Mater 2016;5:319-25.
Park SH, Kang BK, Lee JE, Chun SW, Jang K, Kim YH, et al.
Design and fabrication of a thin-walled free-form scaffold on the basis of medical image data and a 3D printed template: Its potential use in bile duct regeneration. ACS Appl Mater Interfaces 2017;9:12290-8.
Radenkovic D, Solouk A, Seifalian A. Personalized development of human organs using 3D printing technology. Med Hypotheses 2016;87:30-3.
Wengerter BC, Emre G, Park JY, Geibel J. Three-dimensional printing in the intestine. Clin Gastroenterol Hepatol 2016;14:1081-5.
Youssef RF, Spradling K, Yoon R, Dolan B, Chamberlin J, Okhunov Z, et al.
Applications of three-dimensional printing technology in urological practice. BJU Int 2015;116:697-702.
Potamianos P, Amis AA, Forester AJ, McGurk M, Bircher M. Rapid prototyping for orthopaedic surgery. Proc Inst Mech Eng Part H J Eng Med 1998;212:383-93.
Burg KJ, Porter S, Kellam JF. Biomaterial developments for bone tissue engineering. Biomaterials 2000;21:2347-59.
Eltorai AE, Nguyen E, Daniels AH. Three-dimensional printing in orthopedic surgery. Orthopedics 2015;38:684-7.
Ackland DC, Robinson D, Redhead M, Lee PV, Moskaljuk A, Dimitroulis G, et al.
Apersonalized 3D-printed prosthetic joint replacement for the human temporomandibular joint: From implant design to implantation. J Mech Behav Biomed Mater 2017;69:404-11.
Christensen AM. Method for Design and Production of a Custom-Fit Prosthesis. Google Patents; 2011.
Wong KC, Kumta SM, Geel NV, Demol J. One-step reconstruction with a 3D-printed, biomechanically evaluated custom implant after complex pelvic tumor resection. Comput Aided Surg 2015;20:14-23.
Klein TJ, Rizzi SC, Reichert JC, Georgi N, Malda J, Schuurman W, et al.
Strategies for zonal cartilage repair using hydrogels. Macromol Biosci 2009;9:1049-58.
Corona PS, Vicente M, Tetsworth K, Glatt V. Preliminary results using patient-specific 3d printed models to improve preoperative planning for correction of post-traumatic tibial deformities with circular frames. Injury 2018;49 Suppl 2:S51-9.
Tetsworth K, Block S, Glatt V. Putting 3D modelling and 3D printing into practice: Virtual surgery and preoperative planning to reconstruct complex post-traumatic skeletal deformities and defects. SICOT J 2017;3:16.
Seramak T, Zasinska K, Zielinski A, Gubanski M. 3D Printing of metallic implants. World J Res Rev 2017;5:1-4.
Chae MP, Rozen WM, McMenamin PG, Findlay MW, Spychal RT, Hunter-Smith DJ, et al.
Emerging applications of bedside 3D printing in plastic surgery. Front Surg 2015;2:25.
Handels H, Ehrhardt J, Plötz W, Pöppl SJ. Three-dimensional planning and simulation of hip operations and computer-assisted construction of endoprostheses in bone tumor surgery. Comput Aided Surg 2001;6:65-76.
Cai H. Application of 3D printing in orthopedics: Status quo and opportunities in China. Ann Transl Med 2015;3:S12.
Li X, Wang Y, Zhao Y, Liu J, Xiao S, Mao K, et al.
Multilevel 3D printing implant for reconstructing cervical spine with metastatic papillary thyroid carcinoma. Spine (Phila Pa 1976) 2017;42:E1326-30.
Arabnejad S, Johnston B, Tanzer M, Pasini D. Fully porous 3D printed titanium femoral stem to reduce stress-shielding following total hip arthroplasty. J Orthop Res 2017;35:1774-83.
Sun AX, Lin H, Beck AM, Kilroy EJ, Tuan RS. Projection stereolithographic fabrication of human adipose stem cell-incorporated biodegradable scaffolds for cartilage tissue engineering. Front Bioeng Biotechnol 2015;3:115.
Trauner KB. The emerging role of 3D printing in arthroplasty and orthopedics. J Arthroplasty 2018;33:2352-4.
Yang Y, Chu L, Yang S, Zhang H, Qin L, Guillaume O, et al.
Dual-functional 3D-printed composite scaffold for inhibiting bacterial infection and promoting bone regeneration in infected bone defect models. Acta Biomater 2018;79:265-75.
Trenfield SJ, Awad A, Goyanes A, Gaisford S, Basit AW. 3D printing pharmaceuticals: Drug development to frontline care. Trends Pharmacol Sci 2018;39:440-51.
Peng W, Datta P, Ayan B, Ozbolat V, Sosnoski D, Ozbolat IT, et al.
3D bioprinting for drug discovery and development in pharmaceutics. Acta Biomater 2017;57:26-46.
Scoutaris N, Ross S, Douroumis D. Current trends on medical and pharmaceutical applications of inkjet printing technology. Pharm Res 2016;33:1799-816.
Gupta MK, Meng F, Johnson BN, Kong YL, Tian L, Yeh YW, et al.
3D printed programmable release capsules. Nano Lett 2015;15:5321-9.
Goyanes A, Wang J, Buanz A, Martínez-Pacheco R, Telford R, Gaisford S, et al.
3D printing of medicines: Engineering novel oral devices with unique design and drug release characteristics. Mol Pharm 2015;12:4077-84.
Dawood A, Marti BM, Sauret-Jackson V, Darwood A. 3D printing in dentistry. Br Dent J 2015;219:521.
Winder J, Bibb R. Medical rapid prototyping technologies: State of the art and current limitations for application in oral and maxillofacial surgery. J Oral Maxillofac Surg 2005;63:1006-15.
Wurm G, Tomancok B, Pogady P, Holl K, Trenkler J. Cerebrovascular stereolithographic biomodeling for aneurysm surgery. Technical note. J Neurosurg 2004;100:139-45.
Müller A, Krishnan KG, Uhl E, Mast G. The application of rapid prototyping techniques in cranial reconstruction and preoperative planning in neurosurgery. J Craniofac Surg 2003;14:899-914.
Cho MJ, Kane AA, Hallac RR, Gangopadhyay N, Seaward JR. Liquid latex molding: A Novel application of 3D printing to facilitate flap design. Cleft Palate Craniofac J 2017;54:453-6.
Msallem B, Beiglboeck F, Honigmann P, Jaquiéry C, Thieringer F. Craniofacial reconstruction by a cost-efficient template-based process using 3D printing. Plast Reconstr Surg Glob Open 2017;5:e1582.
Cheng CH, Chuang HY, Lin HL, Liu CL, Yao CH. Surgical results of cranioplasty using three-dimensional printing technology. Clin Neurol Neurosurg 2018;168:118-23.
Madrazo I, Zamorano C, Magallón E, Valenzuela T, Ibarra A, Salgado-Ceballos H, et al.
Stereolithography in spine pathology: A 2-case report. Surg Neurol 2009;72:272-5.
Gibbs DM, Vaezi M, Yang S, Oreffo RO. Hope versus hype: What can additive manufacturing realistically offer trauma and orthopedic surgery? Regen Med 2014;9:535-49.
Ravnic DJ, Leberfinger AN, Koduru SV, Hospodiuk M, Moncal KK, Datta P, et al.
Transplantation of bioprinted tissues and organs: Technical and clinical challenges and future perspectives. Ann Surg 2017;266:48-58.
Asa'ad F, Pagni G, Pilipchuk SP, Giannì AB, Giannobile WV, Rasperini G, et al.
3D-printed scaffolds and biomaterials: Review of alveolar bone augmentation and periodontal regeneration applications. Int J Dent 2016;2016:1239842.
Marga F, Jakab K, Khatiwala C, Shepherd B, Dorfman S, Hubbard B, et al.
Toward engineering functional organ modules by additive manufacturing. Biofabrication 2012;4:022001.
Cui H, Nowicki M, Fisher JP, Zhang LG. 3D bioprinting for organ regeneration. Adv Healthc Mater 2017;6: 1601118.
Pekkanen AM, Mondschein RJ, Williams CB, Long TE. 3D printing polymers with supramolecular functionality for biological applications. Biomacromolecules 2017;18:2669-87.
Lang M. Systems for the automated 3D assembly of micro-tissue and bio-printing of tissue engineered constructs. 2012. Available at: ir.canterbury.ac.nz/bitstream/handle/10092/7237/thesis_fulltext.pdf?sequence=1.[Last accessed on 2018 Nov 21].
Nakamura M, Iwanaga S, Henmi C, Arai K, Nishiyama Y. Biomatrices and biomaterials for future developments of bioprinting and biofabrication. Biofabrication 2010;2:014110.
Levato R, Visser J, Planell JA, Engel E, Malda J, Mateos-Timoneda MA, et al.
Biofabrication of tissue constructs by 3D bioprinting of cell-laden microcarriers. Biofabrication 2014;6:035020.
Ratheesh G, Venugopal JR, Chinappan A, Ezhilarasu H, Sadiq A, Ramakrishna S. 3D fabrication of polymeric scaffolds for regenerative therapy. ACS Biomater Sci Eng 2017;3:1175-94.
Mohamed TA. Development of a 3D bioprinting software toolchain. Vancouver, Canada: University of British Columbia; 2014.
Baumers M. Economic Aspects of Additive Manufacturing: Benefits, Costs and Energy Consumption.©
Martin Baumers; 2012.
Murphy SV, Atala A. Organ engineering – Combining stem cells, biomaterials, and bioreactors to produce bioengineered organs for transplantation. Bioessays 2013;35:163-72.
Visconti RP, Kasyanov V, Gentile C, Zhang J, Markwald RR, Mironov V, et al.
Towards organ printing: Engineering an intra-organ branched vascular tree. Expert Opin Biol Ther 2010;10:409-20.
Morrison RJ, Kashlan KN, Flanangan CL, Wright JK, Green GE, Hollister SJ, et al.
Regulatory considerations in the design and manufacturing of implan[table 3]D-printed medical devices. Clin Transl Sci 2015;8:594-600.
Vertes AA, Qureshi N, Caplan AI, Babiss LE. Stem Cells in Regenerative Medicine: Science, Regulation & Business Strategies. Hoboken, New Jersey: John Wiley and Sons; 2015.
Mosadegh B, Xiong G, Dunham S, Min JK. Current progress in 3D printing for cardiovascular tissue engineering. Biomed Mater 2015;10:034002.
Song J, Millman JR. Economic 3D-printing approach for transplantation of human stem cell-derived β-like cells. Biofabrication 2016;9:015002.
Lee N. The lancet technology: 3D printing for instruments, models, and organs? Lancet 2016;388:1368.
Naftulin JS, Kimchi EY, Cash SS. Streamlined, inexpensive 3D printing of the brain and skull. PLoS One 2015;10:e0136198.
Randazzo M, Pisapia JM, Singh N, Thawani JP. 3D printing in neurosurgery: A systematic review. Surg Neurol Int 2016;7:S801-9.
Lee YB, Polio S, Lee W, Dai G, Menon L, Carroll RS, et al.
Bio-printing of collagen and VEGF-releasing fibrin gel scaffolds for neural stem cell culture. Exp Neurol 2010;223:645-52.
Taneva E, Kusnoto B, Evans CA. 3D scanning, imaging, and printing in orthodontics. In: Issues in Contemporary Orthodontics. London, England: InTech; 2015.
Morrison RJ, Hollister SJ, Niedner MF, Mahani MG, Park AH, Mehta DK, et al.
Mitigation of tracheobronchomalacia with 3D-printed personalized medical devices in pediatric patients. Sci Transl Med 2015;7:285ra64.
Chang JW, Park SA, Park JK, Choi JW, Kim YS, Shin YS, et al.
Tissue-engineered tracheal reconstruction using three-dimensionally printed artificial tracheal graft: Preliminary report. Artif Organs 2014;38:E95-105.
Nakada T, Akiba T, Inagaki T, Morikawa T. Thoracoscopic anatomical subsegmentectomy of the right S2b+S3 using a 3D printing model with rapid prototyping. Interact Cardiovasc Thorac Surg 2014;19:696-8.
[Figure 1], [Figure 2], [Figure 3]
[Table 1], [Table 2]