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 Table of Contents  
REVIEW ARTICLE
Year : 2018  |  Volume : 4  |  Issue : 3  |  Page : 252-265

Medical applications of stereolithography: An overview


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 Submission11-Nov-2018
Date of Acceptance19-Nov-2018
Date of Web Publication24-Dec-2018

Correspondence Address:
Dr. Stanislaw P Stawicki
Department of Research and Innovation, St. Luke's University Health Network, Bethlehem, Pennsylvania
USA
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/IJAM.IJAM_54_18

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  Abstract 


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 Jan 23];4:252-65. Available from: http://www.ijam-web.org/text.asp?2018/4/3/252/248331




  Introduction and Definitions Top


During the past two decades, three-dimensional printing (3DP) technologies have seen rapid growth and increasing number of practical implementations.[1],[2] 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.[3],[4] 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.[5],[6],[7],[8],[9],[10] 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.[11],[12],[13],[14]

At its core, 3DP is an important component of a much larger trend, “health industrialization”.[14],[15] 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.[10],[16] In health-care, the primary approaches utilizing 3DP include stereolithography, selective laser sintering (SLS), electrospinning, and bioprinting [Table 1].[17],[18] 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.[19],[20],[21]
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.[22],[23] 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].[22],[23],[24] 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.[25],[26] 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.[27],[28],[29]
Figure 1: Different types of three-dimensional printers/approaches: (a) Bioprinter; (b) selective laser sintering; (c) electrospinning; and (d) stereolithography; Source: Wikimedia commons

Click here to view


In the area of orthodontics, stereolithography has been used to create highly customized dental implants and other prosthetic constructs applicable to oral-maxillofacial surgery.[30],[31],[32] Within this important area of practical clinical application, 3DP uses high-energy lasers to shape and to harden a polymer into the intended configuration.[33] SLS is another method of manufacturing computer-aided structural models, utilizing serial applications of powdered substrate material exposed to focused laser energy [Figure 1].[34],[35]

Electrospinning is a relatively new 3DP method, currently subject to significant research efforts.[36],[37],[38] This approach enables researchers to generate ultrathin fibers from a diverse number of materials (e.g., ceramics, composites, polymers).[38] 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.[37] 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].[39],[40] 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 Top


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.[41] 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.[42],[43],[44] 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.[44] 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.[12],[45],[46]


  Stereolithography: Materials, Methods, and Challenges Top


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.[12],[47] 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.[48] 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.[49],[50] 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.[51] 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.[52] 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.[53],[54] 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.[51],[54]

With continued technological and methodological advances, it is hoped that biomedical applications of 3DP will expand to include bioprinting of human organs.[55],[56] 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.[51],[57],[58],[59] 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.[57],[60],[61] 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.[60] 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.[62] 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.[51] Subsequent sections of this manuscript will discuss the status of research pertaining to individual organs/organ systems.


  Kidneys and Urinary System Top


The renal system is critical to human physiological homeostasis.[63] It regulates serum pH, electrolyte levels, and is vital for eliminating metabolic/nitrogenous waste from the body.[64] Renal dysfunction may progress to chronic kidney failure, resulting in the patient becoming dependent on hemodialysis as the primary management approach.[65] 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.[66],[67],[68],[69] Moreover, the cost of dialysis can become a significant burden on patients, their families, and the overall health-care system.[69]

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.[70],[71] Given the recent advances in stereolithography, researchers began to examine innovative ways to bioprint various parts of individual organs.[72],[73] 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.[74],[75] Using multiple gel-like inks; the researchers can print hollow tubes, to which cells can be added that subsequently mature into the intended tissue.[76],[77],[78] With trial/error and time, small, complex tubes that work much like the major components of kidneys have been developed through 3DP technology.[73],[79],[80] 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.[57],[81] Researchers at The Wake Forest Institute of Regenerative Medicine developed a bioengineered urinary bladder that was successfully implanted into a patient.[82],[83] A urethral injury bioprinting model has also been studied, with the intent to use 3DP to replace an injured urethra using various cell blends.[84],[85] Theoretically, similar concepts and approaches could be applied to other tubular structures such as the bile ducts and blood vessels.[86],[87] 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.[88],[89],[90] Other potential applications of bioprinting involving the renal system include the testing of tissue response to radiation[91] and drug dosing (e. g., in patients with chronic renal disease).[92],[93] 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.[94],[95],[96]


  The Pancreas Top


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.[97],[98],[99],[100] 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.[101] Due to the flexibility of the PLA model, the seeded cells were able to differentiate and assume some characteristics of the adult pancreas.[101] 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[102] and testing of novel drug delivery systems for pancreatic malignancies.[103] It is hoped that the above developments may help improve our understanding and ability to effectively manage pancreatic cancer.[104]


  The Liver Top


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.[105],[106],[107] 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.[108],[109]

In the past, there have been studies examining 3D hepatocyte cell cultures, with limited ability to sustain function for long periods of time.[110],[111] 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.[112],[113] In one recent report, scaffold-free 3D-printed liver tissue was created that can maintain metabolic function for longer periods of time.[114] 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.[115],[116],[117] As with other areas of 3DP applications, surgeons have utilized 3DP models in operative planning for complex hepatic procedures.[118],[119]


  Cardiovascular System Top


The cardiovascular system is responsible for transporting oxygen, nutrients, and various metabolites throughout the human body.[120],[121] 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).[122] 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.[50],[123],[124],[125]

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.[123],[126] Aortic valves were successfully printed using polyethylene glycol-diacrylate hydrogels supplemented with alginate.[21],[127],[128],[129] 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,[130] 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.[131],[132] As with other implantable devices, potential problems involving 3DP heart valves may include temporal changes within the bioprinted material[130] and the risk of host immune response directed against the implant.[133] 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,[134],[135],[136] facilitating preoperative planning for procedures ranging from stent placement to cardiac transplantation.[137],[138],[139]

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.[140],[141] 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].[142] It has been projected that fully functional bioprinted hearts may be feasible within the next two decades.[12]
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

Click here to view



  Pulmonary System Top


The pulmonary system's primary function is an exchange of gases through respiration, with secondary roles including regulation of acid-base homeostasis.[143],[144] 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.[145],[146] 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.[147],[148] 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.[149] 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.[147],[150]

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).[151],[152]


  Trachea and Other Tubular Structures Top


Among the most advanced applications of 3DP is the area of bioprinting of tubular structures, from large vessel grafts to the trachea.[153],[154] In fact, 3D printing has been used to create tracheal scaffolds that are suitable for human implantation.[154],[155] In the area of bioprinted tracheal implants, further work is being conducted to better approximate in vivo tissue behavior, and tissue-tissue interactions.[156],[157] 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.[153],[158],[159] 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,[160],[161] bowel,[162] and hollow urinary structures.[85],[163] 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 Top


Stereolithography has made tremendous strides in the area of orthopedic surgery, from rapid prototyping and anatomical modeling to 3D-printed instruments and implants.[164],[165],[166] 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].[167],[168],[169] 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.[170],[171],[172]
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.[173] Since the human anatomy is symmetrical, researchers can “reverse” 3D images using human anatomy data to reconstruct tailored prosthetics.[174],[175],[176] One practical example of the latter includes the report of the successful creation of customized implants for acetabular reconstructive surgery.[176] In another example, spinal reconstruction was determined to be plausible using 3D printed material.[177] Finally, porous 3D-printed titanium femoral stems may help facilitate better tissue healing following total hip arthroplasty.[178]

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.[40],[176],[179],[180] If sufficient reproducibility and reliability can be achieved, the number of patients who require large joint replacements may be reduced.[40],[176],[180] 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.[181]


  Pharmacological Applications of Stereolithography Top


As outlined throughout this review, pharmacological testing – including drug metabolism and toxicity– has benefited significantly from 3DP applications.[182],[183] Novel methods of drug delivery are being designed using stereolithography, from microneedles to innovative capsule designs.[8],[184],[185] Collectively, such advances would not be possible without the tremendous progress in 3DP outlined herein.[186] 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.[12]


  Stereolithography: Other Applications, Challenges, and Miscellaneous Topics Top


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,[187] oral and maxillofacial surgery,[188] neurosurgery,[189],[190] plastic and reconstructive surgery [Figure 3],[191],[192],[193] spine surgery,[194] and traumatology.[195]
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.[12] The availability of highly customized and personalized 3DP tissues, organs, implants, prosthetics, and drugs promises to revolutionize existing health-care paradigms.[12],[196],[197] 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.[23],[198],[199],[200]


  Challenges and Special Considerations Top


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.[201],[202] Other challenges involve finding the best biomaterials that will help optimize the process of printing and maturing the bioprinted tissues and organs.[57],[203],[204] 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.[79],[205] 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.[79]

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.[206],[207] 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.[79]

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”.[79] 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).[79],[208] The cost of the bioprinting of organs will be considerable, although economically justifiable if eventual implantations lead to lower long-term health-care costs.[209] 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.[210] 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.[211] 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.[212] 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.[222]


  Conclusion Top


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

Nil.

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.





 
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