Application of 3D bioprinting in the prevention and the therapy for Of these studies, more than half of them (53%) reported quantitative findings of 3D-printed model accuracy in displaying renal structures or renal tumors, or reduction in intraoperative examination time, while the remaining seven studies reported qualitative analysis of 3D-printed kidney models in improving patients understanding of normal anatomy and pathology, and clinical value of 3D-printed in models in pre-surgical planning or simulation of renal procedures and reduction of complications associated with operations. It's a win-win situation for both dentists and their patients. Since its introduction in the 1980s, the three-dimensional (3D) printing technology has evolved to revolutionize both scientific community and academician. Despite most of the studies being case reports in the review, qualitative and quantitative results showed the usefulness of the 3D-printed models in the preoperative planning and simulation of surgical procedures of liver lesions, as well as in medical education and training (Figure 4). Industrial applications of 3D printing to scale-up - Future Medicine The .gov means its official. However, various 3D printing techniques and materials have been applied successfully to create vasculature as simple as a single channel, as well as more complex geometries, such as bifurcated or branched channels.6,10,13 Recently, collaborators from a network of academic institutions, including the University of Sydney, Harvard University, Stanford University, and the Massachusetts Institute of Technology, announced that they had bioprinted a functional and perfusable network of capillaries, an achievement that represents a significant stride toward overcoming this problem.14, Implants and prostheses can be made in nearly any imaginable geometry through the translation of x-ray, MRI, or CT scans into digital .stl 3D print files.2,3,6 In this way, 3D printing has been used successfully in the health care sector to make both standard and complex customized prosthetic limbs and surgical implants, sometimes within 24 hours.3,7,9 This approach has been used to fabricate dental, spinal, and hip implants.3 Previously, before implants could be used clinically, they had to be validated, which is very time-consuming.3, The ability to quickly produce custom implants and prostheses solves a clear and persistent problem in orthopedics, where standard implants are often not sufficient for some patients, particularly in complex cases.3 Previously, surgeons had to perform bone graft surgeries or use scalpels and drills to modify implants by shaving pieces of metal and plastic to a desired shape, size, and fit.3,7 This is also true in neurosurgery: Skulls have irregular shapes, so it is hard to standardize a cranial implant.3 In victims of head injury, where bone is removed to give the brain room to swell, the cranial plate that is later fitted must be perfect.9 Although some plates are milled, more and more are created using 3D printers, which makes it much easier to customize the fit and design.3, There have been many other commercial and clinical successes regarding the 3D printing of prostheses and implants.2,3,6 A research team at the BIOMED Research Institute in Belgium successfully implanted the first 3D-printed titanium mandibular prosthesis.2 The implant was made by using a laser to successively melt thin layers of titanium powders.2 In 2013, Oxford Performance Materials received FDA approval for a 3D-printed polyetherketoneketone (PEKK) skull implant, which was first successfully implanted that year.2 Another company, LayerWise, manufactures 3D-printed titanium orthopedic, maxillofacial, spinal, and dental implants.6 An anatomically correct 3D-printed prosthetic ear capable of detecting electromagnetic frequencies has been fabricated using silicon, chondrocytes, and silver nanoparticles.6 There is a growing trend toward making 3D-printed implants out of a variety of metals and polymers, and more recently implants have even been printed with live cells.9, 3D printing has already had a transformative effect on hearing aid manufacturing.3 Today, 99% of hearing aids that fit into the ear are custom-made using 3D printing.3 Everyones ear canal is shaped differently, and the use of 3D printing allows custom-shaped devices to be produced efficiently and cost-effectively.3 The introduction of customized 3D-printed hearing aids to the market was facilitated by the fact that class I medical devices for external use are subject to fewer regulatory restrictions.3 Invisalign braces are another successful commercial use of 3D printing, with 50,000 printed every day.9 These clear, removable, 3D-printed orthodontic braces are custom-made and unique to each user.9 This product provides a good example of how 3D printing can be used efficiently and profitably to make single, customized, complex items.9, The individual variances and complexities of the human body make the use of 3D-printed models ideal for surgical preparation (Figure 4).2 Having a tangible model of a patients anatomy available for a physician to study or use to simulate surgery is preferable to relying solely on MRI or CT scans, which arent as instructive since they are viewed in 2D on a flat screen.6 The use of 3D-printed models for surgical training is also preferable to training on cadavers, which present problems with respect to availability and cost.3 Cadavers also often lack the appropriate pathology, so they provide more of a lesson in anatomy than a representation of a surgical patient.3, Researchers at the National Library of Medicine generate digital files from clinical data, such as CT scans, that are used to make custom 3D-printed surgical and medical models.12, 3D-printed neuroanatomical models can be particularly helpful to neurosurgeons by providing a representation of some of the most complicated structures in the human body (Figure 5).2 The intricate, sometimes obscured relationships between cranial nerves, vessels, cerebral structures, and skull architecture can be difficult to interpret based solely on radiographic 2D images.2 Even a small error in navigating this complex anatomy can have potentially devastating consequences.2 A realistic 3D model reflecting the relationship between a lesion and normal brain structures can be helpful in determining the safest surgical corridor and can also be useful for the neurosurgeon to rehearse challenging cases.2 Complex spinal deformities can also be studied better through the use of a 3D model.2 High-quality 3D anatomical models with the right pathology for training doctors in performing colonoscopies are also vital, since colorectal cancer is the second leading cause of cancer-related deaths in the U.S.3,15, A 3D model used for surgical planning by neurosurgeons at the Walter Reed National Military Medical Center.12, Although still largely exploratory, 3D-printed models have been used in numerous cases to gain insight into a patients specific anatomy prior to a medical procedure.6 Pioneering surgeons at Japans Kobe University Hospital have used 3D-printed models to plan liver transplantations.2 They use replicas of a patients organs to determine how to best carve a donor liver with minimal tissue loss to fit the recipients abdominal cavity.2 These 3D models are made of partially transparent, low-cost acrylic resin or polyvinyl alcoholmaterials that have a water content and texture similar to living tissues, allowing a more realistic penetration by the surgical blades.2, Other surgeons have used a 3D-printed model of a calcified aorta for surgical planning of plaque removal.6 A premature infants airway was also reconstructed in order to study aerosol drug delivery to the lungs.6 It has been reported that an orthopedic surgery trainee used CT image scans and 3D modeling software to create print files representing a patients bones.11 The files were then sent to Shapeways to print custom models used for planning surgery.11 The cost for 3D printing was a fraction of what it would normally cost to have custom models made, and the turn-around time was faster.11, 3D-printed models can be useful beyond surgical planning.6 Recently, a polypeptide chain model was 3D printed in such a way that it could fold into secondary structures because of the inclusion of bond rotational barriers and degrees of freedom considerations.6 Similar models could be utilized to aid the understanding of other types of biological or biochemical structures (Figure 6).6 Pre- and post-comprehension study results have shown that students are better able to conceptualize molecular structures when such 3D models are used.6, A 3D-printed representation of an influenza hemagglutinin trimer.12, 3D printing technologies are already being used in pharmaceutical research and fabrication, and they promise to be transformative.5 Advantages of 3D printing include precise control of droplet size and dose, high reproducibility, and the ability to produce dosage forms with complex drug-release profiles.5, Complex drug manufacturing processes could also be standardized through use of 3D printing to make them simpler and more viable.3 3D printing technology could be very important in the development of personalized medicine, too.3, The purpose of drug development should be to increase efficacy and decrease the risk of adverse reactions, a goal that can potentially be achieved through the application of 3D printing to produce personalized medications.3,5,16, Oral tablets are the most popular drug dosage form because of ease of manufacture, pain avoidance, accurate dosing, and good patient compliance.16 However, no viable method is available that could routinely be used to make personalized solid dosage forms, such as tablets.16 Oral tablets are currently prepared via well-established processes such as mixing, milling, and dry and wet granulation of powdered ingredients that are formed into tablets through compression or molds.16 Each of these manufacturing steps can introduce difficulties, such as drug degradation and form change, possibly leading to problems with formulation or batch failures.16 In addition, these traditional manufacturing processes are unsuitable for creating personalized medicines and restrict the ability to create customized dosage forms with highly complex geometries, novel drug-release profiles, and prolonged stability.16, Personalized 3D-printed drugs may particularly benefit patients who are known to have a pharmacogenetic polymorphism or who use medications with narrow therapeutic indices.5 Pharmacists could analyze a patients pharmacogenetic profile, as well as other characteristics such as age, race, or gender, to determine an optimal medication dose.5 A pharmacist could then print and dispense the personalized medication via an automated 3D printing system.5 If necessary, the dose could be adjusted further based on clinical response.5, 3D printing also has the potential to produce personalized medicines in entirely new formulationssuch as pills that include multiple active ingredients, either as a single blend or as complex multilayer or multireservoir printed tablets.16 Patients who have multiple chronic diseases could have their medications printed in one multidose form that is fabricated at the point of care.16 Providing patients with an accurate, personalized dose of multiple medications in a single tablet could potentially improve patient compliance.16 Ideally, compounding pharmacies could dispense 3D-printed drugs, since their customers are already familiar with purchasing customized medications.5, The primary 3D printing technologies used for pharmaceutical production are inkjet-based or inkjet powder-based 3D printing.5 Whether another material or a powder is used as the substrate is what differentiates 3D inkjet printing from powder-based 3D inkjet printing.5, In inkjet-based drug fabrication, inkjet printers are used to spray formulations of medications and binders in small droplets at precise speeds, motions, and sizes onto a substrate.5 The most commonly used substrates include different types of cellulose, coated or uncoated paper, microporous bioceramics, glass scaffolds, metal alloys, and potato starch films, among others.5 Investigators have further improved this technology by spraying uniform ink droplets onto a liquid film that encapsulates it, forming microparticles and nanoparticles.5 Such matrices can be used to deliver small hydrophobic molecules and growth factors.5 In powder-based 3D printing drug fabrication, the inkjet printer head sprays the ink onto the powder foundation.5 When the ink contacts the powder, it hardens and creates a solid dosage form, layer by layer.5 The ink can include active ingredients as well as binders and other inactive ingredients.5 After the 3D-printed dosage form is dry, the solid object is removed from the surrounding loose powder substrate.5, These technologies offer the ability to create limitless dosage forms that are likely to challenge conventional drug fabrication.5 3D printers have already been used to produce many novel dosage forms, such as: microcapsules, hyaluronan-based synthetic extracellular matrices, antibiotic printed micropatterns, mesoporous bioactive glass scaffolds, nanosuspensions, and multilayered drug delivery devices.5 Ink formulations used in 3D drug printing have included a variety of active ingredients, such as: steroidal anti-inflammatory drugs, acetaminophen, theophylline, caffeine, vancomycin, ofloxacin, tetracycline, dexamethasone, paclitaxel, folic acid, and others.5 Inactive ingredients used in 3D drug printing have included: poly(lacticco-glycolic acid), ethanol-dimethyl sulfoxide, surfactants (such as Tween 20), Kollidon SR, glycerin, cellulose, propylene glycol, methanol, acetone, and others.5, The creation of medications with complex drug-release profiles is one of the most researched uses of 3D printing.5 Traditional compressed dosage forms are often made from a homogeneous mixture of active and inactive ingredients, and are thus frequently limited to a simple drug-release profile.6 However, 3D printers can print binder onto a matrix powder bed in layers typically 200 micro meters thick, creating a barrier between the active ingredients to facilitate controlled drug release.6 3D-printed dosage forms can also be fabricated in complex geometries that are porous and loaded with multiple drugs throughout, surrounded by barrier layers that modulate release.6, Implantable drug delivery devices with novel drug-release profiles can also be created using 3D printing.6 Unlike traditional systemic treatments that can affect nonafflicted tissue, these devices can be implanted to provide direct treatment to the area involved.6 Bone infections are one example where direct treatment with a drug implant is more desirable than systemic treatment.6 Fortunately, powder-based 3D-printed bone scaffolding can be created in high-resolution models with complex geometries that mimic the natural bone extracellular matrix.5 The printing of medications with customized drug-release profiles into such bone implant scaffolds has been studied.5 One example is the printing of a multilayered bone implant with a distinct drug-release profile alternating between rifampicin and isoniazid in a pulse release mechanism.5 3D printing has also been used to print antibiotic micropatterns on paper, which have been used as drug implants to eradicate Staphylococcus epidermidis.5, In other research concerning drug-release profiles, chlorpheniramine maleate was 3D printed onto a cellulose powder substrate in amounts as small as 10 to 12 moles to demonstrate that even a minute quantity of drug could be released at a specified time.5 This study displayed improved accuracy for the release of very small drug doses compared with conventionally manufactured medications.5 Dexamethasone has been printed in a dosage form with a two-stage release profile.5 Levofloxacin has been 3D printed as an implantable drug delivery device with pulsatile and steady-state release mechanisms.5, Despite the many potential advantages that 3D printing may provide, expectations of the technology are often exaggerated by the media, governments, and even researchers.3 This promotes unrealistic projections, especially regarding how soon some of the more exciting possibilitiessuch as organ printingwill become a reality.3 Although progress is being made toward these and other goals, they are not expected to happen soon.3,4 3D printing will require vision, money, and time for the technology to evolve into the anticipated applications.3 While it is certain that the biomedical sector will be one of the most fertile fields for 3D printing innovations, it is important to appreciate what has already been achieved without expecting that rapid advances toward the most sophisticated applications will occur overnight.3, 3D printing has given rise to safety and security issues that merit serious concern.8,11 3D printers have already been employed for criminal purposes, such as printing illegal items like guns and gun magazines, master keys, and ATM skimmers.7,11 These occurrences have highlighted the lack of regulation of 3D printing technology.7 In theory, 3D printing could also be used to counterfeit substandard medical devices or medications.12 Although 3D printing should not be banned, its safety over the long term will clearly need to be monitored.7, In 2012, in response to the news that a functioning plastic handgun had been 3D printed, several local and state legislators introduced bills banning access to this technology.8 However, such fear-based policy responses could stifle the culture of openness necessary for 3D printing to thrive.8 Such a ban could push 3D printing underground at the expense of important scientific, medical, and other advances.8 There have already been reports of garage biology being conducted that could potentially lead to innovations in the life sciences.8 However, it is being conducted in secrecy to avoid interference from law enforcementeven though the research is legal.8, Manufacturing applications of 3D printing have been subject to patent, industrial design, copyright, and trademark law for decades.11 However, there is limited experience regarding how these laws should apply to the use of 3D printing by individuals to manufacture items for personal use, nonprofit distribution, or commercial sale.11 Patents with a finite duration usually provide legal protection for proprietary manufacturing processes, composition of matter, and machines.11 To sell or distribute a 3D-printed version of a patented item, a person would have to negotiate a license with the patent owner, since distribution of the item without permission would violate patent law.11, Copyright is also an issue encountered in 3D printing.11 The fact that copyrights traditionally dont apply to functional objects beyond their aesthetic value may limit the significance in this area.11 However, that does not mean that concerns about copyrights are inconsequential.11 In at least one case, a designer filed a copyright takedown notice demanding that a 3D print file repository remove another participants design because the complainant considered the design to infringe on his copyright.11, Securing approval from regulators is another significant barrier that may impede the widespread medical application of 3D printing.5,7 A number of fairly simple 3D-printed medical devices have received the FDAs 510(k) approval.17 However, fulfilling more demanding FDA regulatory requirements could be a hurdle that may impede the availability of 3D-printed medical products on a large scale.5,17 For example, the need for large randomized controlled trials, which require time and funding, could present a barrier to the availability of 3D-printed drug dosage forms.5 In addition, manufacturing regulations and state legal requirements could impose obstacles regarding the dispensing of 3D-printed medications.5 3D drug printers must also be legally defined as manufacturing or compounding equipment to better determine what laws they are subject to.5, Ultimately, the regulatory decisions that are made should be based on sound science and technology.8 With this goal in mind, the FDA recently created a working group to assess technical and regulatory considerations regarding 3D printing.17 The FDA is also sponsoring a 3D printing workshop and webinar regarding technical considerations of 3D-printed medical devices, which will be held on October 8 and 9, 2014.17,18 Members of industry and academia have been invited to participate so that they may help shape future regulatory guidance.17,18, 3D printing is expected to play an important role in the trend toward personalized medicine, through its use in customizing nutritional products, organs, and drugs.3,9 3D printing is expected to be especially common in pharmacy settings.5 The manufacturing and distribution of drugs by pharmaceutical companies could conceivably be replaced by emailing databases of medication formulations to pharmacies for on-demand drug printing.1 This would cause existing drug manufacturing and distribution methods to change drastically and become more cost-effective.1 If most common medications become available in this way, patients might be able to reduce their medication burden to one polypill per day, which would promote patient adherence.5, The most advanced 3D printing application that is anticipated is the bioprinting of complex organs.3,11 It has been estimated that we are less than 20 years from a fully functioning printable heart.8 Although, due to challenges in printing vascular networks, the reality of printed organs is still some way off, the progress that has been made is promising.3,7 As the technology advances, it is expected that complex heterogeneous tissues, such as liver and kidney tissues, will be fabricated successfully.9 This will open the door to making viable live implants, as well as printed tissue and organ models for use in drug discovery.9 It may also be possible to print out a patients tissue as a strip that can be used in tests to determine what medication will be most effective.1 In the future, it could even be possible to take stem cells from a childs baby teeth for lifelong use as a tool kit for growing and developing replacement tissues and organs.3, In situ printing, in which implants or living organs are printed in the human body during operations, is another anticipated future trend.13 Through use of 3D bioprinting, cells, growth factors, and biomaterial scaffolding can be deposited to repair lesions of various types and thicknesses with precise digital control.10
Circular Economy In Manufacturing, Solvent-based Vs Solvent Less Lamination, Articles H