key: cord-0973268-ex65pkjo authors: Oladapo, Bankole I.; Ismail, Sikiru O.; Afolalu, Temitope D.; Olawade, David B.; Zahedi, Mohsen title: Review on 3D printing: Fight against COVID-19 date: 2020-10-22 journal: Mater Chem Phys DOI: 10.1016/j.matchemphys.2020.123943 sha: 778f45c351c5561119493f14fc44a4d29cea75fa doc_id: 973268 cord_uid: ex65pkjo The outbreak of Coronavirus in 2019 (COVID-19) caused by the SARS-CoV-2 virus and its pandemic effects have created a demand for essential medicines equipment. To date, there are no specific, clinically significant licensed drugs and vaccines available for COVID-19. Hence, mapping out COVID-19 problems and preventing the spread with relevant technology is urgent. This work is a review of research the last week of May 2020 on solving COVID-19 with 3D printing. Many patients who need to be hospitalized because of Covid-19 can only survive on bio-macromolecules antiviral respiratory assistance and other medical devices. A bio cellular face shield with relative comfortability made of bio-macromolecules polymerized polyvinyl chloride (BPVC) and other biomaterials are produced with 3D printers. Summarily, it was evident from this review study that AM is a proffered technology for efficient production of an improved Bio-macromolecules capable of significant COVID-19 test and personal preventive equipment (PPE) to reduce the effect of Covid-19 on the world economy. Innovative AM applications can play an essential role to combat invisible killers (COVID-19) and its hydra-headed pandemic effects on humans, economics, and society. 4 by printing about 20 masks made of antibacterial bio-cellulose masks in a day and delivered them to public health care providers every week. The shortage of medical supplies is increasing as the COVID-19 pandemic strains global supply chains. Malaysia team uses 3D printing technology to manufacture medical devices and supplies worldwide, including medical devices such as bio-cellulose swabs, antibacterial bio-cellulose masks, and test boxes [24] [25] [26] . According to Fig. 2 , the highest number of cases from the World Health Organization as of September 14, 2020 is in the American continent. The lowest occurs in Africa and some other Asian countries. There are countries without any reported new case, according to the figure. This is a 14-day COVID-19 case notification rate per 100,000. American continent recorded above 120,000 out of the total confirmed number of COVID-19 cases and how rapidly they increase in the American continent. The number of confirmed COVID-19 instances is lower than the number of total points. This is due to limited testing materials, such as PPE, to protect the sample collector/health workers and sweb for testing. The evolution of medical 3D printing over the past decade has followed imagination and problem-solving ways. Starting as a novelty with limited practical value, 3D printing has grown to find primary uses and acceptances in various industries, including engineering, car manufacturing, military manufacturing, and healthcare. Although the variety of these paths is impressive, it requires to combine efforts to satisfy a collective need. The concentrated efforts of 3D printing enthusiasts and 3D printing laboratories can address the critical deficiency of PPE during the global COVID-19 outbreak. This research aim at reviewing the role of 3D printing, especially in the production of face shields, to examine feasibility and engagement under the new CDCP and FDA pandemic guidelines, and to propose a concentrated effort towards improvement of the 3D printing industries [30] [31] [32] , as depicted in Fig. 4 . Therefore, with these new and comfortable guidelines, 3D-printed face shields have an exact role to play. Support and encouragement must be continued efforts across the country. Professional companies, such as Prusa Research, based in the Czech Republic, began sharing open-source mask designs and allowed anyone with a 3D printer to download and use the free plan. The family that buys 3D home printers can now remove several hundred face shields in a week. On a larger scale, 3D printing manufacturers are also transforming their efforts to produce face shields and other PPE In particular, the military and automotive industries include news organizations reporting joint efforts to work together in the military, consolidate resources, and determine the scope and volume of 3D printing resources [33] [34] [35] . Ford Motor Company has facilities that operate on 3D-printed PPE, including a facility that produces approximately 1,000,000 face shields per week in Plymouth, United Kingdom [36] [37] [38] . 3D printing factories have machines that support wireless connectivity and sensors. These sensors are connected to a system that can view and monitor the entire production line and make its own decisions. 3D printing uses smart manufacturing processes to manufacture primary disposable products to solve the COVID-19 outbreak deficiency [39] [40] [41] . This crisis provides a supply chain and intelligent disposable medical supplies of equipment, where patients can obtain J o u r n a l P r e -p r o o f essential medical supplies on time. In this comprehensive review, the applications and benefits of 3D printing technologies to manage the COVID-19 outbreak have been subsequently considered. Additive manufacturing technology has the capability of providing better digital solutions for daily lives during this crisis. More also, digital technologies include, but are not limited to, virtual reality, holography, 3D scanning, 3D printing, and biosensing. These modern technologies support the effective printing of several and specially designed PPE relevant to combat the COVID-19 pandemic, with less stress, time, and material usage. The effects of limited testing and challenges in the attribution of death mean before the use of masks and lockdown and after the introduction of mask are represented in Fig. 5 . Some highly affected countries controlled the death rate: China, UK, and Iran, because of the quick intervention of lockdown and face mask to prevent the spread of the invisible killer. The 3D printing of different PPE helped to meet the demand. While some affected countries still experienced some loss, due to their slow intervention. But for many countries, the spread was minima due to the introduction of PPE use, which can be majorly attributed to 3D printing materials. The information presented in Fig. 5 J o u r n a l P r e -p r o o f As earlier mentioned, the Manufacturer Volumic has 3D-printed thousands of test tubes validated by the competent laboratories to detect the virus. This is good news for the health sector, which can rely on this type of solution and technology in emergencies. Volumic 3D prints the test tubes needed to screen for COVID-19. Further south, on the Nice side, Cerballiance, Volumic, and LaFerme3D Laboratories have joined forces to produce COVID-19 testing tools using 3D printing. In 3 days, a solution to the Cerballiance laboratory problem was provided, as explained by Stéphane Malaussena, co-founder of Volumic 3D. As of today, there are thousands of test tubes printed in France daily in an attempt to expedite COVID-19 screenings. Cerballiance, an initiator of the project, shipped the test tubes produced in Nice to its various laboratories on the territory (600 in France) and its conferees who need the equipment [42-45]. Volumic's boss stated that they continue to produce to date since there is no instruction to stop production (Fig. 6 ). J o u r n a l P r e -p r o o f Furthermore, printing glass objects is now possible, and the most common method involves either extruding melted glass, or selective sintering laser heating ceramic powder, which is converted into glass. The former requires high temperatures and therefore requires heat-resistant equipment, while the latter cannot produce incredibly complex objects. ETH's new technology aims to improve these two disadvantages. It contains a photosensitive resin consisting of liquid plastics and organic macromolecules that bond with silicon-containing macromolecules, in other words, ceramic macromolecules. Using an existing process called digital light treatment, the resin is exposed to the pattern of UV light. Plastic monomers are cross-linked to form solid polymers wherever the light hits the wax. The polymer has a maze-like internal structure, and the space inside the maze is filled with ceramic macromolecules [46] [47] [48] . The resulting 3D object is then burned at a temperature of 600 o C, burning the polymer, leaving only the ceramic. In the second roasting, the roasting weather is about 1000 o C, and the ceramic is compacted into the transparent porous glass. The object does shrink significantly when converted to glass, which is a factor that must be taken into account in the design process. Although the objects created so far are small, the shapes are somewhat complicated, as reported. Also, the aperture can be adjusted by changing the UV intensity, or other properties of the glass can be altered by mixing borate or phosphate into the resin. A major Swiss glassware distributor has expressed interest in using the technology, which is similar to the equipment developed by the Karlsruhe Institute of The team behind the programme, which builds a web platform that allows users to freely download mask design files to print antibacterial bio-cellulose masks at home with 3D printing devices, as reported by their program's leaders. They built a platform that everyone can adapt, improve, and spread, and hope to find other applications in the future, in addition to fighting viruses. Also, 250 patients with coronavirus were in intensive care at a hospital in Brescia, Italy. Still, they all needed respirators, which were in short supply and must be replaced for up to eight hours each, but suppliers have suddenly burst into collection, because of market demand [58] [59] [60] . At this point, Cristian Fracassi, chief executive of Isinnova, an Italian 3D printing manufacturer, decided to come forward and, within three hours of studying the valve, returned to the hospital with a 3D-printed respirator valve prototype ( Fig. 8a -b) to test the patient. When they found out that the valves made out of 3D printing could work, they immediately returned to the Company to start a large number of printing, quickly put into production. In just one day, it took a day to design and print 100 respirator valves for a hospital, successfully solving the shortage of hospital medical equipment [61] [62] [63] [64] . Under the outbreak of new COVID-19 pneumonia, some local medical supplies are in short supply, 3D printing technology is widely available, print protective antibacterial bio-cellulose masks, among others. It helps to ease the tension of materials. There are also some 3D printing epidemic prevention supplies. The UK has set up its online platform, 3D Crowd UK to recruit volunteers to work on 3D-printed antibacterial bio-cellulose masks. As of Friday, April 10, 2020, the website received requests from local health care for 500,000 3D-printed antibacterial biocellulose masks, bringing together more than 6,000 volunteers as of preceding Monday. In Hertfordshire, England, a software engineer responded to the call by using two 3D-printed macromolecular mechanisms to remove 150 masks from his home and gave 39 of them to local nurses and midwives. Maker Nexus, a California-based non-profit organization, uses 13 3D printers and three laser cutters to make 1,800 protective antibacterial bio-cellulose masks for local hospitals, and General Manager Eric Hess says 300 volunteers help search the web for raw materials for making. In daily life, the door attendant is less necessary to touch the door handle. Still, the door handle is easy to become a virus temperature, Belgian Company materializes a screw-free hand door opener, as previously shown in In this race against time to equip caregivers, machine manufacturers have made all their capabilities available. The American Hewlett-Packard (HP) Company has published in open source five digital plans validated and adapted to its machines. Its emergency catalog ranges from the elbow handle for doors to protective visors. Nicolas Aubert, director of 3D printing at HP France, argues that they are reaching relatively large production volumes. This is the advantage of an industrial system. HP's machines, such as fellow Stratasys, use powder bed fusion technology rather than wire-depositing technology from desktop printers [86] [87] [88] . They can produce several parts at the same time: in a single print, an HP machine has 70 visors simultaneously, in 24 hours. And the details are more vital, resistant in particular to high-temperature sterilization in an autoclave, making them reusable. Another advantage is that production is relocated to customers. Jos Burger, CEO of desktop printer brand Ultimaker reported that they connected more than 4,000 printers worldwide in less than a week to Universities, designers, makers, engineers, among others. It has a whole network coming together [89] [90] [91] . HP mobilized its L'Oréal and Decathlon customers, and Stratasys formed a coalition of more than 150 companies, including Boeing, Toyota, and Medtronic. It is the brands that link the requests of the hospitals to different points of production. They also connect with design experts, biocompatibility, and designers. This is enough to create an entire ecosystem of open innovation, involved in an unprecedented mobilization [92] [93] [94] . A year ago, some medical practitioners were worried that advances in 3D printing would put them out of work. Medical is one of the fields that will have a revolutionary impact on 3D printing. In contrast, repair doctors and other medical practitioners are worried that traditional industries that were otherwise "calm" have been invaded by the new 3D printing technology [94] [95] [96] . According to the research firm Industry Arc, the global 3D printing market will reach $1.2 billion by 2020 [96] [97] [98] . It is a technology that uses a digital object created in the software, with melted plastic or metal powder, superimposed on layers on a 3D scale. 3D printing technology existed as early as the 1980s. However, 3D printers, priced between $2,000 and $8,000 and small enough to be on a table, have only begun to appear in the last decade. The latest medical applications of 3D printing started a few decades ago. In 2016, 3D printing continued to thrive in the healthcare industry. The world's first 3D-printed prescription drug, Spritam, was approved by the US FDA in March 2020, it has gone on sale. 3D-printed medical devices now cover surgical instruments and human implants, such as certified Medical Shape titanium bone connecting plates [98] [99] [100] . Institutions, such as Boston Children's Hospital, are also increasingly using 3D-printed organ and bone models Analysts have predicted that 3D printing will be a disruptive force in the healthcare industry by 2020. According to research by Gartner Study, one in ten people in developed countries will have 3D printing devices physically or in the body by 2019. Also, about one-third of remediation and implant surgery will use 3D printing as a core tool [101] [102] [103] . Prosthetics are a good example. It shows how 3D printing can improve people's lives. Typically, making a prosthesis involves measuring the rest of the limb's size, creating a plastic replica, and then hand-out the specification improvement score. Standard Cyborg, a San Francisco-based start-up, sells 3D scanners and software that allow customers to make prosthetics, modify shapes and print them out. The result is a fully functional prosthesis that is made available in a short time. In contrast, traditional methods of making prosthetics take four hours [66] [67] [68] [69] . Lei Feng stated that, at first, practitioners considered 3D printing as a threat. Now, Jeff Huber, co-founder of Standard Cyborg, said that his clients and the repair doctors are more likely to introduce 3D printing and design into clinical applications [68] [69] [70] . The main reason for the shift is that 3D printing allows experts to create complex geometric shapes to ensure a precise fit. Machines are not intimidated by complexity, and for patients, a more refined design delivers superior comfort. 3D printing also allows surgeons to treat patients with the help of a copy of the human anatomy. Researchers at the University of Michigan, for example, worked with surgeons at C.S. Mott Children's Hospital to develop 3D-printed trachea splints that were implanted into five children with congenital bronchitis. Developers are applying for special FDA permission to treat more patients [68] [69] [70] [71] , as the quest to improve health care continues. It is evidence that Additive manufacturing has complete applications in biomedical engineering. It has been well integrated into the medicine and pharmaceuticals for organ/tissue bio-printing and drug delivery, respectively [104] [105] . This is attributed to its capability to provide patient-specific design, on-demand, cost-effective printing, high productivity, and complexity, to mention but a few [106] . Presently, AM/3D printing technology has been effectively used to print various PPE to combat the invisible killer (COVID-19) . The conceptual design stage of PPE, creation of low-price and customized precise anatomic prostheses (such as lower limbs, hands, and arms) and J o u r n a l P r e -p r o o f orthoses (foot, ankle-foot, and wrist splints) [106] , among other artificial body parts utilized in various medical applications. The use of those above 3D-printed medical safety devices/PPE, patient-specific prostheses, and orthoses required careful ethical considerations and approval by the authorized medical/health organizations. The ethical issue includes whether AM products meet the stringent medical requirements, especially given AM's potential to be employed for long-term COVID-19 and other related medical applications. For example, there is an ethical concern (challenge) with the 3D printing of PPE against COVID-19. This includes PPE material reaction with other substances: water, sweat, chemicals, such as different types of sanitizers, among other medical sterilization materials, with human body parts (especially face/head and hand). Care must be taken to ensure that none of these materials has health risks or hazardous effects on the users. Also, PPE's cost should be affordable to avoid widening the gap between the rich and poor. Both the 3D printing process and product tests are very pertinent for human safety. Importantly, the government has started regulating the workflow associated with 3D printing in medicine by weighing the benefits and disadvantages of this innovative and revolutionary technology. This involves preventing the possibility of making unprofessional and destructive changes to the digital file when creating an organ after hacking into the 3D printers. The concern is that how will this injurious act be known earlier than the time that the 3D-printed organ started displaying trouble, shortly after transplant and when it is in full use [107] . The principal ethical consideration in device regulation is to avoid acceptance of a high level of risk during the market approval stage. Hence, both pre-market and post-market studies, investigation or compliance must be enforced [108] to protect health care providers and patients. Furthermore, the cost of 3D printing-assisted treatment offer to the patient is a serious ethical issue. This may not be affordable or inexpensive if the medical application of 3D printing is left in the hand of the private health care sector. It is worth remembering that one of the main goals of a private company is to maximize profits. Also, there is an anticipated lengthy procedure and time before the patient can benefit. Therefore, patients may decide to pay more to get the service. This may lead to the crime through organ smuggling. It is an ethical measure for the government to regulate the cost of 3D printing-assisted treatment. Also, it may end up becoming a technology for wealthy people only. What will be the hope of the poor? If measures are not properly taken, there may be a repetition of the past with 3D printing technology. There was a wide discrepancy between the poor and rich in terms of medical treatments. Though 3D printing is already in the customer-use domain, 3D printers designed for medical applications are insufficient [107] . Close to this point is to know the efficient method to test the 3D printing-assisted treatment. Foremost, the treatment's safety must be guaranteed before the treatment is made available for the patients. It is expected and mandatory that all the human or in-vivo tests must be accurately conducted, and the results obtained must be 100% satisfactory. Moving forward, the usage of the 3D printing-assisted medical treatment must be stringently regulated. This should involve numerous 3D printing applications in the medical sector, including essential and personal J o u r n a l P r e -p r o o f enhancements, such as cosmetic surgeries. The essential medical treatment should be regulated, while the noncrucial counterparts are ignored. To identify the differences between the two may be a challenge because it depends on individual interest. The government can help to find the difference and make decisive regulations [107] . These regulations include design control (21CFR820.30), purchasing controls (21CFR820.50), traceability (21CFR820.65), production and process control (21CFR820.70), process validation (21CFR820.75) as well as acceptance activities (21CFR820.80), among others [108] . The introduction of new and manageable regulatory considerations are expected from new processes, materials, and value chains of 3D printing technology [108] . Moreover, present ethical challenges of using 3D printing technology for medical purposes include, but are not limited to, availability, acceptance, and approval of some AM processes and volunteers for in-vivo tests. Also, the absence of recent international regulatory directives to guide these tests is a part of the limitations [110] . [108, 109] . Also, xenotransplantation has some ethical dilemmas (cross-species transplantation, especially from animal/human to human). When it is between humans, it is unethical if the donor is not well informed of either current or future use (or both) of his/her cells and tissues. Therefore, a consent form is needed to contain full details of the bio-printed part composition, implantation procedure, all possible results, all conflicts of interest as well as prospective adverse effects [111] . Summarily, in a bid to maximize the potentials of 3D printing to fight COVID-19 in addition to other related medical applications, it must be well regulated by carefully bearing in mind all the possible related ethical issues. Now, can mutated organs be 3D-printed for a healthier lifestyle and, consequently, a longer life span, probably to live for 15 decades on earth? [107] . The bright and promising future of 3D printing-assisted medical treatment has the answer to give. Therefore, a comprehensive evaluation of relevant biological safety endpoints in compliance with applicable safety standards, such as the physical safety standards series ISO 10993 for antibacterial bio-cellulose masks and Ventilator, is essential. Any vapors, wear debris, degradation products, and processing residues that may be released from the 3D printed part must be demonstrated to be non-toxic to a high level of assurance. The respiratory illness due to the COVID-19 pandemic can be reduced and maybe stop eventually using AM technology. The steps involved in the supply chain management of ventilators must be increased with AM to produce more PPE to prevent the spread of Covid-19. The 3D-printed face shield is well accepted in several interventions. 3D printing provides an automated solution for various manufacturing industries and other related fields to produce medical equipment during the Covid-19 crisis. AM technologies provide an innovative method to isolate the infected patient to reduce high mortality risk adequately. With the application of 3D printing technologies, efficient production of PPE and other medical equipment is possible. 3D printing can work remotely with smart technologies that are useful for monitoring and prevention of COVID-19 spread. In any environment with a high oxygen atmosphere, fire risk is certainly a concern and should be discussed and mitigated. In the authors' opinion, during the COVID-19 pandemic, all of the above risks are outweighed by the benefits of protecting healthcare professionals and enhancing patient safety during this global crisis with 3D printing. As a respiratory disease, due to the COVID-19 pandemic spreads across the world, healthcare systems and national governments face the difficult challenges of getting a ventilator to help patients. AM/3D printing technology can ensure that antibacterial bio-cellulose masks and ventilators, among other equipment, get to patients and prepare us better for such viral outbreaks in the future, probably and undesirably in the next ten decades. [40] J.L. Penarredonda, Covid-19: the race to build coronavirus ventilators, (accessed April 1, 2020), https://www.bbc.com/future/article/20200401-covid-19-the-race-to-build-coronavirus-ventilators (2020). [41] Coronavirus, President von der Leyen and Commissioner Breton discuss solutions with industry to ramp up production of products needed to tackle the crisis, EU Comm Press (2020), https://www.pubaffairsbruxelles.eu/coronavirus-president-von-der-leyen-and-commissioner-breton-discusssolutions-with-industry-to-ramp-up-production-of-products-needed-to-tackle-the-crisis-eu-commission-press/ [45] ITN, Dutch companies offer free innovative COVID-19 AI software, https://www.itnonline.com/content/dutchcompanies-offer-free-innovative-covid-19-ai-software (2020). [46] Klaviyo, Key trends in brands, https://www.klaviyo.com/covid-19-ecommerce-marketing-poll (2020), (Accessed March 28 2020). 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