A Review on Significant Role of Additive Manufacturing in Biomedical Applications

3D printing has advanced significantly in recent years. Its rapid emergence has led to the development of many new products in various industries [1]. These include forming, subtractive, and additive manufacturing. Forming is a process where a work piece is molded without adding or reducing material [2]. Subtractive manufacturing is a process that involves using tools to remove unwanted material [3]. In additive manufacturing, the process involves adding material to a finished product [4]. This eliminates the need for removing the material to create a finished item. Originally, the term 3D printing was associated with additive processing. But it is now commonly used as the term additive manufacturing. Conceived by computer-aided design, rapid prototyping was the first method that allowed engineers to quickly prototype physical models. The rapid emergence and evolution of physical models has driven the 3D printing market. Its continuous improvement is expected to propel the demand for end-use parts that are more customized. A major component of the printed structures market is the creation of mold forms. 3D printing is a process that allows manufacturers to produce specialized products with complex structures. In dentistry, it is becoming a promising career option due to its ability to provide patient-personalized models [5]. Kantaros et al. [6] share a review on 3D printing-assisted design of scaffold structures. This review compare the mechanical properties of various scaffold designs. The compressive testing results shows good properties and also be in good agreement with the computational analysis. Hajje et al. [7] studied the 3DP titanium mechanical and physical properties and compared to properties of bone. The mechanical and physical properties were tailored by changing the binder (polyvinyl alcohol) content. The developed titanium had a porosity of 32.2–53.4% and compressive modulus of 0.86–2.48 GPa. Kantaros et al. [8] discussed the porous Bio-Engineered scaffold for tissue regeneration. Kantaros et al. [9] studied the fabrication process with embedded sensor in Additive manufacturing, controlling and monitoring fabricated product during its functional life. Due to the wide variety of properties and processing approaches involved in polymer printing, it is widely used in medical applications. 3D printing is a highly desirable process because it allows the design to be built with complex structures and geometries that are not possible with traditional manufacturing processes. Stereolithography (SLA) and polyjet printing can also produce tissue scaffolds that are designed to mimic the natural structures of bone [10]. The advantages of 3D printing over metal printing are numerous. For instance, it can avoid metal implants that can break down in the body. In addition, the rapid fabrication of polymers allows for energy absorption in equipment that require special care. 3D printing can be done using various processes such as extrusion, resin, or powder. These can provide flexibility in terms of material selection and support designs. Due to the large design space that 3D printing offers, we conducted a review to identify the most critical factors that affect the success of an application. A variety of strategies can be utilized to reduce the development of residuals has increase the speed at which photopolymers can be converted [11]. The photopolymerization process is a process that involves the cross-linking of a polymer chain to a substrate. Various processes such as stereolithography, polyjet, and two-photon lithography are also utilized for photopolymerization [12]. These processes can achieve high-quality images at low cost. Aside from being durable, photopolymers can also be made more resilient by developing new types of plastic or elastomers with high ductility. Although most of the AM parts exhibit anisotropic properties, the continuous liquid interphase printing (CLIP) technique can still produce parts that are almost isotropic. The increasing popularity of photopolymerization techniques has greatly affected the development of AM polymers in recent years. Various studies related to shape memory effect have also been presented in an effort to improve the understanding of anisotropic properties. Experimental and modeling studies are also conducted to study the mechanical properties of the finished products produced by photopolymerization. This type of study is still in its early stages and needs more follow-up studies to fully understand the properties of photopolymers. Stender et al. [13] discussed the reduction of the processing time of the product by additive manufacturing. The additive manufacturing technique saves more than 90% of the fabrication time compared to standard fabrication, and 1 cm2 lens arrays with high filling factors can be fabricated within only a few hours—a big step towards high throughput and industrial scalability. Kantaros et al. [14] describes the emerging trends of makerspaces and outsourced 3D printing services, and examines the natural progression between them. It also investigates the reasons why individual users and enterprises have started to choose such services and the benefits acquired from this choice, that lead to the promotion of creativity, innovation, and competition. Fundamental working principles both for makerspaces and outsourced 3D printing services are being analysed. Tsaramirsis et al. [15] reviewed modern approach towards an industry 4.0 model: starting from the driving technologies to management. It illustrate the confluence of all these technologies in a single model factory. This new factory model succinctly demonstrates the advancements in manufacturing introduced by these modern technologies, which qualifies this as a seminal industrial revolutionary event in human history. Stender et al. [16] defines manufacturing strategies for scalable high-precision 3d printing of structure from micro to the macro range. Kantaros et al [17] describe the current trends and limitations in Digital Twins (DTs) for additive manufacturing, in order to provide more insights for further research on DT systems. Kantaros et al. [18] illustrates utilization of 3D and 4D printing in sectors like aerospace, regenerative medicine and dental, and automotive to create complex geometries and parts that would be challenging or impossible to create using conventional production techniques. Furthermore, 4D printing opens up new opportunities in emerging, novel, sectors where the ability to create materials that adapt and change over time can be highly beneficial. In order to create high-quality parts, the monomers used in photopolymerization-based printing should be relatively low to mid-viscosities. Although acrylates and epoxy monomers are commonly used in photopolymerization-based printing, other monomer types are also used as well. Due to the properties of these monomers, they can be used to achieve fast and limited depth of cure. With the use of fast curing monomers, residual remain can be utilized to promote the completion of the UV process. The use of relatively resin systems could eliminate the need for sacrificial support structures for certain parts. A similar approach is used to create support structures that can be used for a variety of materials. This method allows a permanent structure to be developed and released from the supporting material. The mechanical strength of SLA-based parts is limited by the resin’s viscosity restrictions and the preference for faster curing acrylate monomers. Since the new layer is connected with the pre-existing layer, this allows for better strength and anisotropy. Ideally, initiators should have high molar absorptivity and good irradiation efficiency. UV-cured multi Jet printing allows for the production of complex geometries without requiring surface finishing. The UV-curable polymer materials are only applied where desired. They can also be co-deposited with a wax or other gel-like material. Due to the simultaneous availability of multiple printing heads, different colored building materials can be easily identified with respect to their spatial properties. Non-Newtonian fluids are commonly used for inks due to their viscosity. However, they can also be compensated for with various additives. Instead of using wax, objects can be formed from jetted wax and then deposited directly into investment casting applications. Numerous studies have been successfully carried out on UV-curable inks for 2D printing. They are usually composed of various additives such as photo initiators and monomers [19]. An oil-in-water emulsion ink has been used to create well-controlled porosity in parts following the UV-curable printing process. An interconnected phase structure in the ink can allow for the formation of porous components that can be used for conductive applications. Inks can also contain various nano-fillers, such as silica, clay, and other suitable materials. These additives can provide better viscosity control and reinforced mechanical properties. A levelling blade can be used to prevent the formation of unstable layers during the UV curing stage. The printed parts can be robustly built with good mechanical properties. However, they can also be prone to wear and tear due to the build orientation. Due to the properties of the 3D printing process, the degree of mechanical properties can vary depending on the material used. Kiselevskiy et al. [20] focus on the recent findings achieved in the field of model-driven development of additively manufactured porous materials for the development of a new generation of bioactive implants for orthopedic applications. This review critically analyze the recent advances in the field featuring model design approaches, virtual testing of the designed structures, capabilities of additive printing of porous structures, biomedical issues of the engineered scaffolds, and so on. Special attention is paid to highlighting the actual problems in the field and the ways of their solutions. Mirkhalaf et al. [21] reviewed the outline of the recent progress and challenges of engineering an ideal synthetic bone scaffold and to provide suggestions for overcoming these challenges through bioinspiration, high-resolution 3D printing, and advanced modeling techniques. It also provides a short overview of the progress in developing the 3D printed scaffolds for the repair and regeneration of critical size bone defects. Kantaros [22] discussed utilization of various resources and technologies of 3D Printing in regenerative medicine. Kantaros [23] reviewed on Bio-Inspired Materials. This aims not only to list the most important biomaterials used in these techniques but also to bring up their pros and cons in meeting the aforementioned characteristics that are vital in their use. Kantaros [24] discussed on 4d printing. 4D printing is an exciting and rapidly advancing technology that has the potential to revolutionize the way we design and create structures. The ability to create structures that can change shape or behavior over time opens up new possibilities for a wide range of applications. As the technology continues to evolve, we can expect to see more innovative uses of 4D printing in a wide range of scientific fields such as architecture, aerospace, and biomedical engineering demanding the creation of highly complex and dynamic structures that can adapt to changing environments. Kantaros [25] work (3D scanning, 3D printing, and CAD design software) aims to depict the added value of their combined use in a proposed workflow where a customized product needs to be developed. The geometry of an existing physical item’s geometry needs to be defined in order to fabricate and seamlessly integrate an additional component. In this instance, a 3D scanning technique was used to digitize an e-bike’s frame geometry. This was essential for creating a peripheral component (in this case, a rear rack) that would be integrated into the frame of the bicycle. In lieu of just developing a tail rack from scratch, a CAD generative design process was chosen in order to produce a design that favored both light weight and optimal mechanical behaviors. FDM 3D printing was utilized to build the final design using ABS-CF10 materials, which, although being a thermoplastic ABS-based material, was introduced as a metal replacement for lighter and more ergonomic component production. Consequently, the component was manufactured in this manner and successfully mounted onto the frame of the e-bike. The proposed process is not limited to the manufacturing of this component, but may be used in the future for the fabrication of additional peripheral components and tooling. Arif et al. [26] discussed highlights recent advancements in different types of biopolymers, such as proteins and polysaccharides, which are employed to develop different biomedical products by using extrusion, vat polymerization, laser and inkjet 3D printing techniques in addition to normal bioprinting and four-dimensional (4D) bioprinting techniques. Kantaros et al. [27] study explores the integration of various reinforcements, including carbon fibers, glass fibers, and nanoparticles, into the polymer matrix of FDM/FFF filaments. The utilization of advanced materials for reinforcing the filaments has led to the enhancement in mechanical strength, stiffness, and toughness of the 3D-printed parts in comparison to their pure polymer counterparts. Furthermore, the incorporation of fillers facilitates improved thermal conductivity, electrical conductivity, and flame retardancy, thereby broadening the scope of potential applications for FDM/FFF 3D-printed components. Kantaros and Ganetsos [28] describes the pivotal role of smart materials in this transformative journey, where materials are endowed with dynamic responsiveness to biological cues and environmental changes. By delving into the innovative integration of smart materials, such as shape memory polymers and stimulus-responsive hydrogels, into additive manufacturing processes, this research illuminates the potential to engineer tissue constructs with unparalleled biomimicry. From dynamically adapting scaffolds that mimic the mechanical behavior of native tissues to drug delivery systems that respond to physiological cues, the convergence of smart materials and additive manufacturing heralds a new era in regenerative medicine. Selective laser sintering (SLS) is a process that uses a high-pressure laser to produce semi-finished polymers [29]. The process utilizes two energy sources. The first is used for the formation of the particles, which are then cooled to a temperature that’s above the melting point. The heated powder bed limits the energy needed to trigger the process, which avoids the large thermal distortions that usually occur during sintering. The laser produces a melt zone within a particle-bed that has a comparable radius to the vertical and horizontal dimensions. The melt zone can be loosely bound and subjected to low temperatures. It is composed of a dense core and a less dense boundary layer. When the processing conditions are right, the mechanical strength and good toughness of a given material can be achieved. One technique that can improve the mechanical properties of a material is by applying pressure in the build chamber. Most of the commercial materials used in the SLS market are polyamides, such as nylon 12, PA6, and PA10 [30]. Other polyamides such as polystyrenes, are also being developed for use in powder form. Due to their high performance, high-heat temperatures are required to be used for the production of PEEK [31]. This process consumes a large amount of energy and increases the production cost. Semi-crystalline polymers are commonly used for the production of high-purity, heat-resistant, and/or transparent conductive films. They can be selected depending on their intrinsic properties. The surface of the particle is also required to be sufficiently thick to avoid inter-particle fusion. The polymers can be used to produce parts that are glassy or elastomeric. They can also be subjected to different melting temperatures to achieve the desired result. Amorphous polymers such as polystyrene tend to have weaker, more porous structures than semi-crystalline ones. However, they can be strengthened by substituting other materials. Despite their porous structure, amorphous polymers do not undergo the significant thermal contraction typically associated with crystallization. In certain cases, a more porous structure is required to provide a secondary infiltration for enhanced mechanical properties. While poly (methyl methacrylate) is commonly used in dentistry [32], PMMA has been developed for 3D printing. Like all the polymers in the market, stocks are required to be high-grade. Due to the increasing popularity of polymers, the prices are still significantly lower than those of comparable materials. Aside from polymers, a wide range of materials such as glass, aluminum, and silica can also be used to modify the appearance of the printed parts. A study conducted by researchers at the University of California, Berkley, showed that the addition of silica to PA parts can improve their flow properties. The challenges of mixing various components in a mixed powder system are complex. For instance, the density and particle size differences involved in the production of polymers are known to affect the system’s final product. Today, the latest state-of-the-art SLS technology allows materials to have varying mechanical properties depending on their orientation and processing conditions. Although some materials are more forgiving than others, the transition from printed structures to 3D printed parts is still a bit challenging. A process known as Selective Heat Sintering (SHS) uses a thermal printhead to fuse a layer of a powdered thermo-plastic into a printed part [33]. Despite being investigated for decades, laser-assisted melting (LAS) is not as common as extrusion or photopolymerization due to the high cost. Currently, both thermoplastics and their related composite materials can be fabricated. One of the most popular is polyamide due to their high strength and low density. Usually, these particles have spherical shapes. Through laser melting, they can be molded into various products. Laser-sintered polyamides exhibit a spherulite-like structure, which is dependent on the processing speed and power. Also, these materials have anisotropic mechanical properties due to their printing orientation and the existence of micropores. Due to the properties of these materials, their thermomechanical modeling is very useful in predicting the residual stress and distortion during the laser sintering process. Despite their properties, the modeling of AM polymers is similar to that of traditional plastics and elastomers. Due to their layered processing characteristics, AM polymers have anisotropy. This characteristic can cause the model to model the polymers’ response. The phase transitions during the processing of AM polymers are also known to cause the model to model their responses. Due to the anisotropic properties of AM polymers, their brittle behavior is different from that of their conventional counterparts. The inter-bead bonding condition and the low interlayer strength are some of the factors that influence the strength of AM components. The degree of melting of the particles and the strength of the interlayer are also affected by the degree of porosity and interlayer strength. The properties of AM components are also studied using various techniques such as micro-CT, ultrasonic, and digital. Due to the nature of AM components, their modeling research has been very rare compared to that of metals and polymers [34]. It is expected that the use of AM components will increase significantly in the next couple of years due to their improved mechanical properties compared to metals and polymers. In addition, AM components can be designed to have various functionalities such as heat control and actuation. This area has huge research opportunities in the near future. Although modeling for AM components is challenging, we believe that their development is already in the pipeline. A new type of active polymer is being studied for its ability to alter the shape of structures. This new material can be used for the development of robots and structures. Aside from polymers, researchers also experimented with other techniques such as printing composite materials using hydrogel. This material can be used to create structures that can change their shape due to its anisotropic expansion behavior. The modeling of the material properties of AM components is an exciting area that can help design and control the structures that they will be made from. The mechanics of AM polymers can also be utilized to design and develop parts that can meet the needs of the biomedical industry. Currently, the design-optimization of AM implants hinges on high-fidelity models. These models are used to study the degradation of the AM polymers’ mechanical properties. Aside from the implants, AM polymers are also used as scaffolds for tissue engineering. Their properties can be studied to determine how they can affect the growth and development of tissues. The mechanical properties of AM scaffolds and their cell-scaffold interactions are also studied to determine their effects on the development of tissues [35]. This field is still in its early stages, so it will take a long time to fully understand how scaffolds can help the development of organs and tissues. Bio-printing, which involves the printing of structures made from cells and other components, is becoming more prevalent in the field of bioengineering. Labs where bio-printing is being conducted are usually focused on creating prototype organs such as heart valves, cartilage, and joints. Through additive processing, tissue engineering could be conducted with the possibility of creating vascularized tissue constructs that are capable of sustaining and improving upon their physical properties. Aside from being printed, various physical features such as the structure of a scaffold can also be manipulated using a 3D printing process. This process is commonly used for the production of poly(lactic acid). Due to the various properties of polycaprolactone, it has been considered as a bio-compatible scaffold material. This material can be used for the creation of scaffolds for various bio-based applications. Bio-materials are also being used in dentistry to create custom-made constructs for patients. This technology is expected to help repair soft and hard tissue injuries. Although it’s already been used for cosmetic purposes, it’s still in its early stages. Currently, 3D printing is being widely used in the cosmetic dentistry industry, such as cosmetic wax-ups and bridge mold. In the US, some dental labs are already using 3D printing to produce fixed prosthodontics and surgical guides. Based on the data collected by the patient, the guides and patterns are created using 3D printing. In addition, these products are being used in dental offices to promote the profession. Various digital scanners, such as MRI, CT, and laser scanning, can be used to create 3D models of tissues and structures, allowing them to be quickly realized. Due to the advancements in 3D printing technology, materials are being designed to produce textures and colors for teeth that are life-like. One example of this technology is the ability to produce printed structures that contain bioactive components. For instance, a 3D printing technique was used to develop a device that can prevent the growth of Staphylococcus aureus. The development of 3D printed drug delivery devices is also expected to expand the technology’s applications in the field of dentistry. A study revealed that the printed die spacers produced by 3D printing exhibited inconsistencies and inaccuracies in their dimension. Due to the increasing popularity of 3D printing in dentistry, further applications of this technology are expected to be established in the coming years. A tissue scaffold composed of beam-based unit cells can be used for designing biological and mechanical systems. In this case, the strategy involved designing a printing process that mimics the structure of bone. The material choice was made to ensure that the scaffold’s structural integrity was maintained while maintaining its biocompatibility [36]. Through SLA printing, the layers were created to form the complex hierarchical truss structure. The structure’s design should also take into account the uncertainties associated with the 3D printing process and its component variations. Studies for tissue scaffolds can reveal various design strategies that can be utilized based on different material and printing process decisions. For instance, tissue scaffolds made from polycaprolactone (PCL) can have more biodegradability than those made from titanium. Also, choosing the right material can affect the structure’s topological design. For instance, printing polycaprolactone on a scaffold can be challenging since it requires the use of a truss-based structure. In most cases, the decisions related to the design, material selection, and printing process are made in a nonlinear fashion. This course aims to analyze the various factors involved in the design, material selection, and printing process of polymers for medical applications. Through reviews, the materials are compared to various materials available for different mechanical applications. This paper will cover different approaches for printing polymers. It will also discuss the various considerations involved in the printing process. This paper will gear the students who are interested in studying the various aspects of polymers for medical applications, which aims to provide a framework for researchers to improve the quality of their work in the field of medicine. In manufacturing sectors, the product can be produced by two major methods: subtracting manufacturing and additive manufacturing. The subtracting manufacturing includes production of the product by removing or cutting or subtracting the workpiece with various cutting tools to get the desired final product. Due to this removing of the material from the workpiece, there is huge loss of materials. However, in the additive manufacturing technology the final product is obtained by layer-by-layer addition of the material instead of removing materials from the workpiece. Hence, material loss is minimized. However, the additive manufacturing technology is creating substantial change to the product manufacturing, particularly in prototyping new advanced products, with different aesthetics in visualizing abstract concepts. During earlier manufacturing process, the system initiates with the collection of raw materials, then transformed into bulk forms and then manipulated, machined and reduced to create final perceived object form. These processes have been followed by the past few years in the production sector, as based on the application level, it has been changed. But now, the entire process has been changed from top to bottom, with the invasion of computer aided manufacturing. This technique has effectively involved the manufacturing division, to a great extent. The production process reduces the work load and lead time of the manufacturing products. Within a single limited space, a single device has completed the manufacturing process of a product. This technology is termed as additive manufacturing or 3D Printing. History of 3D Printing The creation of 3D printing through the additive manufacturing process was initiated with a Japanese inventor named Hideo Kodama in the year of 1981. He invented a product that harden polymeric material with the help of ultraviolet light. This channels to the invention of stereolithography (SLA). He wrote a research article on 1980, under the proposed scheme for the conception of “Three-dimensional system” (rapid prototyping), named as ‘Automatic method for fabricating a three-dimensional plastic model with photo hardening polymer’ [37]. The research article was followed as based on a patent work had done on 1977. But Kodama has failed to submit the full patent application to the officials, so as the published paper is considered as the historical contribution and beginning of the new era in the field of manufacturing [38]. After few years, as based on the Kodama’s work, Charles invented SLA (stereolithographic apparatus), subsequently held the patent on 1986 [39]. The development of SLA is known to be the beginning of commercial 3D printing technology. After that a multinational company named 3D System introduced the first commercial type SLA–3D printer to the world. After a decade, several pioneers came into this field and developed their new alternative additive manufacturing processes and commercialized through international patentship. As a continuation of the spark, Scott crump invented an alternative 3D printing modelling technology and patented the invention with his wife, and named the technological product as fusion deposition modelling (FDM) in 1989 [40] and became the co-founder of Stratasys, Ltd. Now he is the chairman of Stratasys, and the company is producing global level additive manufacturing machines. During the starting of 1990’s, three young inventors named Deckard, Beaman, and Darrah, introduced the technology for selective laser sintering (SLS) in 1992 (US Pat., 5155324, 1992). Then very next year 4 inventors Sachs, Haggerty, Cima, and Williams, patented ‘three-dimensional printing’, now it is commonly referred to as ‘3D inkjet printing’ in 1993 (US Pat., 5204055, 1993). Finally, Feygin, Shkolnik, Diamond, and Dvorskiy, combinedly patented another rapid prototyping system named laminated object manufacturing (LOM) in 1998 (US Pat., 5730817, 1998). The early days of 2000’s made historical changes to the manufacturing, through addictive manufacturing system. The striking alternative technology to traditional manufacturing process, hit the wide spectrum of industrial sector to great extent. Not only with the industries, but also with the scientific, educational and social activities. After the invasion of additive manufacturing (AM), it improves the productivity, and reduces the work load mostly in the automobile industries. With regard to this technology, various new terms have born—like rapid manufacturing, rapid casting and so on. The history of 3D printing is shown in Figure 1.