Jiangsu Laser Alliance Introduction:
Recently, the team of Academician Lu Jian of the City University of Hong Kong published a review paper "Additive manufacturing of structural materials" at Materials Science and Engineering: R: Reports, which made a systematic introduction to the development history of the field of additive manufacturing, material selection, 4D printing, application prospects and trend prospects. Jiangsu Laser Alliance will successively introduce its main contents, this article is the sixth part, the application of additive manufacturing structure in medical treatment.
4.2. Biomedical field
Another area of active AM application is medical.
Figure 1. Atlas of AM technology references in medical treatment
4.2.1. Dental implants and orthopedic prostheses
The use of AM technology to manufacture biological implants has attracted a lot of people's attention. Compared with applications in other fields, medical implants have unique uses and needs, including high complexity, good customization of individual needs, and small batch production, which are the corresponding characteristics of AM technology to meet this field. Orthopedic prostheses and dental implants are designed to be installed in the patient's body to repair damaged bones or teeth, requiring high biocompatibility, appropriate mechanical properties, and good individual customization. Fine osseointegration is key to implant surgery, with three factors influencing the implant's design: mainly material selection, surface treatment, and structural design. An unsuitable material can lead to mismatch of mechanical forces and uneven stress distribution, resulting in osteolysis and eventually failure of implants such as loosening of implants or fractures around the surface of implants and prostheses. In addition, the interface between the implant and the host's tissue also determines its long-term stability. The anchoring point of an orthopedic implant depends on the interface between the implant and the host bone. Finally, the optimized structure also plays a very important role in the conduction of mechanical forces and the growth of tissue frontals, especially in personalized orthopedic design.
4.2.1.1. Materials
Suitable mechanical properties and good biocompatibility are the basic requirements for material selection. There are three types of materials that are mainly used in the field of bone and dentistry: they are metals, ceramics and polymers. Although the traditional Ti-based materials have good biocompatibility and corrosion resistance, and a wide range of applications and have received extensive research and attention. However, the stress shielding effect can lead to abnormal growth of bone. Alloys, which have good biocompatibility and biodegradable properties, are becoming more popular materials in implant manufacturing projects. Controlled degradation rates of Mg-Nd-Zn-Zr screws coated with dehydrated calcium bisphosphate have been shown to have good biosafety and bioavailability. Ceramic materials, because of their similar mechanical properties and composition to bones and teeth, are more suitable for biomedical applications. 3D printed zirconia ceramic materials, such as teeth and crowns, have mechanical properties comparable to traditional manufacturing processes. In addition to the factors associated with mechanical properties, bone conductivity is also an important indicator when evaluating bone implantability. Dienel et al. mixed trimethylene carbonate and β-calcium phosphate for implant printing, improving the tensile properties and biocompatibility of implants. In addition to metals and ceramics, polymers are also the more popular materials used for dental and orthopedic prostheses because polymers have good manufacturing properties. Polycaprolactone-coated liquid crystals developed for use in tricalcium phosphate scaffolds to regulate the release of proteins, resulting in high compressive strength.
4.2.1.2. Surface finishing
As shown above, the modified surface leads to better osseointegration between the foreign implant and the host bone. Many of the findings also confirm the effect of chemical factors on osseointegration. Polycaprolactone scaffolds are embedded in the connectivity bubbles, where the tissue growth factor leads to thick and dense mineral tissue growth on the implanted dentin surface. In addition to chemical factors, the microstructured surface of the Ti6Al4V alloy also regulates the differentiation of bone cells. For dental implants, Tu et al. proposed a biologically active dental implant and designed a porous Ti6Al4V alloy dental implant using laser AM technology that resulted in better osseointegration due to its porous surface and individualized structure. Nano-modified 3D printed ceramics are also used in personalized design when they have antibacterial properties.
4.2.1.3. Structural Design
An orthopedic prosthesis is a medical device used to replace or form a bone or connector. In the past, bone implants or prostheses were limited to fixed models or versions, and the orthopedic physiology of patients differed in thousands of ways. Implantation of suitable structures can facilitate postoperative recovery. Many of the findings have determined the optimized structure, as shown in Figure 2.
Figure 2. Structural design is critical for dental and prosthetic implantation: (a) the design of the mandibular prosthesis provides enhanced therapeutic results; (b) the use of 3D printing has more bone formation capacity in bioactive materials compared to traditional commercial products; (c) reduced stress shielding effect due to topology optimization;
These studies provide recommendations for designing implants. In addition to attempting to generate random structures and structural parameters, such as random pore sizes, effective methods also need to be used to guide the design of structures. Topological optimization is based on the design of implants with adaptive bone behavior. Based on topology optimization, Wu et al. proposed a local density limiting method to generate a porous microstructure, similar to trabecular bone, with light weight and robustness, and the use of FDM printing methods to manufacture and confirm its manufacturing performance. A high-intensity, fully porous prosthesis applied to hip replacement through topology optimization has shown that the SLM prosthesis can reduce stress concentration and bone resorption in the imitation femur. In addition, the goals of different optimization methods can be used to solve different problems. A cage uses topology optimization to design and maximize permeability and maintain connectivity while maintaining connectivity. It was then printed using 3D printing technology and implanted into the dog's body, and the results showed no mutilations or other complications due to personalized design.
In addition to research results, AM technology is also used in some commercial products. For example, Zimmer Biometals has developed Osseo's porous titanium technology, which integrates CT scans of the human body for 3D printing. This technique has been used to create porous structures that directly mimic the body's cancellous bone and are widely used in acetabular cups and wedges. The bone-like structure presents a material strength located in the cancellous bone and the trabecular bone, and is a structure suitable for osseointegration. Stryker used AM technology to create cervical cage and knee implants, at which point the porous structure was designed to mini-cancellous bone.
Clinical studies have been reported, including Hyemi pelvic prolapse, personalized porous implants, designed vertebral bodies, absorbable cleft lip stents and palate treatment. After 12 months of follow-up observation, no loose or other problems were found, and its evaluation index increased. In another case, a porous implant structure was designed and 3D printing technology was used to support the graft and subchondral areas, thus avoiding mechanical failure and regeneration. Limb function is very satisfactory and no other injuries have been found. Taking into account the patient's special requirements for transplantation, a personalized 3D printed vertebral body is designed for reconstruction and exhibits good bone regeneration. There are bone marrow cell bioresorbable scaffolds for cleft lip and palate treatment, thanks to the advantages of personalized customization that 3D printing technology has. Chimene et al. have developed a nanoengineering ionic covalent entanglement bioink for 3D printing bones. After 60 days of cell-induced remodeling experiments, the deposition of extracellular matrix proteins, whereby regeneration was manufactured, shown results that accelerated the growth of blood vessels and the formation of new bones.
The application of AM technology in medical treatment is growing with the availability of materials, and the design of intelligent structures and the advancement of surface modification technology have further accelerated its application. AM technology is the link between a patient's special location and an individualized surgical plan. With the help of scientific optimization and strong manufacturing capabilities, personalized medical processing technology will further guide 3D printing technology into a golden age in the medical field.
4.2.2. Tissue engineering and artificial organs
The purpose of tissue engineering is to promote cell proliferation through functional reconstruction or scaffolding, and the principle of layered AM manufacturing allows complex structures to be precisely controlled from the microscopic scale to the macroscopic scale. The ideal scaffold needs to be able to provide a simulated environment for cell migration, proliferation and differentiation into different tissues and even organs. Intelligent 4D printed polymers have been reported to have good shape memory ability, adhesion ability of bone marrow mesenchymal stem cells, proliferation and differentiation. This work has significantly improved the design capabilities of active stents with the help of 4D printing technology. Printing with different AM technologies, including 3D printing multi-scale brackets. This scaffold can promote the proliferation and differentiation of nerve cells. For the skull system, an in situ printed bioink was reported to deal with muscle volume loss.
During tissue regeneration, the formation of blood vessels is key to nutrient transport and gas exchange, and it is still very difficult to manufacture and study multi-vessel biological stents. Printing artificial blood vessels containing cells has been reported. Three weeks after the implantation of these blood vessels, great potential was shown for the treatment of cardiovascular disease.
More recently, a biocompatible PEDA-based photopolymerization hydrogel was fabricated into multi-vessel and intravascular networks using the SLA process. The acoustic and functional processes of oxygen and the flow of erythrocytes have been studied, see Figure 3a-c. In addition, the biodegradable carrier of this material, built on a model of chronic liver injury, enhances the potential capacity of transplantation. Many 3D printed heart meshes and hearts have been developed. The naturally structured heart, after being printed with fully personalized bioink, reveals great potential for printing customized tissues and organs.
Figure 3. Application of AM technology in the medical field: (a-c) the use of hydrogel networks for multi-vessel and intravascular network structures that are larger than and used for ventilation processes and oxygenation functions; (d-f) the printing manufacturing process and morphology of burr-like magnetic microscopic robots with cell delivery capabilities
▲ Expanded figure 3: Professor Jordan Miller of Rice University and Professor Kelly Stevens of the University of Washington published the first NCS of biological 3D printing, which provides a method for the construction of complex vascular network structures using high-precision lithography technology, making it possible to construct complex tissues and organs.
▲Enlarged image of Figure 3: The team of Professor Adam W. Feinberg of Carnegie Mellon University published "3D bioprinting of collagen torebuild components of the human heart" in Science, which used fresh adhesive as a printing support (Supporting Bath) to print complex structures such as heart valves and hearts with high precision. The study printed ventricles have functions such as synchronous contraction (no longer a mesh), directional action potential propagation, and thickening of the ventricular wall up to 14% during contraction.
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4.2.3. Medical diagnosis and treatment
AM technology has been applied in medical treatment as a powerful auxiliary disease diagnosis and surgical means. Based on CT scan and MRI to achieve the establishment of personalized 3D printing models for patients. These tactics can help plan and simulate surgery. In particular, the achievements in minimally invasive surgery are even greater. Novel smart materials or structures can be used for medical diagnosis and treatment, and have been reported in recent years. The earlier mentioned sub-micron-level magnetic continuous soft robot with controlled navigation can achieve diagnostic treatment of narrow areas, such as distal blood vessels, by further optimizing the vision and magnetron system. This robot could open up a new world for minimally invasive surgery and overcome existing challenges. Li et al. designed and built a burr-shaped porous miniature robot that was manufactured using laser lithography. And the robot is coated with Ni and Ti for magnetic excitation and improved biocompatibility, see Figures 3d and e. Experimental results show that cells loaded on microrobots can be transported and released to the ideal place. This robot shows great potential for regenerative medicine and cell therapy, see Figure 3f. In addition, personalized, customized head support properties are achieved by JOnathan et al., and the advantages it shows include quality hydrogen, low cost, and high safety. AM technology has become a powerful tool for manufacturing delicate and complex parts due to its high resolution and high efficiency. Personalized and customized artificial organs and tissues with unique characteristics will become possible in the near future using AM technology.
Figure 4. Application of 3D printing technology in microneedle systems
4.2.4.3D printing technology and its application on COVID-19 (novel coronavirus).
Recently, the novel coronavirus has taken a global toll and has had a huge and far-reaching impact on the world's economic and social fabric. Lu et al. designed a new and simple simple projection device for the COVID-18 virus that predicts its outbreak and development trends. AM technology presents unique advantages in the research and manufacture of novel antivirus masks and other medical tools, such as respirators and virus detection equipment.
Different materials have been used to print masks and protective glasses, such as polyethylene terephthalate-1,4-cyclohexyldimethyl terephthalate (PETG), polyurethane (PU) and ABS. 3D printing technology can be used to print and manufacture protective masks and protective glasses with complex structures and multiple functions. At the same time, wasted materials can also be greatly reduced and at the same time increase manufacturing efficiency and reduce costs. Protecting glasses is crucial for anti-virus workers because of the many problems with traditional glasses. Researchers from Zhejiang University have invented a platform to design personalized glasses that can solve the functionality and consistency problems of protective glasses manufactured by existing standards.
Summary of applications in medicine:
Different researchers have used significantly different 3D printing techniques to conduct research in different areas of medical treatment. According to the American Medical Professionals Association, the application of AM's output value in the dental field is estimated to reach 9.79 billion in the dental field in 2027 (equivalent to a 35% increase per year). The adoption of 3D printing technology in medical applications is also growing. Studies show that about 11% of the medical industry's revenue comes from 3D printed parts, while medical devices or implants account for a large proportion. The growing growth of AM technology is due to the need for personalized medicine. According to the web of science database, a total of 1157 research papers were applied to the biomedical field of AM technology, and the search period was from 2011 to October 2020. The detailed publication of the literature in journals and the number of research papers is shown in Figure 5(ab). Although so much literature has been published in these areas, here we have only counted the journals ranked in the top 10 for presentation. Among the top 10 journals, Rapid Prototyping (RP) journals have the most publications. In addition, the proportion of 3D printing research in the medical field in different countries is shown in Figure 6. As can be seen from Figure 6, the United States still occupies the top spot.
Figure 5.(a) Application of AM technology in the medical field: SCI papers published in top 10 journals; (b) Application of AM technology in the medical field: Annual publication volume, data source: Web of Science
Figure 6. The proportion of 3D printing applications in the medical field when classified by country, data source: Web of Science
To be continued, Jiangsu Laser Alliance Laser Red welcomes your continued attention.
文章来源：Additive manufacturing of structural materials，https://doi.org/10.1016/j.mser.2020.100596，https://www.sciencedirect.com/science/article/pii/S0927796X20300541，Materials Science and Engineering: R: Reports，Available online 1 April 2021, 100596
参考资料：1，Science 03 May 2019:Vol. 364, Issue 6439, pp. 458-464，DOI: 10.1126/science.aav9750,2，3D printing as a transformative tool for microneedle systems: Recent advances, manufacturing considerations and market potential，Advanced Drug Delivery Reviews，Volume 173, June 2021, Pages 60-69，https://doi.org/10.1016/j.addr.2021.03.007
3，The role of additive manufacturing for biomedical applications: A critical review，Journal of Manufacturing Processes，Volume 64, April 2021, Pages 828-850，https://doi.org/10.1016/j.jmapro.2021.02.022
4，Lee, A., et al. "3D bioprinting of collagen to rebuild components of the human heart." Science 365.6452 (2019): 482-487.