Application and potential of 4D printing in medicine

The addition of the time dimension to three-dimensional (3D) printing has introduced four-dimensional (4D) printing technology, which has gained considerable attention in different fields such as medical, art, and engineering. Nowadays, bioscience has introduced some ideas which can be fulfilled by 4D printing. Blending time with variations caused by the situation has many beneficial aspects such as perceptibility and adaptability. Since 4D printing can create a dynamic structure with stimuli-responsive materials, the applications of smart materials, stimulus, and 3D printing are the effective criteria in 4D printing technology. Smart materials with their flexible properties can reshape, recolor, or change function under the effect of the internal or exterior stimuli. Thus, an attractive prospect in the medical field is the integration of the 4D printing approach along with smart materials. This research aims to show the most recent applications of 4D printing technology and smart materials in medical engineering which can show better prospective of 4D printing applications in the future. Also, it describes smart medical implants, tissue engineering, and bioprinting and how they are being used for the 4D printing approach in medical engineering applications. In this regard, a particular emphasis is dedicated to the latest progress in the innovation and development of stimuli-responsive materials that are activated and respond over time to physical, chemical, and biological stimuli and their exploitation through 3D printing methods to fabrication 4D printing smart parts such as intelligent tissue-engineered scaffolds, smart orthopedic implants, and targeted drug delivery systems. On the other hand, major challenges in this technology are explained along with some suggestions for future works to address existing limitations. It is worth noting that despite significant research that has been carried out into 4D printing, it might be more valuable if some investigation is done into 4D bio-printing applications and how this approach will be developed.

The advancement of four-dimensional (4D) printing has been fueled by the rise in demand for additive manufacturing and the expansion in shape-memory materials. The printing of smart substances that respond to external stimuli is known as 4D printing. 4D printing allows highly controlled shapes to simulate the physiological milieu by adding time dimensions. The 4D printing is suitable with current progress in smart compounds, printers, and its mechanism of action. The 4D printing paradigm, a revolutionary enhancement of 3D printing, was anticipated by various engineering disciplines. Tissue engineering, medicinal, consumer items, aerospace, and organ engineering use 4D printing technology. The current review mainly focuses on the basics of 4D printing and the methods used therein. It also discusses the time-dependent behavior of stimulus-sensitive compounds, which are widely used in 4D printing. In addition, this review highlights material aspects, specifically related to shape-memory polymers, stimuli-responsive materials (classified as physical, chemical, and biological), and modified materials, the backbone of 4D printing technology. Finally, potential applications of 4D printing in the biomedical sector are also discussed with challenges and future perspectives.

Organ or cell transplantation is medically evaluated for end-stage failure saving or extending the lives of thousands of patients who are suffering from organ failure disorders. The unavailability of adequate organs for transplantation to meet the existing demand is a major challenge in the medical field. This led to day-day-increase in the number of patients on transplant waiting lists as well as in the number of patients dying while on the queue. Recently, technological advancements in the field of biogenerative engineering have the potential to regenerate tissues and, in some cases, create new tissues and organs. In this context, major advances and innovations are being made in the fields of tissue engineering and regenerative medicine which have a huge impact on the scientific community is three-dimensional bioprinting (3D bioprinting) of tissues and organs. Besides this, the decellularization of organs and using this as a scaffold for generating new organs through the recellularization process shows promising results. This review discussed about current approaches for tissue and organ engineering including methods of scaffold designing, recent advances in 3D bioprinting, organs regenerated successfully using 3D printing, and extended application of 3D bioprinting technique in the field of medicine. Besides this, information about commercially available 3D printers has also been included in this article.Lay SummaryToday’s need for organs for the transplantation process in order to save a patient’s life or to enhance the survival rate of diseased one is the prime concern among the scientific community. Recent, advances in the field of biogenerative engineering have the potential to regenerate tissues and create organs compatible with the patient’s body. In this context, major advances and innovations are being made in the fields of tissue engineering and regenerative medicine which have a huge impact on the scientific community is three-dimensional bioprinting (3D bioprinting) of tissues and organs. Besides this, the decellularization of organs and using this as a scaffold for generating new organs through the recellularization process shows promising results. This review dealt with the current approaches for tissue and organ engineering including methods of scaffold designing, recent advances in 3D bioprinting, organs regenerated successfully using 3D printing, and extended application of 3D bioprinting technique in the field of medicine. Furthermore, information about commercially available 3D printers has also been included in this article.

BackgroundRecent advances in 3D printing technology, and biomaterials are revolutionizing medicine. The beneficiaries of this technology are primarily patients, but also students of medical faculties. Taking into account that not all students have full, direct access to the latest advances in additive technologies, we surveyed their opinion on 3D printing and education in this area. The research aimed to determine what knowledge about the use of 3D printing technology in medicine, do students of medical faculties have.MethodsThe research was carried out in the form of a questionnaire among 430 students of the Medical University of Silesia in Katowice (Poland) representing various fields of medicine and health sciences. The questions included in the survey analyzed the knowledge of the respondents for 3D printing technology and the opportunities it creates in medicine.ResultsThe results indicate that students do have knowledge about 3D printing obtained mainly from the internet. They would be happy to deepen their knowledge at specialized courses in this field. Students appreciated the value of 3D printing in order to obtain accurate anatomical models, helpful in learning. However, they do not consider the possibility of complete abandonment of human cadavers in the anatomy classes. Their knowledge includes basic information about current applications of 3D printing in medicine, but not in all areas. However, they have no ethical doubts regarding the use of 3D printing in any form. The vast majority of students deemed it necessary to incorporate information regarding 3D printing technology into the curriculum of different medical majors.ConclusionThis research is the first of its kind, which allows for probing students' knowledge about the additive technologies in medicine. Medical education should be extended to include issues related to the use of 3D printing for medical applications.

Using most widespread technology of rapid prototyping (RP) in medicine focus on the development of models for diagnosis, for training and planned surgery, as well as the direct manufacture of implants for bone reconstruction. The applications of 3D printing in the field of medicine are giving extraordinary results and tissue and prosthetic 3D printing, medical and engineering research professionals are conducting 3D printing organ bind. Researchers worldwide are pursuing the creation of artificial bone using 3D printers, bones that can be later implanted to humans. In near future, many body parts could be manufactured in a turn and successfully implanted to patients. Although medical advances in 3D printing are used in orthopaedic field, research in 4D printing has already started. Flat objects made with 3D printing, using a regular plastic, combined with smart material, were able to become a hub without an external intervention. In nutshell, the future of additive manufacturing (AM) in trauma and orthopedic surgery is relatively bright with the inclusion of 3D printing in medicine. Bioprinting in this area will be focused on fractures, nonunions, deformities and bone, cartilage and soft tissue reconstruction. CONCLUSION: The innovative technology not only assists the medical staff but is also beneficial for the patients because the medical problems, which were not curable in the past, are now possible with modern technology (Fig. 4, Ref. 52) Keywords: bone defect, tissue engineering, 3D printing, biomaterials, bone, porous scaffold.

The application of three-dimensional (3D) printing in medicine has increased rapidly in the last few years. Various new commercial 3D printers and 3D bioprinters are introduced into the current market. 3D printing scientific community has witnessed a rapid growth in the application of 3D printing for various medical needs. There has been a research advancement in 4D printing with a widened scope of 3D bioprinting. The growing demand for 3D printing and its use for commercial and industrial purposes in medical technology have facilitated the need for introduction of new international standards and regulations. The need for organ replacement has generated curiosity and competition among researchers to race for organ 3D printing, which can be identified with increased publications and patents that are filed in recent years. Hence, there is a need to update the readers with the latest information. The second edition of this chapter updates the contents of first section to fourth section with current information and some modified pictorial representations. New section describes the relevance of the new chapters added to this edition and updates the readers with insights on advancement of 3D printing in the last decade. Briefly, this chapter introduces the reader with a brief history of 3D printing in medical technology, components of 3D printing, 3D bioprinting, organ 3D bioprinting, advantages of 3D printing with current challenges and commercially available 3D printers in the current market. New sections introduced in this edition detail about the ASTM and ISO standards that are used for 3D printing in medicine, the regulatory framework with current challenges, ethical and social concerns with the current 3D printing scientific community, and the importance of intellectual property in safeguarding the interests of the innovators.

4D (bio-)printing endows 3D printed (bio-)materials with multiple functionalities and dynamic properties. 4D printed materials have been recently used in biomedical engineering for the design and fabrication of biomedical devices, such as stents, occluders, microneedles, smart 3D-cell engineered microenvironments, drug delivery systems, wound closures, and implantable medical devices. However, the success of 4D printing relies on the rational design of 4D printed objects, the selection of smart materials, and the availability of appropriate types of external (multi-)stimuli. Here, this work first highlights the different types of smart materials, external stimuli, and design strategies used in 4D (bio-)printing. Then, it presents a critical review of the biomedical applications of 4D printing and discusses the future directions of biomedical research in this exciting area, including in vivo tissue regeneration studies, the implementation of multiple materials with reversible shape memory behaviors, the creation of fast shape-transformation responses, the ability to operate at the microscale, untethered activation and control, and the application of (machine learning-based) modeling approaches to predict the structure-property and design-shape transformation relationships of 4D (bio)printed constructs.

Three-dimensional printing technology has been used for more than three decades in many industries, including the automotive and aerospace industries. So far, the use of this technology in medicine has been limited only to 3D printing of anatomical models for educational and training purposes, which is due to the insufficient functional properties of the materials used in the process. Only recent advances in the development of innovative materials have resulted in the flourishing of the use of 3D printing in medicine and pharmacy. Currently, additive manufacturing technology is widely used in clinical fields. Rapid development can be observed in the design of implants and prostheses, the creation of biomedical models tailored to the needs of the patient and the bioprinting of tissues and living scaffolds for regenerative medicine. The purpose of this review is to characterize the most popular 3D printing techniques.

The existing 3D printing methods exhibit certain fabrication-dependent limitations for printing curved constructs that are relevant for many tissues. Four-dimensional (4D) printing is an emerging technology that is expected to revolutionize the field of tissue engineering and regenerative medicine (TERM). 4D printing is based on 3D printing, featuring the introduction of time as the fourth dimension, in which there is a transition from a 3D printed scaffold to a new, distinct, and stable state, upon the application of one or more stimuli. Here, we present an overview of the current developments of the 4D printing technology for TERM, with a focus on approaches to achieve temporal changes of the shape of the printed constructs that would enable biofabrication of highly complex structures. To this aim, the printing methods, types of stimuli, shape-shifting mechanisms, and cell-incorporation strategies are critically reviewed. Furthermore, the challenges of this very recent biofabrication technology as well as the future research directions are discussed. Our findings show that the most common printing methods so far are stereolithography (SLA) and extrusion bioprinting, followed by fused deposition modelling, while the shape-shifting mechanisms used for TERM applications are shape-memory and differential swelling for 4D printing and 4D bioprinting, respectively. For shape-memory mechanism, there is a high prevalence of synthetic materials, such as polylactic acid (PLA), poly(glycerol dodecanoate) acrylate (PGDA), or polyurethanes. On the other hand, different acrylate combinations of alginate, hyaluronan, or gelatin have been used for differential swelling-based 4D transformations. TERM applications include bone, vascular, and cardiac tissues as the main target of the 4D (bio)printing technology. The field has great potential for further development by considering the combination of multiple stimuli, the use of a wider range of 4D techniques, and the implementation of computational-assisted strategies.

Three-dimensional (3D) printing is a new paradigm in customized manufacturing and allows the fabrication of complex optical components and metaphotonic structures that are difficult to realize via traditional methods. Conventional lithography techniques are usually limited to planar patterning, but 3D printing can allow the fabrication and integration of complex shapes or multiple parts along the out-of-plane direction. Additionally, 3D printing can allow printing on curved surfaces. Four-dimensional (4D) printing adds active, responsive functions to 3D-printed structures and provides new avenues for active, reconfigurable optical and microwave structures. This review introduces recent developments in 3D and 4D printing, with emphasis on topics that are interesting for the nanophotonics and metaphotonics communities. In this article, we have first discussed functional materials for 3D and 4D printing. Then, we have presented the various designs and applications of 3D and 4D printing in the optical, terahertz, and microwave domains. 3D printing can be ideal for customized, nonconventional optical components and complex metaphotonic structures. Furthermore, with various printable smart materials, 4D printing might provide a unique platform for active and reconfigurable structures. Therefore, 3D and 4D printing can introduce unprecedented opportunities in optics and metaphotonics and may have applications in freeform optics, integrated optical and optoelectronic devices, displays, optical sensors, antennas, active and tunable photonic devices, and biomedicine. Abundant new opportunities exist for exploration.

Objective This study aims to explain the mechanisms of the four-dimensional (4D) printing technique and its potential applications in dental and orthodontic practice. General Information Rapid advances in science and technology have led to significant developments in production systems. Described as additive manufacturing or rapid prototyping, a positive innovation has been the introduction of three-dimensional (3D) printers in the 1980s. The technology quickly became popular because it allowed complex structures to be produced using less material compared to traditional manufacturing methods. Objects are designed in three dimensions using dedicated computer programs and 3D printed using materials such as composites, resins, metals, and polymers. Orthodontics has also benefitted from 3D printing in the fields of clear aligner treatment, indirect bonding using bracket transfer trays, dental modelling, and the production of guides for mini-screw and implant placement, as well as the manufacture of removable appliances. As 3D printers continued to evolve and new ‘smart’ materials were specifically developed, 4D printing techniques emerged. 4D printing allows objects, produced by 3D printers to change shape in response to stimuli, usually in the form of heat and light, thereby enabling the performance of specific functions. The objects can also self-assemble into larger structures without external intervention. The applications of 4D printing are expanding across a wide range of clinical fields. Conclusion 4D printing is an evolving technology that requires further research. However, if integrated into dentistry, it holds great potential as an efficient printing method, similar to its applications in other fields.

Four-dimensional (4D) printing, which enables 3D printed structures to alter shapes over time, is attracting increasing attention because of its exciting potential in various applications. Among all the 4D printing materials, shape memory polymers (SMPs) have a higher stiffness and faster response rate and therefore are considered as one of the most promising 4D printing materials. However, the current studies of SMP-based 4D printing mainly focused on the deformation behavior and structural design of 4D printed structures. An additional function such as color change is desired for 4D printed structure, which would be potentially beneficial to the applications such as anti-counterfeiting, encryption, and bioinspired camouflage. In this paper, we report an ultraviolet (UV)-curable and thermochromic (UVT) SMP system that enables color-changeable 4D printing. The UVT SMP system is acrylate-based, thus highly UV-curable and compatible with PμSL-based high-resolution 3D printing technique. Thermochromism is imparted by adding the thermochromic microcapsules to the UVT SMP system, which allows the printed structures to reversibly change colors upon heating and cooling. To demonstrate its extraordinary thermochromic and mechanical performance, we use UVT SMP to print QR codes and multilevel anti-counterfeiting patterns which can hide the visible information at room temperature and visualize the information by encrypting, decrypting, and encrypting again steps with the shape-color recovery process. The development of UVT SMP will significantly advance current applications of SMP-based 4D printing, especially for anti-counterfeiting and safe data recording.

Four-dimensional (4D) printing technology is a revolutionary development that produces structures that can adapt in response to external stimuli. However, the responsiveness and printability of smart materials with shape memory properties, which are necessary for 4D printing, remain limited. Biomass materials derived from nature have offered an effective solution due to their various excellent and unique properties. Biomass materials have been abundant in resources and low in carbon content, contributing to the then-current global green energy-saving goals, including carbon peaking and carbon neutrality. This review focused on different sources of biomass materials used in 4D printing, including plant-based, animal-based, and microbial-based biomass materials. It systematically outlined the responsive deformation mechanisms of printed objects that contained biomass materials and delved into the roles and unique advantages of biomass materials in those printed objects. Leveraging these advantages, the review discussed the potential applications of biomass materials in biomedicine, food printing, and other fields to support ongoing development and application efforts. Additionally, it emphasized the crucial role played by bio-fabrication technologies utilizing biomass materials in the integration of biomass materials with 4D printing. Finally, this paper discussed the then-current challenges and potential future directions of biomass materials in 4D printing, aiming to promote the effective development of biomass materials in 4D printing applications.

Chapter 2 - 4D printing: definition, smart materials, and applications

The sector of 4D printing represents a new frontier in additive manufacturing that allows for a material's capability to adapt and respond to various stimuli, such as thermal transitions, humidity, and pH levels. The adaptability of such a material has great potential in healthcare applications, especially in designing personalized and responsive medical devices. This article looks into the revolutionary potential of healthcare applications of 4D printing, referencing applications in self-repairable implants, smart stents, personalized drug delivery systems, and response-based prosthetic devices. The advances in 3D printing have created a platform for such innovations to take place, while the material properties unique to 4D printing allow new methods of tackling existing health issues. However, the large-scale application of 4D printing in medicine is currently hampered by material limitations, regulation challenges, and financial challenges. In spite of these challenges, ongoing advances in technologies, combined with artificial intelligence and machine learning, provide the potential to surpass such challenges, hence improving the precision, efficacy, and personalization of medical devices. This work outlines existing applications, looks at potential areas of application in the future, and analyzes potential applications of 4D printing contributing to healthcare, recognizing challenges that need to be overcome in order to unlock its full potential.