4D printing: Pragmatic progression in biofabrication

Over the past few decades, threedimensional (3D) printing has greatly aided in the creation of patient-specific prosthesis, drug administration, tissue and organ manufacturing, and surgery planning. Since the US established its Precision Medicine Initiative in 2015, there has been a surge in interest in personalized healthcare. The term "personalized medicine" basically describes patient-specific medical treatment. However, the biomedical materials used in 3D printing are frequently stable and incapable of responding to or being intelligently and adaptively adapted to the inside environment of the body. A disparity between the printed section and the target portions may result from ex-situ manufacturing of these materials, which involves printing on a flat substrate before releasing it onto the target surface. One technique that could be applied to offer individualized care is 3D printing. The components used in the development of four-dimensional (4D) printing can be adjusted through stimulation. Recently, a number of academics have begun examining a novel field that combines 3D and 4D printing with medications. Many of these problems are resolved by the development of 4D printing, which also bodes well for thebiomedical sector going forward. Pre-programmed smart materials can be utilized in 4D printing to produce structures that respond interactively to external stimuli

3D Printing, sometimes referred to as additive manufacturing, has made the concept of personalized medicine a reality. The primary objective of 3D and 4D printing is to produce intricate, customized pharmaceuticals at a reasonable cost. With improvements in materials, resolution, and speed, 3D printing technology is quickly developing. It includes faster construction, cost efficiency through reduced waste, design flexibility for complex structures, and sustainability through optimized material usage. An extensive literature survey was done on 3D and 4D printing of pharmaceuticals using PubMed, Elsevier, ScienceDirect, and Springer. The results were then filtered based on the titles, abstracts, and accessibility of the complete texts. The search engine Google Scholar was accessed for literature data mining. From the data mining, it was found that from the year 2009 to 2024 the number of research publications surged more than 200 times on the current topic. Even though 3-D and 4-D printing technologies have advanced significantly in a short amount of time, the most often used ones are still stereolithography, nozzle-based deposition, inkjet, and selective laser sintering. Their use has been modified for the production of nanoparticles, polypills, tablets, and implants, etc. Pharma's aspirations for tailored medications are being revolutionized by 3D printing, but cost, flexibility, and bioequivalence still need to be investigated. The present review offers a thorough analysis of various 3D and 4D printing methods and emphasizes the major advantages and disadvantages and major key challenges of 3D and 4D printing related to pharmaceuticals. Compared to 3D Printing, 4D printing offers better quality, efficacy, and functionality.

4 - 4D-printed low-voltage electroactive polymers modeling and fabrication

Three-dimensional (3D) bioprinting is a versatile technique for biomedical applications, and includes organ printing, 3D disease model development, and drug delivery. The bioprintable materials combined with live cells have been utilized as bioinks in 3D bioprinter to fabricate versatile 3D printed structures. The 3D structures developed with smart and responsive materials can change their dimension, a technique similar to self-assembly, unfolding a new branch termed as four-dimensional (4D) printing. This manuscript reviews the details of various bioprintable materials and 3D printers, the application of 3D printing in biomedicine, smart materials, and stimulations for 4D printing. Further, this article also summarizes the regulatory issues and the limitations involved with the bioprinting. The advancements in 3D and 4D printing technology have significantly contributed to the medical field, and adequate research and amalgamation of engineering and science ideas will strengthen the application of this technology and bring solution for the existing problems.Graphical abstract

Three dimensional printing (3D printing), also known as additive manufacturing, are now being widely studied and developed, as well as in the constructional domain, where the 3D printing is beginning to move from an architect's modelling tool to delivering full-scale architectural components and elements of buildings such as walls and facades. 3D printing process is an additive manufacturing method from one dimensional dot/line to a two dimensional plane, then to a three dimensional object. In this study, magnesium phosphate cement (MPC), which has properties as fast setting, early strength, is introduced to one of the 3D printing techniques, powder based 3D printing. This study is focused on the designing of a 3D printer, the study of raw material print-ability, and the properties of the printed result. A final 3D printer has been built and MPC samples have been successfully printed. The printed result, which is sandwich-like structure, are acceptable with compression strength at 19.4MPa, direct tensile strength at 10.6KPa, and flexural strength at 6.5MPa, maximum in three dimensions. Many other properties can also be derived from this new printing method due to this sandwich structure of the printed result. The major contributions of the study are: 1. Introducing magnesium phosphate cement into the 3D printing technique. The printing material is the key factor to the development of the 3D printing. An acceptable work procedure of magnesium phosphate cement mix is found and applied in this 3D printing research. The raw material is separated to solid and liquid parts, while the particle size of the solid powder mix should be less than 300 micro meter, and both of the solid and liquid could be controlled automatically. 2. A printing strategy is invented to adapt the printing material and the selected printing nozzle. Horizontal scanning is the best choice for this liquid-jetting printing technique. The printing nozzle is a standard needle, with which the liquid is jetted out under a specified pressure. 3. The key parameters of this powder printing technique are found: liquid / solid ratio, and the designed layer thickness. The liquid / solid ratio, as the water /cement ratio in this study, should remain relatively low (around 0.05) to accomplish the printing request. The mechanical properties of the printed results are mainly determined by the designed layer thickness and the degree of the combination between the printing components. 4. A prototype printer has been installed, and designed product is successfully printed out of the magnesium phosphate cement material. The basic properties of the printed result have been tested and studied.

Recent 3D and 4D intelligent printing technologies: A comparative review and future perspective

Chapter 15 - 3D and 4D printing of biomaterials and biocomposites, bioinspired composites, and related transformers

The field of neural tissue engineering has undergone a revolution due to advancements in three-dimensional (3D) printing technology. This technology now enables the creation of intricate neural tissue constructs with precise geometries, topologies, and mechanical properties. Currently, there are various 3D printing techniques available, such as stereolithography and digital light processing, and a wide range of materials can be utilized, including hydrogels, biopolymers, and synthetic materials. Furthermore, the development of four-dimensional (4D) printing has gained traction, allowing for the fabrication of structures that can change shape over time using techniques such as shape-memory polymers. These innovations have the potential to facilitate neural regeneration, drug screening, disease modeling, and hold tremendous promise for personalized diagnostics, precise therapeutic strategies against brain cancers. This review paper provides a comprehensive overview of the current state-of-the-art techniques and materials for 3D printing in neural tissue engineering and brain cancer. It focuses on the exciting possibilities that lie ahead, including the emerging field of 4D printing. Additionally, the paper discusses the potential applications of five-dimensional and six-dimensional printing, which integrate time and biological functions into the printing process, in the fields of neuroscience.

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.

Every industry need helps to modify its working style quickly with the improvement of existing technology. New developing technologies improve production speed, reduce industrial process costs, etc. Technical specialists carry out continuous research and development to increase efficiency. A significant advance in 4D printing over 3D Printing is its capacity to alter shape over time because external elements such as pressure, air, heat, water, etc., use controlled impact. 4D Printing has one “D" instead of 3D Printing, and the fourth aspect is time. Therefore, its capacity to alter shape over time is a significant advancement of 4D printing over 3D printing technologies. It is evident that 4D printing will be of tremendous value to manufacturers regarding features and advances in dentistry. Its applications cover medical modelling, surgical guides manufacture, prosthodontics, dentistry, orthodontics, implantology, and dentistry instruments. This paper is brief about 4D printing and its printing of smart materials through 4D printing. Process workflow and Bio-Oriented 4D printable smart materials for dentistry are presented diagrammatically. Further, the paper identifies and discusses the significant potential of 4D printing for dentistry. 4D printing is an innovative technology that uses the inputs from smart materials, and the 3D printed item becomes another structure via the impact of external energy sources such as temperature, light, or other environmental stimuli. The objective is to integrate technology and design to create self-assembly and programmable material technologies that better design, production, and performance.

Alumina (Al2O3) suspensions were prepared for the effective application in the stereolithography three-dimensional (3D) printing process. Thermal treatment of -Al2O3 could optimize the ceramic slurries to meet the requirements of stereolithography 3D printing technique. In this study, alumina powders were modified by thermal treatment at different temperatures for the preparation of well dispersed ceramic slurries. The influence of thermal treatment on the raw powder, printed green bodies, and sintered alumina parts was systematically studied. Thermogravimetric analysis indicated that the decomposition temperature of photosensitive resin was between 390C and 460C. The alumina powders became denser, the crystal grains changed from round sphere-shaped to long cylinder-shaped, and the pores disappeared with increasing thermal treatment temperature. After the 3D printing process, the microstructure of green bodies and sintered alumina ceramics exhibited significant variation. Decomposition and removal of photosensitive resin led to higher water absorption, higher porosity, and lower bulk density of alumina ceramics compared to the printed green bodies. The scattering phenomenon in ceramic slurries and layer-by-layer forming characteristic determined the different shrinkage in three directions. Experimental results suggested that 1500C was considered as the optimal thermal treatment temperature, with the water absorption of 107%, open porosity of 91%, and bulk density of 0.67g·cm3. The higher thermal treatment temperatures would cause alumina powders to clump and agglomerate.

Four-dimensional (4D) printing is regarded as a methodology that links 3D printing to time, which is characterized by the evolution of predetermined structures or functions for the printed object after applying stimulation. This dynamic feature endows 4D printing the potential to be intelligent, attracting wide attention from academia and industry. The transformation of shape and function is both obtained from the programming of the object endowed by the intrinsic characteristics of the material or by the manufacturing technology. Therefore, it is necessary to understand 4D printing from the perspective of both mechanism and manufacturing. Here, the state-of-the-art 4D printing polymer was summarized, beginning with the classifications, and leading to the mechanisms, stimulations, and technologies. The links and differences between 4D printing polymer and shape memory polymer, between 4D printing and 3D printing were highlighted. Finally, the biomedical applications were outlined and the perspectives were discussed.

Thermocompression (with also extrusion and injection molding) is a classical polymer shaping manufacturing, but it does not easily allow designing sophisticated shapes without using a complex mold, on the contrary to 3D printing (or polymer additive manufacturing), which is a very flexible technique. Among all 3D printing techniques, fused deposition modeling is of high potential for product manufacturing, with the capability to compete with conventional polymer processing techniques. This is a quite low cost 3D printing technique, but the range of filaments commercially available is limited. However, in some specific 3D printing processes, no filaments are necessary. Polymers pellets feed directly the printing nozzle allowing to investigate many polymeric matrices with no commercial limitation. This is of high interest for the design of flame‐retarded materials, but literature is scarce in that field. In this paper, a comparison between thermocompression and 3D printing processes was performed on both neat ethylene‐vinyl acetate (EVA) copolymer and EVA flame retarded with aluminum triHydroxyde (ATH) containing different loadings (30 or 65 wt%) and with expandable graphite (EG), ie, EVA/ATH (30 wt%), EVA/ATH (65 wt%), and EVA/EG (10 wt%), respectively. Morphological comparisons, using microscopic and electronic microprobe analyses, revealed that 3D printed plates have lower apparent density and higher porosity than thermocompressed plate. The fire‐retardant properties of thermocompressed and 3D printed plates were then evaluated using mass loss calorimeter test at 50 kW/m2. Results highlight that 3D printing can be used to produce flame‐retardant systems. This work is a pioneer study exploring the feasibility of using polymer additive manufacturing technology for designing efficient flame‐retarded materials.

3D printing technology has revolutionized the way products are manufactured, and it has opened up new possibilities in the field of smart materials. Smart materials are materials that can change their properties in response to external stimuli, such as temperature, pressure, or light. By combining 3D printing technology with smart materials, highly customizable and responsive products are created. The addition of the time dimension to 3D printing has introduced 4D printing technology, which has gained considerable attention in different fields such as medical, art, and engineering. To bridge the gap in knowledge of 4D, this paper assessed the revolution in healthcare with 3D/4D printing and smart materials. Data was generated as part of a broader empirical study which sought to explore healthcare personnel and electrical engineers’ perception on the practices around the use of 3D/4D printing technology and smart materials. The main method used was structured interviews. 12 participant were purposively selected and interviewed including healthcare personnel and electrical engineers form Philippines and Nigeria. The findings reveal an array of activities undertaken using both 3D and 4D. Furthermore, the study revealed that 4D printing is a new generation of 3D printing. Another aspect of the 3D usage is the integration of electrical stimulation and smart implant as a new area of study in healthcare. 3D could also be used to monitoring the smart implant performance. The study also evaluate the possibility of using Internet of things (IoT) in the smart implant as some device embeds smart materials. Smart implant commonly used includes orthopedic applications, such as knee and hip replacement, spine fusion, and fracture fixation. The smart materials used in this technology are important because 3D printing allows printed structures to be dynamic. The paper highpoints is that 4D printing has great potential for the future.

Despite great progress in four-dimensional (4D) printing, i.e. three-dimensional (3D) printing of active (stimuli-responsive) materials, the relatively low actuation force of the 4D printed structures often impedes their engineering applications. In this study, we use multimaterial inkjet 3D printing technology to fabricate shape memory structures, including a morphing wing flap and a deployable structure, which consist of active and flexible hinges joining rigid (non-active) parts. The active hinges, printed from a shape memory polymer (SMP), lock the structure into a second temporary shape during a thermomechanical programming process, while the flexible hinges, printed from an elastomer, effectively increase the actuation force and the load-bearing capacity of the printed structure as reflected in the recovery ratio. A broad range of mechanical properties such as modulus and failure strain can be achieved for both active and flexible hinges by varying the composition of the two base materials, i.e. the SMP and the elastomer, to accommodate large deformation induced during programming step, and enhance the recovery in the actuating step. To find the important design parameters, including local deformation, shape fixity and recovery ratio, we conduct high fidelity finite element simulations, which are able to accurately predict the nonlinear deformation of the printed structures. In addition, a coupled thermal-electrical finite element analysis was performed to model the heat transfer within the active hinges during the localized Joule heating process. The model predictions showed good agreement with the measured temperature data and were used to find the major parameters affecting temperature distribution including the applied voltage and the convection rate.