Advances in 4D printing: from stimulation to simulation.

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.

4D printing of polymeric materials for tissue and organ regeneration.

Four-dimensional (4D) printing technology, as a next-generation additive manufacturing method, enables printed objects to further change their shapes, functionalities, or properties upon exposure to external stimuli. The 4D printing of programmable and deformable materials such as thermo-responsive shape-memory polymers (trSMPs), which possess the ability to change shape by exposure to heat, has attracted particular interest in recent years. Three-dimensional objects based on SMPs have been proposed for various potential applications in different fields, including soft robotics, smart actuators, biomedical and electronics. To enable the manufacturing of complex multifunctional 3D objects, SMPs are often coupled with other functional polymers or fillers during or before the 3D printing process. This review highlights the 4D printing of state-of-the-art multi-component SMP formulations. Commonly used 4D printing technologies such as material extrusion techniques including fused filament fabrication (FFF) and direct ink writing (DIW), as well as vat photopolymerization techniques such as stereolithography (SLA), digital light processing (DLP), and multi-photon polymerization (MPP), are discussed. Different multicomponent SMP systems, their actuation methods, and potential applications of the 3D printed objects are reviewed. Finally, current challenges and prospects for 4D printing technology are summarized.

Most of the biomedical materials printed using 3D bioprinting are static and are unable to alter/transform with dynamic changes in the internal environment of the body. The emergence of four-dimensional (4D) printing addresses this problem. By preprogramming dynamic polymer materials and their nanocomposites, 4D printing is able to produce the desired shapes or transform functions under specific conditions or stimuli to better adapt to the surrounding environment. In this review, the current and potential applications of 4D-printed materials are introduced in different aspects of the biomedical field, e.g., tissue engineering, drug delivery, and sensors. In addition, the existing limitations and possible solutions are discussed. Finally, the current limitations of 4D-printed materials along with their future perspective are presented to provide a basis for future research.

4D printing applications in medical field: A brief review

In these times of Industrial 4.0 and Health 4.0, people currently want to enhance the ability of science and technology, to focus on patient aspects. However, with intelligent, green energy and biomedicine these days, traditional three-dimensional (3D) printing technology has been unable to meet our needs, so 4D printing has now arisen. In this research, a shape-memory composite material with 3D printing technology was used for 4D printing technology. The authors used fused deposition modeling (FDM) to print a polylactic acid (PLA) strip onto the surface of paper to create a shape-memory composite material, and a stimulus (heat) was used to deform and recover the shape of this material. The deformation angle and recovery angle of the material were studied with various processing parameters (heating temperature, heating time, pitch, and printing speed). This research discusses optimal processing related to shape-memory situations of stimulus-responsive composite materials. The optimal deformation angle (maximum) of the stimulus-responsive composite material was found with a thermal stimulus for an optimal heating temperature of 190 °C, a heating time of 20 s, a pitch of 1.5 mm, and a printing speed of 80 mm/s. The optimal recovery angle (minimum) of this material was found with a thermal stimulus for an optimal heating temperature of 170 °C, a heating time of 90 s, a pitch of 2.0 mm, and a printing speed of 80 mm/s. The most important factor affecting both the deformation and recovery angle of the stimulus-responsive composite material was the heating temperature.

4D printing has attracted tremendous worldwide attention during the past decade. This technology enables the shape, property, or functionality of printed structures to change with time in response to diverse external stimuli, making the original static structures alive. The revolutionary 4D-printing technology offers remarkable benefits in controlling geometric and functional reconfiguration, thereby showcasing immense potential across diverse fields, including biomedical engineering, electronics, robotics, and photonics. Here, a comprehensive review of the latest achievements in 4D printing using various types of materials and different additive manufacturing techniques is presented. The state-of-the-art strategies implemented in harnessing various 4D-printed structures are highlighted, which involve materials design, stimuli, functionalities, and applications. The machine learning approach explored for 4D printing is also discussed. Finally, the perspectives on the current challenges and future trends toward further development in 4D printing are summarized.

Four-dimensional (4D) printing, an evolution of additive manufacturing (AM), integrates stimuli-responsive materials like thermal-induced shape memory polymers (TSMPs) to enable programmable, time-dependent transformations in structures. This review systematically examines recent advancements in TSMPs, 4D printing technologies, and fabrication strategies, emphasizing their interdisciplinary convergence and applications. TSMPs, with their unique phase-separated microstructures, modulus disparity, and tailorable recovery behaviors, form the foundation of 4D-printed systems, enabling innovations in aerospace, healthcare, and soft robotics [1–3, 33–45]. Key printing methods—including fused deposition modeling (FDM), direct ink writing (DIW), PolyJet, stereolithography (SLA), and digital light processing (DLP)—are analyzed for their strengths and limitations. FDM dominates due to cost-effectiveness but faces challenges in resolution and anisotropy [88, 91–93], while SLA and DLP offer high precision and speed but require material optimization [105, 111–115]. Advanced fabrication strategies, such as localized TSMP printing, composite reinforcement with carbon nanotubes or Fe 3O 4 particles, and sacrificial mold templating, expand design possibilities for multi-functional and multi-scale structures [117–120, 140–144]. Despite progress, challenges persist, including environmental sensitivity of TSMPs, interlayer bonding in AM, and dynamic modeling of non-equilibrium thermal responses [74, 77, 146]. Future directions focus on multi-responsive materials, machine learning-driven constitutive models, and sustainable bio-based formulations to address scalability and cyclic durability [31, 77, 147–149]. By bridging material science, computational modeling, and advanced manufacturing, this work provides a roadmap for harnessing 4D-printed TSMPs in real-world applications, from self-deploying biomedical devices to adaptive aerospace systems [28, 85, 137].

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

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

Compression property and energy absorption capacity of 4D-printed deformable honeycomb structure

Scientists have developed smart shape memory materials that can adapt their structure or function to external stimuli. The demand for dynamic oral bone tissue repair is driven by continuous changes in bone and surrounding tissues during the repair process, such as tooth growth, movement, and reconstruction of oral soft tissues, as well as skeletal differences of alveolar and craniofacial bones. These changes challenge the mechanical stability of bone implants and the precision of printing. Consequently, 4D printing technology introduces "time", allowing pre-programmed changes in material shape or functionality which enables scaffolds to intelligently respond to complex oral environments, achieving dynamic repair of bone and surrounding tissues. Despite its theoretical benefits in oral bone tissue engineering, the study and use of 4D printing technology is still in its infancy. This review explores the most recent advances in 4D- printing in dentistry, discussing skeletal structure, etiology of bone defects, and bone repair mechanisms. It also provides an overview of the materials, cells, and growth factors used in 4D-printing bone tissue engineering. Thus, by reviewing existing studies, this review provides valuable insights for the future development of 4D printing technology in oral bone tissue engineering.  

Four-dimensional (4D) printing combines shape-morphing materials and three-dimensional (3D) printing technology, enabling efficient fabrication of complex shape-changing structures. However, 4D printing of hydrogels into structures with complex shapes suffers from poor printability, which limit their practical applications. Here, we present an efficient strategy for direct 4D printing of hydrogels, leveraging intricate structural designs and highly viscous hydrogels. This strategy facilitates programmable shape-morphing through precise control of filament spacing and orientation, resulting in gradient swelling behaviours when the structures are immersed in a Ca2+-ion solution. Our study also reveals the critical role of printability in improving shape-morphing performance. On this basis, we propose a practical solution to enhance the shape-morphing capability of hydrogels with limited inherent performance by improving their printability through the addition of viscous additives such as MC or PVA. Overall, this strategy expands the list of hydrogels suitable for 4D printing, demonstrating compatibility with both synthetic and natural hydrogels, including Alginate/Methylcellulose (ALG/MC), gelatin methacryloyl (GELMA), and ALG/polyvinyl alcohol (PVA). Various sophisticated plant-inspired shape-morphing behaviours can be achieved in 4D-printed hydrogels through precise control of structural topology. The combined strategy of employing highly viscous hydrogel with intricate structural design demonstrates vast potential for applications in biomimetic soft robotics.

Reversible energy absorbing meta-sandwiches by FDM 4D printing