Direct 4D printing of hydrogels driven by structural topology

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.

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.

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.

4D printing applications in medical field: A brief review

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

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

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

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.

Three-dimensional (3D)/four-dimensional (4D) printing, also known as additive manufacturing or fast prototyping, is a manufacturing technique that uses a digital model to generate a 3D/4D solid product. The usage of biomaterials with 3D/4D printers in the pharma and healthcare industries is gaining significant popularity. 3D printing has mostly been employed in the domain of otolaryngology to build portable anatomical models, personalized patient-centric implants, biologic tissue scaffolds, surgical planning in individuals with challenging conditions, and surgical training. Although identical to 3D printing technology in this application, 4D printing technology comprises a fourth dimension of time. With the use of 4D printing, a printed structure may alter over time under various stimuli. Smart polymeric materials are also generally denoted as bioinks are frequently employed in tissue engineering applications of 3D/4D printing. In general, 4D printing could significantly improve the safety and efficacy of otolaryngology therapies. The use of bioprinting in otolaryngology has an opportunity to transform the treatment of diseases influencing the ear, nose, and throat as well as the field of tissue regeneration. The present review briefs on polymeric material including biomaterials and cells used in the manufacturing of patient centric 3D/4D bio-printed products utilized in management of otolaryngology.

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

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].

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.

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.

Two-photon polymerization (TPP) is a cutting-edge micro/nanoscale three-dimensional (3D) printing technology based on the principle of two-photon absorption. TPP surpasses the diffraction limit in achieving feature sizes and excels in fabricating intricate 3D micro/nanostructures with exceptional resolution. The concept of 4D entails the fabrication of structures utilizing smart materials capable of undergoing shape, property, or functional changes in response to external stimuli over time. The integration of TPP and 4D printing introduces the possibility of producing responsive structures with micro/nanoscale accuracy, thereby enhancing the capabilities and potential applications of both technologies. This paper comprehensively reviews TPP-based 4D printing technology and its diverse applications. First, the working principles of TPP and its recent advancements are introduced. Second, the optional 4D printing materials suitable for fabrication with TPP are discussed. Finally, this review paper highlights several noteworthy applications of TPP-based 4D printing, including domains such as biomedical microrobots, bioinspired microactuators, autonomous mobile microrobots, transformable devices and robots, as well as anti-counterfeiting microdevices. In conclusion, this paper provides valuable insights into the current status and future prospects of TPP-based 4D printing technology, thereby serving as a guide for researchers and practitioners.

Reversible energy absorbing meta-sandwiches by FDM 4D printing