Limpet Tooth-Inspired Painless Microneedles Fabricated by Magnetic Field-Assisted 3D Printing

Microneedle arrays show many advantages in drug delivery applications due to their convenience and reduced risk of infection. Compared to other microscale manufacturing methods, 3D printing easily overcomes challenges in the fabrication of microneedles with complex geometric shapes and multifunctional performance. However, due to material characteristics and limitations on printing capability, there are still bottlenecks to overcome for 3D printed microneedles to achieve the mechanical performance needed for various clinical applications. The hierarchical structures in limpet teeth, which are extraordinarily strong, result from aligned fibers of mineralized tissue and protein-based polymer reinforced frameworks. These structures provide design inspiration for mechanically reinforced biomedical microneedles. Here, a bioinspired microneedle array is fabricated using magnetic field-assisted 3D printing (MF-3DP). Micro-bundles of aligned iron oxide nanoparticles (aIOs) are encapsulated by polymer matrix during the printing process. A bioinspired 3D-printed painless microneedle array is fabricated, and suitability of this microneedle patch for drug delivery during long-term wear is demonstrated. The results reported here provide insights into how the geometrical morphology of microneedles can be optimized for the painless drug delivery in clinical trials.     

A Stimuli‐Responsive Nanocomposite for 3D Anisotropic Cell‐Guidance and Magnetic Soft Robotics

Stimuli‐responsive materials have the potential to enable the generation of new bioinspired devices with unique physicochemical properties and cell‐instructive ability. Enhancing biocompatibility while simplifying the production methodologies, as well as enabling the creation of complex constructs, i.e., via 3D (bio)printing technologies, remains key challenge in the field. Here, a novel method is presented to biofabricate cellularized anisotropic hybrid hydrogel through a mild and biocompatible process driven by multiple external stimuli: magnetic field, temperature, and light. A low‐intensity magnetic field is used to align mosaic iron oxide nanoparticles (IOPs) into filaments with tunable size within a gelatin methacryloyl matrix. Cells seeded on top or embedded within the hydrogel align to the same axes of the IOPs filaments. Furthermore, in 3D, C2C12 skeletal myoblasts differentiate toward myotubes even in the absence of differentiation media. 3D printing of the nanocomposite hydrogel is achieved and creation of complex heterogeneous structures that respond to magnetic field is demonstrated. By combining the advanced, stimuli‐responsive hydrogel with the architectural control provided by bioprinting technologies, 3D constructs can also be created that, although inspired by nature, express functionalities beyond those of native tissue, which have important application in soft robotics, bioactuators, and bionic devices.     

3D Printing of Functional Magnetic Materials: From Design to Applications

The research of functional magnetic materials has become a hot topic in the past few years due to their fast, long-range, and precise response in diverse environments. Functional magnetic devices using different magnetic materials and structure designs have been developed and demonstrated good advantages to enable various applications. However, the required magnetic materials and structure designs for diverse functions also increase the fabrication difficulties while developing such devices. 3D printing technology presents a powerful and promising manufacturing approach to rapidly fabricate functional magnetic devices of complex geometries in multiple materials and scales. Here, various 3D printing strategies and the underlying mechanisms of functional magnetic materials for several primary applications are systematically reviewed, including, magnetic anisotropy for property enhancement, magnetic robots, magnetic components in electronics, and magneto-thermal devices. Finally, the current challenges and future perspectives in engineering 3D printed functional magnetic devices are discussed.     

Inherent Photodegradability of Polymethacrylate Hydrogels: Straightforward Access to Biocompatible Soft Microstructures

Hydrogels are important functional materials useful for 3D cell culture, tissue engineering, 3D printing, drug delivery, sensors, or soft robotics. The ability to shape hydrogels into defined 3D structures, patterns, or particles is crucial for biomedical applications. Here, the rapid photodegradability of commonly used polymethacrylate hydrogels is demonstrated without the need to incorporate additional photolabile functionalities. Hydrogel degradation depths are quantified with respect to the irradiation time, light intensity, and chemical composition. It can be shown that these parameters can be utilized to control the photodegradation behavior of polymethacrylate hydrogels. The photodegradation kinetics, the change in mechanical properties of polymethacrylate hydrogels upon UV irradiation, as well as the photodegradation products are investigated. This approach is then exploited for microstructuring and patterning of hydrogels including hydrogel gradients as well as for the formation of hydrogel particles and hydrogel arrays of well‐defined shapes. Cell repellent but biocompatible hydrogel microwells are fabricated using this method and used to form arrays of cell spheroids. As this method is based on readily available and commonly used methacrylates and can be conducted using cheap UV light sources, it has vast potential to be applied by laboratories with various backgrounds and for diverse applications.     

Magnetic Assembly of Soft Robots with Hard Components

This paper describes the modular magnetic assembly of reconfigurable, pneumatically actuated robots composed of soft and hard components and materials. The soft components of these hybrid robots are actuators fabricated from silicone elastomers using soft lithography, and the hard components are acrylonitrile–butadiene–styrene (ABS) structures made using 3D printing. Neodymium–iron–boron (NdFeB) ring magnets are embedded in these components to make and maintain the connections between components. The reversibility of these magnetic connections allows the rapid reconfiguration of these robots using components made of different materials (soft and hard) that also have different sizes, structures, and functions; in addition, it accelerates the testing of new designs, the exploration of new capabilities, and the repair or replacement of damaged parts. This method of assembling soft actuators to build soft machines addresses some limitations associated with using soft lithography for the direct molding of complex 3D pneumatic networks. Combining the self‐aligning property of magnets with pneumatic control makes it possible for a teleoperator to modify the structures and capabilities of these robots readily in response to the requirements of different tasks.     

Biodegradable,Sustainable Hydrogel Actuators with Shape and Stiffness Morphing Capabilities via Embedded 3D Printing

Despite the impressive performance of recent marine robots, many of their components are non-biodegradable or even toxic and may negatively impact sensitive ecosystems. To overcome these limitations, biologically-sourced hydrogels are a candidate material for marine robotics. Recent advances in embedded 3D printing have expanded the design freedom of hydrogel additive manufacturing. However, 3D printing small-scale hydrogel-based actuators remains challenging. In this study, Free form reversible embedding of suspended hydrogels (FRESH) printing is applied to fabricate small-scale biologically-derived, marine-sourced hydraulic actuators by printing thin-wall structures that are water-tight and pressurizable. Calcium-alginate hydrogels are used, a sustainable biomaterial sourced from brown seaweed. This process allows actuators to have complex shapes and internal cavities that are difficult to achieve with traditional fabrication techniques. Furthermore, it demonstrates that fabricated components are biodegradable, safely edible, and digestible by marine organisms. Finally, a reversible chelation-crosslinking mechanism is implemented to dynamically modify alginate actuators' structural stiffness and morphology. This study expands the possible design space for biodegradable marine robots by improving the manufacturability of complex soft devices using biologically-sourced materials.     

Shape-Memory Balloon Structures by Pneumatic Multi-material 4D Printing

4D printing is an attractive approach for manufacturing structures that can adopt new shapes or functionalities after printing. However, 4D printing methods and materials that can be used to achieve structures with complex shapes and excellent mechanical properties simultaneously are still lacking. Here, a novel 4D printing is developed where multi-material digital light process 3D printing of shape memory polymers (SMPs) fabricates a structure that is later transformed into a complex 3D shape with robust mechanical properties by pneumatic manipulation. In this method, the shape change is controlled by the spatial distributions of SMPs, which is designed by finite element analysis. Experimental investigations are carried out to print various structured balloons with predefined intricate shapes, including a structure in dog-like shape and a surface with the human face contour. These structures are also endowed with robust mechanical stiffness and lightweight features, which allow this new 4D printing approach for potential applications in biomedical devices, reconfigurable structures, and metamaterials.     

3D Printing of Multifunctional Hydrogels

3D printing technology has been widely explored for the rapid design and fabrication of hydrogels, as required by complicated soft structures and devices. Here, a new 3D printing method is presented based on the rheology modifier of Carbomer for direct ink writing of various functional hydrogels. Carbomer is shown to be highly efficient in providing ideal rheological behaviors for multifunctional hydrogel inks, including double network hydrogels, magnetic hydrogels, temperature‐sensitive hydrogels, and biogels, with a low dosage (at least 0.5% w/v) recorded. Besides the excellent printing performance, mechanical behaviors, and biocompatibility, the 3D printed multifunctional hydrogels enable various soft devices, including loadable webs, soft robots, 4D printed leaves, and hydrogel Petri dishes. Moreover, with its unprecedented capability, the Carbomer‐based 3D printing method opens new avenues for bioprinting manufacturing and integrated hydrogel devices.     

3D Patterning within Hydrogels for the Recreation of Functional Biological Environments

Biological structures are inherently complex in nature. Structural hierarchy, chemical anisotropy, and compositional heterogeneity are ubiquitous in biological systems and play a key role in the functionality of living systems. For decades, methods such as soft lithography have enabled recreation of such arrangements through precise spatial control of molecular patterns in 2D. With technological advances and increasing understanding of molecular and structural biology, there has been an increasing interest in recreating such spatial organizations in 3D. In this review, a comprehensive summary of the latest technologies being used to create 3D patterns of functional molecules within hydrogels for tissue engineering applications is presented. The review is divided into five groups of technologies defined according to the main driving force used to fabricate the patterns including light, precise chemical design, microfluidics, 3D printing, and non-contact forces (i.e. electric, magnetic, or acoustic fields and self-assembly).     

Magnetic Helical Hydrogel Motor for Directing T Cell Chemotaxis

Micro/nanomotors are attracting booming research enthusiasm with their revolutionary potential in biomedicine, sensing, and nanoengineering. Among the motors proposed, magnetic micro/nanomotors are of great interest with their high controllability and field biocompatibility. Yet the fabrication of magnetic actuated especially helical motors requires expensive and complicated instruments, 3D printing or glancing angle deposition, etc. Here, a soft and biocompatible helical poly(vinyl alcohol) (PVA) hydrogel motor via a versatile set-up is engineered. The obtained helical hydrogel motor offers high capacity for chemokine CXCL12 and superparamagnetic iron oxide (Fe₃O₄) nanoparticles, which can then allow magnetic manipulation. With a low strength rotating magnetic field, the system is able to perform 3D precision navigation, necessary to steer the robotic system to a model diseased area. The chemokine cues from the hydrogel motor, acting as the synthetic leader cell, then directs immune T cell chemotactic migration. In a previously reported cell manipulating motor system, towing or pushing a single/two cell was demonstrated, with limited efficiency. This motor platform represents a novel approach for directing endogenous cell chemotaxis and organizing immune response.     

Conformal Printing of Graphene for Single‐ and Multilayered Devices onto Arbitrarily Shaped 3D Surfaces

Printing has drawn a lot of attention as a means of low per‐unit cost and high throughput patterning of graphene inks for scaled‐up thin‐form factor device manufacturing. However, traditional printing processes require a flat surface and are incapable of achieving patterning onto 3D objects. Here, a conformal printing method is presented to achieve functional graphene‐based patterns onto arbitrarily shaped surfaces. Using experimental design, a water‐insoluble graphene ink with optimum conductivity is formulated. Then single‐ and multilayered electrically functional structures are printed onto a sacrificial layer using conventional screen printing. The print is then floated on water, allowing the dissolution of the sacrificial layer, while retaining the functional patterns. The single‐ and multilayer patterns can then be directly transferred onto arbitrarily shaped 3D objects without requiring any postdeposition processing. Using this technique, conformal printing of single‐ and multilayer functional devices that include joule heaters, resistive deformation sensors, and proximity sensors on hard, flexible, and soft substrates, such as glass, latex, thermoplastics, textiles, and even candies and marshmallows, is demonstrated. This simple strategy promises to add new device and sensing functionalities to previously inert 3D surfaces.     

Mechanical Properties Tailoring of 3D Printed Photoresponsive Nanocellulose Composites

3D printing technologies allow control over the alignment of building blocks in synthetic materials, but compositional changes often require complex multimaterial printing steps. Here, 3D printable materials showing locally tunable mechanical properties are produced in a single printing step of Direct Ink Writing. These new inks consist of a polymer matrix bearing biocompatible photoreactive cinnamate derivatives and up to 30 wt% of anisotropic cellulose nanocrystals. The printed materials are mechanically versatile and can undergo further crosslinking upon illumination. When illuminating the material and controlling the irradiation doses, the Young's moduli can be adjusted between 15 and 75 MPa. Moreover, spatially controlled illumination allows patterning stiff geometries, resulting in 3D printed structures with segments of different mechanical properties tailoring the mechanical behavior under compression. The high design freedom implemented by 3D printing and photopatternability opens the venue to rapid manufacturing of devices for applications such as prosthetics or soft robotics where the 3D shapes and mechanical properties must be tailored for personalized load cases.     

A Review of 3D Printing Technologies for Soft Polymer Materials

Soft polymer materials, which are similar to human tissues, have played critical roles in modern interdisciplinary research. Compared with conventional methods, 3D printing allows rapid prototyping and mass customization and is ideal for processing soft polymer materials. However, 3D printing of soft polymer materials is still in the early stages of development and is facing many challenges including limited printable materials, low printing resolution and speed, and poor functionalities. The present review aims to summarize the ideas to address these challenges. It focuses on three points: 1) how to develop printable materials and make unprintable materials printable, 2) how to choose suitable methods and improve printing resolution, and 3) how to directly construct functional structures/systems with 3D printing. After a brief introduction on this topic, the mainstream 3D printing technologies for printing soft polymer materials are reviewed, with an emphasis on improving printing resolution and speed, choosing suitable printing techniques, developing printable materials, and printing multiple materials. Moreover, the state‐of‐the‐art advancements in multimaterial 3D printing of soft polymer materials are summarized. Furthermore, the revolutions brought about by 3D printing of soft polymer materials for applications similar to biology are highlighted. Finally, viewpoints and future perspectives for this emerging field are discussed.     

Engineering Natural Pollen Grains as Multifunctional 3D Printing Materials

The development of multifunctional 3D printing materials from sustainable natural resources is a high priority in additive manufacturing. Using an eco-friendly method to transform hard pollen grains into stimulus-responsive microgel particles, we engineered a pollen-derived microgel suspension that can serve as a functional reinforcement for composite hydrogel inks and as a supporting matrix for versatile freeform 3D printing systems. The pollen microgel particles enabled the printing of composite inks and improved the mechanical and physiological stabilities of alginate and hyaluronic acid hydrogel scaffolds for 3D cell culture applications. Moreover, the particles endowed the inks with stimulus-responsive controlled release properties. The suitability of the pollen microgel suspension as a supporting matrix for freeform 3D printing of alginate and silicone rubber inks was demonstrated and optimized by tuning the rheological properties of the microgel. Compared with other classes of natural materials, pollen grains have several compelling features, including natural abundance, renewability, affordability, processing ease, monodispersity, and tunable rheological features, which make them attractive candidates to engineer advanced materials for 3D printing applications.     

In Situ Inkjet Printing Strategy for Fabricating Perovskite Quantum Dot Patterns

Perovskite quantum dots are emerging as attractive materials for photonic and optoelectronic applications. Patterning is an important step to incorporate them into display, anti‐counterfeiting, and optical chip applications. In this work, an in situ inkjet printing strategy is demonstrated for fabricating perovskite quantum dots patterns by printing perovskite precursor solutions onto a polymeric layer. Importantly, this strategy can achieve bright photoluminescence with a quantum yield up to 80% and shows broad applicability to a variety of perovskites and polymers. Moreover, the as‐fabricated perovskite quantum dots patterns are composed of a microdisks array on the surface of polymeric layer. The size of these microdisks can be varied by adjusting the printing temperature. To demonstrate the potential use in display and advanced anti‐counterfeiting applications, color pixel patterns and 2D code pattern are fabricated by varying the precursor solutions. The combination of superior photoluminescence properties, simple process, and low cost makes the in situ inkjet printing strategy very promising for patterning perovskite quantum dots toward photonic integrations.     

Development of Thermoinks for 4D Direct Printing of Temperature-Induced Self-Rolling Hydrogel Actuators

4D printing has emerged as an important technique for fabricating 3D objects from programmable materials capable of time-dependent reshaping. In the present investigation, novel 4D thermoinks composed of laponite (LAP), an interpenetrating network of poly(N-isopropylacrylamide) (PNIPAAm), and alginate (ALG) are developed for direct printing of shape-morphing structures. This approach consists of the design and fabrication of 3D honeycomb-patterned hydrogel discs self-rolling into tubular constructs under the stimulus of temperature. The shape morphing behavior of hydrogels is due to shear-induced anisotropy generated via 3D printing. The compositionally tunable hydrogel discs can be programmed to exhibit different actuation behaviors at different temperatures. Upon immersion in 12 °C water, singly crosslinked sheets roll up into a tubular construct. When transferred to 42 °C water, the tubes first rapidly unfold and then slightly curve up in the opposite direction. Through a dual photocrosslinking of PNIPAAm, it is possible to inverse temperature-dependent shape morphing and induce self-folding at higher and unrolling at lower temperatures. The extensive self-assembling motion is essential to developing thermal actuators with broad applications in, e.g., soft robotics and active implantology, whereas controllable self-rolling of planar hydrogels is of the highest interest to biomedical engineering as it allows for effective fabrication of hollow tubes.     

Fabrication of Complex Hydrogel Structures Using Suspended Layer Additive Manufacturing (SLAM)

There have been a number of recently reported approaches for the manufacture of complex 3D printed cell‐containing hydrogels. Given the fragility of the parts during manufacturing, the most successful approaches use a supportive particulate gel bed and have enabled the production of complex gel structures previously unattainable using other 3D printing methods. The supporting gel bed provides protection to the fragile printed part during the printing process, preventing the structure from collapsing under its own weight prior to crosslinking. Despite the apparent similarity of the particulate beds, the way the particles are manufactured strongly influences how they interact with one another and the part during fabrication, with implications to the quality of the final product. Recently, the process of suspended layer additive manufacture (SLAM) is demonstrated to create a structure that recapitulated the osteochondral region by printing into an agarose particulate gel. The manufacturing process for this gel (the application of shear during gelation) produced a self‐healing gel with rapid recovery of its elastic properties following disruption. Here, the physical characteristics of the supporting fluid‐gel matrix used in SLAM are explored, and compared to other particulate gel supporting beds, highlighting its potential for producing complex hydrogel‐based parts.     

Multi-Material 3D Microprinting of Magnetically Deformable Biocompatible Structures

Two-photon polymerization (2PP) allows precise 3D printing at the micrometer scale, and by associating it with magnetic materials, the creation of remotely actuatable micro-structures. Such structures attract a growing interest for biomedical applications, thanks to their size and to the biocompatibility of some photoresist materials. Gelatin methacryloyl (Gel-MA) is one such material, and can be used to create physiological scaffolds for cell culture. Here, the physico-chemical properties of two resins are exploited, the first being a silica-based hybrid polymer, the OrmoComp, and the second a Gel-MA-based hydrogel. A 2PP manufacturing protocol is defined and designed to print both materials in succession as a single structure, which is then linked to a neodymium-iron-boron (NdFeB) magnetic bead for actuation. By this combination, a magnetically deformable 3D culture substrate is created to study cells in an environment that mimics soft, curved, and dynamic properties of tissues in vivo. The structure is actuated via an external magnetic field and bends back and forth along its longest axis. Lastly, preliminary cell culture trials are conducted showing the proliferation of cells on the structures.     

XMCD and XMCD‐PEEM Studies on Magnetic‐Field‐Assisted Self‐Assembled 1D Nanochains of Spherical Ferrite Particles

Quasi‐1D nanochains of spherical magnetic ferrite particles with a homogeneous particle size of ≈200 nm and a micrometer‐sized chain length are fabricated via a self‐assembly method under an external magnetic field. This assisting magnetic field (H_assist), applied during synthesis, significantly modifies the distribution of the Fe²⁺O_h, Fe³⁺T_d, and Fe³⁺O_h cations in the chains, as demonstrated by X‐ray magnetic circular dichroism (XMCD) combined with theoretical analysis. This provides direct evidence of the nontrivial role of external synthetic conditions for defining the crystal chemistry of nanoscale ferrites and in turn their magnetic properties, providing an extra degree of freedom for intentional control over the performances of 1D magnetic nanodevices for various applications. Magnetic imaging, performed via XMCD in photoemission electron microscopy, further shows the possibility of creating and trapping a series of adjacent magnetic domain walls in a single chain, suggesting that there is great application potential for these nanochains in 1D magnetic nanodevices, as determined by field‐ or current‐driven domain wall motions. Practical control over the magnetic properties of the nanochains is also achieved by extrinsic dopants of cobalt and zinc, which are observed to occupy the ferrite ionic sites in a selective manner.     

Easy-Cone Magnetic State Induced Ultrahigh Sensitivity and Low Driving Current in Spin-Orbit Coupling 3D Magnetic Sensors

Measurement of 3D vector magnetic field is of vital importance for the development of magnetic navigation, biomedical diagnosis, and microimaging. Traditional 3D magnetic sensors require cooperation of multiple sensors on three orthogonal planes, resulting in disadvantages of bulky size and low spatial resolution. Recently proposed spin orbit torque sensor based on ferromagnetic/heavy-metal heterostructures can detect three magnetic field components individually due to the different symmetries of current-polarity-dependent magnetization dynamic. However, the large driving current density and complex driving procedure hinder their practical application, especially in AC magnetic field detection. Herein, 3D magnetic sensors with dramatically reduced driving current density are reported, one fifth of the original value, by exquisite engineering of the magnetic anisotropy in Pt/Co/Ta heterostructures. With further reduced perpendicular magnetic anisotropy, the sensor in the easy-cone state demonstrates a record-high sensitivity of 31196 V A⁻¹ T⁻¹. More importantly, the easy-cone state sensor can work with an ultralow driving current density of 3.8 kA cm⁻², which is three orders lower than previous results. Although easy-cone state sensor can only measure the z-axis field, highly compact 3D magnetic sensor can be realized by adoption of two anisotropic magnetoresistance sensors, promising great potential application in space- and energy-restricted scenarios.