Formation Theory and Printability of Photocurable Hydrogel for 3D Bioprinting

Bio-ink has gradually transited from ionic-crosslinking to photocrosslinking due to photocurable bio-hydrogel having good formability and biocompatibility. It is very important to understand and quantify the crosslinking process of photocurable hydrogels, otherwise, bioprinting cannot be standardized and scalable. However, there are few studies on hydrogel formation process and its photocrosslinking behavior which cannot be accurately predicted. Herein, the photoinitiated radical polymerized bio-hydrogels are taken as an example to establish the formation theory. Three typical crosslinking reactions are first distinguished. It is further proposed that not all double-bonds consumed during crosslinking contributeequally to polymerization. Then the concept of effective double-bond conversion (EDBC) is elicited. Deriving from EDBC, several important formation indices are defined. According to theory, it is predicted that slow crosslinking can improve the crosslinking degree. Furthermore, based on the slow crosslinking effect, a new strategy of projection-based 3D printing (PBP) is proposed, which significantly improved printing quality and efficiency. Overall, this work will fill the gap in hydrogel's formation theory, making it possible to accurately quantify the formation process.     

A Bionic-Gill 3D Hydrogel Evaporator with Multidirectional Crossflow Salt Mitigation and Aquaculture Applications

In recent years, interfacial solar-driven steam generation has gained huge attention as a sustainable and energy-efficient technology. However, salt scaling on and inside the evaporator structure induced by insufficient ion distribution control will lower the evaporation performance and hinder the stability and durability of evaporators. Herein, inspired by the highly efficient salt-expelling property of the gill filaments of large yellow croaker, a bionic-gill 3D hydrogel evaporator is proposed with fabulous multidirectional ion migration controllability. A 3D structure composed of arrayed beaded hollow columns with beaded hollow holes inspired by gill filaments ensuring longitudinal ion backflow and the peristome-mimetic arrayed grooves of microcavities ensuring lateral ion advection is designed and constructed to achieve fabulous multidirectional crossflow salt ion migration, which ensures high evaporation performance for pure water (an evaporation rate of 2.53 kg m⁻² h⁻¹ with an energy efficiency of 99.3%) as well as for high salinity brine (2.11 kg m⁻² h⁻¹ for 25.0 wt.% NaCl solution), with no salt crystallizing after long-term use. Furthermore, the 3D hydrogel evaporator has excellent chemical stability, mechanical properties, folding-irrelevant evaporation performance, and portability so that it can be used for the preliminary desalination of breeding wastewater through the proposed self-circulation koi aquaculture system.     

3D Printing Hydrogel Scaffolds with Nanohydroxyapatite Gradient to Effectively Repair Osteochondral Defects in Rats

Osteochondral (OC) defects pose an enormous challenge with no entirely satisfactory repair strategy to date. Herein, a 3D printed gradient hydrogel scaffold with a similar structure to that of OC tissue is designed, involving a pure hydrogel-based top cartilage layer, an intermediate layer for calcified cartilage with 40% (w w⁻¹) nanohydroxyapatite (nHA) and 60% (w w⁻¹) hydrogel, and a 70/30% (w w⁻¹) nHA/hydrogel-based bottom subchondral bone layer. This study is conducted to evaluate the efficacy of the scaffold with nHA gradients in terms of its ability to promote OC defect repair. The fabricated composites are evaluated for physicochemical, mechanical, and biological properties, and then implanted into the OC defects in 56 rats. Overall, bone marrow stromal cells (BMSCs)-loaded gradient scaffolds exhibit superior repair results as compared to other scaffolds based on gross examination, micro-computed tomography (micro-CT), as well as histologic and immunohistochemical analyses, confirming the ability of this novel OC graft to facilitate simultaneous regeneration of cartilage-subchondral bone.     

3D Printing Personalized,Photocrosslinkable Hydrogel Wound Dressings for the Treatment of Thermal Burns

Considering the variations in burns depending on the circumstances that caused them, the need for personalized medicine and care for burn victims is vital to ensure that optimal treatment is provided. With the level of accuracy and customization that 3D printing brings as a technology, there is potential in its use to fabricate wound dressings that can provide better treatment for burn patients, provided that the material of choice has good printability and can be customized while facilitating wound healing. In this study, the versatility of chitosan methacrylate as said material to be used to fabricate customizable wound dressings via 3D printing is investigated. Synthesized chitosan methacrylate is evaluated to be printable, biodegradable, and biocompatible during wound healing. Various drugs relevant to the treatment of burns are then loaded and different multimaterial wound dressing designs containing different dosages are fabricated via 3D printing. The incorporation of said drugs does not significantly affect the printability of chitosan methacrylate, and the incorporation of antimicrobial agents significantly improves its antimicrobial capabilities. Through in vivo models, these variations in wound dressing designs have good wound healing properties and do not cause any adverse effects in the process.     

A 3D Printable and Bioactive Hydrogel Scaffold to Treat Traumatic Brain Injury

Traumatic brain injury accompanied by intracranial hypertension remains one of the most fatal injuries worldwide. Usually, patients must undergo two surgeries, craniectomy and cranioplasty, to reduce the intracranial pressure and then repair the skull. Traditional biomaterials, such as autologous bones and titanium meshes, which have poor stretchability and very high Young's modulus values up to hundreds of GPa, tend to constrain intracranial tissue and cannot be implanted directly after craniectomy. Thus far, finding elastic and degradable biomaterials to be immediately implanted after a craniectomy has remained a great challenge, which should not only repair cranial defects but also avoid secondary surgery and reduce the risk of complications, has remained a great challenge. Herein, a 3D printable bioactive hydrogel scaffold with high elasticity that can protect brain tissue, adapt to intracranial pressure changes, allow for the transport of nutrients and the proliferation and osteogenic differentiation of bone mesenchymal stem cells is presented. As indicated by in vivo experiments, the hydrogel scaffold helps to treat traumatic brain injury within 8 weeks and degrades safely. With these advantages, this material shows the potential to open up new horizons for cranioplasty and to help patients survive traumatic brain injury.     

A Multiresponsive Anisotropic Hydrogel with Macroscopic 3D Complex Deformations

As one of the most promising smart materials, stimuli‐responsive polymer hydrogels (SPHs) can reversibly change volume or shape in response to external stimuli. They thus have shown promising applications in many fields. While considerable progress of 2D deformation of SPHs has been achieved, the realization of 3D or even more complex deformation still remains a significant challenge. Here, a general strategy towards designing multiresponsive, macroscopically anisotropic SPHs (MA‐SPHs) with the ability of 3D complex deformations is reported. Through a local UV‐reduction of graphene oxide sheets (GOs) with a patterned fashion in the GO‐poly(N‐isopropylacrylamide) (GO‐PNIPAM) composite hydrogel sheet, MA‐SPHs can be achieved after the introduction of a second poly(methylacrylic acid) network in the unreduced part of GO‐PNIPAM hydrogel sheet. The resulting 3D MA‐SPHs can provide remote‐controllable light‐driven, as well as thermo‐, pH‐, and ionic strength‐triggered multiresponsive 3D complex deformations. Approaches in this study may provide new insights in designing and fabricating intelligent soft materials for bioinspired applications.     

3D Printing of Strong and Tough Double Network Granular Hydrogels

Many soft natural tissues display a fascinating set of mechanical properties that remains unmatched by manmade counterparts. These unprecedented mechanical properties are achieved through an intricate interplay between the structure and locally varying the composition of these natural tissues. This level of control cannot be achieved in soft synthetic materials. To address this shortcoming, a novel 3D printing approach to fabricate strong and tough soft materials is introduced, namely double network granular hydrogels (DNGHs) made from compartmentalized reagents. This is achieved with an ink composed of microgels that are swollen in a monomer-containing solution; after the ink is additive manufactured, these monomers are converted into a percolating network, resulting in a DNGH. These DNGHs are sufficiently stiff to repetitively support tensile loads up to 1.3 MPa. Moreover, they are more than an order of magnitude tougher than each of the pure polymeric networks they are made from. It is demonstrated that this ink enables printing macroscopic, strong, and tough objects, which can optionally be rendered responsive, with high shape fidelity. The modular and robust fabrication of DNGHs opens up new possibilities to design adaptive, strong, and tough hydrogels that have the potential to advance, for example, soft robotic applications.     

3D Fluorescent Hydrogel Origami for Multistage Data Security Protection

Current fluorescence‐based anti‐counterfeiting strategies primarily encode information onto single 2D planes and underutilize the possibility of encrypting data inside 3D structures to achieve multistage data security. Herein, a fluorescent‐hydrogel‐based 3D anti‐counterfeiting platform is demonstrated, which extends data encryption capability from single 2D planes to complex 3D hydrogel origami geometries. The materials are based on perylene‐tetracarboxylic‐acid‐functionalized gelatin/poly(vinyl alcohol) hydrogels, which simultaneously show Fe³⁺‐responsive fluorescence quenching, borax‐triggered shape memory, and self‐healing properties. By employing an origami technique, various complex 3D hydrogel geometries are facilely fabricated. On the basis of these results, a 3D anti‐counterfeiting platform is demonstrated, in which the data printed by using Fe³⁺ as the ink are safely protected inside complex 3D hydrogel origami structures. In this way, the encrypted data cannot be read until after specially predesigned procedures (both the shape recovery and UV light illumination actions), indicating higher‐level information security than the traditional 2D counterparts. This facile and general strategy opens up the possibility of utilizing 3D fluorescent hydrogel origami for data information encryption and protection.     

3D Laser Nanoprinting of Functional Materials

3D laser nanoprinting represents a revolutionary manufacturing approach as it allows maskless fabrication of 3D nanostructures at a resolution beyond the optical diffraction limit. Specifically, it endows the printed structures novel physical, chemical, or mechanical properties not observed at macroscopic scale. However, 3D laser nanoprinting typically relies on the photopolymerization process, indicating its limitation on the printable materials and functionalities. The capability to print diverse functional materials beyond polymer will enable a lot of new device applications in nanophotonics, microelectronics, and so on. One of the strategies is to use the 3D-printed polymer structures as skeletons for functional material deposition, while another is to mix the functional components with the photocurable molecules and print the nanocomposites. More recently, several laser nanoprinting techniques beyond photopolymerization are also developed. In this review, the cutting-edge technical innovation is summarized and a couple of examples are highlighted showing exciting applications of the printed structures in magnetic microrobots, photonics, and optoelectronics. Finally, the vision for existing challenges and future development in this field is shared.     

3D Printed Template-Assisted Casting of Biocompatible Polyvinyl Alcohol-Based Soft Microswimmers with Tunable Stability

The past decade has seen an upsurge in the development of small-scale magnetic robots for various biomedical applications. However, many of the reported designs comprise components with biocompatibility concerns. Strategies for fabricating biocompatible and degradable microrobots are required. In this study, polyvinyl alcohol (PVA)-based magnetic hydrogel microrobots with different morphologies and tunable stability are developed by combining a 3D printed template-assisted casting with a salting-out process. 3D sacrificial micromolds are prepared via direct laser writing to shape PVA-magnetic nanoparticle composite hydrogel microrobots with high architectural complexity. By adjusting the PVA composition and salting-out parameters, the hydrogel dissolubility can be customized. Due to their high mobility, tunable stability, and high biocompatibility, these PVA-based magnetic microrobots are suitable platforms for targeted drug and cell delivery.     

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.     

3D Electrophoresis‐Assisted Lithography (3DEAL): 3D Molecular Printing to Create Functional Patterns and Anisotropic Hydrogels

The ability to easily generate anisotropic hydrogel environments made from functional molecules with microscale resolution is an exciting possibility for the biomaterials community. This study reports a novel 3D electrophoresis‐assisted lithography (3DEAL) platform that combines elements from proteomics, biotechnology, and microfabrication to print well‐defined 3D molecular patterns within hydrogels. The potential of the 3DEAL platform is assessed by patterning immunoglobulin G, fibronectin, and elastin within nine widely used hydrogels and characterizing pattern depth, resolution, and aspect ratio. Furthermore, the technique's versatility is demonstrated by fabricating complex patterns including parallel and perpendicular columns, curved lines, gradients of molecular composition, and patterns of multiple proteins ranging from tens of micrometers to centimeters in size and depth. The functionality of the printed molecules is assessed by culturing NIH‐3T3 cells on a fibronectin‐patterned polyacrylamide‐collagen hydrogel and selectively supporting cell growth. 3DEAL is a simple, accessible, and versatile hydrogel‐patterning platform based on controlled molecular printing that may enable the development of tunable, chemically anisotropic, and hierarchical 3D environments.     

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.     

Combining 3D Printing with Electrospinning for Rapid Response and Enhanced Designability of Hydrogel Actuators

Porous structures have emerged as a breakthrough of shape‐morphing hydrogels to achieve a rapid response. However, these porous actuators generally suffer from a lack of complexity and diversity in obtained 3D shapes. Herein, a simple yet versatile strategy is developed to generate shape‐morphing hydrogels with both fast deformation and enhanced designability in 3D shapes by combining two promising technologies: electrospinning and 3D printing. Elaborate patterns are printed on mesostructured stimuli‐responsive electrospun membranes, modulating in‐plane and interlayer internal stresses induced by swelling/shrinkage mismatch, and thus guiding morphing behaviors of electrospun membranes to adapt to changes of the environment. With this strategy, a series of fast deformed hydrogel actuators are constructed with various distinctive responsive behaviors, including reversible/irreversible formations of 3D structures, folding of 3D tubes, and formations of 3D structures with multi low‐energy states. It is worth noting that although poly(N‐isopropyl acrylamide) is chosen as the model system in the present research, our strategy is applicable to other stimuli‐responsive hydrogels, which enriches designs of rapid deformed hydrogel actuators.     

Engineering Tridimensional Hydrogel Tissue and Organ Phantoms with Tunable Springiness

Biomimicking organ phantoms with vivid biological structures and soft and slippery features are essential for in vitro biomedical applications yet remain hither to unmet challenges in their fabrication such as balancing between spatial structural complexity and matchable mechanical properties. Herein, 3D printable tissue-mimicking elastomeric double network hydrogels with tailorable stiffness are evolved to idiosyncratically match diverse biological soft tissues by regulating the compositions of hydrogel matrix and the density of metal coordination bonds. Relying on digital light processing 3D printing, various mechanically tunable biomimetic volumetric hydrogel organ constructs with structural complexity and fidelity, including kidney, brain, heart, liver, stomach, lung, trachea, intestine, and even the intricate vascularized tissues, are fabricated faultlessly. Proof-of-concept 3D printed hydrogel heart and liver phantoms provide sophisticated internal channels and cavity structures and external realistic anatomical architectures that more closely mimic native organs. For the in vitro application demonstration, a 3D printed hydrogel brain phantom with tortuous cerebral arteries and slippery characters serves as an effective neurosurgical training platform for realistic simulation of endovascular interventions. This platform offers a means to construct mechanically precisely tunable hydrogel-based biomimetic organ phantoms that are expected to be used in surgical training, medical device testing, and organs-on-chips.     

3D Printing of Hydrogels for Stretchable Ionotronic Devices

In the booming development of flexible electronics represented by electronic skins, soft robots, and human–machine interfaces, 3D printing of hydrogels, an approach used by the biofabrication community, is drawing attention from researchers working on hydrogel-based stretchable ionotronic devices. Such devices can greatly benefit from the excellent patterning capability of 3D printing in three dimensions, as well as the free design complexity and easy upscale potential. Compared to the advanced stage of 3D bioprinting, 3D printing of hydrogel ionotronic devices is in its infancy due to the difficulty in balancing printability, ionic conductivity, shape fidelity, stretchability, and other functionalities. In this review, a guideline is provided on how to utilize the power of 3D printing in building high-performance hydrogel-based stretchable ionotronic devices mainly from a materials’ point of view, highlighting the systematic approach to balancing the printability, printing quality, and performance of printed devices. Various 3D printing methods for hydrogels are introduced, and then the ink design principles, balancing printing quality, printed functions, such as elastic conductivity, self-healing ability, and device (e.g., flexible sensors, shape-morphing actuators, soft robots, electroluminescent devices, and electrochemical biosensors) performances are discussed. In conclusion, perspectives on the future directions of this exciting field are presented.     

Photo-Curing 3D Printing of Thermosetting Sacrificial Tooling for Fabricating Fiber-Reinforced Hollow Composites

Carbon fiber-reinforced hollow composites play a vital role in lightweighting modern cars and aircrafts. Fabrication of such hollow composites with seamless internal finish requires sacrificial tooling that can be used under pressure and high temperature. For the very first time, high performance sacrificial tooling that can be used to fabricate fiber-reinforced hollow composites is produced using photocuring 3D printing technology. This is achieved by developing UV-curable resins containing highly soluble yet hydrolysable acetal acrylate cross-linker and hydrophilic 4-acryloylmorpholine monomer. It is found that the cross-linker content greatly affects the printing speed. Further, the widely adopted UV post-curing method is found to have negligible impact on improving the thermal-mechanical properties of printed structures. After thermal post-treatment, printed sacrificial tooling exhibits a heat deflection temperature of 112 °C at 0.455 MPa and an average coefficient of linear thermal expansion of 59 ppm °C⁻¹ between 30 and 100 °C. As a result, printed tooling enables fabrication of carbon fiber-reinforced hollow composites with complex geometry, which shows a tensile strength of 802 MPa and an elastic modulus of 50.2 GPa.     

Strong and Ultra-Tough Supramolecular Hydrogel Enabled by Strain-Induced Microphase Separation

Architected hydrogels are widely used in biomedicine, soft robots, and flexible electronics while still possess big challenges in strong toughness, and shape modeling. Here, inspired with the universal hydrogen bonding interactions in biological systems, a strain-induced microphase separation path toward achieving the printable, tough supramolecular polymer hydrogels by hydrogen bond engineering is developed. Specifically, it subtly designs and fabricates the poly (N-acryloylsemicarbazide-co-acrylic acid) hydrogels with high hydrogen bond energy by phase conversion induced hydrogen bond reconstruction. The resultant hydrogels exhibited the unique strain-induced microphase separation behavior, resulting in the excellent strong toughness with, for example, an ultimate stress of 9.1 ± 0.3 MPa, strain levels of 1020 ± 126%, toughness of 33.7 ± 6.6 MJ m⁻³, and fracture energy of 171.1 ± 34.3 kJ m⁻². More importantly, the hydrogen bond engineered supramolecular hydrogels possess dynamic shape memory character, i.e shape fixing at low temperature while recovery after heating. As the proof of concept, the tailored hydrogel stents are readily manufactured by 3D printing, which showed good biocompatibility, load-bearing and drug elution, being beneficial for the biomedical applications. It is believed that the present 3D printing of the architected dynamic hydrogels with ultrahigh toughness can broaden their applications.     

3D Particle-Free Printing of Biocompatible Conductive Hydrogel Platforms for Neuron Growth and Electrophysiological Recording

Electrically conductive 3D periodic microscaffolds are fabricated using a particle-free direct ink writing approach for use as neuronal growth and electrophysiological recording platforms. A poly (2-hydroxyethyl methacrylate)/pyrrole ink, followed by chemical in situ polymerization of pyrrole, enables hydrogel printing through nozzles as small as 1 µ m. These conductive hydrogels can pattern complex 2D and 3D structures and have good biocompatibility with test cell cultures ( ≈ 94.5% viability after 7 days). Hydrogel arrays promote extensive neurite outgrowth of cultured Aplysia californica pedal ganglion neurons. This platform allows extracellular electrophysiological recording of steady-state and stimulated electrical neuronal activities. In summation, this 3D conductive ink printing process enables the preparation of biocompatible and micron-sized structures to create customized in vitro electrophysiological recording platforms.     

Photocurable 3D Printing of High Toughness and Self-Healing Hydrogels for Customized Wearable Flexible Sensors

Currently, most customized hydrogels can only be processed via extrusion-based 3D printing techniques, which is limited by printing efficiency and resolution. Here, a simple strategy for the rapid fabrication of customized hydrogels using a photocurable 3D printing technique is presented. This technique has been rarely used because the presence of water increases the molecular distance between the polymer chains and reduces the monomer polymerization rate, resulting in the failure of rapid solid-liquid separation during printing. Although adding cross-linkers to printing inks can effectively accelerate 3D cross-linked network formation, chemical cross-linking may result in reduced toughness and self-healing ability of the hydrogel. Therefore, an interpenetrated-network hydrogel based on non-covalent interactions is designed to form physical cross-links, affording fast solid-liquid separation. Poly(acrylic acid (AA)-N-vinyl-2-pyrrolidone (NVP)) and carboxymethyl cellulose (CMC) are cross-linked via Zn²⁺-ligand coordination and hydrogen bonding; the resulting mixed AA-NVP/CMC solution is used as the printing ink. The printed poly(AA-NVP/CMC) hydrogel exhibited high tensile toughness (3.38 MJ m⁻³) and superior self-healing ability (healed stress: 81%; healed strain: 91%). Some objects like manipulator are successfully customized by photocurable 3D printing using hydrogels with high toughness and complex structures. This high-performance hydrogel has great potential for application in flexible wearable sensors.