Biodegradable Self‐Folding Polymer Films with Controlled Thermo‐Triggered Folding

Self‐folding films are a unique kind of thin film. They are able to deform in response to a change in environmental conditions or internal stress and form complex 3D structures. They are very promising candidates for the design of bioscaffolds, which resemble different kinds of biological tissues. In this paper, a very simple and cheap approach for the fabrication of fully biodegradable and biocompatible self‐rolled tubes is reported. The tubes' folding can be triggered by temperature. A bilayer approach is used, where one component is active and another one is passive. The passive one can be any biocompatible, biodegradable, hydrophobic polymer. Gelatin is used as an active component: it allows the design of (i) self‐folding polymer films, which fold at room temperature (22 °C) and irreversibly unfold at 37 °C, and (ii) films, which are unfolded at room temperature (22 °C), but irreversibly fold at 37 °C. The possibilities of encapsulation of neural stem cells are also demonstrated using self‐folded tubes.     

Thermoresponsive Shape‐Memory Hydrogel Actuators Made by Phototriggered Click Chemistry

This article describes the design and synthesis of a new series of hydrogel membranes composed of trialkyne derivatives of glycerol ethoxylate and bisphenol A diazide (BA‐diazide) or diazide‐terminated PEG600 monomer via a Cu(I)‐catalyzed photoclick reaction. The water‐swollen hydrogel membranes display thermoresponsive actuation and their lower critical solution temperature (LCST) values are determined by differential scanning calorimetry. Glycerol ethoxylate moiety serves as the thermoresponsive component and hydrophilic part, while the azide‐based component acts as the hydrophobic comonomer and most likely provides a critical hydrophobic/hydrophilic balance contributing also to the significant mechanical strength of the membranes. These hydrogels exhibit a reversible shape‐memory effect in response to temperature through a defined phase transition. The swelling and deswelling behavior of the membranes are systematically examined. Due to the click nature of the reaction, easy availability of azide and alkyne functional‐monomers, and the polymer architecture, the glass transition temperature (T_g) is easily controlled through monomer design and crosslink density by varying the feed ratio of different monomers. The mechanical properties of the membranes are studied by universal tensile testing measurements. Moreover, the hydrogels show the ability to absorb a dye and release it in a controlled manner by applying heat below and above the LCST.     

Hole‐Programmed Superfast Multistep Folding of Hydrogel Bilayers

Two important aspects of actuation behavior of stimuli‐responsive hydrogels are the complexity of the shape change and its speed. Here, it is shown that varying the shape of simple polymer bilayers can result in very complex and very fast spontaneous folding. The complexity and high folding rate arise from the choice of the shape and from the presence of inhomogeneous swelling within the thermoresponsive layer entrapped between the top hydrophobic layer and the substrate. In contrast to homogeneous swelling of a freestanding bilayer, which leads to a gradual increase of curvature throughout the whole bilayer, inhomogeneous swelling first results in complete rolling of the periphery of the film, which changes its mechanical properties and affects the subsequent morphing process. Further swelling of the thermoresponsive layer generates more stress that builds up until a buckling threshold is overcome, allowing very fast switching from the flat edge‐rolled configuration into a folded one. The research demonstrates how the introduction of holes into actuating bilayers gives rise not only to a novel geometric control over the folding fate of the films but also adds the ability to tune the rate of folding, through the careful selection of hole size, location, and shape.     

Embedded Shape‐Memory Alloy Wires for Improved Performance of Self‐Healing Polymers

We report the first measurements of self‐healing polymers with embedded shape‐memory alloy (SMA) wires. The addition of SMA wires shows improvements of healed peak fracture loads by up to a factor of 1.6, approaching the performance of the virgin material. Moreover, the repairs can be achieved with reduced amounts of healing agent. The improvements in performance are due to two main effects: (i) crack closure, which reduces the total crack volume and increases the crack fill factor for a given amount of healing agent and (ii) heating of the healing agent during polymerization, which increases the degree of cure of the polymerized healing agent.     

Light‐Coded Digital Crystallinity Patterns Toward Bioinspired 4D Transformation of Shape‐Memory Polymers

Spatially heterogeneous distribution of active components is key to the diverse shape‐morphing behaviors of biological species and their associated functions. Artificial morphing materials employing similar strategies have widened the design space for advanced functional devices. Typically, the spatial heterogeneity is introduced during the material synthesis/fabrication step and cannot be altered afterward. An approach that allows spatio‐selective programming of crystallinity in a shape‐memory polymer (SMP) by a digital photothermal effect is reported. The light‐patternable crystallinity affects greatly the shape morphing behavior. Consequently, a pre‐stretched 2D film with spatial heterogeneity in crystallinity can morph with time into designable 3D permanent shapes, achieving the 4D transformation. This approach utilizes a reprocessible thermoplastic SMP (polylactide) and the programming relies on a physical phase transformation (crystallization) instead of chemical heterogeneity. This allows repeated erasing and reprogramming using the same material, suggesting a versatile and sustainable means for manufacturing advanced morphing devices.     

Gradient Porous Elastic Hydrogels with Shape‐Memory Property and Anisotropic Responses for Programmable Locomotion

Programmable locomotion of responsive hydrogels has gained increasing attention for potential applications in soft robotics, microfluidic components, actuators, and artificial muscle. Modulation of hydrogel pore structures is essential for tailoring their mechanical strength, response speeds, and motion behaviors. Conventional methods forming hydrogels with homogeneous or stepwise‐distributed pore structures are limited by the required compromise to simultaneously optimize these aspects. Here, a heterobifunctional crosslinker enabled hydrothermal process is introduced to synthesize responsive hydrogels with well‐defined gradient pore construction. According to gradient porosity controls, the hydrogels simultaneously exhibit rapid responses to external stimuli, high elasticity/compressibility, and programmable locomotion capability. By incorporating polypyrrole nanoparticles as photothermal transducers, photo/thermal responsive composite hydrogels are formed to enable programmable control of locomotion such as bending, curving, twisting, and octopus‐like swimming under near‐infrared laser stimulation. The tunable pore structures, mechanical properties, and locomotion of this new class of materials make these gradient porous hydrogels potentially suitable for a variety of applications.     

Bioinspired Electro‐Thermo‐Hygro Reversible Shape‐Changing Materials by 4D Printing

Hygromorph composites are moisture‐induced shape‐changing materials that are increasingly studied to develop autonomously actuated deployable structures. The morphing mechanism is based on the high affinity for moisture and the hygroexpansive nature of at least one component, combined with a bilayer microstructure. Among available hygromorphs, those consisting of cellulosic or hydrogel material‐based actuators trigger fast responses to moisture. Their stiffness however decreases significantly with the moisture content and that restricts their potential application as soft actuators. This work proposes a novel 4D printed multistimuli‐responsive structural material based on conductive carbon reinforcements and combined with a moisture sensitive polymer. These 4D printed materials possess a microstructure that provides the capability of natural actuators like pine cones. The actuation of these functional materials could be either triggered passively by the variation of the ambient moisture, or by electroheating, with the latter leading to the control of the moisture content in initially wet samples via Joule effects. This new class of functional materials shows an increase of the actuation speed by a factor 10 compared to other existing hygromorphs with the same responsiveness. When the electrical heating is turned off, passive cooling and moisture driven actuation is triggered in a full reversible mode.     

Shape‐Memory Microfluidics

Materials with embedded vascular networks afford rapid and enhanced control over bulk material properties including thermoregulation and distribution of active compounds such as healing agents or stimuli. Vascularized materials have a wide range of potential applications in self‐healing systems and tissue engineering constructs. Here, the application of vascularized materials for accelerated phase transitions in stimuli‐responsive microfluidic networks is reported. Poly(ester amide) elastomers are hygroscopic and exhibit thermo‐mechanical properties (T_g ≈ 37 °C) that enable heating or hydration to be used as stimuli to induce glassy‐rubbery transitions. Hydration‐dependent elasticity serves as the basis for stimuli‐responsive shape‐memory microfluidic networks. Recovery kinetics in shape‐memory microfluidics are measured under several operating modes. Perfusion‐assisted delivery of stimulus to the bulk volume of shape‐memory microfluidics dramatically accelerates shape recovery kinetics compared to devices that are not perfused. The recovery times are 4.2 ± 0.1 h and 8.0 ± 0.3 h in the perfused and non‐perfused cases, respectively. The recovery kinetics of the shape‐memory microfluidic devices operating in various modes of stimuli delivery can be accurately predicted through finite element simulations. This work demonstrates the utility of vascularized materials as a strategy to reduce the characteristic length scale for diffusion, thereby accelerating the actuation of stimuli‐responsive bulk materials.     

Accordion‐like Actuators of Multiple 3D Patterned Liquid Crystal Polymer Films

This work describes the fabrication, characterization, and modelling of liquid crystalline polymer network films with a multiple patterned 3D nematic director profile, a stimuli‐responsive material that exhibits complex mechanical actuation under change of temperature or pH. These films have a discrete alternating striped or checkerboard director profile in the plane, and a 90‐degree twist through the depth of the film. When actuated via heating, the striped films deform into accordion‐like folds, while the film patterned with a checkerboard microstructure buckles out‐of‐plane. Furthermore, striped films are fabricated so that they also deform into an accordion shaped fold, by a change of pH in an aqueous environment. Three‐dimensional finite element simulations and elasticity analysis provide insight into the dependence of shape evolution on director microstructure and the sample's aspect ratio.     

Highly Efficient Self‐Healable and Dual Responsive Cellulose‐Based Hydrogels for Controlled Release and 3D Cell Culture

To face the increasing demand of self‐healing hydrogels with biocompatibility and high performances, a new class of cellulose‐based self‐healing hydrogels are constructed through dynamic covalent acylhydrazone linkages. The carboxyethyl cellulose‐graft‐dithiodipropionate dihydrazide and dibenzaldehyde‐terminated poly(ethylene glycol) are synthesized, and then the hydrogels are formed from their mixed solutions under 4‐amino‐DL‐phenylalanine (4a‐Phe) catalysis. The chemical structure, as well as microscopic morphologies, gelation times, mechanical and self‐healing performances of the hydrogels are investigated with ¹H NMR, Fourier transform infrared spectroscopy, atomic force microscopy, rheological and compression measurements. Their gelation times can be controlled by varying the total polymer concentration or 4a‐Phe content. The resulted hydrogels exhibit excellent self‐healing ability with a high healing efficiency (≈96%) and good mechanical properties. Moreover, the hydrogels display pH/redox dual responsive sol‐gel transition behaviors, and are applied successfully to the controlled release of doxorubicin. Importantly, benefitting from the excellent biocompatibility and the reversibly cross‐linked networks, the hydrogels can function as suitable 3D culture scaffolds for L929 cells, leading to the encapsulated cells maintaining a high viability and proliferative capacity. Therefore, the cellulose‐based self‐healing hydrogels show potential applications in drug delivery and 3D cell culture for tissue engineering.     

4D Printing of Hydrogels: A Review

3D printing permits the construction of objects by layer‐by‐layer deposition of material, resulting in precise control of the dimensions and properties of complex printed structures. Although 3D printing fabricates inanimate objects, the emerging technology of 4D printing allows for animated structures that change their shape, function, or properties over time when exposed to specific external stimuli after fabrication. Among the materials used in 4D printing, hydrogels have attracted growing interest due to the availability of various smart hydrogels. The reversible shape‐morphing in 4D printed hydrogel structures is driven by a stress mismatch arising from the different swelling degrees in the parts of the structure upon application of a stimulus. This review provides the state‐of‐the‐art of 4D printing of hydrogels from the materials perspective. First, the main 3D printing technologies employed are briefly depicted, and, for each one, the required physico‐chemical properties of the precursor material. Then, the hydrogels that have been printed are described, including stimuli‐responsive hydrogels, non‐responsive hydrogels that are sensitive to solvent absorption/desorption, and multimaterial structures that are totally hydrogel‐based. Finally, the current and future applications of this technology are presented, and the requisites and avenues of improvement in terms of material properties are discussed.     

4D Corneal Tissue Engineering: Achieving Time‐Dependent Tissue Self‐Curvature through Localized Control of Cell Actuators

While tissue engineering is widely used to construct complex tridimensional biocompatible structures, researchers are now attempting to extend the technique into the fourth dimension. Such fourth dimension consists in the transformation of 3D materials over time, namely, by changing their shape, composition, and/or function when subjected to specific external stimuli. Herein, producing a 4D biomaterial with an internal mechanism of stimulus, using contractile cells as bio‐actuators to change tissue shape and structure, is explored. Specifically, producing cornea‐shaped, curved stromal tissue equivalents via the controlled, cell‐driven curving of collagen‐based hydrogels. This is achieved by modulating the activity of the bio‐actuators in delimited regions of the gels using a contraction‐inhibiting peptide amphiphile. The self‐curved constructs are then characterized in terms of cell and collagen fibril reorganization, gel stiffness, cell phenotype, and the ability to sustain the growth of a corneal epithelium in vitro. Overall, the results show that the structural and mechanical properties of self‐curved gels acquired through a 4D engineering method are more similar to those of the native tissue, and represent a significant improvement over planar 3D scaffolds. In this perspective, the study demonstrates the great potential of cell bio‐actuators for 4D tissue engineering applications.     

Programmed Shape‐Morphing Scaffolds Enabling Facile 3D Endothelialization

Rapid formation of a confluent endothelial monolayer is the key to the success of small‐diameter vascular grafts, which is significantly important for treating dangerous and even sometimes deadly vascular disorders. However, the difficulty to homogenously locate endothelial cells onto the lumen of small‐diameter tubular scaffolds makes 3D endothelialization greatly challenging. Here, novel shape‐morphing scaffolds enabling programmed deformation from planar shapes to small‐diameter tubular shapes are designed and developed by combining biocompatible shape memory polymer and electrospun nanofibrous membrane. Endothelial cells can be conveniently seeded and attached on the 2D surface of the scaffolds and subsequently self‐rolled into 3D organization at physiological temperature. Endothelial cell responses and functions are varied on the shape‐morphing scaffolds with different nanofibrous electrospun membranes as the inner layer, arisen from the inducement of scaffolds with different morphological, physical, and biochemical characteristics. Owing to excellent properties of the nanofibrous membrane fabricated by the coelectrospinning of poly‐ε‐caprolactone (PCL) and gelatin methacrylate (GelMA), the shape‐morphing scaffolds with a nanofibrous PCL/GelMA inner layer support desirable homogeneous endothelial cell attachment as well as the rapid formation of biomimetic cell–scaffold interaction and cell–cell interaction under the 3D cell culture condition, therefore offering a visible approach for facile 3D endothelialization.     

Biasing Buckling Direction in Shape‐Programmable Hydrogel Sheets with Through‐Thickness Gradients

A photocrosslinkable poly( N , N ′‐diethylacrylamide) copolymer allows for the photolithographic fabrication of hydrogel sheets with nonuniform crosslinking density and swelling ratio. Using this material system, different 3D shapes with nonzero Gaussian curvature K are successfully programmed by prescribing a “metric” defined by in‐plane variations in swelling. However, this methodology does not control the direction of buckling adopted by each positive K feature, and therefore cannot controllably select between different isometric shapes defined by a single metric. Here, by introducing gradients in swelling through the thickness of the gel sheet by tuning the absorption of the UV‐light used for crosslinking, a preferential buckling direction is locally specified for each feature by the direction of UV exposure. By also controlling the strength of coupling between neighboring features, this is shown to be an effective method to program buckling direction of each unit within a canonical corrugated surface shape.     

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).     

Deformable,Programmable, and Shape‐Memorizing Micro‐Optics

The use of shape memory polymers is demonstrated for deformable, programmable, and shape‐memorizing micro‐optical devices. A semi‐crystalline shape memory elastomer, crosslinked poly(ethylene‐co‐vinyl acetate), is used to prepare various micro‐optic components, ranging from microlens and microprism arrays to diffraction gratings and holograms. The precise replication of surface features at the micro‐ and nanoscale and the formation of crosslinked shape memory polymer networks can be achieved in a single step via compression molding. Further deformation via hot pressing or stretching of micro‐optics formed in this manner allows manipulation of the microscopic surface features, and thus the corresponding optical properties. Due to the shape memory effect, the original surface structures and the optical properties can be recovered and the devices be reprogrammed, with excellent reversibility in the optical properties. Furthermore, arrays of transparent resistive microheaters can be integrated with deformed micro‐optical devices to selectively trigger the recovery of surface features in a spatially programmable manner, thereby providing additional capabilities in user‐definable optics.