Wet‐Spun Stimuli‐Responsive Composite Fibers with Tunable Electrical Conductivity

Wet‐spun stimuli‐responsive composite fibers made of covalently crosslinked alginate with a high concentration of single‐walled carbon nanotubes (SWCNTs) are electroconductive and sensitive to humidity, pH, and ionic strength, due to pH‐tunable water absorbing properties of the covalently crosslinked alginate. The conductivity depends on the material swelling in humid atmosphere and aqueous solutions: the greater the swelling, the smaller is the electrical conductivity. The covalently crosslinked fibers reversibly deform during the swelling/shrinking. In the swollen state, the fibers are less conductive, while they return to the same level of conductivity after shrinking. This unique reversible change of electroconductivity of the SWCNT‐alginate fibers is due to the elastic deformation of the alginate network in the area of electrical contacts between SWCNT bundles arrested in the alginate matrix. Fibers of this kind can be used as a simple, robust, disposable, and biocompatible platform for electrotextiles, biosensors, and flexible electronics in biomedical and biotechnological applications.     

Multi‐Stimuli‐Responsive Microcapsules for Adjustable Controlled‐Release

Novel multi‐stimuli‐responsive microcapsules with adjustable controlled‐release characteristics are prepared by a microfluidic technique. The proposed microcapsules are composed of crosslinked chitosan acting as pH‐responsive capsule membrane, embedded magnetic nanoparticles to realize “site‐specific targeting”, and embedded temperature‐responsive sub‐microspheres serving as “micro‐valves”. By applying an external magnetic field, the prepared smart microcapsules can achieve targeting aggregation at specific sites. Due to acid‐induced swelling of the capsule membranes, the microcapsules exhibit higher release rate at specific acidic sites compared to that at normal sites with physiological pH. More importantly, through controlling the hydrodynamic size of sub‐microsphere “micro‐valves” by regulating the environment temperature, the release rate of drug molecules from the microcapsules can be flexibly adjusted. This kind of multi‐stimuli‐responsive microcapsules with site‐specific targeting and adjustable controlled‐release characteristics provides a new mode for designing “intelligent” controlled‐release systems and is expected to realize more rational drug administration.     

Harnessing the Power of Stimuli‐Responsive Polymers for Actuation

A common behavior found in nature is the ability of plants and animals to naturally respond to their surroundings through actuation. Stimuli‐responsive polymers exhibit the same ability to naturally respond to changes in their environment, although manipulating them in a manner that allows their responses to be harnessed to do work via actuation is far from trivial. In this Review, examples that use temperature, pH, light, and electric field (and other) stimulation for actuation are highlighted. The actuation can result in materials that can be used to grip, lift, and move objects as well as for their own movement. As tremendous progress is being made in this research area, it is hard to imagine a future without these materials impacting lives in some way.     

Stimuli‐Responsive Materials for Controlled Release of Theranostic Agents

Stimuli‐responsive materials are so named because they can alter their physicochemical properties and/or structural conformations in response to specific stimuli. The stimuli can be internal, such as physiological or pathological variations in the target cells/tissues, or external, such as optical and ultrasound radiations. In recent years, these materials have gained increasing interest in biomedical applications due to their potential for spatially and temporally controlled release of theranostic agents in response to the specific stimuli. This article highlights several recent advances in the development of such materials, with a focus on their molecular designs and formulations. The future of stimuli‐responsive materials will also be explored, including combination with molecular imaging probes and targeting moieties, which could enable simultaneous diagnosis and treatment of a specific disease, as well as multi‐functionality and responsiveness to multiple stimuli, all important in overcoming intrinsic biological barriers and increasing clinical viability.     

Stimuli‐Responsive Colloidal Systems from Mixed Brush‐Coated Nanoparticles

We report on the application of mixed polymer brushes to the reversible in situ switching colloidal systems (suspensions of responsive 200 nm in diameter particles in individual solvents and immiscible liquids). We used mixed copolymer brushes to fabricate responsive nanoparticles and employed the particles to prepare responsive colloidal systems, which demonstrated drastic transformation/switching of material properties upon external stimuli. The interaction between the particles themselves and the particles and their environment can be precisely tuned by a change of solvent and pH. We show that this behavior can be used for a reversible formation of particle aggregates, stabilization and switching between w/o and o/w emulsions, and regulation of the particle transport between immiscible liquids across the interface. We demonstrate an example of the application of the responsive colloids for the fabrication of ultrahydrophobic coatings with textured surfaces from aqueous dispersion, and no surfactant application, using the switching properties of the responsive particles.     

In‐Film Bioprocessing and Immunoanalysis with Electroaddressable Stimuli‐Responsive Polysaccharides

Advances in thin‐film fabrication are integral to enhancing the power of microelectronics while fabrication methods that allow the integration of biological molecules are enabling advances in bioelectronics. A thin‐film‐fabrication method that further extends the integration of biology with microelectronics by allowing living biological systems to be assembled, cultured, and analyzed on‐chip with the aid of localized electrical signals is described. Specifically, the blending of two stimuli‐responsive film‐forming polysaccharides for electroaddressing is reported. The first, alginate, can electrodeposit by undergoing a localized sol–gel transition in response to electrode‐imposed anodic signals. The second, agarose, can be co‐deposited with alginate and forms a gel upon a temperature reduction. Electrodeposition of this dual polysaccharide network is observed to be a simple, rapid, and spatially selective means for assembly. The bioprocessing capabilities are examined by co‐depositing a yeast clone engineered to display a variable lymphocyte receptor protein on the cell surface. Results demonstrate the in‐film expansion and induction of this cell population. Analysis of the cells' surface proteins is achieved by the electrophoretic delivery of immunoreagents into the film. These results demonstrate a simple and benign means to electroaddress hydrogel films for in‐film bioprocessing and immunoanalysis.     

Stimuli‐Responsive DNA‐Gated Nanoscale Porous Carbon Derived from ZIF‐8

Stimuli‐responsive nanoscale porous carbon derived from ZIF‐8 (NCZIF) gated by DNA capping units is reported. The NCZIF is first obtained by calcination of nano‐ZIF‐8 crystals under an inert atmosphere. It is further conjugated with amine‐modified single‐stranded DNA after carboxylation (DNA/NCZIF). The guest molecules are sealed in the pore of NCZIF by the formation of a DNA duplex structure on the surface of NCZIF. As proof of principle, two systems that can be, respectively, used for controlled drug delivery and biosensing are introduced. In the first system, the drug model (rhodamine 6G, Rh6G) is locked in the NCZIF by the DNA capping units composed of rich‐G sequences and its complementary DNA strand. The in vitro cellular experiments reveal that DNA/NCZIF has good biocompatibility and can controllably release Rh6G upon the K⁺‐stimuli in cells. In the second system, the signal probe (methylene blue, MB) is locked in the NCZIF and then released after the unlocking of the pores triggered by the dissociation of the aptamer‐hybrid capping units. The MB‐loaded DNA/NCZIF can linearly respond to target molecules in the range from 1 × 10^?9 to 10 × 10^?6 m and has good specificity.     

Biofabricating Multifunctional Soft Matter with Enzymes and Stimuli‐Responsive Materials

Methods that allow soft matter to be fabricated with controlled structure and function would be beneficial for applications ranging from flexible electronics to regenerative medicine. Here, the assembly of a multifunctional gelatin matrix is demonstrated by triggering its self‐assembly and then enzymatically assembling biological functionality. Triggered self‐assembly relies on electrodeposition of the pH‐responsive hydrogelator, 9‐fluorenylmethoxycarbonyl‐phenylalanine (Fmoc‐Phe), in response to electrical inputs that generate a localized pH‐gradient. Warm solutions of Fmoc‐Phe and gelatin are co‐deposited and, after cooling to room temperature, a physical gelatin network forms. Enzymatic assembly employs the cofactor‐independent enzyme microbial transglutaminase (mTG) to perform two functions: crosslink the gelatin matrix to generate a thermally stable chemical gel and conjugate proteins to the matrix. To conjugate globular proteins to gelatin these proteins are engineered to have short lysine‐rich or glutamine‐rich fusion tags to provide accessible residues for mTG‐catalysis. Viable bacteria can be co‐deposited and entrapped within the crosslinked gelatin matrix and can proliferate upon subsequent incubation. These results demonstrate the potential for enlisting biological materials and mechanisms to biofabricate multifunctional soft matter.     

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.     

Double Stimuli‐Responsive Isoporous Membranes via Post‐Modification of pH‐Sensitive Self‐Assembled Diblock Copolymer Membranes

Double stimuli‐responsive membranes are prepared by modification of pH‐sensitive integral asymmetric polystyrene‐b‐poly(4‐vinylpyridine) (PS‐b‐P4VP) diblock copolymer membranes with temperature‐responsive poly(N‐isopropylacrylamide) (pNIPAM) by a surface linking reaction. PS‐b‐P4VP membranes are first functionalized with a mild mussel‐inspired polydopamine coating and then reacted via Michael addition with an amine‐terminated pNIPAM‐NH₂ under slightly basic conditions. The membranes are thoroughly characterized by nuclear magnetic resonance (¹H‐NMR), Fourier transform infrared spectroscopy and X‐ray‐induced photoelectron spectroscopy. Additionally dynamic contact angle measurements are performed comparing the sinking rate of water droplets at different temperatures. The pH‐ and thermo‐double sensitivities of the modified membranes are proven by determining the water flux under different temperature and pH conditions.     

Multifunctional Graphene Oxide‐based Triple Stimuli‐Responsive Nanotheranostics

Construction of multifunctional stimuli‐responsive nanosystems intelligently responsive to inner physiological and/or external irradiations based on nanobiotechnology can enable the on‐demand drug release and improved diagnostic imaging to mitigate the side‐effects of anticancer drugs and enhance the diagnostic/therapeutic outcome simultaneously. Here, a triple‐functional stimuli‐responsive nanosystem based on the co‐integration of superparamagnetic Fe₃O₄ and paramagnetic MnO_x nanoparticles (NPs) onto exfoliated graphene oxide (GO) nanosheets by a novel and efficient double redox strategy (DRS) is reported. Aromatic anticancer drug molecules can interact with GO nanosheets through supramolecular π stacking to achieve high drug loading capacity and pH‐responsive drug releasing performance. The integrated MnO_x NPs can disintegrate in mild acidic and reduction environment to realize the highly efficient pH‐responsive and reduction‐triggered T₁‐weighted magnetic resonance imaging (MRI). Superparamagnetic Fe₃O₄ NPs can not only function as the T₂‐weighted contrast agents for MRI, but also response to the external magnetic field for magnetic hyperthermia against cancer. Importantly, the constructed biocompatible GO‐based nanoplatform can inhibit the metastasis of cancer cells by downregulating the expression of metastasis‐related proteins, and anticancer drug‐loaded carrier can significantly reverse the multidrug resistance (MDR) of cancer cells.     

Chain Extension of Stimuli‐Responsive Polymer Brushes: A General Strategy to Overcome the Drawbacks of the “Grafting‐To” Approach

Stimuli‐responsive polymer brushes are smart materials for the design of bio‐interactive and responsive interfaces. The “grafting‐to” approach is a convenient preparation procedure that allows the modification of surfaces with preformed and most notably well‐defined functionalized macromolecules. However, the shortcoming of this approach is an intrinsic limitation of the grafting density, which in turn affects the stimuli‐responsive properties of the brush system. Here, a general strategy to overcome this limitation and to simultaneously improve the switching behavior of a temperature‐responsive poly(N‐isopropylacrylamide) (PNiPAAm) brush is reported. A technically simple processing step is used in combination with the thermal azide–alkyne cycloaddition to perform the chain extension of alkyne‐functionalized PNiPAAm brushes with azide‐functionalized PNiPAAm molecules.     

Reversibly and Irreversibly Humidity‐Responsive Motion of Liquid Crystalline Network Gated by SO2 Gas

Manipulating functional liquid crystalline networks (LCNs) by multiple stimuli has been a hot topic in the research of smart actuators and fabrication of biomimetic robots. Here, a single‐layer LCN film showing dual responsiveness to humidity and SO₂ gas is prepared. Interestingly, the humidity sensitivity of the LCN film can be gated by exposing the film to SO₂. At the same time, the SO₂ sensitivity is strongly affected by the ambient relative humidity (RH) and the response time is able to be tuned by changing the RH over a wide range. The mechanism of this dual response of the LCN film is ascribed to the neutralization of carboxylic acid and in situ acidification of the carboxylic salt. The reversibly and irreversibly humidity‐induced motion gated by SO₂ renders the LCN film valuable in the design and preparation of multifunctional devices.