Preparation of Responsive Micrometer‐Sized Microgel Particles with a Highly Functionalized Shell

We describe a facile approach for the synthesis of micrometer‐sized (∼3.5 μm), pH‐responsive microgel particles, which have functional carboxylic acid groups concentrated in the shell. The large size offers the possibility to directly study the interactions between individual, isolated microgel particles with active ingredients by optical microscopy. Our results show that the synthesized microgel particles can load and release active ingredients via changing pH values. The complexation of Ca²⁺ with the ‐COOH functional groups located at the microgel surfaces not only regulates the active ingredient's uptake efficiency, but also provides a novel way to reveal the spatial distribution of the functional groups inside the microgel particles.     

Responsive DNA‐Based Hydrogels and Their Applications

The term hydrogel describes a type of soft and wet material formed by cross‐linked hydrophilic polymers. The distinct feature of hydrogels is their ability to absorb a large amount of water and swell. The properties of a hydrogel are usually determined by the chemical properties of their constituent polymer(s). However, a group of hydrogels, called “smart hydrogels,” changes properties in response to environmental changes or external stimuli. Recently, DNA or DNA‐inspired responsive hydrogels have attracted considerable attention in construction of smart hydrogels because of the intrinsic advantages of DNA. As a biological polymer, DNA is hydrophilic, biocompatible, and highly programmable by Watson‐Crick base pairing. DNA can form a hydrogel by itself under certain conditions, and it can also be incorporated into synthetic polymers to form DNA‐hybrid hydrogels. Functional DNAs, such as aptamers and DNAzymes, provide additional molecular recognition capabilities and versatility. In this Review, DNA‐based hydrogels are discussed in terms of their stimulus response, as well as their applications.

     

Self‐healing in Nanocomposite Hydrogels

Polymer hydrogels with characteristics distinct from those of solid materials are one of the most promising candidates for smart materials. Here, we report that a nanocomposite hydrogel (NC gel) consisting of a unique polymer/clay network structure, can exhibit complete self‐healing through autonomic reconstruction of crosslinks across a damaged interface. Mechanical damage in NC gels can be repaired without the use of a healing agent, and even sections of NC gels separated by cutting, from whichever the same or different kinds of NC gel, perfectly (re‐)combine by just contacting the cut surfaces together at mildly elevated temperatures. In NC gels, the autonomic fusion of cut surfaces as well as the self‐healing could be achieved not only immediately after being cut but also after a long waiting time.

     

Microporous Polymeric 3D Scaffolds Templated by the Layer‐by‐Layer Self‐Assembly

Polymeric scaffolds serve as valuable supports for biological cells since they offer essential features for guiding cellular organization and tissue development. The main challenges for scaffold fabrication are i) to tune an internal structure and ii) to load bio‐molecules such as growth factors and control their local concentration and distribution. Here, a new approach for the design of hollow polymeric scaffolds using porous CaCO₃ particles (cores) as templates is presented. The cores packed into a microfluidic channel are coated with polymers employing the layer‐by‐layer (LbL) technique. Subsequent core elimination at mild conditions results in formation of the scaffold composed of interconnected hollow polymer microspheres. The size of the cores determines the feature dimensions and, as a consequence, governs cellular adhesion: for 3T3 fibroblasts an optimal microsphere size is 12 μm. By making use of the carrier properties of the porous CaCO₃ cores, the microspheres are loaded with BSA as a model protein. The scaffolds developed here may also be well suited for the localized release of bio‐molecules using external triggers such as IR‐light.

     

Coordination‐Driven In Situ Self‐Assembly Strategy for the Preparation of Metal–Organic Framework Hybrid Membranes

Metal–organic frameworks (MOFs) have emerged as porous solids of a superior type for the fabrication of membranes. However, it is still challenging to prepare a uniformly dispersed robust MOF hybrid membrane. Herein, we propose a simple and powerful strategy, namely, coordination‐driven in situ self‐assembly, for the fabrication of MOF hybrid membranes. On the basis of the coordination interactions between metal ions and ligands and/or the functional groups of the organic polymer, this method was confirmed to be feasible for the production of a stable membrane with greatly improved MOF‐particle dispersion in and compatibility with the polymer, thus providing outstanding separation ability. As an experimental proof of concept, a high‐quality ZIF‐8/PSS membrane was fabricated that showed excellent performance in the nanofiltration and separation of dyes from water.     

Thermo‐Responsive Hydrogels with Nanodomains: Rapid Shrinking of a Nanogel‐Crosslinking Hydrogel of Poly(N‐isopropyl acrylamide)

Rapidly shrinking poly(N‐isopropyl acrylamide) (PNIPAM) hydrogels are prepared by crosslinking with self‐assembled nanogels that consist of cholesteryl‐ and methacryloyl‐substituted pullulan (CHPMA). The CHPMA nanogel (R_h = 26.4 nm) was used as a crosslinker for a hydrophilic nanodomain. Transmission electron microscopy images of the nanogel‐crosslinked PNIPAM hydrogel reveal a well‐defined nanoporous structure. The nanogel‐crosslinked PNIPAM hydrogel shows rapid shrinking based on its structure. The shrinking half‐time was ≈2 min, which is about 3 400 times faster than that of a PNIPAM hydrogel crosslinked by methylene(bisacrylamide).

     

Silver Nanoparticles Stabilized by Thermoresponsive Microgel Particles: Synthesis and Evidence of an Electron Donor‐Acceptor Effect

Well‐dispersed silver nanoparticles were successfully fabricated within poly[(N‐isopropylacrylamide)‐co‐(acrylic acid)] [P(NIPAM‐co‐AA)] microgel particles which were synthesized with different cross‐linking densities. Their structures were studied by field‐emission scanning electron microscopy, transmission electron microscopy, UV‐vis spectroscopy, X‐ray diffraction and FT‐IR spectroscopy. The interactions between the microgel particles and the incorporated silver nanoparticles were investigated by X‐ray photoelectron spectroscopy. The results revealed that there was charge transfer from the carbonyl groups of the microgel particles to the silver nanoparticles. Moreover, as the diameter of the AgNPs decreases, the charge‐transfer efficiency increases accordingly. The P(NIPAM‐co‐AA)/AgNPs hybrid microgel particles were thermoresponsive and their behavior completely reversible with several heating/cooling cycles.

     

Molecular Structure of Physiologically‐Responsive Hydrogels Controls Diffusive Behavior

Polymeric networks and the ensuing hydrogels of MAA and NVP were successfully synthesized using a UV‐initiated free radical polymerization and characterized to assess their applicability as carriers for directed drug delivery. FT‐IR spectroscopy revealed shifts in peak absorbances that indicated the presence of hydrogen bonding complexes between functional groups, while SEM imaging showed that the different comonomers affect the surface morphology of the microparticles. Dynamic pH swelling studies demonstrated the pH responsiveness of the carriers in gastric and intestinal conditions and revealed that systems containing higher concentrations of MAA experienced the highest degree of hydrogen bonding complexation in gastric conditions. The presence of NVP in the systems enhanced swelling. Equilibrium swelling studies revealed that the mesh size was sufficiently large to allow drug diffusion across the networks.

     

Cross‐Linking Density and Temperature Effects on the Self‐Assembly of SiO2—PNIPAAm Core–Shell Particles at Interfaces

SiO₂–PNIPAAm core–shell microgels (PNIPAAm=poly(N‐isopropylacrylamide)) with various internal cross‐linking densities and different degrees of polymerization were prepared in order to investigate the effects of stability, packing, and temperature responsiveness at polar–apolar interfaces. The effects were investigated using interfacial tensiometry, and the particles were visualized by cryo‐scanning electron microscopy (SEM) and scanning force microscopy (SFM). The core–shell particles display different interfacial behaviors depending on the polymer shell thickness and degree of internal cross‐linking. A thicker polymer shell and reduced internal cross‐linking density are more favorable for the stabilization and packing of the particles at oil–water (o/w) interfaces. This was shown qualitatively by SFM of deposited, stabilized emulsion droplets and quantitatively by SFM of particles adsorbed onto a hydrophobic planar silicon dioxide surface, which acted as a model interface system. The temperature responsiveness, which also influences particle–interface interactions, was investigated by dynamic temperature protocols with varied heating rates. These measurements not only showed that the particles had an unusual but very regular and reversible interface stabilization behavior, but also made it possible to assess the nonlinear response of PNIPAAm microgels to external thermal stimuli.     

Supramolecular Assembly of Self‐Healing Nanocomposite Hydrogels

Hierarchical self‐assembly of transient composite hydrogels is demonstrated through a two‐step, orthogonal strategy using nanoparticle tectons interconnected through metal–ligand coordination complexes. The resulting materials are highly tunable with moduli and viscosities spanning many orders of magnitude, and show promising self‐healing properties, while maintaining complete optical transparency.

     

Synthesis and Characterization of PEG‐Based Drug‐Responsive Biohybrid Hydrogels

Interactive materials being responsive to a biocompatible stimulus represent a promising approach for future therapeutic applications. In this study, we present a novel biohybrid material synthesized from biocompatible components being stimulus‐responsive to the pharmaceutically approved small‐molecule novobiocin. The hydrogel design is based on the gyrase B (GyrB) protein, which is covalently grafted to multi‐arm polyethylene glycol (PEG) using a Michael‐type addition reaction. Upon addition of the GyrB‐dimerizing substance coumermycin, stable hydrogels form which can be dissolved in a dose‐adjustable manner by the antibiotic novobiocin. The switchable properties of this PEG‐based hydrogel are favorable for future applications in tissue engineering and as externally controlled drug depot.     

Synergy of Single‐ion Conductive and Thermo‐responsive Copolymer Hydrogels Achieving Anti‐Arrhenius Ionic Conductivity

Artificial intelligence sensations have aroused scientific interest from electronic conductors to bio‐inspired ionic conductors. The conductivity of electrons decreases with increasing temperature, while the ionic conductivity agrees with an Arrhenius equation or a modified Vogel–Tammann–Fulcher (VTF) equation. Herein, thermo‐responsive poly(N‐isopropyl amide) (PNIPAm) and single‐ion‐conducting poly(2‐acrylamido‐2‐methyl‐1‐propanesulfonic lithium salt) (PAMPSLi) were copolymerized via a facile radical polymerization to demonstrate a very intriguing anti‐Arrhenius ionic conductivity behaviour during thermally induced volume‐phase transition. These smart hydrogels presented very promising scaffolds for architecting flexible, wearable or advanced functional ionic devices.     

Surface‐Assisted Self‐Assembly of a Hydrogel by Proton Diffusion

Controlling supramolecular growth at solid surfaces is of great importance to expand the scope of supramolecular materials. A dendritic benzene‐1,3,5‐tricarboxamide peptide conjugate is described in which assembly can be triggered by a pH jump. Stopped‐flow kinetics and mathematical modeling provide a quantitative understanding of the nucleation, elongation, and fragmentation behavior in solution. To assemble the molecule at a solid–liquid interface, we use proton diffusion from the bulk. The latter needs to be slower than the lag phase of nucleation to progressively grow a hydrogel outwards from the surface. Our method of surface‐assisted self‐assembly is generally applicable to other gelators, and can be used to create structured supramolecular materials.     

Strong,Self‐Healable,and Recyclable Visible‐Light‐Responsive Hydrogel Actuators

The most pressing challenges for light‐driven hydrogel actuators include reliance on UV light, slow response, poor mechanical properties, and limited functionalities. Now, a supramolecular design strategy is used to address these issues. Key is the use of a benzylimine‐functionalized anthracene group, which red‐shifts the absorption into the visible region and also stabilizes the supramolecular network through π–π interactions. Acid–ether hydrogen bonds are incorporated for energy dissipation under mechanical deformation and maintaining hydrophilicity of the network. This double‐crosslinked supramolecular hydrogel developed via a simple synthesis exhibits a unique combination of high strength, rapid self‐healing, and fast visible‐light‐driven shape morphing both in the wet and dry state. As all of the interactions are dynamic, the design enables the structures to be recycled and reprogrammed into different 3D objects.     

Light‐ and Solvent‐Controlled Self‐Assembly Behavior of Spiropyran–Polyoxometalate–Alkyl Hybrid Molecules

A molecular photochromic spiropyran–polyoxometalate–alkyl organic–inorganic hybrid has been synthesized and fully characterized. The reversible switching of the hydrophobic spiropyran fragment to the hydrophilic merocyanine one can be easily achieved under light irradiation at different wavelengths. This switch changes the amphiphilic feature of the hybrid, leading to a light‐controlled self‐assembly behavior in solution. It has been shown that the hybrid can reversibly self‐assemble into vesicles in polar solvents and irreversibly into reverse vesicles in non‐polar solvents. The sizes of the vesicles and the reverse vesicles are both tunable by the polarity of the solvent, with the hydrophobic interactions being the main driving force.     

Self‐Healing Supramolecular Hydrogels for Tissue Engineering Applications

Self‐healing supramolecular hydrogels have emerged as a novel class of biomaterials that combine hydrogels with supramolecular chemistry to develop highly functional biomaterials with advantages including native tissue mimicry, biocompatibility, and injectability. These properties are endowed by the reversibly cross‐linked polymer network of the hydrogel. These hydrogels have great potential for realizing yet to be clinically translated tissue engineering therapies. This review presents methods of self‐healing supramolecular hydrogel formation and their uses in tissue engineering as well as future perspectives.     

Self‐Healing in Tough Graphene Oxide Composite Hydrogels

Polymer hydrogels that are capable of spontaneously healing injury are being developed at a rapid pace because of their great potential in biomedical applications. Here, the self‐healing property of tough graphene nanocomposite hydrogels fabricated by using graphene peroxide as polyfunctional initiating and cross‐linking centers is reported. The hydrogels show excellent self‐healing ability at ambient temperature or even lower temperatures for a short time and very high recovery degrees (up to 88% tensile strength) can be achieved at a prolonged healing time. The healed gels exhibit very high tensile strengths (up to 0.35 MPa) and extremely high elongations (up to 4900%). The strong interactions between the polyacrylamide chains and the graphene oxide sheets are essential to the mechanical strengths of the healed gels.