Liposome Crosslinked Polyacrylamide/DNA Hydrogel: a Smart Controlled‐Release System for Small Molecular Payloads

A novel stimuli‐responsive hydrogel system with liposomes serving as both noncovalent crosslinkers and functional small molecules carriers for controlled‐release is developed. Liposomes can crosslink polyacrylamide copolymers functionalized with cholesterol‐modified DNA motifs to yield a DNA hydrogel system, due to the hydrophobic interaction between cholesteryl groups and the lipid bilayer of liposomes. Functional information encoded DNA motifs on the polymer backbones endow the hydrogel with programmable smart responsive properties. In a model system, the hydrogel exhibits stimuli‐responsive gel‐to‐sol transformation triggered by the opening of DNA motifs upon the presence of a restriction endonuclease enzyme, EcoR I, or temperature change, realizing the controlled‐release of liposomes which are highly efficient carriers of active small molecules payloads. Two active molecules, 1,1‐dioctadecyl‐3,3,3,3‐tetramethylindodicarbocyanine perchlorate (DiIC18(5)) and calcein, are chosen as the hydrophobic and hydrophilic model payloads, respectively, to address the feasibility of the releasing strategy. Moreover, the hydrogel exhibits injectable property as well as self‐recovery behaviors.     

Direct Evidence for Structural Transition Promoting Shear Thinning in Cylindrical Colloid Assemblies

In this paper, we describe stimuli‐responsive hydrogels prepared from a rigid rod‐like polyelectrolyte ‘imogolite’ and a dicarboxylic acid. The hydrogel exhibited thixotropy in response to mechanical shock within the order of seconds or sub‐seconds. Here, using the latest structural/rheological characterisation techniques, the relationship between the structural transition processes and the shear thinning was estimated. The evidence obtained by the experiments revealed for the first time the direct relationship between the microscopic structural change and the macroscopic thixotropic behavior that have been extensively discussed. The thixotropic hydrogel has the hierarchical architecture in the combination of imogolite and dicarboxylic acid, i.e., sheathed nanotubes/hydroclusters of cross‐bridged nanotubes/frameworks. The formation and disintegration of the network structure upon resting and agitating, respectively, were the origin of gel/sol transition (thixotropy), although the hydroclusters of cross‐bridged nanotubes were maintained throughout the transition.     

Dynamic Coordination of Eu–Iminodiacetate to Control Fluorochromic Response of Polymer Hydrogels to Multistimuli

New fluorochromic materials that reversibly change their emission properties in response to their environment are of interest for the development of sensors and light‐emitting materials. A new design of Eu‐containing polymer hydrogels showing fast self‐healing and tunable fluorochromic properties in response to five different stimuli, including pH, temperature, metal ions, sonication, and force, is reported. The polymer hydrogels are fabricated using Eu–iminodiacetate (IDA) coordination in a hydrophilic poly(N,N‐dimethylacrylamide) matrix. Dynamic metal–ligand coordination allows reversible formation and disruption of hydrogel networks under various stimuli which makes hydrogels self‐healable and injectable. Such hydrogels show interesting switchable ON/OFF luminescence along with the sol–gel transition through the reversible formation and dissociation of Eu–IDA complexes upon various stimuli. It is demonstrated that Eu‐containing hydrogels display fast and reversible mechanochromic response as well in hydrogels having interpenetrating polymer network. Those multistimuli responsive fluorochromic hydrogels illustrate a new pathway to make smart optical materials, particularly for biological sensors where multistimuli response is required.     

Multicomponent DNA Polymerization Motor Gels

Hydrogels with the ability to change shape in response to biochemical stimuli are important for biosensing, smart medicine, drug delivery, and soft robotics. Here, a family of multicomponent DNA polymerization motor gels with different polymer backbones is created, including acrylamide‐co‐bis‐acrylamide (Am‐BIS), poly(ethylene glycol) diacrylate (PEGDA), and gelatin‐methacryloyl (GelMA) that swell extensively in response to specific DNA sequences. A common mechanism, a polymerization motor that induces swelling is driven by a cascade of DNA hairpin insertions into hydrogel crosslinks. These multicomponent hydrogels can be photopatterned into distinct shapes, have a broad range of mechanical properties, including tunable shear moduli between 297 and 3888 Pa and enhanced biocompatibility. Human cells adhere to the GelMA‐DNA gels and remain viable during ≈70% volumetric swelling of the gel scaffold induced by DNA sequences. The results demonstrate the generality of sequential DNA hairpin insertion as a mechanism for inducing shape change in multicomponent hydrogels, suggesting widespread applicability of polymerization motor gels in biomaterials science and engineering.     

Dynamic Hyaluronan Hydrogels with Temporally Modulated High Injectability and Stability Using a Biocompatible Catalyst

Injectable and biocompatible hydrogels have become increasingly important for cell transplantation to provide mechanical protection of cells during injection and a stable scaffold for cell adhesion post‐injection. Injectable hydrogels need to be easily pushed through a syringe needle and quickly recover to a gel state, thus generally requiring noncovalent or dynamic cross‐linking. However, a dilemma exists in the design of dynamic hydrogels: hydrogels with fast exchange of cross‐links are easier to eject using less force, but lack long‐term stability; in contrast, slow exchange of cross‐links improves stability, but compromises injectability and thus the ability to protect cells under flow. A new concept to resolve this dilemma using a biocompatible catalyst to modulate the dynamic properties of hydrogels at different time points of application to have both high injectability and high stability is presented. Hyaluronic acid based hydrogels are formed through dynamic covalent hydrazone cross‐linking in the presence of a biocompatible benzimidazole‐based catalyst. The catalyst accelerates the formation and exchange of hydrazone bonds, enhancing injectability, but rapidly diffuses away from the hydrogel after injection to retard the exchange and improve the long‐term stability for cell culture.     

Skin‐Inspired Multifunctional Autonomic‐Intrinsic Conductive Self‐Healing Hydrogels with Pressure Sensitivity,Stretchability, and 3D Printability

The advent of conductive self‐healing (CSH) hydrogels, a class of novel materials mimicking human skin, may change the trajectory of the industrial process because of their potential applications in soft robots, biomimetic prostheses, and health‐monitoring systems. Here, the development of a mechanically and electrically self‐healing hydrogel based on physically and chemically cross‐linked networks is reported. The autonomous intrinsic self‐healing of the hydrogel is attained through dynamic ionic interactions between carboxylic groups of poly(acrylic acid) and ferric ions. A covalent cross‐linking is used to support the mechanical structure of the hydrogel. Establishing a fair balance between the chemical and physical cross‐linking networks together with the conductive nanostructure of polypyrrole networks leads to a double network hydrogel with bulk conductivity, mechanical and electrical self‐healing properties (100% mechanical recovery in 2 min), ultrastretchability (1500%), and pressure sensitivity. The practical potential of CSH hydrogels is further revealed by their application in human motion detection and their 3D‐printing performance.     

Engineering the pH‐Responsive Catalytic Behavior of AuNPs by DNA

Noble metal nanoparticles have attracted much interest in the heterogeneous catalysis. Particularly, efficient manipulation of the responsive catalytic properties of the metal nanoparticles is an interesting topic. In this work, a simple and efficient strategy is developed to regulate the pH‐responsive catalytic activities of glucose oxidase (GOx)‐mimicking gold nanoparticles (AuNPs). Four DNA strands (regulating strands) that differ slightly in sequences are used to interact non‐covalently with citrate‐capped AuNPs, resulting in markedly distinct pH‐dependent catalytic behavior of AuNPs. This is ascribed to the characteristic pH‐induced conformational change of the DNA strands that leads to the different adsorption capability to the NPs surface, as demonstrated by pH‐CD profiles of the respective DNA molecules. The pH‐dependent catalysis of AuNPs is also encoded with structural information of the double‐stranded DNA (including regulating strands and their complementary strands) that has conformation resistant or responsive to pH change. As a result, the catalysis can be programmed into an AND gate, a XNOR gate or a NOT gate, using pH and complementary strand as the inputs, the nanoparticle activity as the output and the regulating strands as the programs. This work can be expanded by engineering the catalytic behavior of noble metal nanoparticles to respond smartly to a variety of environmental stimuli, such as metal ions or light wavelengths. These results may provide insight into understanding ligand‐regulated nanometallic catalysis.     

Self‐Assembly of Enzyme‐Like Nanofibrous G‐Molecular Hydrogel for Printed Flexible Electrochemical Sensors

Conducting hydrogels provide great potential for creating designer shape‐morphing architectures for biomedical applications owing to their unique solid–liquid interface and ease of processability. Here, a novel nanofibrous hydrogel with significant enzyme‐like activity that can be used as “ink” to print flexible electrochemical devices is developed. The nanofibrous hydrogel is self‐assembled from guanosine (G) and KB(OH)₄ with simultaneous incorporation of hemin into the G‐quartet scaffold, giving rise to significant enzyme‐like activity. The rapid switching between the sol and gel states responsive to shear stress enables free‐form fabrication of different patterns. Furthermore, the replication of the G‐quartet wires into a conductive matrix by in situ catalytic deposition of polyaniline on nanofibers is demonstrated, which can be directly printed into a flexible electrochemical electrode. By loading glucose oxidase into this novel hydrogel, a flexible glucose biosensor is developed. This study sheds new light on developing artificial enzymes with new functionalities and on fabrication of flexible bioelectronics.     

Proteolytically Degradable Photo‐Polymerized Hydrogels Made From PEG–Fibrinogen Adducts

We develop a biomaterial based on protein–polymer conjugates where poly(ethylene glycol) (PEG) polymer chains are covalently linked to multiple thiols on denatured fibrinogen. We hypothesize that conjugation of large diacrylate‐functionalized linear PEG chains to fibrinogen could govern the molecular architecture of the polymer network via a unique protein–polymer interaction. The hypothesis is explored using carefully designed shear rheometry and swelling experiments of the hydrogels and their precursor PEG/fibrinogen conjugate solutions. The physical properties of non‐cross‐linked and UV cross‐linked PEGylated fibrinogen having PEG molecular weights ranging from 10 to 20 kDa are specifically investigated. Attaching multiple hydrophilic, functionalized PEG chains to the denatured fibrinogen solubilizes the denatured protein and enables a rapid free‐radical polymerization cross‐linking reaction in the hydrogel precursor solution. As expected, the conjugated protein‐polymer macromolecular complexes act to mediate the interactions between radicals and unsaturated bonds during the free‐radical polymerization reaction, when compared to control PEG hydrogels. Accordingly, the cross‐linking kinetics and stiffness of the cross‐linked hydrogel are highly influenced by the protein–polymer conjugate architecture and molecular entanglements arising from hydrophobic/hydrophilic interactions and steric hindrances. The proteolytic degradation products of the protein–polymer conjugates proves to be were different from those of the non‐conjugated denatured protein degradation products, indicating that steric hindrances may alter the proteolytic susceptibility of the PEG–protein adduct. A more complete understanding of the molecular complexities associated with this type of protein‐polymer conjugation can help to identify the full potential of a biomaterial that combines the advantages of synthetic polymers and bioactive proteins.     

Stimuli‐Responsive Self‐Assembled DNA Nanomaterials for Biomedical Applications

Stimuli‐responsive DNA‐based materials represent a major class of remarkable functional nanomaterials for nano‐biotechnological applications. In this review, recent progress in the development of stimuli‐responsive systems based on self‐assembled DNA nanostructures is introduced and classified. Representative examples are presented in terms of their design, working principles and mechanisms to trigger the response of the stimuli‐responsive DNA system upon expose to a large variety of stimuli including pH, metal ions, oligonucleotides, small molecules, enzymes, heat, and light. Substantial in vitro studies have clearly revealed the advantages of the use of stimuli‐responsive DNA nanomaterials in different biomedical applications, particularly for biosensing, drug delivery, therapy and diagnostic purposes in addition to bio‐computing. Some of the challenges faced and suggestions for further development are also highlighted.     

Hydrogel Paint

For a hydrogel coating on a substrate to be stable, covalent bonds polymerize monomer units into polymer chains, crosslink the polymer chains into a polymer network, and interlink the polymer network to the substrate. The three processes—polymerization, crosslinking, and interlinking—usually concur. This concurrency hinders widespread applications of hydrogel coatings. Here a principle is described to create hydrogel paints that decouple polymerization from crosslinking and interlinking. Like a common paint, a hydrogel paint divides the labor between the paint maker and the paint user. The paint maker formulates the hydrogel paint by copolymerizing monomer units and coupling agents into polymer chains, but does not crosslink them. The paint user applies the paint on various materials (elastomer, plastic, glass, ceramic, or metal), and by various operations (brush, cast, dip, spin, or spray). During cure, the coupling agents crosslink the polymer chains into a network and interlink the polymer network to the substrate. As an example, hydrogels with thickness in the range of 2–20 µm are dip coated on medical nitinol wires. The coated wires reduce friction by eightfold, and remain stable over 50 test cycles. Also demonstrated are several proof‐of‐concept applications, including stimuli‐responsive structures and antifouling model boats.     

Photodetachable Adhesion

Peeling from strong adhesion is hard, and sometimes painful. Herein, an approach is described to achieve both strong adhesion and easy detachment. The latter is triggered, on‐demand, through an exposure to light of a certain frequency range. The principle of photodetachable adhesion is first demonstrated using two hydrogels as adherends. Each hydrogel has a covalent polymer network, but does not have functional groups for bonding, so that the two hydrogels by themselves adhere poorly. The two hydrogels, however, adhere strongly when an aqueous solution of polymer chains is spread on the surfaces of the hydrogels and is triggered to form a stitching polymer network in situ, in topological entanglement with the pre‐existing polymer networks of the two hydrogels. The two hydrogels detach easily when the stitching polymer network is so functionalized that it undergoes a gel–sol transition in response to a UV light. For example, two pieces of alginate–polyacrylamide hydrogels achieve adhesion energies about 1400 and 10 J m^?2, respectively, before and after the UV radiation. Experiments are conducted to study the physics and chemistry of this strong and photodetachable adhesion, and to adhere and detach various materials, including hydrogels, elastomers, and inorganic solids.     

Stimuli‐Responsive Polymeric Systems for Biomedical Applications

Smart polymeric‐based devices and surfaces that reversibly alter their physico‐chemical characteristics in response to their environment are the center of many studies related to the development of materials and concepts in a broad‐range of biomedical fields. Although the initial interests were more focused in systems for the delivery of therapeutic molecules, other applications have been raised in topics ranging from actuators to biomaterials for tissue engineering and regenerative medicine. The general aspects of the different types of stimuli that can be used to modulate the response are reviewed mainly for the case of hydrogels and surfaces, based on natural‐origin or biodegradable macromolecules. Thermosensitive or light responsive surfaces that can modulate cell adhesion or protein adsorption are addressed as well as less conventional smart surfaces, such as substrates onto which biomineralization may be triggered. Injectable liquids that turn to gels by the action of heating (sol‐gel thermo‐reversible hydrogels) or by changing pH or the ionic milieu (bioinspired self‐assembling systems) may find great applicability as temporary scaffolds in non invasive procedures to deliver drugs or cells to particular places in the body. Examples of systems that recognize independently or simultaneously more than one stimulus will also be presented. Besides the typical response to temperature and pH, recent developments on materials that react to biochemical stimuli, including specific enzymes, antibodies or cells, are also highlighted.     

多重响应性P(AAEA-co-DMAA)水凝胶的合成及其性能研究

以具有多重响应性的新型单体4-乙酰基丙烯酰乙酸乙酯(AAEA)和N,N′-二甲基丙烯酰胺(DMAA)为原料,采用溶液自由基聚合法合成了具有多重响应性的水凝胶,研究了凝胶的溶胀行为以及在不同离子强度、温度、pH值条件下共聚水凝胶的响应性能。结果表明,随凝胶中AAEA含量的增加,凝胶的溶胀方式由Fick型转变为非Fick型;凝胶对外界离子强度、温度、pH值的变化产生响应,当NaCl浓度约为0.1mol/L时,凝胶的离子响应性出现较大的突变;随温度的升高,凝胶疏水性增大,85℃时凝胶的保水率只有60%;低pH值时,凝胶收缩,随pH值的增大,凝胶内P-AAEA部分解离加剧,静电斥力使凝胶溶胀。     

A Novel Design of Multi‐Mechanoresponsive and Mechanically Strong Hydrogels

A newly developed polyacrylamide‐co ‐methyl acrylate/spiropyran (SP) hydrogel crosslinked by SP mechanophore demonstrates multi‐stimuli‐responsive and mechanically strong properties. The hydrogels not only exhibit thermo‐, photo‐, and mechano‐induced color changes, but also achieve super‐strong mechanical properties (tensile stress of 1.45 MPa, tensile strain of ≈600%, and fracture energy of 7300 J m^?2). Due to a reversible structural transformation between spiropyran (a ring‐close) and merocyanine (a ring‐open) states, simple exposure of the hydrogels to white light can reverse color changes and restore mechanical properties. The new design approach for a new mechanoresponsive hydrogel is easily transformative to the development of other mechanophore‐based hydrogels for sensing, imaging, and display applications.     

Transducing Protease Activity into DNA Output for Developing Smart Bionanosensors

DNA can process information through sequence‐based reorganization but cannot typically receive input information from most biological processes and translate that into DNA compatible language. Coupling DNA to a substrate responsive to biological events can address this limitation. A two‐component sensor incorporating a chimeric peptide‐DNA substrate is evaluated here as a protease‐to‐DNA signal convertor which transduces protease activity through DNA gates that discriminate between different input proteases. Acceptor dye‐labeled peptide‐DNAs are assembled onto semiconductor quantum dot (QD) donors as the input gate. Addition of trypsin or chymotrypsin cleaves their cognate peptide sequence altering the efficiency of Förster resonance energy transfer (FRET) with the QD and frees a DNA output which interacts with a tetrahedral output gate. Downstream output gate rearrangement results in FRET sensitization of a new acceptor dye. Following characterization of component assembly and optimization of individual steps, sensor ability to discriminate between the two proteases is confirmed along with effects from joint interactions where potential for cross‐talk is highest. Processing multiple bits of information for a sensing outcome provides more confidence than relying on a single change especially for the discrimination between different targets. Coupling other substrates to DNA that respond similarly could help target other types of enzymes.     

High‐Performance pH‐Switchable Supramolecular Thermosets via Cation–π Interactions

Supramolecular chemistry has provided versatile and affordable solutions for the design of intelligent soft materials, but it cannot be applied in stiff materials. This paper describes a new concept for the design of high‐performance supramolecular thermosets by using the noncovalent cation–π interaction as cross‐linking. These supramolecular thermosets are a class of infusible and insoluble stiff polymers having excellent mechanical properties even at temperatures exceeding 300 °C. The cation–π interaction can be locally and reversibly installed and removed by aqueous treatments at high or low pH, respectively. Local manipulation of cross‐linking confers these thermosets with multiple stimuli‐responsive functions, such as recyclability, healability, adhesion, and nondestructive detection of cross‐linking and mechanical properties.     

Muscle‐Inspired Highly Anisotropic,Strong, Ion‐Conductive Hydrogels

Biological tissues generally exhibit excellent anisotropic mechanical properties owing to their well‐developed microstructures. Inspired by the aligned structure in muscles, a highly anisotropic, strong, and conductive wood hydrogel is developed by fully utilizing the high–tensile strength of natural wood, and the flexibility and high‐water content of hydrogels. The wood hydrogel exhibits a high–tensile strength of 36 MPa along the longitudinal direction due to the strong bonding and cross‐linking between the aligned cellulose nanofibers (CNFs) in wood and the polyacrylamide (PAM) polymer. The wood hydrogel is 5 times and 500 times stronger than the bacterial cellulose hydrogels (7.2 MPa) and the unmodified PAM hydrogel (0.072 MPa), respectively, representing one of the strongest hydrogels ever reported. Due to the negatively charged aligned CNF, the wood hydrogel is also an excellent nanofluidic conduit with an ionic conductivity of up to 5 × 10^?4 S cm^–1 at low concentrations for highly selective ion transport, akin to biological muscle tissue. The work offers a promising strategy to fabricate a wide variety of strong, anisotropic, flexible, and ionically conductive wood‐based hydrogels for potential biomaterials and nanofluidic applications.     

Injectable and Radiopaque Liquid Metal/Calcium Alginate Hydrogels for Endovascular Embolization and Tumor Embolotherapy

Improved endovascular embolization can contribute to assistant treatment for patients. However, many traditional embolic materials, such as metal microcoils or liquid embolic agents, are associated with limitations of coil migration or recanalization. Herein, as the first trial, an injectable and radiopaque liquid metal/calcium alginate (LM/CA) hydrogel is introduced and fabricated as a candidate for endovascular embolization and tumor embolotherapy through developing LM droplets as radiopaque units into biocompatible calcium alginate cross‐linked network. The adoption of LM droplets makes hydrogels radiopaque under X‐ray and CT scan, which significantly facilitates the tracking of material location during surgical vascular operation. In addition, in vitro and in vivo experiments prove that such smart hydrogel could convert from liquid to solid rapidly via cross‐linking, showing pretty flexible and controllable functions. Benefiting from these properties, the hydrogel can be performed in blood vessels through injection via syringes and then served as an embolic material for endovascular embolization procedures. In vivo experiments demonstrate that such hydrogels can occlude arteries and block blood flow until they ultimately lead to ischemic necrosis of tumors and partial healthy tissues. Overall, the present LM/CA hydrogels are promising to be developed as new generation embolic materials for future tumor embolotherapy.     

Solution‐Controlled Conformational Switching of an Anchored Wireframe DNA Nanostructure

Self‐assembled DNA origami nanostructures have a high degree of programmable spatial control that enables nanoscale molecular manipulations. A surface‐tethered, flexible DNA nanomesh is reported herein which spontaneously undergoes sharp, dynamic conformational transitions under physiological conditions. The transitions occur between two major macrostates: a spread state dominated by the interaction between the DNA nanomesh and the BSA/streptavidin surface and a surface‐avoiding contracted state. Due to a slow rate of stochastic transition events on the order of tens of minutes, the dynamic conformations of individual structures can be detected in situ with DNA PAINT microscopy. Time series localization data with automated imaging processing to track the dynamically changing radial distribution of structural markers are combined. Conformational distributions of tethered structures in buffers with elevated pH exhibit a calcium‐dependent domination of the spread state. This is likely due to electrostatic interactions between the structures and immobilized surface proteins (BSA and streptavidin). An interaction is observed in solution under similar buffer conditions with dynamic light scattering. Exchanging between solutions that promote one or the other state leads to in situ sample‐wide transitions between the states. The technique herein can be a useful tool for dynamic control and observation of nanoscale interactions and spatial relationships.