Assembly Of Hydrogels Research Articles

Multifunctional Network-Shaped Hydrogel Assemblies.

The previously reported hydrogel assemblies carry bulky shapes, for which the unitary assembly form immensely restricted further applications. Yet there are abundant natural examples of network-shaped assemblies constructed by animals, of which it is brought up inspirations for constructing hydrogel assemblies. Herein, the network-shaped assemblies with diverse functions are reported. The precursor solutions are prepared by acrylamide, 4-acryloylmorpholine, choline chloride, and photo-initiators. By means of three dimension (3D) printing, the hydrogel networks are formed driven by hydrogen bonds, and then the prepared jagged hydrogel blocks are assembled into network-shaped hydrogel assembly NSHA-0 by weaving method. Benefitting from the modifiability of hydrogels, hydrogel assemblies with different properties and functions are prepared by incorporating different functional monomers including ion pair acryloyloxyethyl trimethyl ammonium chloride, and sodium p-styrenesulfonate, N-isopropylacrylamide, spiropyran derivative and tetra-(4-pyridylphenyl)ethylene. The incorporation of these monomers bestowed the assemblies self-healing ability, thermo-responsiveness, ultraviolet-responsiveness as well as acid-responsiveness respectively.

Supramolecular oligo-thymine/melamine nanobridge-driven macroscopic engineering: reprogrammable hydrogels for multi-stimuli responsive architectures

The arbitrary, modular, and reprogrammable engineering of macroscopic objects by DNA interactions remains a challenge, despite the well-established use of DNA to drive constructs at nano/micro-scale. Moreover, achieving adaptive responsiveness in assembled architectures under dynamic environmental triggers has yet to be realized. In this study, we introduce the association of oligo-thymine strands (polyT) and melamine (MA), as a low-molecular-weight cofactor, into a supramolecular DNA duplex, termed polyT-MA nanobridge. This unique nanostructure exhibits responsiveness to five external stimuli, including temperature, DNA strand, small molecule, acidic pH, and alkaline pH. The polyT-MA nanobridge is developed as the dynamic crosslinking elements for constructing multi-stimuli responsive DNA hydrogels, which exhibit physiochemical properties changes (e.g., rigidity, thermal stability) and hydrogel-to-liquid phase transitions in response to the five external triggers. Notably, the assembly of macroscopic hydrogel blocks at millimeter scale (cubes in 5 × 5 × 5 mm dimensions) into diverse architectures, e.g., linear type, cross, P-shape, T-shape, or heteromorphy, is achieved by using the non-canonical supramolecular polyT-MA nanobridges. Sequential, dynamic, and selective disassembly of polyT-MA bridged hydrogel constructs is triggered by multiple external stimuli and the rearrangement of these separated individual cubes into other architectures in LEGO styles is presented. This study provides insights into the development of advanced materials and devices with reconfigurable architectures and functionalities for intelligent nanoengineering applications.

Biosynthesis of a Functional Fragment of Human Collagen II in Pichia pastoris.

Collagen II (COL2) is the major component of cartilage tissue and is widely applied in pharmaceuticals, food, and cosmetics. In this study, COL fragments were extracted from human COL2 for secretory expression in Pichia pastoris. Three variants were successfully secreted by shake flask cultivation with a yield of 73.3-100.7 mg/L. The three COL2 variants were shown to self-assemble into triple-helix at 4 °C and capable of forming higher order assembly of nanofiber and hydrogel. The bioactivities of the COL2 variants were validated, showing that sample 205 exhibited the best performance for inducing fibroblast differentiation and cell migration. Meanwhile, sample 205 and 209 exhibited higher capacity for inducing in vitro blood clotting than commercial mouse COL1. To overexpress sample 205, the expression cassettes were constructed with different promoters and signal peptides, and the fermentation condition was optimized, obtaining a yield of 172 mg/L for sample 205. Fed-batch fermentation was carried out using a 5 L bioreactor, and the secretory protease Pep4 was knocked out to avoid sample degradation, finally obtaining a yield of 3.04 g/L. Here, a bioactive COL2 fragment was successfully identified and can be overexpressed in P. pastoris; the variant may become a potential biomaterial for skin care.

Harnessing true capacitive activity of nitrogen-doped MXene through hydrogel assembly and theoretical understanding of the role of dopant sites

Heteroatom nitrogen (N) doping in MXene can significantly push its energy storage metric. However, translating the intrinsic improvement of individual sheets into macroscopic electrodes is challenging due to the blockage of dopant sites by restacking. Here, we report the development of restack-controlled N-doped MXene hydrogel through speedy interfacial assembly methods to keep the dopant sites electrochemically accessible. Application of a small voltage between two zinc plates in an aqueous dispersion of N-doped MXene leads to the rapid development of doped hydrogel over the positive zinc plate via electrophoretic drag and linking by interfacial released zinc ions. As-developed hydrogels having continuous porosity and quasi-oriented sheet arrangement preserve ion transporting channels, thus allowing the surface dopant sites to participate in the supercapacitive energy storage actively. N-doped hydrogel displays a high capacitance of 488 F g−1 at 5 mV s−1 much higher as compared to compact film. The N-doped MXene hydrogels display excellent rate performance with retention over 88 % at 1000 mV s−1 and cyclic stability of 87 % over 10000 cycles. The detailed density functional theory (DFT) calculation reveals a major pseudocapacitive contribution from the surface adsorption and functional group substitution type N dopant sites as compared to another dopant site, namely, lattice substitution.

Long-Acting Antibacterial Hydrogels Constructed by Interface-Induced Directional Assembly.

Self-assembled supermolecular hydrogels of therapeutic agents without structural modification are of great significance in biomedical applications. Nevertheless, the complex conformations and elusive interactions of therapeutic molecules limit the controlled assembly of hydrogels. Molecules at the interface might have different arrangements and assemblies compared to those in bulk aqueous solution, which could potentially alter the selectivity of supramolecular polymorphs. However, this effect is still not well understood. Here, we demonstrate the interface-induced self-assembly of fibers for hydrogels, which is distinct from the spherical aggregates in the bulk aqueous solution, using cephradine (CEP) as a model compound. This phenomenon is caused by the packing of anisotropic molecules at the interface, and it can be applied to control the supramolecular polymorphism for the direct self-assembly of hydrogels of therapeutic agents. The interface-induced hydrogel exhibits a high degree of adjustable release and a long-acting bactericidal effect.

A Universal Strategy for Constructing Hydrogel Assemblies Enabled by PAA Hydrogel Adhesive.

Hydrogel is a significant type of building block for constructing macroscopic assemblies, the construction of which usually entails the incorporation of supramolecular groups. However, supramolecular group recognition is specific and only suitable for assembling two particular modified hydrogels, but not a versatile strategy. Herein, a universal strategy without modification process is proposed using polyacrylic acid (PAA) hydrogel as the adhesive layer to assemble different kinds of hydrogels. Furthermore, hydrogel assemblies with various shapes and multi-stimuli responsiveness are constructed by assembling different stimuli-responsive hydrogels with PAA hydrogel. Therefore, hydrogel assemblies are able to complete bending motions upon applying corresponding stimuli. This strategy provides a universal approach for constructing hydrogel assemblies, and also shows the potential for developing soft robots with versatile functions.

Photocontrolled polymer adhesives facilitate the assembly of hydrogels for soft robotics

Photocontrolled polymer adhesives facilitate the assembly of hydrogels for soft robotics

Distance-Based Visual miRNA Biosensor with Strand Displacement Amplification-Mediated DNA Hydrogel Assembly

Distance-Based Visual miRNA Biosensor with Strand Displacement Amplification-Mediated DNA Hydrogel Assembly

Novel Natural Polymer‐Based Hydrogel Patches with Janus Asymmetric‐Adhesion for Emergency Hemostasis and Wound Healing

AbstractAn asymmetrical wound dressing functions akin to human skin by serving as a protective barrier between a wound and its immediate environment. However, significant challenges persist concerning the robust adhesion and asymmetrical adhesion properties of hydrogels, particularly when applied in emergency hemostasis and wound healing contexts. Herein, the study has successfully synthesized hydrogel patches with Janus asymmetric‐adhesion, denoted as HGO‐C, exclusively comprised of natural polymers. This achievement is realized through the assembly of adhesive hydrogel (HGO) and non‐adhesive hydrogel (CGC), thereby amalgamating their distinct functionalities. The non‐adhesive hydrogel component served as a physical shield and safeguarding the wound against contamination, while the adhesive hydrogel, when in contacted with the wound surface, firmly adhered to it, swiftly arresting bleeding and facilitating wound healing. Cytocompatibility tests, hemolysis tests, antibacterial assays, and coagulation assays demonstrated excellent biocompatibility, antibacterial, and hemostatic properties of HGO‐C. Finally, the in vivo experiments, including a liver hemorrhage assay and a wound healing assay, unequivocally showed the rapid hemostatic and enhanced wound healing capabilities of HGO‐C. Consequently, these distinctive hydrogel patches, derived from natural polymers and characterized by their asymmetric adhesion properties, may have great potential for real‐life usage in clinical patients.

Reconfiguring hydrogel assemblies using a photocontrolled metallopolymer adhesive for multiple customized functions

Stimuli-responsive hydrogels with programmable shape changes are promising materials for soft robots, four-dimensional printing, biomedical devices and artificial intelligence systems. However, these applications require the fabrication of hydrogels with complex, heterogeneous and reconfigurable structures and customizable functions. Here we report the fabrication of hydrogel assemblies with these features by reversibly gluing hydrogel units using a photocontrolled metallopolymer adhesive. The metallopolymer adhesive firmly attached individual hydrogel units via metal–ligand coordination and polymer chain entanglement. Hydrogel assemblies containing temperature- and pH-responsive hydrogel units showed controllable shape changes and motions in response to these external stimuli. To reconfigure their structures, the hydrogel assemblies were disassembled by irradiating the metallopolymer adhesive with light; the disassembled hydrogel units were then reassembled using the metallopolymer adhesive with heating. The shape change and structure reconfiguration abilities allow us to reprogramme the functions of hydrogel assemblies. The development of reconfigurable hydrogel assemblies using reversible adhesives provides a strategy for designing intelligent materials and soft robots with user-defined functions.

Tilapia-Derived Granular Hydrogel as a 3D Scaffold Promoting Rapid Wound Healing.

The skin, a crucial organ that protects the body, is vulnerable to external damage. Traditional tissue regeneration methods, including bulk hydrogels, aim to facilitate wound healing by interacting with host cells and providing a conducive environment. However, the nanoscale porosity of conventional hydrogels limits cell penetration and tissue regeneration. To overcome this, hydrogels composed of microgels have emerged as promising alternatives. In this study, we propose a granular hydrogel using decellularized tilapia skin. The tilapia skin-based microgels are cost-effective, immune-friendly, and have a high collagen content. Microgels based on the decellularized extracellular matrix of tilapia were successfully fabricated by using microfluidics. Through the assembly of these microgels using adhesive hyaluronic acid-catechol, the resulting 3D granular hydrogel scaffold facilitated enhanced cell growth, accelerated cell differentiation, and successful healing of full-thickness wounds in a mouse model. This study reveals the potential of tilapia skin-based granular hydrogel assembly in wound healing, overcoming conventional hydrogel limits.

Encoded Magnetization for Programmable Soft Miniature Machines by Covalent Assembly of Modularly Coupled Microgels

AbstractThe bottom‐up assembly of premagnetized microgels offers remarkable flexibility in programmability, material selection, and complexity for fabricating programmable magnetic soft machines with discrete 3D magnetization profiles. However, the current microgel bonding encounters challenges due to the utilization of adhesives for attachment, biocompatibility for in vivo applications, and the need for elevated temperature for self‐healing materials. Here, an approach is presented that leverages N‐hydroxysuccinimide ester‐activated sodium alginate (SA‐NHS) and chitosan (CS) to form modular gels for on‐demand assembly through covalent bonding, yielding a tough and durable interface. Photolithography‐based patterning and magnetic maneuverability are imparted by introducing poly(ethylene glycol) diacrylate and ferromagnetic particles into SA‐NHS or CS, resulting in the creation of modularized magnetic or nonmagnetic microgels. Different magnetization profiles of the modular microgel can be achieved by magnetizing the ferromagnetic particles inside the microgel. To prove the versatility of the proposed method, several programmable magnetic soft machines are developed for various application scenarios, including heterogeneous cell‐laden hydrogel assemblies, multisegmented magnetic soft swimmers, programmable magnetic switches for electric circuits, and magnetically triggered release from drug‐encapsulated magnetic capsules. This proposed approach holds great potential to engineer highly intricate and hierarchical architectures, enhancing the functionality, versatility, and adaptability of programmable soft machines.

Advances in NIR-Responsive Natural Macromolecular Hydrogel Assembly Drugs for Cancer Treatment.

Cancer is a serious disease with an abnormal proliferation of organ tissues; it is characterized by malignant infiltration and growth that affects human life. Traditional cancer therapies such as resection, radiotherapy and chemotherapy have a low cure rate and often cause irreversible damage to the body. In recent years, since the traditional treatment of cancer is still very far from perfect, researchers have begun to focus on non-invasive near-infrared (NIR)-responsive natural macromolecular hydrogel assembly drugs (NIR-NMHADs). Due to their unique biocompatibility and extremely high drug encapsulation, coupling with the spatiotemporal controllability of NIR, synergistic photothermal therapy (PTT), photothermal therapy (PDT), chemotherapy (CT) and immunotherapy (IT) has created excellent effects and good prospects for cancer treatment. In addition, some emerging bioengineering technologies can also improve the effectiveness of drug delivery systems. This review will discuss the properties of NIR light, the NIR-functional hydrogels commonly used in current research, the cancer therapy corresponding to the materials encapsulated in them and the bioengineering technology that can assist drug delivery systems. The review provides a constructive reference for the optimization of NIR-NMHAD experimental ideas and its application to human body.

Facile Physicochemical Reprogramming of PEG-Dithiolane Microgels.

Granular biomaterials have found widespread applications in tissue engineering, in part because of their inherent porosity, tunable properties, injectability, and 3D printability. However, the assembly of granular hydrogels typically relies on spherical microparticles and more complex particle geometries have been limited in scope, often requiring templating of individual microgels by microfluidics or in-mold polymerization. Here, we use dithiolane-functionalized synthetic macromolecules to fabricate photopolymerized microgels via batch emulsion, and then harness the dynamic disulfide crosslinks to rearrange the network. Through unconfined compression between parallel plates in the presence of photoinitiated radicals, we transform the isotropic microgels are transformed into disks. Characterizing this process, we find that the areas of the microgel surface in contact with the compressive plates are flattened while the curvature of the uncompressed microgel boundaries increases. When cultured with C2C12 myoblasts, cells localize to regions of higher curvature on the disk-shaped microgel surfaces. This altered localization affects cell-driven construction of large supraparticle scaffold assemblies, with spherical particles assembling without specific junction structure while disk microgels assemble preferentially on their curved surfaces. These results represent a unique spatiotemporal process for rapid reprocessing of microgels into anisotropic shapes, providing new opportunities to study shape-driven mechanobiological cues during and after granular hydrogel assembly.

Mechanistic Analysis and Control of Electro‐Fabrication with Soft Matter: Polysaccharide Self‐Assembly with Electrochemically Produced Metal Ions

AbstractElectro‐fabrication is an emerging additive manufacturing approach that includes a variety of mechanisms and crosslinking chemistries to induce the self‐assembly‐ of soft matter. Within electro‐fabrication techniques, anodic electro‐fabrication is of great interest, because it can use the electrode as a sacrificial source of metal ions for the controlled formation of chelated hydrogels. However, it remains challenging to understand how the various solution conditions (e.g., buffer capacity, ligands) and imposed voltages must be controlled to achieve the chelation and sol‐gel transition. Herein, a comprehensive thermodynamics‐based framework is built to guide the selection of conditions for the self ‐assembly of polysaccharide hydrogels by crosslinking with transition metal ions generated via corrosion. This methodology is demonstrated through real‐time spectro‐electrochemical monitoring and employed for the electro‐fabrication of chitosan hydrogels chelated with Au3+, Ag+, Cu2+, and Pd2+, and alginate hydrogels chelated with Cu2+. The presented guidelines are intended to extend the capabilities of the controlled fabrication of assemblies crosslinked with metal ions, opening new horizons for unprecedented materials design with precisely tailored structures and functions.

Visible and selective gel assembly via covalent click chemistry

AbstractThis study marks the birth of visible and selective click covalent assembly. It is achieved by amplifying orthogonal alkyne−azide click chemistry through interfacial multisite interactions between azide/alkyne functionalized polymer hydrogels. Macroscopic assembly of hydrogels via host−guest chemistry or noncovalent interactions such as electrostatic interactions has been reported. Unlike macroscopic supramolecular assembly, here we report visible and selective “click” covalent assembly of hydrogels at the macroscale. LEGO‐like hydrogels modified with alkyne and azide groups, respectively, can click together via the formation of covalent bonds. Monomer concentration‐dependent assembly and selective covalent assembly have been studied. Notably, macroscopic gel assembly clearly elucidates click preferences and component selectivity not observed in the solution reactions of competing monomers.

Solvent triggering assembly of self-supported MXene hydrogel for high performance asymmetric supercapacitors

Constructing 3D porous structure of MXene (Ti3C2Tx) is an efficient approach to prevent nanosheets restacking and realize prominent electrochemical functionality. However, the assembly of self-supported 3D Ti3C2Tx architecture is difficult due to the inherent rigidity and superior hydrophilicity of Ti3C2Tx nanosheets. Herein, a solvent-triggering gelation strategy is developed using polar aprotic N,N-Dimethylformamide and polar protic H2O as co-solvent to enhance hydrogen bonding and Ti-O-Ti covalent bonding between Ti3C2Tx nanosheets. Thereby, self-supported Ti3C2Tx hydrogel (MH12/5:5) in absence of any crosslinkers or substrates has been successfully fabricated. The MH12/5:5 hydrogel exhibits excellent specific capacitance of 384.4 F g1 and superb rate capability of 61 % in a broad current density range of 1–100 A g−1. Asymmetric supercapacitor has been assembled using MH12/5:5 hydrogel as negative electrode and a polyaniline hydrogel as positive electrode, which presents high energy density of 21.2 Wh kg−1. This solvent-triggering gelation strategy points toward a promising direction to develop self-supported MXene hydrogels for high performance energy storage devices.

Cascade Reaction of Thiol-Disulfide Exchange Potentiates Rapid Fabrication of Polymer Hydrogels.

We report a rapid cross-linking strategy for the fabrication of polymer hydrogels based on a thiol-disulfide cascade reaction. Specifically, thiolated polymers (e.g., poly(ethylene glycol), hyaluronic acid, sodium alginate, poly(acrylic acid), and poly(methylacrylic acid)) can be cross-linked via the trigger of Ellman's reagent, resulting in the rapid formation of hydrogels over 20-fold faster than that via the oxidation in air. The gelation kinetics of hydrogels can be tuned by varying the polymer concentration and the molar ratio of Ellman's reagent and free thiols. The obtained hydrogels can be further functionalized with functional moieties (e.g., targeting ligands) for the selective adhesion of cells. This approach is applicable to various natural and synthetic polymers for the assembly of hydrogels with a minimized gelation time, which is promising for various biological applications.

Electrochemically Driven Assembly of Chitosan Hydrogels on PEDOT Surfaces

AbstractHydrogels are attracting interest in the field of bioelectronics due to their ability to serve as coatings on electrodes, improving the electrochemical interface, addressing the mechanical mismatch, and offering potential for localized drug or cell delivery. Challenges persist in integrating hydrogels with electrodes typically composed of metals and/or organic semiconductors. Here, an electrochemically driven method is introduced for direct growth of chitosan hydrogels onto poly(3,4‐ethylenedioxythiophene) (PEDOT) surfaces. The growth of ionic gelation chitosan is triggered by electrical release of a specific dopant, tripolyphosphate (TPP), from PEDOT. As a result, chitosan hydrogels grow directly from the PEDOT surface and firmly attach to it. Although this process temporarily reduces PEDOT to the benzoid structure, its unique electroactivity allows for reversible conversion to the quinoid structure after chitosan hydrogel assembly. Once assembled, the chitosan hydrogel coating can be further functionalized. The introduction of covalent cross‐links and incorporation of additional interpenetrating polymer networks (IPNs) are explored. Electrochemical characterization reveals that an interface with favorable properties is formed between PEDOT and ionic‐covalent chitosan, functionalized with a PEDOT IPN. The electroactivity of the proposed method surpasses any other PEDOT/chitosan system reported in the literature. These results underscore the potential of this material for bioelectronics applications.

Bioinspired Supramolecular Hydrogel from Design to Applications.

Nature offers a wealth of opportunities to solve scientific and technological issues based on its unique structures and function. The dynamic non-covalent interaction is considered to be the main base of living functions of creatures including humans, animals, and plants. Supramolecular hydrogels formed by non-covalent bonding interactions has become a unique platform for constructing promising materials for medicine, energy, electronic, and biological substitute. In this review, the self-assemble principle of supramolecular hydrogels is summarized. Next, the stimulation of external environment that triggers the assembly or disassembly of supramolecular hydrogels are recapitulated, including temperature, mechanics, light, pH, ions, etc. The main applications of bioinspired supramolecular hydrogels in terms of bionic objects including humans, animals, and plants are also described. Although so many efforts are done for revealing the synergized mechanism of the function and non-covalent interactions on the supramolecular hydrogel, the complexity and variability between stimulus and non-covalent bonding in the supramolecular system still require impeccable theories. As an outlook, the bioinspired supramolecular hydrogel is just beginning to exhibit its great potential in human life, offering significant opportunities in drug delivery and screening, implantable devices and substitutions, tissue engineering, micro-fluidic devices, and biosensors.