Hybrid Supramolecular Hydrogel Research Articles

Supramolecular hydrogels mediated by cucurbit[6]uril-modified Fe3O4 with self-healing, photothermal responsiveness and stretchability for flexible electronics

The development of supramolecular hydrogels with multifunction is in high demand. In this work, Fe3O4 hybrid supramolecular hydrogels were fabricated via dynamic host–guest interactions between the host molecule CB[6] and guest units. The “supramolecular crosslinker” formed by CB[6]-modified Fe3O4 (Fe3O4@CB[6]) nanoparticles, was used to generate a 3D network of supramolecular hydrogels. Results indicate that the tensile stress of the sample is 0.31 MPa, and the self-healing efficiency of the supramolecular hydrogels at room temperature is nearly 100% (fracture strain) after 48 h. The hydrogels exhibited a self-healing property without a loss of conductivity. Furthermore, these supramolecular hydrogels were used to detect the bending of human fingers and knees. The hybrid supramolecular hydrogels with photothermal responsiveness, self-healing, injectability, stretchability, conductive ability and biocompatibility, can find applications in flexible electronics.

Gallic acid-doped multifunctional hybrid hydrogel for antioxidant and antibacterial studies

The design and fabrication of multifunctional hybrid hydrogels for various biomedical applications have sparked tremendous scientific interest and still remain a formidable challenge. Here, we report the construction of a multifunctional supramolecular hybrid hydrogel through a facile preparation route by co-assembling the L-phenylalanine-derivative (LPF) gelator with agarose (AG) and gallic acid (GA). The experimental analysis demonstrates that the components of hybrid hydrogel co-assembled to form a cross-linked interpenetrating network that is mainly formed through non-covalent interactions, thereby resulting in remarkable enhancement in rheological properties with an elastic modulus (G′) of 12715 Pa. Due to the inherent antimicrobial property of GA, this hybrid hydrogel exhibited antibacterial activities against both Gram-negative (Pseudomonas aeruginosa, Escherichia coli) and Gram-positive (Staphylococcus aureus) bacterial cells. Furthermore, the presence of GA enabled hybrid hydrogels to offer efficient antioxidant properties by scavenging free radicals such as DPPH· and ABTS·+. The cell adhesion, proliferation, and spreading behavior of L929 cells were significantly improved on the hybrid hydrogel substrate. These experimental findings suggest that this high-performance hybrid hydrogel possessing antibacterial, antioxidant, and biocompatible properties, opens new avenues for extensive applications in the biomedical field.

Impact of Molecular Dynamics of Polyrotaxanes on Chondrocytes in Double-Network Supramolecular Hydrogels under Physiological Thermomechanical Stimulation.

Hyaline cartilage, a soft tissue enriched with a dynamic extracellular matrix, manifests as a supramolecular system within load-bearing joints. At the same time, the challenge of cartilage repair through tissue engineering lies in replicating intricate cellular-matrix interactions. This study attempts to investigate chondrocyte responses within double-network supramolecular hybrid hydrogels tailored to mimic the dynamic molecular nature of hyaline cartilage. To this end, we infused noncovalent host-guest polyrotaxanes, by blending α-cyclodextrins as host molecules and polyethylene glycol as guests, into a gelatin-based covalent matrix, thereby enhancing its dynamic characteristics. Subsequently, chondrocytes were seeded into these hydrogels to systematically probe the effects of two concentrations of the introduced polyrotaxanes (instilling different levels of supramolecular dynamism in the hydrogel systems) on the cellular responsiveness. Our findings unveiled an augmented level of cellular mechanosensitivity for supramolecular hydrogels compared to pure covalent-based systems. This is demonstrated by an increased mRNA expression of ion channels (TREK1, TRPV4, and PIEZO1), signaling molecules (SOX9) and matrix-remodeling enzymes (LOXL2). Such outcomes were further elevated upon external application of biomimetic thermomechanical loading, which brought a stark increase in the accumulation of sulfated glycosaminoglycans and collagen. Overall, we found that matrix adaptability plays a pivotal role in modulating chondrocyte responses within double-network supramolecular hydrogels. These findings hold the potential for advancing cartilage engineering within load-bearing joints.

Versatile Graphene Oxide Hybrid Supramolecular Hydrogel Driven by Host–Guest Interaction Showing Excellent Mechanical and Sensing Properties and Photothermal Responsiveness

Versatile Graphene Oxide Hybrid Supramolecular Hydrogel Driven by Host–Guest Interaction Showing Excellent Mechanical and Sensing Properties and Photothermal Responsiveness

Hybrid cross-linked sodium carboxymethyl starch/polyacrylamide flexible sensing hydrogels with adhesion, antimicrobial properties and multiple responses

Ionic hydrogels used as ideal and flexible strain sensor materials should have excellent mechanical, adhesive and antimicrobial properties. However, it is challenging to achieve these multifunctional requirements simultaneously. Herein, we designed and prepared a multifunctional ionic hydrogel with a multi-length tentacle bentonite backbone to initiate the free radical polymerization of acrylic acid bentonite (AABT) and acrylamide (AAm). The interactions of covalent cross-linking, hydrogen bonding cross-linking, charge interactions and physical entanglement between hybrid polyacrylamide-AABT (PAAm-AABT), sodium carboxymethyl starch (SCMS) and PAAm form an multi-in-one hybrid supramolecular network hydrogel (CABZ). This CABZ ion-conductive hydrogel is capable of detecting weak deformation with a detection limit of 1 % strain, high tensile properties of 995 %, excellent strength of 254.5 kPa, fast response (≈0.21 s), high sensitivity of 0.86 and high conductivity of 0.37 S/m. In addition, this CABZ ion-conductive hydrogel has impressive adhesion properties with shear adhesion strength up to 50.78 kPa and broad-spectrum antibacterial properties achieved by AABT-loaded ZnO nanoparticles. Through special AABT hybrid cross-linking, the CABZ ion-conductive hydrogel achieves stable mechanical properties, highly sensitive signal response and antimicrobial properties, which will make it a good choice for flexible wearable sensor materials.

Supramolecular hybrid hydrogels as rapidly on-demand dissoluble, self-healing, and biocompatible burn dressings.

Despite decades of efforts, state-of-the-art synthetic burn dressings to treat partial-thickness burns are still far from ideal. Current dressings adhere to the wound and necessitate debridement. This work describes the first "supramolecular hybrid hydrogel (SHH)" burn dressing that is biocompatible, self-healable, and on-demand dissoluble for easy and trauma-free removal, prepared by a simple, fast, and scalable method. These SHHs leverage the interactions of a custom-designed cationic copolymer via host-guest chemistry with cucurbit[7]uril and electrostatic interactions with clay nanosheets coated with an anionic polymer to achieve enhanced mechanical properties and fast on-demand dissolution. The SHHs show high mechanical strength (>50kPa), self-heal rapidly in ∼1min, and dissolve quickly (4-6min) using an amantadine hydrochloride (AH) solution that breaks the supramolecular interactions in the SHHs. Neither the SHHs nor the AH solution has any adverse effects on human dermal fibroblasts or epidermal keratinocytes in vitro. The SHHs also do not elicit any significant cytokine response in vitro. Furthermore, in vivo murine experiments show no immune or inflammatory cell infiltration in the subcutaneous tissue and no change in circulatory cytokines compared to sham controls. Thus, these SHHs present excellent burn dressing candidates to reduce the time of pain and time associated with dressing changes.

An eco-friendly photo-responsive hyaluronic acid-based supramolecular polysaccharide hybrid hydrogels for plant growth regulation and heavy metal ions adsorption

Agrochemicals are widely used in agricultural production, but they may cause agrochemicals residues and environmental pollution. Polysaccharide-based materials have emerged as a promising biopolymer carrier for agrochemicals delivery. Herein, an eco-friendly, photo-responsive supramolecular polysaccharide hybrid hydrogels (HA-AAP-Guano-CD@LP) was constructed from arylazopyrazole-modified hyaluronic acid (HA-AAP), guanidinium functionalized β-cyclodextrin (Guano-CD), and laponite clay (LP) via synergistic host-guest and electrostatic interactions, which could realize the controlled release of plant growth regulators such as naphthalene acetic acid (NAA) and gibberellin (GA) and promote the growth of Chinese cabbage and alfalfa. More interestingly, after releasing the cargo, the hydrogels could be used to capture heavy metal ions via strong complexation between the ions and carboxyl groups. This polysaccharide-based supramolecular hybrid hydrogels may provide a new strategy to realize the precision agriculture by the controlled delivery of plant growth regulators and synergetic adsorption of pollutants.

Injectable Supramolecular Hybrid Hydrogel Delivers IL-1β-Stimulated Exosomes to Target Neuroinflammation

Long-term neuroinflammation is a major barrier to neurological recovery after cerebral ischemia-reperfusion injury (CIRI). Here, a thermosensitive injectable supramolecular hybrid hydrogel is developed to sustainably deliver exosomes derived from interleukin-1β-stimulated bone marrow stromal cells (BMSCs) (βExos) with improved exosome production and anti-inflammatory capacity for neuroinflammation inhibition and neurological recovery. The supramolecular hydrogel displays self-healing and injectable features, along with high biocompatibility and tissue-like softness. The βExos effectively reduce the lipopolysaccharide-induced inflammatory responses in the immortalized mouse microglia (BV2) cell line, and the in situ formed hydrogel improves the exosome retention in the ischemic core area. More remarkably, in the middle cerebral artery occlusion in vivo model, glial scar formation and neuronal loss are significantly reduced by regulating neuroinflammation using the released βExos. Therefore, the combination of interleukin-1β-stimulated exosomes with injectable supramolecular hydrogel provides an appealing strategy for treating central nervous system diseases.

Graphene oxide supramolecular hybrid hydrogels based on host−guest assembled electrostatic cross-linker

Non-covalent self-assembly of multi-components is a promising strategy for constructing supramolecular hydrogels. However, it remains challenging to achieve the multi-responsiveness to external stimuli for supramolecular hydrogels through a low-molecular-weight hydrogelator. Herein, we report a host−guest complex as low-molecular-weight hydrogelator for constructing graphene oxide (GO)-based supramolecular hybrid hydrogels. A 1:2 homoternary complex (CB[8]·NMAH+2) was formed through host−guest encapsulation of two protonated naphthalen-2-ylmethanamine (NMAH+) molecules in cucurbit[8]uril (CB[8]) host and worked as dynamically assembled electrostatic cross-linker in the presence of GO. The resulted GO hydrogels showed shear-thinning, self-healing properties, and were stimuli-responsive to pH and competing guests. The proposed concept of “assembled electrostatic cross-linker” (AEC) would be extended to construct other novel stimuli-responsive supramolecular materials.

Self-healing, injectable hydrogel based on dual dynamic covalent cross-linking against postoperative abdominal cavity adhesion

Clinically, increasing the peritoneal barrier is an effective adjunct to reducing postoperative peritoneal adhesion. This study presents a facile template for preparing a supramolecular hybrid hydrogel through dynamic covalent cross-linking between carboxymethyl chitosan (CMCS), 2-formylphenylboronic acid (2-FPBA), and quercetin (Que). The as-prepared complex CMCS/2-FPBA/Que (CFQ) hydrogel exhibited favorable antibacterial, anti-inflammatory, and antioxidant effects. A L929 cytotoxicity evaluation confirmed the favorable cytocompatibility of the CFQ hydrogel. The postoperative anti-adhesion ability of the CFQ hydrogel was further evaluated in rats with lateral wall defects and cecal abrasions. Compared with control groups, the tissue adhesion rate was significantly reduced by increasing the Que concentration in all the hydrogel-treated groups. Additionally, the sustained-release time of the C3F0.8Q0.08 hydrogel can exceed 14 days, which is highly desirable for clinical wound treatment. Statement of significancePostoperative adhesions are a very common postoperative complication that seriously affects the quality of life of patients. The currently commonly used methods for preventing adhesion mainly use degradable barrier materials for physical separation. In this study, we prepared a dual dynamic covalently cross-linked CFQ hydrogel, which is not only degradable and injectable, but also has multiple properties such as antibacterial, antioxidant and anti-inflammatory, which can effectively prevent postoperative adhesion and promote wound healing.

Dynamically Phototunable and Redox‐Responsive Hybrid Supramolecular Hydrogels for 3D Culture of Chondrocytes

AbstractDespite the promising application of chondrocyte encapsulated within supramolecular hydrogels to create cartilage‐like tissue, matching the degradation of supramolecular hydrogels with the cartilage matrix is challenging. Here, an appropriate phototunable and redox‐responsive hybrid supramolecular hydrogel are reported through the synergic crosslinking strategy, in which the gelatinization is driven by quadruple hydrogen bonding stabilized by thermo‐triggered hydrophobic interactions of branched hyaluronic acid supramolecular polymer and dynamic disulfide bond. The non‐covalently cross‐linked network endows hydrogel scaffold with unique self‐healed and shear‐thinning behavior, while the dynamic covalent network endows hydrogels with phototunable and redox‐responsive performance. The mechanical performance of hybridized supramolecular hydrogel can be modulated by controlling photoinitiators (PI) or thiol bonds (SH) content. Besides, the gene expression, protein secretion and histological staining results show that the chondrocytes encapsulated within the hybrid supramolecular hydrogels can maintain chondrocyte phenotype and facilitate the secretion of the cartilaginous specific matrix. Thus, the developed hybrid supramolecular hydrogels hold great potential in chondrocyte carrier for chondrogenesis.

Bioinspired Hydroxyapatite Coating Infiltrated with a Graphene Oxide Hybrid Supramolecular Hydrogel Orchestrates Antibacterial and Self-Lubricating Performance.

Hydroxyapatite (HA) bioceramic coating has been extensively applied for the modification of metallic implants to improve their biocompatibility and service life after implantation. Unfortunately, HA coating often suffers from high friction, severe wear, and bacterial invasion, which restrict its application in artificial joints. According to a bioinspired soft/hard combination strategy, a novel HA composite coating that is infiltrated with a vancomycin-loaded graphene oxide (GO) hybrid supramolecular hydrogel is developed via vacuum infiltration and a subsequent host-guest interaction-induced self-assembly process. The holes of textured HA ceramic coating act just like a "magic pocket", offering a stable container to form and store GO hybrid hydrogels and even to recycle wear debris as well. The drug-loaded hybrid hydrogels stored in textured HA coating possess a unique shear force and/or frictional heat triggered gel-sol transition and sustained drug release behavior, acting like the extrusion of synovial fluid during articular cartilage movement, leading to a remarkable self-lubrication, anti-wear performance, and promising antibacterial property against Staphylococcus aureus. The friction coefficient and wear rate of composite coating reduced by nearly five times and three orders of magnitude compared with textured HA coating, respectively, which benefited from the synergistic lubricate effect of cyclodextrin-based pseudopolyrotaxane supramolecular hydrogel and GO lubricants.

Injectable Tripeptide/Polymer Nanoparticles Supramolecular Hydrogel: A Candidate for the Treatment of Inflammatory Pathologies.

Supramolecular peptide-based hydrogels attract great attention in several fields, i.e., biomedicine, catalysis, energy, and materials chemistry, due to the noncovalent nature of the self-assembly and functional tunable properties defined by the amino acid sequence. In this work, we developed an injectable hybrid supramolecular hydrogel whose formation was triggered by electrostatic interactions between a phosphorylated tripeptide, Fmoc-FFpY (F: phenylalanine, pY: phosphorylated tyrosine), and cationic polymer nanoparticles made of vinylimidazole and ketoprofen (poly(HKT-co-VI) NPs). Hydrogel formation was assessed through inverted tube tests, and its fibrillary structure, around polymer NPs, was observed by transmission electron microscopy. Interestingly, peptide self-assembly yields the formation of nontwisted and twisted fibers, which could be attributed to β-sheets and α-helix structures, respectively, as characterized by circular dichroism and infrared spectroscopies. An increase of the elastic modulus of the Fmoc-FFpY/polymer NPs hybrid hydrogels was observed with peptide concentration as well as its injectability property, due to its shear thinning behavior and self-healing ability. After checking their stability under physiological conditions, the cytotoxicity properties of these hybrid hydrogels were evaluated in contact with human dermal fibroblasts (FBH) and murine macrophages (RAW 264.7). Finally, the Fmoc-FFpY/polymer NPs hybrid hydrogels exhibited a great nitric oxide reduction (∼67%) up to basal values of pro-inflammatory RAW 264.7 cells, thus confirming their excellent anti-inflammatory properties for the treatment of localized inflammatory pathologies.

Injectable Supramolecular Hybrid Hydrogel Delivers Interleukin-1β-Engineered Exosomes to Target Neuroinflammation in Cerebral Ischemia–Reperfusion Injury

Injectable Supramolecular Hybrid Hydrogel Delivers Interleukin-1β-Engineered Exosomes to Target Neuroinflammation in Cerebral Ischemia–Reperfusion Injury

Study the Effects of Supramolecular Interaction on Diffusion Kinetics in Hybrid Hydrogels of Zwitterionic Polymers and CNTs

AbstractHybrid hydrogel systems of functionalized multi‐walled carbon nanotubes and zwitterionic sulfobetaine copolymer of thermo‐responsible poly(N‐isopropylacrylamide) (PNIPAM) are synthesized and testified against different existing diffusion kinetic models in neutral, acidic, and basic environments. Evaluating these hybrid hydrogels’ swelling patterns at different pH indicates that changing pH can tailor the diffusion mechanism without affecting its diffusion kinetics. Interestingly, it is also revealed that diffusion kinetics and diffusion mechanisms are two distinct phenomena and can be viewed separately for supramolecular hybrid hydrogel systems. Elovich kinetic model best describes the swelling kinetics of only PNIPAM hydrogel. Diffusion kinetics of hybrid hydrogel of PNIPAM and CNTs or PNIPAM, zwitterion, and CNTs follow pseudo‐first‐order, while pseudo‐second‐order‐kinetics best describe hydrogels with only zwitterions. Evaluation of diffusion mechanism at different pH reveals that hydrogels with only zwitterions follow anomalous non‐Fickian diffusion, whereas only CNTs follow normal Fickian diffusion irrespective of pH; combining both systems leads to a dual‐stage diffusion mechanism at pH 2, which in turn reduces as the pH increases. These observations suggest that synergistic effects of supramolecular interactions can provide a novel property profile to hybrid hydrogels, requiring attention while designing such a system where diffusion is a decisive parameter.

Localized Enzyme-Assisted Self-Assembly in the Presence of Hyaluronic Acid for Hybrid Supramolecular Hydrogel Coating.

Hydrogel coating is highly suitable in biomaterial design. It provides biocompatibility and avoids protein adsorption leading to inflammation and rejection of implants. Moreover, hydrogels can be loaded with biologically active compounds. In this field, hyaluronic acid has been largely studied as an additional component since this polysaccharide is naturally present in extracellular matrix. Strategies to direct hydrogelation processes exclusively from the surface using a fully biocompatible approach are rare. Herein we have applied the concept of localized enzyme-assisted self-assembly to direct supramolecular hydrogels in the presence of HA. Based on electronic and fluorescent confocal microscopy, rheological measurements and cell culture investigations, this work highlights the following aspects: (i) the possibility to control the thickness of peptide-based hydrogels at the micrometer scale (18–41 µm) through the proportion of HA (2, 5 or 10 mg/mL); (ii) the structure of the self-assembled peptide nanofibrous network is affected by the growing amount of HA which induces the collapse of nanofibers leading to large assembled microstructures underpinning the supramolecular hydrogel matrix; (iii) this changing internal architecture induces a decrease of the elastic modulus from 2 to 0.2 kPa when concentration of HA is increasing; (iv) concomitantly, the presence of HA in supramolecular hydrogel coatings is suitable for cell viability and adhesion of NIH 3T3 fibroblasts.

The Testing Method of Graphene Oxide (GO) and NAA Ramification

Organic/inorganic supramolecular system has been obtained by graphene oxide grafting with a-cyclodextrins (a-CDs) and NAA ramification. Tourer transform infrared spectra (FTIR), thermogravimetric analyse (TGA), X-ray diffraction (XRD), differential scanning calorimetry (DSC), and X-ray photoelectron spectroscopy (XPS) were employed to identify the characters and morphology of the supramolecular structure. The features might make our supramolecular hybrid hydrogel a pretty candidate in a drug delivery system.

Supramolecular hydrogel-infiltrated ceramics composite coating with combined antibacterial and self-lubricating performance.

Inspired by the structure and dynamic weeping lubricating mechanism of articular cartilage, a novel composite coating composed of a textured Y2O3-stabilized ZrO2 (YSZ) ceramics reservoir and silver nanoparticles (AgNPs) hybrid supramolecular hydrogel was developed on the basis of a soft/hard combination strategy. The precursor solution including the poly(ethylene glycol) (PEG)-modified AgNPs and α-cyclodextrins (α-CDs) could be infiltrated deep into (50-60 μm) the pores of a textured YSZ ceramics substrate by a vacuum infiltration method, in situ forming a supramolecular hydrogel within the pores through host-guest inclusion between α-CDs and PEG chains distributed onto the surface of AgNPs. The AgNPs hybrid hydrogel showed thixotropic and thermoresponsive gel-sol transition behavior, low cytotoxicity, and excellent drug-loading capacity, as well as significant antibacterial properties. The textured YSZ ceramics not only provided a hard supporting skeleton and stable reservoir to protect the supramolecular hydrogel from destruction under load-bearing or shear condition, but also allowed retaining the stimuli-responsive gel-sol transition property and drug-release capability of the infiltrated hydrogel, endowing the composite coating with excellent antibacterial properties, and self-lubrication and wear-resistance performance. The composite coating in this work brings a new insight into the design of antibacterial and self-lubricating ceramic coatings for artificial joint applications.

A graphene hybrid supramolecular hydrogel with high stretchability, self-healable and photothermally responsive properties for wound healing.

Wound healing is a ubiquitous healthcare problem in clinical wound management. In this paper, the fabrication of a graphene hybrid supramolecular hydrogel (GS hydrogel) for wound dressing applications is demonstrated. The hydrogel is composed of two components, including N-acryloyl glycinamide (NAGA) as the scaffold and graphene as the photothermally responsive active site for photothermal therapy. Based on the multiple hydrogen bonds between the dual amide motifs in the side chain of N-acryloyl glycinamide, the hydrogel exhibits high tensile strength (≈1.7 MPa), good stretchability (≈400%) and self-recoverability. In addition, the GS hydrogel shows excellent antibacterial activity towards methicillin-resistant Staphylococcus aureus (MRSA), benefiting from the addition of graphene that possesses great photothermal transition activity (≈85%). Significantly, in vivo animal experiments also demonstrated that the GS hydrogel effectively accelerates the wound healing processes by eradicating microbes, promoting collagen deposition and angiogenesis. In summary, this GS hydrogel demonstrates excellent mechanical performance, photothermal antimicrobial activity, and promotes skin tissue regeneration, and so has great application potential as a promising wound dressing material in clinical use.

Self-Assembled Supramolecular Hybrid Hydrogels Based on Host-Guest Interaction: Formation and Application in 3D Cell Culture.

In recent decades, in vitro three-dimensional (3D) cell culture has been rapidly developed and widely used in many biomedical fields. Based on this background, a kind of self-assembled supramolecular hybrid hydrogel materials based on host-guest interaction of β-cyclodextrin (βCD) and adamantane (Ad) is designed for 3D cell culture. First, βCD is grafted to poly(methyl vinyl ether-alt-maleic acid) (PMM) to obtain the host polymers of βCD-grafted-PMM (PMM-βCD). Second, the guest polymers of poly(acrylamide-co-N-adamantyl acrylamide) (PAAm-Ad) are synthesized through free-radical copolymerization of acrylamide and N-adamantyl acrylamide. Finally, the self-assembled supramolecular hybrid hydrogels of PMM-βCD/PAAm-Ad are formed by simply mixing the aqueous solution of host and guest polymers with a total concentration of 3.3% (w/v) and a βCD/Ad molar ratio of 1:1. The main cross-linking interactions come from the host-guest interaction of βCD/Ad as well as hydrogen-bonding interaction of carboxyl/amide groups. The prepared hydrogels with good cytocompatibility have been successfully used as 3D cell culture scaffold for SKOV3, HUVEC, and L929 cells culture. Thus, this work provides a way and biomaterial for the preparation of a functionalized 3D cell culture scaffold, which lays an experimental and theoretical basis for cell follow-up research.