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In this paper, Biocompatible supramolecular hydrogels, composed of β-cyclodextrin-modified hyaluronic acid, pluronic F127, α-cyclodextrin and doxorubicin, were constructed, which can be employed for targeted delivery system. The chemical composition and rheological properties of the obtained hydrogels were fully characterised. Considering the controlled complexation between DOX and the hydrogel skeletons, the controlled release of hydrogel G[5, 10, 5] was investigated to exhibit a better pH- and temperature-controlled release behavior. The data of DOX release kinetic was fitted well with Higuchi and Korsmeyer-Peppas models. Moreover, the cellular toxicity experiments indicated that the hydrogel DOX@G[5, 10, 5] exhibited a similar anticancer ability in comparison with free DOX. Due to the hyaluronic acid-targeted effects, the cytotoxicity of the hydrogel DOX@G[5,10,5] to HepG2 cells was lower than that to SKOV-3 cells upon increasing the concentration. Therefore, these hydrogels may act as a potential prospect for the targeting release of anticancer drugs. [ABSTRACT FROM AUTHOR]

Polymeric supramolecular hydrogels (PSHs) leverage the thermodynamic and kinetic properties of non‐covalent interactions between polymer chains to govern their structural characteristics. As these materials are formed via endothermic or exothermic equilibria, their thermal response is challenging to control without drastically changing the nature of the chemistry used to join them. In this study, we introduce a novel class of PSHs utilizing the intercalation of double‐stranded DNA (dsDNA) as the primary dynamic non‐covalent interaction. The resulting dsDNA intercalating supramolecular hydrogels (DISHs) can be tuned to exhibit both endothermically or exothermically driven binding through strategic selection of intercalators. Bifunctional polyethylene glycol (MW~2000 Da) capped with intercalators of varying hydrophobicity, charge, and size (acridine, psoralen, thiazole orange, and phenanthridine) produced DISHs with comparable moduli (500–1000 Pa), but unique thermal viscoelastic responses. Notably, acridine‐based cross‐linkers displayed invariant and even increasing relaxation times with temperature, suggesting an endothermic binding mechanism. This methodology expands the set of structure‐properties available to biomass‐derived DNA biomaterials and promises a new material system where a broad set of thermal and viscoelastic responses can be obtained due to the sheer number and variety of intercalating molecules. [ABSTRACT FROM AUTHOR]

Supramolecular structures are widespread in living system, which are usually spatiotemporally regulated by sophisticated metabolic processes to enable vital biological functions. Inspired by living system, tremendous efforts have been made to realize spatiotemporal control over the self‐assembly of supramolecular materials in synthetic scenario by coupling chemical reaction with molecular self‐assembly process. In this review, we focused on the works related to supramolecular hydrogels that are regulated in space and time using chemical reaction. Firstly, we summarized how spatially controlled self‐assembly of supramolecular hydrogels can be achieved via chemical reaction‐instructed self‐assembly, and the application of such a self‐assembly methodology in biotherapy was discussed as well. Second, we reviewed dynamic supramolecular hydrogels dictated by chemical reaction networks that can evolve their structures and properties against time. Third, we discussed the recent progresses in the control of the self‐assembly of supramolecular hydrogels in both space and time though a reaction‐diffusion‐coupled self‐assembly approach. Finally, we provided a perspective on the further development of spatiotemporally controlled supramolecular hydrogels using chemical reaction in the future. [ABSTRACT FROM AUTHOR]

The polymerization of N‐acryloyl glycineamide (NAGA) in water results in the creation of robust supramolecular hydrogels, exhibiting a network structure through inter‐chain crosslinking formed by hydrogen bonds between NAGA units. The stability of these hydrogen bonds in water is based on the aggregation of NAGA units into microdomains or clusters, thereby effectively shielding the hydrogen bonds from the surrounding aqueous medium. Beyond the inherent water absorption characteristics of these hydrogels, the unique ability for the dissociation and re‐association of their physical crosslinks imparts features such as reversible swelling and shrinking as well as self‐healing and remolding capabilities. In this study, we synthesize a series of supramolecular hydrogels through copolymerization of NAGA and ionic sodium acrylate comonomers for a dual purpose: first, to regulate water absorption levels, and second, to introduce a salt partitioning effect into the hydrogels during their swelling in salt solution. Our findings indicate that the properties of these hydrogels are intricately influenced by the volume fraction of the solid network, the concentration of ionic units, and temperature. Notably, supramolecular samples with ionic units exhibit a 16% salt rejection in a single cycle of salt partitioning during their swelling in a 1 g·L−1 sodium chloride solution. [ABSTRACT FROM AUTHOR]

Achieving a controlled release of several active pharmaceutical ingredients (APIs) remains a challenge for improving their therapeutic effects and reduced their side effects. In the current work, stimulable Drug Delivery Systems (DDS) based on supramolecular hydrogels were designed by combining two APIs featuring anticancer activities, namely the doxorubicin and phenazine 14. In vitro studies revealed promising physicochemical properties for all the investigated API loaded gels. Fluorinated GlycoNucleoLipid (GNF) based supramolecular gels remain stable in the presence of either doxorubicin (Doxo) or phenazine 14 (Phe) as anticancer drugs. Noteworthy, the stiffness of the GNF-based supramolecular gels was enhanced in the presence of both APIs while maintaining their thixotropic properties. We demonstrated that the storage modulus (G') of the GNF gels was increased from 1.3 kPa to 9.3 kPa upon loading of both APIs within the same gels. With a low mechanical stimulation (within the LVR), a passive diffusion out of gels was observed for Dox whereas Phe remained trapped in the GNF gels over several hours. Also, in this work we showed that mechanical stress triggered the release of both Phe and Doxo at different rates. Proof of concept of the dual system sensitive to mechanical stress. [ABSTRACT FROM AUTHOR]

Azobenzene photoswitches are fundamental components in contemporary approaches aimed at light-driven control of intelligent materials. Significant endeavors are directed towards enhancing the light-triggered reactivity of azobenzenes for such applications and obtaining water-soluble molecules able to act as crosslinkers in a hydrogel. Here, we report the rational design and the synthesis of azobenzene/alginate photoresponsive hydrogels endowed with fast reversible sol–gel transition. We started with the synthesis of three cationic azobenzenes (AZOs A, B, and C) and then incorporated them in sodium alginate (SA) to obtain photoresponsive supramolecular hydrogels (SMHGs). The photoresponsive properties of the azobenzenes were investigated by UV–Vis and 1H NMR spectroscopy. Upon irradiation with 365 nm UV light, the azobenzenes demonstrated efficient trans-to-cis isomerization, with complete isomerization occurring within seconds. The return to the trans form took several hours, with AZO C exhibiting the fastest return, possibly due to higher trans isomer stability. In the photoresponsive SMHGs, the minimum gelation concentration (MGC) of azobenzenes was determined for different compositions, indicating that small amounts of azobenzenes could induce gel formation, particularly in 5 wt% SA. Upon exposure to 365 nm UV light, the SMHGs exhibited reversible gel–sol transitions, underscoring their photoresponsive nature. This research offers valuable insights into the synthesis and photoresponsive properties of cationic, water-soluble azobenzenes, as well as their potential application in the development of photoresponsive hydrogels. [ABSTRACT FROM AUTHOR]

Amphiphilic cyclic dipeptides are efficient supramolecular hydrogelators. They can be combined with molecular photoswitches to produce light‐responsive soft materials, which can be applied in controlled drug delivery. Here it is reported that an arginine‐containing cyclic dipeptide decorated with ortho‐fluorinated azobenzene forms hydrogels under physiological conditions that can be reversibly liquefied upon exposure to visible light frequencies (green and violet, respectively). The addition of sodium alginate results in composite supramolecular hydrogels with increased gelating capacity supported with Coulombic interactions, which also reversibly dissipate upon irradiation. [ABSTRACT FROM AUTHOR]

Supramolecular hydrogels based on low-molecular-weight compounds are a unique class of so-called "soft" materials, formed by weak non-covalent interactions between precursors at their millimolar concentrations. Due to the variety of structures that can be formed using different low-molecular-weight gelators, they are widely used in various fields of technology and medicine. In this study, we report for the first time an unusual self-assembly process of mixing a hydrosol obtained from L-cysteine and silver nitrate (cysteine–silver sol—CSS) with sodium halides. Modern instrumental techniques such as viscosimetry, UV spectroscopy, dynamic light scattering, zeta potential measurements, SEM and EDS identified that adding fluoride anions to CSS is able to form stable hydrogels of a thixotropic nature, while Cl−, Br− and I− lead to precipitation. The self-assembly process proceeds using a narrow concentration range of F−. An increase in the fluoride anion content in the system leads to a change in the gel network morphology from elongated structures to spherical ones. This fact is reflected in a decrease in the gel viscosity and a number of gel–sol–gel transition cycles. The mechanism of F−'s interaction with hydrosol includes the condensation of anions on the positive surface of the CSS nanoparticles, their binding via electrostatic forces and the formation of a resulting gel carcass. In vitro analysis showed that the hydrogels suppressed human squamous carcinoma cells at a micromolar sample concentration. The obtained soft gels could have potential applications against cutaneous malignancy and as carriers for fluoride anion and other bioactive substance delivery. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

In the present study, the polyoxometalate (POM), [CoW11O39(CpTi)]7−, known for its significant anti-cancer activity and relatively low toxicity compared to established organic drugs such as CP and 5FU, is investigated. However, it is acknowledged that POMs inherently exhibit toxicity to living cells due to the presence of heavy and toxic metal ions within their core structures and their limited selectivity toward biological targets. Consequently, a methodology to mitigate this toxicity is sought by encapsulating these POMs within hydrogel matrices, with the intention to facilitate slow, sustained release and enhanced target specificity. In this study, the hydrogel of the well-researched anti-cancer POM, K6H[CoW11O39(CpTi)] (hereafter abbreviated as CoW11CpTi), is synthesized through the electrostatic interaction of the positively charged carboxymethyl chitosan (CMC), carboxymethyl cellulose (CMCell), and gelatin, which serve as hydrogelators. Subsequent characterization of the resultant CMC-CoW11CpTi, CMCell-CoW11CpTi, and gelatin-CoW11CpTi gels is performed utilizing Fourier Transform Infrared Spectroscopy (FT-IR), Differential Scanning Calorimetry/Thermogravimetric Analysis (DSC/TGA), Electron Spin Resonance (ESR) Spectroscopy, Scanning Electron Microscopy (SEM), and Tgel analysis. Among these, the gelatin-CoW11CpTi gel demonstrates the highest stability, retaining its structural integrity for in excess of 10 days. In addition, cytotoxicity assays are conducted on an assortment of cell lines including NRK52e (Rattus norvegicus kidney cell line), MDA-MB-231 (human breast adenocarcinoma), and MCF-7 (human breast epithelial adenocarcinoma). It is observed that the release of POM from the hydrogel matrices under physiological pH conditions exhibits a slow and sustained profile. This study therefore offers a promising approach for the effective delivery of POMs in cancer therapy. HIGHLIGHTS: Anti-cancer polyoxometalate (POM) and its encapsulation in hydrogel is optimized. Stabilization and release study of the POM from gel matrix is explored. Suppression of toxicity is evaluated using in-vitro MTT assay. Gelatin gel can be used to design and produce novel drug delivery system. [ABSTRACT FROM AUTHOR]

In the present study, the polyoxometalate (POM), [CoW11O39(CpTi)]7−, known for its significant anti-cancer activity and relatively low toxicity compared to established organic drugs such as CP and 5FU, is investigated. However, it is acknowledged that POMs inherently exhibit toxicity to living cells due to the presence of heavy and toxic metal ions within their core structures and their limited selectivity toward biological targets. Consequently, a methodology to mitigate this toxicity is sought by encapsulating these POMs within hydrogel matrices, with the intention to facilitate slow, sustained release and enhanced target specificity. In this study, the hydrogel of the well-researched anti-cancer POM, K6H[CoW11O39(CpTi)] (hereafter abbreviated as CoW11CpTi), is synthesized through the electrostatic interaction of the positively charged carboxymethyl chitosan (CMC), carboxymethyl cellulose (CMCell), and gelatin, which serve as hydrogelators. Subsequent characterization of the resultant CMC-CoW11CpTi, CMCell-CoW11CpTi, and gelatin-CoW11CpTi gels is performed utilizing Fourier Transform Infrared Spectroscopy (FT-IR), Differential Scanning Calorimetry/Thermogravimetric Analysis (DSC/TGA), Electron Spin Resonance (ESR) Spectroscopy, Scanning Electron Microscopy (SEM), and Tgel analysis. Among these, the gelatin-CoW11CpTi gel demonstrates the highest stability, retaining its structural integrity for in excess of 10 days. In addition, cytotoxicity assays are conducted on an assortment of cell lines including NRK52e (Rattus norvegicus kidney cell line), MDA-MB-231 (human breast adenocarcinoma), and MCF-7 (human breast epithelial adenocarcinoma). It is observed that the release of POM from the hydrogel matrices under physiological pH conditions exhibits a slow and sustained profile. This study therefore offers a promising approach for the effective delivery of POMs in cancer therapy. HIGHLIGHTS: Anti-cancer polyoxometalate (POM) and its encapsulation in hydrogel is optimized. Stabilization and release study of the POM from gel matrix is explored. Suppression of toxicity is evaluated using in-vitro MTT assay. Gelatin gel can be used to design and produce novel drug delivery system. [ABSTRACT FROM AUTHOR]

Nature uses combined covalent (chemical bonds) and non‐covalent (physical bonds) synthesis in a highly, controlled multi‐step fashion to create functional materials with different mechanical and dynamic properties out of similar building blocks. Surprisingly, this control in fully synthetic systems remains elusive, even though the effects of formulation pathways on the assembly processes have been emphasized—highlighting the importance of and relationship between energy landscapes and function in synthetic systems. Here, we control multiple, coherent supramolecular assembly processes (fiber formation and crosslinking) to formulate hydrogels with tunable mechanical and dynamic properties. Hydrogels are prepared via two different formulation methods using similar building blocks (monofunctional and bifunctional supramolecular monomers), including (1) the mixing of the supramolecular monomers under basic conditions (Fbasic) and (2) the mixing of the supramolecular monomers under neutral conditions (Fneutral). In Fbasic, network formation is induced via simultaneous fiber formation and crosslinking, yielding homogeneously mixed networks which are dense, stiff (~10 kPa) and robust. In Fneutral, network formation is induced through sequential fiber formation and crosslinking, yielding heterogenous, soft (~2 kPa) and dynamic networks. With these results, we advance towards the controlled, multistep, non‐covalent synthesis to create larger hierarchical, functional structures, similar to nature. [ABSTRACT FROM AUTHOR]

Metal‐coordinated hydrogels can form a percolated network with transient bonds due to metal ions‐functional group coordination. Each metal ion can link with more than one ligand, leading to intricate speciation of bonding modes. While the mechanics of transient gels made with four‐arm polymers are often studied, less is known about how increasing the number of arms affects the modulus. Using shear rheology, the modulus of hydrogels prepared from four‐, six‐, and eight‐armed poly(ethylene glycols), functionalized with histidine ligands that complex with nickel (II) ions is measured. These gels have matched polymer wt.% and varied pH to compare their moduli. It is considered whether the modulus can be described by established polymer network models by calculating the speciation of metal‐coordinated cross‐links and then incorporating it into a phantom network prediction. This study finds that 1) increasing the number of polymer arms increases the modulus, 2) the phantom network allows reasonable modulus approximation for four‐arm and six‐arm gels, and 3) the modulus of eight‐arm gels exceeds the phantom network prediction. Since polymer cores act as chemical cross‐links and metal‐coordinated cross‐links form network strands, it is possible that increasing the number of metal‐coordinated linkages per molecule reinforces the chemical cross‐link at the polymer core. [ABSTRACT FROM AUTHOR]

Supramolecular hydrogels as biomaterials have been widely investigated for medical applications. However, the inadequate strength and stability of supramolecular hydrogels limit their applications in dressings, stents and drug carriers. In order to improve the mechanical properties of supramolecular hydrogels, a graphene oxide-hyaluronic acid-polyethylene glycol supramolecular hydrogel (GHCAP)is successfully prepared by the host-guest interaction of cyclodextrin and adamantane functional groups, with hyaluronic acid grafted cyclodextrin and graphene oxide (GO)as the main polymers and four-arm polyethylene glycol grafted adamantane as guest polymers. The elastic modulus of GHCAP-functionalized hydrogel is significantly increased compared with that of hyaluronic acid-polyethylene glycol supramolecular hydrogel (HCAP)without graphene oxide, and the loading rate of GHCAP-functionalized hydrogel for cichoric acid drugs reached 43. 38% under the same conditions. Hence, the supramolecular hydrogels of GHCAP are expected to have wide application in the fields of medical biomaterials such as tissue dressings and drug carriers. [ABSTRACT FROM AUTHOR]

Ischemic stroke is a major cause of death and disability worldwide. The poor drug delivery to cerebral ischemic regions remains a challenging issue for ischemic stroke treatment. Curcumin (Cur) and edaravone (EDV) show remarkable therapeutic effects on ischemic stroke. However, the short half‐life and poor aqueous solubility limit their application for long‐term and effective neuroprotection. Cur and EDV with a well‐studied hydrogelator Nap‐Phe‐Phe‐Tyr‐OH (NapFFY) is co‐assembled to prepare a novel supramolecular peptide hydrogel EDV/Cur/NapFFY, which can improve their bioavailability and transport the hydrophobic drugs to ischemic sites precisely by local administration. In vitro release test demonstrate that co‐assembly with NapFFY enables continuous release of Cur and EDV for about two weeks. Animal studies found that EDV/Cur/NapFFY hydrogel can effectively promote brain plasticity and enhance the functional recovery on the photothrombotic mouse model. Overall, the work reveales the great application potential of supramolecular peptide hydrogel delivery system EDV/Cur/NapFFY in promoting repair and recovery of ischemic stroke. [ABSTRACT FROM AUTHOR]

Abstract Amphiphilic cyclic dipeptides are efficient supramolecular hydrogelators. They can be combined with molecular photoswitches to produce light‐responsive soft materials, which can be applied in controlled drug delivery. Here it is reported that an arginine‐containing cyclic dipeptide decorated with ortho‐fluorinated azobenzene forms hydrogels under physiological conditions that can be reversibly liquefied upon exposure to visible light frequencies (green and violet, respectively). The addition of sodium alginate results in composite supramolecular hydrogels with increased gelating capacity supported with Coulombic interactions, which also reversibly dissipate upon irradiation.

Glycyrrhizic acid (GA) is a natural edible chiral triterpene saponin that can undergo hierarchical self-assembly in water to form supramolecular hydrogels. Customizing the properties of GA supramolecular hydrogels is crucial for their wide food and biomedical applications, and the incorporation of specific metal ions can be an attractive way for this purpose. Herein, this study investigates the effects of metal ions with different valence states and concentrations on the linear and nonlinear rheological properties and network structures of GA supramolecular hydrogels. Monovalent metal ions (Na+ and K+), exhibiting weak binding affinity to GA, rely on the electrostatic screening effects at high concentrations (e.g., 50 mM) to enhance the GA interfibrillar interactions and thus the formation of a more compact and ordered gel network, which displays a pronounced nonlinear rheological behavior with a typical transition from elastic to viscous response. Polyvalent metal ions (Ca2+, Zn2+, and Al3+), owing to their greater charge density and stronger binding with GA, significantly enhance the network strength of the hydrogels at low concentrations (e.g., 5 mM). Nonetheless, at high ion concentrations (e.g., 50 mM), the GA-Mn+ forms discrete aggregated network structures due to excessively strong cation-carboxylate complexation, leading to the irregular nonlinear rheological responses and the lower resistance to large deformations. These findings can deepen our understanding of the highly tunable rheological behaviors and network structures of GA hydrogels, which demonstrates a new possibility for the design and development of responsive natural supramolecular hydrogels with controlled properties through the strategy of metal ion complexation.

Photochromic supramolecular hydrogels are versatile materials that show macroscopic effects upon irradiation, like liquefaction or shape changes. Here, we demonstrate a simple photochromic cyclic dipeptide (2,5‐diketopiperazine‐based) supergelator, composed of (S)‐lysine and an azobenzene analogue of phenylalanine, that forms supramolecular hydrogels even at 0.1 wt% loading. The gels can physically encapsulate cargo molecules and release them to the environment in a controllable manner upon irradiation with red light, thus working as a "molecular syringe". As the material is biocompatible and operational in the "therapeutic window" of light (>650 nm) that deeply penetrates soft human tissues, it is applicable to smart drug‐delivery systems. [ABSTRACT FROM AUTHOR]

Supramolecular hydrogels formed by the self‐assembly of N‐Fmoc‐l‐phenylalanine derivatives are gaining relevance for several applications in the materials and biomedical fields. In the challenging attempt to predict or tune their properties, we selected Fmoc‐pentafluorophenylalanine (1) as a model efficient gelator, and studied its self‐assembly in the presence of benzamide (2), a non‐gelator able to form strong hydrogen bonds with the amino acid carboxylic group. Equimolar mixtures of 1 and 2 in organic solvents afforded a 1 : 1 co‐crystal thanks to the formation of an acid⋅⋅⋅amide heterodimeric supramolecular synthon. The same synthon occurred in the transparent gels formed by mixing the two components in 1 : 1 ratio in aqueous media, as revealed by structural, spectroscopic, and thermal characterizations performed on both the co‐crystal powder and the lyophilized hydrogel. These findings revealed the possibility of modulating the properties of amino acid‐based hydrogels by involving the gelator in the formation of a co‐crystal. Such a crystal engineering‐based approach is shown also to be useful for the time‐delayed release of suitable bioactive molecules, when involved as hydrogel coformers. [ABSTRACT FROM AUTHOR]

Functional tissue engineering strategies provide innovative approach for the repair and regeneration of damaged cartilage. Hydrogel is widely used because it could provide rapid defect filling and proper structure support, and is biocompatible for cell aggregation and matrix deposition. Efforts have been made to seek suitable scaffolds for cartilage tissue engineering. Here Alg-DA/Ac-β-CD/gelatin hydrogel was designed with the features of physical and chemical multiple crosslinking and self-healing properties. Gelation time, swelling ratio, biodegradability and biocompatibility of the hydrogels were systematically characterized, and the injectable self-healing adhesive hydrogel were demonstrated to exhibit ideal properties for cartilage repair. Furthermore, the new hydrogel design introduces a pre-gel state before photo-crosslinking, where increased viscosity and decreased fluidity allow the gel to remain in a semi-solid condition. This granted multiple administration routes to the hydrogels, which brings hydrogels the ability to adapt to complex clinical situations. Pulsed electromagnetic fields (PEMF) have been recognized as a promising solution to various health problems owing to their noninvasive properties and therapeutic potentials. PEMF treatment offers a better clinical outcome with fewer, if any, side effects, and wildly used in musculoskeletal tissue repair. Thereby we propose PEMF as an effective biophysical stimulation to be 4th key element in cartilage tissue engineering. In this study, the as-prepared Alg-DA/Ac-β-CD/gelatin hydrogels were utilized in the rat osteochondral defect model, and the potential application of PEMF in cartilage tissue engineering were investigated. PEMF treatment were proven to enhance the quality of engineered chondrogenic constructs in vitro, and facilitate chondrogenesis and cartilage repair in vivo. All of the results suggested that with the injectable self-healing adhesive hydrogel and PEMF treatment, this newly proposed tissue engineering strategy revealed superior clinical potential for cartilage defect treatment.

Supramolecular hydrogels based on low-molecular-weight compounds are a unique class of so-called “soft” materials, formed by weak non-covalent interactions between precursors at their millimolar concentrations. Due to the variety of structures that can be formed using different low-molecular-weight gelators, they are widely used in various fields of technology and medicine. In this study, we report for the first time an unusual self-assembly process of mixing a hydrosol obtained from L-cysteine and silver nitrate (cysteine–silver sol—CSS) with sodium halides. Modern instrumental techniques such as viscosimetry, UV spectroscopy, dynamic light scattering, zeta potential measurements, SEM and EDS identified that adding fluoride anions to CSS is able to form stable hydrogels of a thixotropic nature, while Cl−, Br− and I− lead to precipitation. The self-assembly process proceeds using a narrow concentration range of F−. An increase in the fluoride anion content in the system leads to a change in the gel network morphology from elongated structures to spherical ones. This fact is reflected in a decrease in the gel viscosity and a number of gel–sol–gel transition cycles. The mechanism of F−’s interaction with hydrosol includes the condensation of anions on the positive surface of the CSS nanoparticles, their binding via electrostatic forces and the formation of a resulting gel carcass. In vitro analysis showed that the hydrogels suppressed human squamous carcinoma cells at a micromolar sample concentration. The obtained soft gels could have potential applications against cutaneous malignancy and as carriers for fluoride anion and other bioactive substance delivery.

Azobenzene photoswitches are fundamental components in contemporary approaches aimed at light-driven control of intelligent materials. Significant endeavors are directed towards enhancing the light-triggered reactivity of azobenzenes for such applications and obtaining water-soluble molecules able to act as crosslinkers in a hydrogel. Here, we report the rational design and the synthesis of azobenzene/alginate photoresponsive hydrogels endowed with fast reversible sol–gel transition. We started with the synthesis of three cationic azobenzenes (AZOs A, B, and C) and then incorporated them in sodium alginate (SA) to obtain photoresponsive supramolecular hydrogels (SMHGs). The photoresponsive properties of the azobenzenes were investigated by UV–Vis and 1H NMR spectroscopy. Upon irradiation with 365 nm UV light, the azobenzenes demonstrated efficient trans-to-cis isomerization, with complete isomerization occurring within seconds. The return to the trans form took several hours, with AZO C exhibiting the fastest return, possibly due to higher trans isomer stability. In the photoresponsive SMHGs, the minimum gelation concentration (MGC) of azobenzenes was determined for different compositions, indicating that small amounts of azobenzenes could induce gel formation, particularly in 5 wt% SA. Upon exposure to 365 nm UV light, the SMHGs exhibited reversible gel–sol transitions, underscoring their photoresponsive nature. This research offers valuable insights into the synthesis and photoresponsive properties of cationic, water-soluble azobenzenes, as well as their potential application in the development of photoresponsive hydrogels.

Chronic wounds (CWs) are a growing issue for the health care system. Their treatment requires a synergic approach to reduce both inflammation and the bacterial burden. In this work, a promising system for treating CWs was developed, comprising cobalt-lignin nanoparticles (NPs) embedded in a supramolecular (SM) hydrogel. First, NPs were obtained through cobalt reduction with phenolated lignin, and their antibacterial properties were tested against both Gram-negative and Gram-positive strains. The anti-inflammatory capacity of the NPs was proven through their ability to inhibit myeloperoxidase (MPO) and matrix metalloproteases (MMPs), which are enzymes involved in the inflammatory process and wound chronicity. Then, the NPs were loaded in an SM hydrogel based on a blend of α-cyclodextrin and custom-made poly(ether urethane)s. The nano-enabled hydrogel showed injectability, self-healing properties, and linear release of the loaded cargo. Moreover, the SM hydrogel's characteristics were optimized to absorb proteins when in contact with liquid, suggesting its capacity to uptake harmful enzymes from the wound exudate. These results render the developed multifunctional SM material an interesting candidate for the management of CWs. [ABSTRACT FROM AUTHOR]

The field of supramolecular peptides self-assembly has undergone outstanding growth since the early 1990s after the serendipitously discovery by Shuguang Zhang of an ionic self-complementary peptide as a repeating segment in a yeast protein. From then on, the field expanded at an accelerating pace and these self-assembled materials have become an integral part of a broad plethora of designer supramolecular nanomaterials useful for different applications ranging from 3D tissue cell cultures, regenerative medicine, up to optoelectronics. However, the supramolecular peptide based-nanomaterials available thus far for regenerative medicine still lack the dynamic complexity found in the biological structures that mediate regeneration. Indeed, self-assembling peptide (SAPs) suffer from poor mechanical stability, losing mechanical properties at low strains. Just like the extracellular matrix (ECM) of living systems, the chemical structure of the SAP-biomaterials should concurrently contain non-covalent and covalent bonds, bringing, respectively, infinite and finite lifetimes of interactions to obtain a reversibly dynamic matrix. In this review, will be highlighted the major advantages and current limitations of SAP-based biomaterials, and it will be discussed the most widely used strategies for precisely tune their mechanical properties (stiffness, resilience, strain-failure, stress resistance), describing recent and promising approaches in tissue engineering, regenerative medicine, and beyond.

The current effective method for treatment of spinal cord injury (SCI) is to reconstruct the biological microenvironment by filling the injured cavity area and increasing neuronal differentiation of neural stem cells (NSCs) to repair SCI. However, the method is characterized by several challenges including irregular wounds, and mechanical and electrical mismatch of the material-tissue interface. In the current study, a unique and facile agarose/gelatin/polypyrrole (Aga/Gel/PPy, AGP3) hydrogel with similar conductivity and modulus as the spinal cord was developed by altering the concentration of Aga and PPy. The gelation occurred through non-covalent interactions, and the physically crosslinked features made the AGP3 hydrogels injectable. In vitro cultures showed that AGP3 hydrogel exhibited excellent biocompatibility, and promoted differentiation of NSCs toward neurons whereas it inhibited over-proliferation of astrocytes. The in vivo implanted AGP3 hydrogel completely covered the tissue defects and reduced injured cavity areas. In vivo studies further showed that the AGP3 hydrogel provided a biocompatible microenvironment for promoting endogenous neurogenesis rather than glial fibrosis formation, resulting in significant functional recovery. RNA sequencing analysis further indicated that AGP3 hydrogel significantly modulated expression of neurogenesis-related genes through intracellular Ca2+ signaling cascades. Overall, this supramolecular strategy produces AGP3 hydrogel that can be used as favorable biomaterials for SCI repair by filling the cavity and imitating the physiological properties of the spinal cord.

Photochromic supramolecular hydrogels are prospective materials for light‐triggered drug release and bionanotechnology. Here we present a structural analysis of peptide‐derived photochromic supramolecular hydrogels, which were physically loaded with a selection of biologically related compounds, using advanced techniques of nuclear magnetic resonance. The results enable detailed and correct understanding of the loading process and will allow for correct design of pharmacologically relevant systems for phototriggered drug delivery. [ABSTRACT FROM AUTHOR]

The cucurbit[n]uril supramolecular hydrogels are driven by weak intermolecular interactions, of which exhibit good stimuli responsiveness and excellent self-healing properties. According to the composition of the gelling factor, supramolecular hydrogels comprise Q[n]-cross-linked small molecules and Q[n]-cross-linked polymers. According to different driving forces, hydrogels are driven by the outer-surface interaction, the host–guest inclusion interaction, and the host–guest exclusion interaction. Host–guest interactions are widely used in the construction of self-healing hydrogels, which can spontaneously recover after being damaged, thereby prolonging their service life. The smart Q[n]s-based supramolecular hydrogel composed is a kind of adjustable and low-toxicity soft material. By designing the structure of the hydrogel or modifying the fluorescent properties, etc., it can be widely used in biomedicine. In this review, we mainly focus on the preparation of Q[n]-based hydrogels and their biomedical applications including cell encapsulation for biocatalysis, biosensors for high sensitivity, 3D printing for potential tissue engineering, drug release for sustained delivery, and interfacial adhesion for self-healing materials. In addition, we also presented the current challenges and prospects in this field. [ABSTRACT FROM AUTHOR]

The development of multifunctional supramolecular hydrogels with high mechanical strength and multifunction is in high demand. In this work, the diblock copolymer poly(acrylamide‐co‐1‐benzyl‐3‐vinylimidazolium bromide)‐block‐polyAzobenzene is synthesized through reversible addition−fragmentation chain transfer polymerization. The dynamic host–guest interactions between the host molecule cucurbit[8] uril and guest units are used to fabricate a 3D network of supramolecular hydrogels. Investigations on the properties of the supramolecular hydrogels show that the tensile stress of the sample is 1.46 MPa, eight times higher than that of hydrogel without liquid‐crystalline block copolymer, and the self‐healing efficiency of the supramolecular hydrogels at room temperature is 88.3% (fracture stress) and 100% (fracture strain) after 24 h. Results show that microphase‐separated structure plays a key role in the high‐strength hydrogel, whereas the host–guest interaction endows the hydrogel with self‐healing properties. The supramolecular hydrogels with high mechanical strength, photo‐responsivity, injectability, and biocompatibility can be used in various potential applications. [ABSTRACT FROM AUTHOR]

Supramolecular structures are of great interest due to their applicability in various scientific and industrial fields. The sensible definition of supramolecular molecules is being set by investigators who, because of the different sensitivities of their methods and observational timescales, may have different views on as to what constitutes these supramolecular structures. Furthermore, diverse polymers have been found to offer unique avenues for multifunctional systems with properties in industrial medicine applications. Aspects of this review provide different conceptual strategies to address the molecular design, properties, and potential applications of self-assembly materials and the use of metal coordination as a feasible and useful strategy for constructing complex supramolecular structures. This review also addresses systems that are based on hydrogel chemistry and the enormous opportunities to design specific structures for applications that demand enormous specificity. According to the current research status on supramolecular hydrogels, the central ideas in the present review are classic topics that, however, are and will be of great importance, especially the hydrogels that have substantial potential applications in drug delivery systems, ophthalmic products, adhesive hydrogels, and electrically conductive hydrogels. The potential interest shown in the technology involving supramolecular hydrogels is clear from what we can retrieve from the Web of Science. [ABSTRACT FROM AUTHOR]

Non‐contact human‐machine interaction is the future trend for wearable technologies. This demand is recently highlighted by the pandemic of coronavirus disease (COVID‐19). Herein, an anti‐fatigue and highly conductive hydrogel thermocell with photo‐thermal conversion ability for non‐contact self‐powering applications is designed. Double hydrogen‐bonding enhanced supramolecular hydrogel is obtained with N‐acryloyl glycinamide (NAGA) and diacrylate capped Pluronic F68 (F68‐DA) via one‐step photo‐initiated polymerization. The supramolecular hydrogel can accommodate saturated electrolytes to fulfill the triple function of ionic crosslinking, heat‐to‐electricity conversion, and light response of thermocell. Eminently, the thermocell stands out by virtue of its high seebeck coefficient (‐2.17 mV K−1) and extraordinary toughness (Fatigue threshold ≈ 3120 J m−2). The self‐powering ability under the control of light heating is explored, and a model of a non‐contact "light‐remoted" sensor with self‐powered and sensing integrated performance remote‐controlled by light is constructed. It is believed that this study will pave the way for the non‐contact energy supply of wearable devices. [ABSTRACT FROM AUTHOR]

Smart hydrogels are interesting materials as they can change their dimensions upon an external trigger. Herein, a photoresponsive double cross‐linked hydrogel system based on polyacrylamide (AAm) with grafted poly(2‐methyl‐2‐oxazoline) (PMOXA) chains with a α‐cyclodextrin/azobenzene host–guest complex is present. Switching azobenzene from the trans to the cis‐conformation through irradiation with UV light breaks the complex reversibly. Well‐defined PMOXA macromonomers have been synthesized and functionalized with the respective host and guest functionalities as well as double bonds for the incorporation into the polymer network as grafted side chains. The chemical structure of the macromonomers and the complex is confirmed by 1H NMR, 2D NOESY NMR, GPC, and UV–VIS measurements. Hydrogels with different ratios of permanent and photoresponsive cross‐linkers as well as different chain lengths of the PMOXA macromonomers are analyzed toward differences in their swelling/deswelling and elastic properties. Successive irradiation of supramolecular hydrogels with UV and VIS light allowed for a repeated swelling and de‐swelling of the hydrogels. This system is studied at both macro and micro scales, showing similar swelling tendencies. The tuned properties of photoresponsive double cross‐linked hydrogel makes this system a promising tool for various applications, for example, as in situ controllable valves in microfluidic flow cells. [ABSTRACT FROM AUTHOR]

Protein-based hydrogels have attracted growing attention for pharmaceutical and biomedical applications. Ovalbumin (OVA), the hen egg white albumin, possessing good foaming and gelling properties and being widely used in the food industry, has recently been indicated as a potential pharmaceutical vehicle. In this study, the binding and release properties of pure OVA hydrogels were investigated by electron paramagnetic resonance (EPR) spin labeling. The comparative analysis between OVA and serum albumin (SA) hydrogels revealed the same release kinetics of hydrophilic 3-carbamoyl-proxyl and 3-carboxy-proxyl, suggesting the diffusion-dominated release of small probes from both hydrogel types. The results obtained with the amphiphilic 16-doxylstearate (16-DS) indicate that OVA, unlike SAs, does not possess a specific fatty acid binding site. However, the OVA hydrogels were able to accommodate a two-fold excess of 16-DS, resulting from protein thermally induced conformational changes, as confirmed by Raman spectroscopy. Similarly, the hydrophobic modified paullone ligand HL, which was initially free in the OVA solution, was bound in the hydrogel. The hydrogels were found to retain a significant amount of 16-DS and HL after 7-day dialysis in physiological saline. The observed facilitated binding of amphiphilic/hydrophobic molecules in OVA hydrogels compared to the solution, and their sustained release, demonstrate the applicability of OVA hydrogels in pharmaceutics. [ABSTRACT FROM AUTHOR]

The field of supramolecular peptides self-assembly has undergone outstanding growth since the early 1990s after the serendipitously discovery by Shuguang Zhang of an ionic self-complementary peptide as a repeating segment in a yeast protein. From then on, the field expanded at an accelerating pace and these self-assembled materials have become an integral part of a broad plethora of designer supramolecular nanomaterials useful for different applications ranging from 3D tissue cell cultures, regenerative medicine, up to optoelectronics. However, the supramolecular peptide based-nanomaterials available thus far for regenerative medicine still lack the dynamic complexity found in the biological structures that mediate regeneration. Indeed, self-assembling peptide (SAPs) suffer from poor mechanical stability, losing mechanical properties at low strains. Just like the extracellular matrix (ECM) of living systems, the chemical structure of the SAP-biomaterials should concurrently contain non-covalent and covalent bonds, bringing, respectively, infinite and finite lifetimes of interactions to obtain a reversibly dynamic matrix. In this review, will be highlighted the major advantages and current limitations of SAP-based biomaterials, and it will be discussed the most widely used strategies for precisely tune their mechanical properties (stiffness, resilience, strain-failure, stress resistance), describing recent and promising approaches in tissue engineering, regenerative medicine, and beyond. [ABSTRACT FROM AUTHOR]

The loss of tissues and organs is a major challenge for biomedicine, and the emerging 3D bioprinting technology has brought the dawn for the development of tissue engineering and regenerative medicine. Chitosan-based supramolecular hydrogels, as novel biomaterials, are considered as ideal materials for 3D bioprinting due to their unique dynamic reversibility and fantastic biological properties. Although chitosan-based supramolecular hydrogels have wonderful biological properties, the mechanical properties are still under early exploration. This paper aims to provide some inspirations for researchers to further explore. In this review, common 3D bioprinting techniques and the properties required for bioink for 3D bioprinting are firstly described. Then, several strategies to enhance the mechanical properties of chitosan hydrogels are introduced from the perspectives of both materials and supramolecular binding motifs. Finally, current challenges and future opportunities in this field are discussed. The combination of chitosan-based supramolecular hydrogels and 3D bioprinting will hold promise for developing novel biomedical implants. [Display omitted] [ABSTRACT FROM AUTHOR]

The design of efficient self‐standing hybrid systems for water purification that combines good adsorption properties with high photodegradation ability is highly challenging owing to the difficulty in simultaneously controlling the band structure and porosity of a semiconductor while maintaining its self‐standing nature. Here, we report the synthesis of carbon‐rich carbon nitride self‐standing filters from supramolecular hydrogels composed of melamine and cyanobenzoic acid. The influence of the chemical structure on the properties of the hydrogels and the final films was studied by tuning parameters such as monomer nature, molar ratio, and pyrolysis temperature. Thanks to their ability to combine the adsorption and photodegradation of organic pollutants, the prepared self‐standing films showed remarkable activity and stability in flow conditions (>95 % efficiency after 10 consecutive cycles). Additionally, the photocatalytic activity of the films was assessed in the powder form for the hydrogen evolution reaction and photocurrent generation in a photoelectrochemical cell. The reported work opens opportunities for the controlled synthesis of multifunctional filters for water purification and other energy‐related and sustainable technologies. [ABSTRACT FROM AUTHOR]

Employing amino acids and peptides as molecular building blocks provides unique opportunities for generating supramolecular hydrogels, owing to their inherent biological origin, bioactivity, biocompatibility, and biodegradability. However, they can suffer from proteolytic degradation. Short peptides (<8 amino acids) attached to an aromatic capping group are particularly attractive alternatives for minimalistic low molecular weight hydrogelators. Peptides with low critical gelation concentrations (CGCs) are especially desirable, as the low weight percentage required for gelation makes them more cost-effective and reduces toxicity. In this work, three dehydrodipeptides were studied for their self-assembly properties. The results showed that all three dehydrodipeptides can form self-standing hydrogels with very low critical gelation concentrations (0.05–0.20 wt%) using a pH trigger. Hydrogels of all three dehydrodipeptides were characterised by scanning tunnelling emission microscopy (STEM), rheology, fluorescence spectroscopy, and circular dichroism (CD) spectroscopy. Molecular modelling was performed to probe the structural patterns and interactions. The cytotoxicity of the new compounds was tested using human keratinocytes (HaCaT cell line). In general, the results suggest that all three compounds are non-cytotoxic, although one of the peptides shows a small impact on cell viability. In sustained release assays, the effect of the charge of the model drug compounds on the rate of cargo release from the hydrogel network was evaluated. The hydrogels provide a sustained release of methyl orange (anionic) and ciprofloxacin (neutral), while methylene blue (cationic) was retained by the network. [ABSTRACT FROM AUTHOR]

The design of photo-responsive supramolecular hydrogels based on coumarin dimerization and de-dimerization is described. The photo-responsive coumarin unit is chemically incorporated into an oligo(ethylene glycol) (OEG) bis-urea amphiphile that is capable of co-assembling with non-functionalized OEG amphiphile, to form supramolecular fibers. UV light with two different wavelengths (365 nm and 254 nm) is employed to induce a photo-reversible dimerization and de-dimerization process of coumarin units, respectively. The co-assembled solutions could be photo-crosslinked to induce a sol-to-gel transition through dimerization of coumarin with 365 nm UV light, and de-dimerization occurs with 254 nm UV light, to provide a weaker gel. In this system, the mechanical strength of supramolecular hydrogels can be tuned using the irradiation time, providing precise control of gelation in a supramolecular hydrogelator. [ABSTRACT FROM AUTHOR]

The bioadhesive hydrogels have been viewed as promising substitutes for surgical sutures in wound closure. However, current bioadhesives face challenges such as weak wet adhesion and hemostatic performance, which hinder their wider clinical application. In this study, a novel poly(thioctic acid)Li + /caffeic acid-grafted sericin (CAS) (PTALi-CAS) supramolecular hydrogel was prepared using facile one-pot method. Among the PTALi-CAS hydrogels with varying CAS content, the PTALi-7%CAS hydrogels exhibited the highest adhesion strength (32.02 ± 2.28 kPa) and could adhere on surfaces of various organs in moist environments. It is noteworthy that the microstructure of the PTALi-7%CAS hydrogels after stretching closely resemble those of mussel byssal adhesion proteins. Additionally, the PTALi-7%CAS hydrogels exhibited rapid hemostatic properties in rat hemorrhage models and significantly accelerated the wound healing in rat skin incision experiments. Therefore, this study proposes a promising approach for developing a versatile hydrogel to aid in healing traumatic wounds., Competing Interests: Declaration of competing interest All authors declare no conflict of interest in this manuscript., (Copyright © 2024. Published by Elsevier B.V.)

Skin wound treatments require efficient and targeted delivery of therapeutic agents to promote fast tissue regeneration and prevent infections. Hydrogels are one of the most popular products in the wound care market, although their use as medicated wound dressings remains a massive challenge when hydrophobic drugs are needed due to the hydrophilic nature of these soft materials. In this study, we developed innovative, dynamic hydrogels based on polyvinyl alcohol (PVA), pyrogallol as a hydrogen bond crosslinker, and casein micelles as hydrophobic reservoirs of silver sulfadiazine (SSD) for enzyme-activated smart delivery at wound sites. The hydrogel formulation was optimized for mechanical strength, viscoelastic behavior, water absorption capacity, and drug-loading efficiency. In vitro drug delivery studies revealed a sustainable release profile of SSD for over 24 h from the micelles within the hydrogel network. Furthermore, biocompatibility evaluation using mouse fibroblast L929 cells demonstrated that the hydrogel did not inhibit cell viability, while in vivo experiments on Caenorhabditis elegans (C. elegans) proved its safety in complex organisms. This versatile hydrogel also has anti-inflammatory and antibacterial effects stemming from the therapeutic polyphenol, which could benefit the healing process. The combination of PVA, pyrogallol, and casein-based nanocarriers could offer an approach to wound healing, providing a new platform for hosting hydrophobic therapeutic substances. Overall, this hydrogel system shows great promise in wound care and could broaden the applications of this family of soft materials for treating various skin injuries., Competing Interests: Declaration of competing interest The authors have no conflicts of interest to declare that are relevant to the content of this article., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The integration of photoswitchable supramolecular units into hydrogels allows for spatiotemporal control over their nanoscale topological network and macroscale properties using light. Nevertheless, the current availability of photoswitchable supramolecular interactions for the development of such materials remains limited. Here, the molecular design of a novel photoswitchable cucurbit[8]uril-spiropyran host-guest complex exhibiting fast and reversible switching of binding ratios between 1:2 and 1:1 is reported. Photoswitchable complexation stoichiometries are rationally exploited as (de)crosslinking units in multiple polymers for the design of supramolecular hydrogels displaying highly dynamic and switchable features that are spatiotemporally controlled by light. The hydrogels exhibit rapid reversible mechanical softening-hardening upon alternating irradiation with blue and UV light, which is used to significantly accelerate and improve the efficiency of self-healing and shape-remolding of hydrogels. Furthermore, spiropyran endows such materials with unique reversible photochromic properties for reproducible patterning/erasing and information storage. Using a dual-light-assisted extrusion process, meter-scale hydrogel fibers with enhanced structural integrity and photoswitchable ionic conductivity are constructed and woven into various slidable knots and fluorescent shapes. This work represents an innovative molecular design strategy for advancing the development of spatiotemporally engineered supramolecular hydrogels using light and opens avenues for their prospective applications in dynamic materials and adaptive systems., (© 2024 Wiley‐VCH GmbH.)

Epithelial cysts and organoids are multicellular hollow structures formed by correctly polarized epithelial cells. Important in steering these cysts from single cells is the dynamic regulation of extracellular matrix presented ligands, and matrix dynamics. Here, control over the effective ligand concentration is introduced, decoupled from bulk and local mechanical properties, in synthetic dynamic supramolecular hydrogels formed through noncovalent crosslinking of supramolecular fibers. Control over the effective ligand concentration is realized by 1) keeping the ligand concentration constant, but changing the concentration of nonfunctionalized molecules or by 2) varying the ligand concentration, while keeping the concentration of non-functionalized molecules constant. The results show that in 2D, the effective ligand concentration within the supramolecular fibers rather than gel stiffness (from 0.1 to 8 kPa) regulates epithelial polarity. In 3D, increasing the effective ligand concentration from 0.5 × 10 -3 to 2 × 10 -3 m strengthens the effect of increased gel stiffness from 0.1 to 2 kPa, to synergistically yield more correctly polarized cysts. Through integrin manipulation, it is shown that epithelial polarity is regulated by tension-based homeostasis between cells and matrix. The results reveal the effective ligand concentration as influential factor in regulating epithelial polarity and provide insights on engineering of synthetic biomaterials for cell and organoid culture., (© 2023 The Authors. Advanced Materials published by Wiley‐VCH GmbH.)

Cartilage tissue engineering remains a formidable challenge due to its complex, avascular structure and limited regenerative capacity. Traditional approaches, such as microfracture, autografts, and stem cell delivery, often fail to restore functional tissue adequately. Recently, there has been a surge in the exploration of new materials that mimic the extracellular microenvironment necessary to guide tissue regeneration. This review investigates the potential of peptide-based hydrogels as an innovative solution for cartilage regeneration. These hydrogels, formed via supramolecular self-assembly, exhibit excellent properties, including biocompatibility, ECM mimicry, and controlled biodegradation, making them highly suitable for cartilage tissue engineering. This review explains the structure of cartilage and the principles of supramolecular and peptide hydrogels. It also delves into their specific properties relevant to cartilage regeneration. Additionally, this review presents recent examples and a comparative analysis of various peptide-based hydrogels used for cartilage regeneration. The review also addresses the translational challenges of these materials, highlighting regulatory hurdles and the complexities of clinical application. This comprehensive investigation provides valuable insights for biomedical researchers, tissue engineers, and clinical professionals aiming to enhance cartilage repair methodologies.

Chronic wounds (CWs) are a growing issue for the health care system. Their treatment requires a synergic approach to reduce both inflammation and the bacterial burden. In this work, a promising system for treating CWs was developed, comprising cobalt-lignin nanoparticles (NPs) embedded in a supramolecular (SM) hydrogel. First, NPs were obtained through cobalt reduction with phenolated lignin, and their antibacterial properties were tested against both Gram-negative and Gram-positive strains. The anti-inflammatory capacity of the NPs was proven through their ability to inhibit myeloperoxidase (MPO) and matrix metalloproteases (MMPs), which are enzymes involved in the inflammatory process and wound chronicity. Then, the NPs were loaded in an SM hydrogel based on a blend of α-cyclodextrin and custom-made poly(ether urethane)s. The nano-enabled hydrogel showed injectability, self-healing properties, and linear release of the loaded cargo. Moreover, the SM hydrogel’s characteristics were optimized to absorb proteins when in contact with liquid, suggesting its capacity to uptake harmful enzymes from the wound exudate. These results render the developed multifunctional SM material an interesting candidate for the management of CWs.

Inosine is proven to promote the proliferation and function of CD8+ cytotoxic lymphocytes (CD8+ T) under glucose restriction and enhance the efficacy of programmed cell death protein ligand‐1 (PD‐L1) blockade therapy. However, systemic administration of high frequencies and large doses of inosine and anti‐PD‐L1 antibody (aPDL1) is required, which inevitably reduces bioavailability and causes severe immunological side effects. Therefore, it is crucial to develop a drug delivery system to achieve gradient release of inosine and aPDL1 for local immunotherapy. In this study, an inosine‐based supramolecular hydrogel, inosine‐phenylenediboronic‐isoguanosine (IPBisoG), is successfully developed following a simple one‐pot procedure. Both in vitro and in vivo studies demonstrate that the biocompatible and biodegradable IPBisoG hydrogel displays excellent stability and self‐healing properties. Furthermore, the IPBisoG hydrogel is shown to achieve the gradual and sequential release of inosine and aPDL1. Inosine, which enhances the proliferation and function of CD8+ T cells, together with aPDL1, the blocker of the immunosuppressive pathway in tumor microenvironment, can highly enhance the in vivo efficacy of PD‐L1 blockade therapy. The employment of IPBisoG hydrogel is also shown to trigger systemic immune responses. These results demonstrate that IPBisoG hydrogel can be a promising platform for tumor‐local immunotherapy in the future. [ABSTRACT FROM AUTHOR]

Conductive hydrogels used as electronics have received much attention due to their great flexibility and stretchability. However, the fabrication of ideal conductive hydrogels fulfilling the excellent mechanical properties and outstanding sensitivity remains a great challenge until now. Moreover, high sensitivity and broad linearity range are pivotal for the feasibility and accuracy of hydrogel sensors. In this study, a conductive supramolecular hydrogel is engineered by directly mixing the aqueous dispersion of MXene with the precursor of N‐acryloyl glycinamide (NAGA) monomer and then rapidly photo cross‐linked by UV irradiation. The resultant PNAGA/MXene hydrogel‐sensors exhibit high mechanical strength (4.8 MPa), great stretchability (630%), and excellent durability. The conductive hydrogel‐based sensor presents excellent conductivity (17.3 S m−1) and a wide scope of linear dependence of sensitivity on strain (0%–125%, gauge factor = 2.05). It displays reliable detection of various motions, including repeated subtle movements and large strain. It also shows good degradation in vitro and antifouling capability. This work may provide a simple and promising platform for engineering conductive supramolecular hydrogels with integrated high performance aiming for smart wearable electronics, electronic skin, soft robots, and human–machine interfacing. [ABSTRACT FROM AUTHOR]