Dynamic Non-covalent Interactions Research Articles

Heterogeneous and Cooperative Rupture of Histidine-Ni2+ Metal-Coordination Bonds on Rationally Designed Protein Templates.

Metal-coordination bonds, a highly tunable class of dynamic noncovalent interactions, are pivotal to the function of a variety of protein-based natural materials and have emerged as binding motifs to produce strong, tough, and self-healing bioinspired materials. While natural proteins use clusters of metal-coordination bonds, synthetic materials frequently employ individual bonds, resulting in mechanically weak materials. To overcome this current limitation, we rationally designed a series of elastin-like polypeptide templates with the capability of forming an increasing number of intermolecular histidine-Ni2+ metal-coordination bonds. Using single-molecule force spectroscopy and steered molecular dynamics simulations, we show that templates with three histidine residues exhibit heterogeneous rupture pathways, including the simultaneous rupture of at least two bonds with more-than-additive rupture forces. The methodology and insights developed improve our understanding of the molecular interactions that stabilize metal-coordinated proteins and provide a general route for the design of new strong, metal-coordinated materials with a broad spectrum of dissipative time scales.

A reusable, healable, and biocompatible PEDOT:PSS hydrogel-based electrical bioadhesive interface for high-resolution electromyography monitoring and time–frequency analysis

As the most ideal interface between bioelectronic devices and biological tissues, the electrical bioadhesive interface (EBI) holds significant potential for various applications, including soft bioelectronics, wearable devices, and electrophysiological signal monitoring. However, most current EBIs are disposable products that lack repeatable adhesion and self-healing properties, thus hindering practical applications. Herein, we develop a reusable EBI by incorporating a dynamic non-covalent interaction enhancer polydopamine (PDA) and conductive PEDOT:PSS into an adhesive hydrogel matrix polyacrylamide (PAM). The EBI exhibits intriguing overall electrical and mechanical properties, including high conductivity (5.57 S m−1), tissue-like Young’s modulus (2.7 kPa), low interfacial impedance (1 kΩ), and excellent adhesion strength (46.45 ± 1.75 kPa on porcine skin) with excellent retention (87 %) after 200 adhering/detaching cycles, high self-healing efficiency of 94.11 %, and outstanding biocompatibility in HDF-a and HaCaT cell models. Benefiting from these superior properties, we further demonstrate the fabrication and application of an EBI-based reusable electromyography monitoring patch (EMP). The reusable EMP enables high-resolution electromyography signal monitoring capability with a higher signal-to-noise ratio (SNR) of 30.05 dB than commercial electrodes (12.06 dB). Remarkably, such reusable EMP maintains very stable SNR of 21.82 dB after 200 adhering/detaching cycles (3.8 times higher than commercial electrodes, 5.74 dB after 30 cycles), and showcases typical time and frequency-domain characteristics. These findings demonstrate a promising reusable EMP to enhance the accuracy and convenience of electromyography monitoring.

Hysteresis-free, fatigue-resistant and self-adhesive conductive hydrogel electronics towards multimodal wearable application

Conductive hydrogel-based electronic skins (e-skins) have attracted great attentions in health monitoring, human-machine interactions, and soft devices. Yet, broad challenges still remain in manufacturing of high-performance units, ingenious assembly of devices and developing of multimodal applications. Here, a typical strategy of combined covalent crosslinking and dynamic non-covalent interaction (multiple hydrogen bonds and electrostatic complexation) is used to prepare the ultra-durable polyacrylic acid (PAA)/ chitosan (CS)/ Ti3C2Tx (MXene) conductive hydrogel. It exhibits matched modulus for human skin, subtle mechanical hysteresis behavior (η=0.27% of 200% stretch, energy loss coefficient), great fatigue-resistant stability (>99%, 400% strain), robust interface adhesion (∼30 kPa) and essential biocompatibility. Benefited of such high performance, a series of hydrogel-based devices are further assembled to demonstrate the multi-mode and multi-scenario applications, including the strain and temperature sensors, triboelectric nanogenerator. Clearly, thereby this work provides a new toolbox for the rational design of high-performance hybrid hydrogel, and points out a general route for further hydrogel-based device assembly and multimodal applications.

Dynamic Non-Covalent Exchange Intrinsic Self-Healing at 20 °C Mechanism of Polyurethane Induced by Interactions among Polycarbonate Soft Segments.

Two polyurethanes (PUs) were similarly synthesized by reacting a cycloaliphatic isocyanate with 1,4-butanediol and two polyols of different nature (polyester, polycarbonate diol) with molecular weights of 1000 Da. Only the PU synthesized with polycarbonate diol polyol (YCD) showed intrinsic self-healing at 20 °C. For assessing the mechanism of intrinsic self-healing of YCD, a structural characterization by molecular weights determination, infrared and X-ray photoelectronic spectroscopies, differential scanning calorimetry, X-ray diffraction, thermal gravimetric analysis, and dynamic mechanical thermal analysis was carried out. The experimental evidence concluded that the self-healing at 20 °C of YCD was due to dynamic non-covalent exchange interactions among the polycarbonate soft segments. Therefore, the chemical nature of the polyol played a key role in developing PUs with intrinsic self-healing at 20 °C.

Mussel inspired sequential protein delivery based on self-healing injectable nanocomposite hydrogel

Polysaccharide based self-healing and injectable hydrogels with reversible characteristics have widespread potential in protein drug delivery. However, it is a challenge to design the dynamic hydrogel for sequential release of protein drugs. Herein, we developed a novel mussel inspired sequential protein delivery dynamic polysaccharide hydrogel. The nanocomposite hydrogel can be fabricated through doping polydopamine nanoparticles (PDA NPs) into reversible covalent bond (imine bonds) crosslinked polymer networks of oxidized hyaluronic acid (OHA) and carboxymethyl chitosan (CEC), named PDA NPs@OHA-l-CEC. Besides multiple capabilities (i.e., injection, self-healing, and biodegradability), the nanocomposite hydrogel can achieve sustained and sequential protein delivery of vascular endothelial growth factor (VEGF) and bovine serum albumin (BSA). PDA NPs doped in hydrogel matrix serve dual roles, acting as secondary protein release structures and form dynamic non-covalent interactions (i.e., hydrogen bonds) with polysaccharides. Moreover, by adjusting the oxidation degree of OHA, the hydrogels with different crosslinking density could control overall protein release rate. Analysis of different release kinetic models revealed that Fickian diffusion drove rapid VEGF release, while the slower BSA release followed a Super Case II transport mechanism. The novel biocompatible system achieved sequential release of protein drugs has potentials in multi-stage synergistic drug deliver based on dynamic hydrogel.

Strategies for Constructing Macrocyclic Arene-Based Color-Tunable Supramolecular Luminescent Materials.

Over the past decades, supramolecular luminescent materials (SLMs) have attracted considerable attention due to their dynamic noncovalent interactions, versatile functions, and intriguing applications in many research fields. From construction to application, great efforts and progress have been made in color-tunable SLMs in recent years. In order to realize multicolor luminescence, various design strategies have been proposed. Macrocyclic chemistry, one of the brightest jewels in the field of supramolecular chemistry, has played a crucial role in the construction of stimuli-responsive and emission-tunable SLMs. Moreover, the flexible and tunable conformation and multiple noncovalent complexation sites of the macrocyclic arenes (MAs) afford a new opportunity to create such dynamic smart luminescent materials. Inspired by our reported work on the color-tunable supramolecular crystalline assemblies modulated by the conformation of naphth[4]arene, this Concept provides a summary of the latest developments in the construction of color-tunable MA-based SLMs, accompanied by the various construction strategies. The aim is to provide researchers with a new perspective to construct color-tunable SLMs with fascinating functions.

Towards flexible and healable strain sensors via a modulated interface between Ti3C2 MXene and epoxidized natural rubber

Critical issues such as inferior mechanical properties, low healing efficiency, complex repair conditions, etc., have posed a great threat to the intelligent sensing implementation of elastomers. Herein, we delicately design Ti3C2 MXene/epoxidized natural rubber (ENR) elastomer composites with superior mechanical and self-healing properties by controlling the confine structure and surface hydroxyl group number of Ti3C2 MXene targeting the realization of advanced strain sensors. The synchrotron radiation X-ray three-dimensional nano-computed tomography results confirm the uniform distribution and of Ti3C2 MXene in ENR, and the outstanding structural stability of composite elastomer throughout the loading and unloading procedure. Such versatile design leads to the synchronous manipulation of the interface density and strength of the composite, maximizing the dynamic non-covalent bond interactions between Ti3C2 MXene and ENR. As a result, the composite elastomer display a high mechanical strength of 4.93 MPa, and a remarkable self-healing efficiency of ∼98% at room temperature, thereby affording superior intelligent strain sensing application. Impressively, the detection range and response time are up to 0.1∼800% strain, and 50 ms, respectively, outperforming the state-of-art self-healable strain sensors. This investigation not only provides a new interfacial engineering strategy for designing elastomer composites with advanced intelligent sensing functions but also propels the underlying interfacial working mechanism deciphering.

Applications of Supramolecular Polymers Generated from Pillar[n]arene-Based Molecules.

Supramolecular chemistry enables the manipulation of functional components on a molecular scale, facilitating a "bottom-up" approach to govern the sizes and structures of supramolecular materials. Using dynamic non-covalent interactions, supramolecular polymers can create materials with reversible and degradable characteristics and the abilities to self-heal and respond to external stimuli. Pillar[n]arene represents a novel class of macrocyclic hosts, emerging after cyclodextrins, crown ethers, calixarenes, and cucurbiturils. Its significance lies in its distinctive structure, comparing an electron-rich cavity and two finely adjustable rims, which has sparked considerable interest. Furthermore, the straightforward synthesis, uncomplicated functionalization, and remarkable properties of pillar[n]arene based on supramolecular interactions make it an excellent candidate for material construction, particularly in generating interpenetrating supramolecular polymers. Polymers resulting from supramolecular interactions involving pillar[n]arene find potential in various applications, including fluorescence sensors, substance adsorption and separation, catalysis, light-harvesting systems, artificial nanochannels, and drug delivery. In this context, we provide an overview of these recent frontier research fields in the use of pillar[n]arene-based supramolecular polymers, which serves as a source of inspiration for the creation of innovative functional polymer materials derived from pillar[n]arene derivatives.

A high‐strength flexible transparent reprocessable polyurea film based on dual dynamic noncovalent interactions

AbstractTo address the issues that waste of resources and environmental pollution caused by discarded materials, dynamic bonds are widely introduced into polymers to endow them with reprocess ability. However, there are some obvious issues in existing research such as poor toughness, low fracture elongation, and inability for repeated reprocessing of materials. Considering above problems, this study introduces dense hydrogen bonding and cation–π interactions into the polyurea system, and develops a high‐performance transparent film based on dual dynamic non‐covalent interactions, which enables the film to be reprocessed. Through the synergy of the dual non‐covalent networks, the film exhibits a high tensile strength of 79.6 ± 3.9 MPa and good hardness (pencil hardness of 4H, elastic modulus of 2.69 GPa). It can effectively resist the scratching of copper brush and maintain more than 97% of its initial mechanical strength after being reprocessed five times. In addition, the film has good adhesion to various substrates, as well as high flexibility (0.5 mm) and excellent optical properties (high light transmission of 91.1% and low haze of 0.94%). This study proposes a novel approach to enable polymer materials to be reprocessed and demonstrates the preparation of a film with great potential in optical protection and wearable devices.

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.

Plant oil-based branched polymer coatings enhanced with nucleobases for achieving strong adhesion and outstanding environmental tolerance

Plant oils as the most typical and widest available biomass feedstocks have been employed to construct organic coatings. In contrast to the conventional plant oil-based thermoset coatings, it is still challenging to fabricate robust supramolecular plant oil-based coatings with reversible and dynamic noncovalent interactions, overcoming the drawbacks of thermoset coatings. In this work, we have reported a series of strong nucleobase-enhanced plant oil-based coatings with multiple supramolecular interactions such as hydrogen bonding, π-π stacking, hydrophobic and coordination interactions. The nucleobase-functionalized supramolecular plant oil-based coatings display strong adhesion and outstanding environmental tolerance towards different pH conditions, the variation of temperatures, and UV irradiation. In order to optimize the polymerization of the plant oil-based monomer, the radical polymerization of methacrylate-type camellia oil monomer (MCO) was studied to understand the influence of the unsaturated carbon–carbon double bond in the appended long fatty chain on the polymerization of the methacrylate. The stable propagation radicals of methacrylate-type monomer result in the formation of branched plant oil-based polymers with high efficacy. The copolymerization of the plant oil-based and nucleobase-functionalized methacrylates and the supramolecular mixing achieves the maximum adhesion of 9.89 MPa, highlighting the potential of fabricating strong supramolecular plant oil-based coatings.

Self-adhesive, ionic-conductive, mechanically robust cellulose-based organogels with anti-freezing and rapid recovery properties for flexible sensors

Cellulose-based functional gels have received considerable attention because of their good mechanical properties, biocompatibility, and low cost. However, the preparation of cellulose gels with self-adhesion, mechanical robustness, ionic conductivity, anti-freezing ability, and environmental stability remains a challenge. Here, gallic acid esterified microcrystalline cellulose (MCC-GA) was obtained by grafting gallic acid (GA) onto the macromolecular chains of microcrystalline cellulose (MCC) through a one-step esterification method. Then the prepared MCC-GA was dissolved in Lithium chloride/dimethyl sulfoxide (LiCl/DMSO) system and polymerized with acrylic acid (AA) to prepare a multi-functional cellulose-based organogel. The prepared MCC-GA/polyacrylic acid (PAA) organogels exhibited enhanced interfacial adhesion through hydrogen bonding, π–π interactions, and electrostatic interactions. Additionally, the MCC–GA/PAA organogels could withstand 95 % of the compressive deformation and rapidly self-recover owing to chemical cross-linking and dynamic non-covalent interactions. The organogels also exhibited excellent anti-freezing properties (up to −80 °C), solvent retention, and ionic conductivity. Considering its excellent overall performance, the MCC–GA/PAA organogel was used as an effective flexible sensor for human motion detection and is expected to play an important role in the future development of flexible bioelectronics.

Revisiting organic charge-transfer cocrystals for wide-range tunable, ambient phosphorescence.

Simple and efficient designs that enable a wide range of phosphorescence emission in organic materials have ignited scientific interest across diverse fields. One particularly promising approach is the cocrystallization strategy, where organic cocrystals are ingeniously formed through relatively weaker and dynamic non-covalent interactions. In our present study, we push the boundaries further by extending this cocrystal strategy to incorporate donor-acceptor components, stabilized by various halogen bonding interactions. This non-covalent complexation triggers ambient, charge-transfer phosphorescence (3CT), which can be precisely tuned across a broad spectrum by a modular selection of components with distinct electronic characteristics. At the core of our investigation lies the electron-deficient phosphor, pyromellitic diimide, which, upon complexation with different donors based on their electron-donating strength, manifests a striking array of phosphorescence emission from CT triplet states, spanning from green to yellow to reddish orange accompanied by noteworthy quantum yields. Through a systematic exploration of the electronic properties using spectroscopic studies and molecular organization through single-crystal X-ray diffraction, we decisively establish the molecular origin of the observed phosphorescence. Notably, our work presents, for the first time, an elegant demonstration of tunable 3CT phosphorescence emission in intermolecular donor-acceptor systems, highlighting their immense significance in the quest for efficient organic phosphors.

Chiral fiber supramolecular hydrogels for tissue engineering.

Tissue engineering (TE), as a new interdisciplinary discipline, aims to develop biological substitutes for repairing damaged tissues and organs. For the success of tissue regeneration, such biomaterials need to support the physiological activities of cells and allow the growth and maturation of tissues. Naturally, this regulation is achieved through the dynamic remodeling of the extracellular matrix (ECM) of cells. In recent years, chiral supramolecular hydrogels have shown higher application potential in the TE field than traditional polymer hydrogels due to their dynamic noncovalent interactions, adjustable self-assembly structure, and good biocompatibility. These advantages make it possible to construct hydrogels under physiological conditions with structure and function similar to those of the natural ECM. Meanwhile, the chiral characteristics of hydrogels play an important role in regulating cellular activities such as differentiation, adhesion, and proliferation, which is beneficial for tissue formation. In this review, a brief introduction is presented to highlight the importance of chiral fiber supramolecular hydrogels for TE at first. Afterward, the considerations for chiral supramolecular hydrogel design, as well as the influence of external stimuli on chiral hydrogel construction, are discussed. Finally, the potential application prospects of these materials in TE and the significant contribution made by our group in this field are summarized. This review not only helps to reveal the importance of chiral properties in TE but also provides new strategies for TE research based on chiral bionic microenvironments. This article is categorized under: Implantable Materials and Surgical Technologies > Nanotechnology in Tissue Repair and Replacement Biology-Inspired Nanomaterials > Peptide-Based Structures Nanotechnology Approaches to Biology > Cells at the Nanoscale Therapeutic Approaches and Drug Discovery > Emerging Technologies.

Highly Conductive, Transparent, Adhesive, and Self-Healable Ionogel Based on a Deep Eutectic Solvent with Widely Adjustable Mechanical Strength.

Ionogels have attracted intensive attentions as promising flexible conductive materials. However, simultaneous integration of excellent mechanical properties, high conductivity, outstanding self-healing ability, and strong adhesiveness is still challenging. Here, an ingenious composition design is proposed to address this long-standing challenge of ionogels. High-performance PEI/PAA/CMC ionogels, consist of a loosely cross-linked poly(acrylic acid) (PAA) network, dynamically cross-linked network based on polycationic polyethyleneimine (PEI) and polyanionic PAA, and carboxymethyl cellulose (CMC) reinforcing filler, are formed in a deep eutectic solvent (DES) composed of choline chloride and urea. Benefiting from the loose PAA network and dynamic noncovalent interactions, ionogels with both highly enhanced mechanical robustness and excellent conductivity are obtained at high loading of DES, overcoming the strength-ductility/conductivity trade-off dilemma. By adjusting PEI/PAA mass ratio, the tensile strength and strain of PEI/PAA/CMC ionogels are effectively controlled in a wide range of 0.15-7.9MPa and 232-1161%, respectively, while maintaining the desirable conductivity of ≈10-4 S cm-1 . Besides, healed tensile strength over 2.1MPa and adhesion strength up to 0.2MPa are achieved for the PEI0.06 /PAA0.25 /CMC0.01 ionogel. The delicate design strategy provides a feasible approach to prepare ionogels with outstanding comprehensive performance, which have potential for applications in flexible electronics.

Multiresponsive, Self-Healing, and Hierarchical Materials Constructed from Anion Recognition-Based Supramolecular Polymer Networks

3A type supramolecular monomers in which three calix[4]pyrrole units connected to a central benzene unit with varying linker lengths were synthesized through azide–alkyne click reactions between two different azide cores and an alkyne-functionalized calix[4]pyrrole. These compounds were then complexed with a BB-type monomer tetrabutylammonium suberate in chloroform and acetonitrile via hydrogen bonding between calix[4]pyrrole units of 3A monomers and carboxylate units of suberate anions, leading to the formation of anion recognition-based supramolecular polymer networks. Owing to the dynamic noncovalent interactions, the resulting systems were found to be responsive against temperature, competing anions, and pH. Rheological analyses of the supramolecular polymer networks revealed that the system with a longer distance between the benzene core and calix[4]pyrrole units exhibits transient network behavior and viscoelastic self-healing ability below 20% deformation ratio. These systems were also used for the fabrication of hierarchical materials ranging from zero-dimensional (0D) to three-dimensional (3D) by utilizing various methods. This work demonstrates for the first time the preparation of anion recognition-based supramolecular polymer networks based on calix[4]pyrroles and their utilization in the formation of multiresponsive, self-healing materials for the fabrication of hierarchical materials.

Guest Molecule-Mediated Energy Harvesting in a Conformationally Sensitive Peptide-Metal Organic Framework.

The apparent piezoelectricity of biological materials is not yet fully understood at the molecular level. In particular, dynamic noncovalent interactions, such as host–guest binding, are not included in the classical piezoelectric model, which limits the rational design of eco-friendly piezoelectric supramolecular materials. Here, inspired by the conformation-dependent mechanoresponse of the Piezo channel proteins, we show that guest–host interactions can amplify the electromechanical response of a conformationally mobile peptide metal–organic framework (MOF) based on the endogenous carnosine dipeptide, demonstrating a new type of adaptive piezoelectric supramolecular material. Density functional theory (DFT) predictions validated by piezoresponse force microscopy (PFM) measurements show that directional alignment of the guest molecules in the host carnosine–zinc peptide MOF channel determines the macroscopic electromechanical properties. We produce stable, robust 1.4 V open-circuit voltage under applied force of 25 N with a frequency of 0.1 Hz. Our findings demonstrate that the regulation of host–guest interactions could serve as an efficient method for engineering sustainable peptide-based power generators.

Complexation of Sulfonate-Containing Polyurethane and Polyacrylic Acid Enables Fabrication of Self-Healing Hydrogel Membranes with High Mechanical Strength and Excellent Elasticity.

Artificial hydrogel membranes with good biocompatibility are strongly needed in biological fields. The preparation of biocompatible hydrogel membranes simultaneously possessing high mechanical strength, excellent elasticity, and satisfactory self-healing properties remains a challenge. Herein, we demonstrate the preparation of such hydrogel membranes by complexation of sulfonate-containing polyurethane (SPU) and poly(acrylic acid) (PAA) in the presence of Zn2+ ions followed by swelling in water (denoted as SPU-PAA/Zn). Originating from the synergy of the coordination and hydrogen-bonding interactions and the reinforcement effect of the in situ formed hydrophobic domains, the SPU-PAA/Zn hydrogel membrane exhibits a high tensile strength of ∼7.1 MPa and a toughness of ∼30.4 MJ m-3. Moreover, the hydrogel membrane is highly elastic, which can restore to its initial state from an ∼500% strain within 40 min rest at room temperature without any external assistance. The dynamic noncovalent interactions and hydrophobic domains allow the fractured hydrogel membrane to heal and completely regain its original integrity and mechanical properties at room temperature. Both in vitro and in vivo tests confirm that the hydrogel membrane exhibits satisfactory biocompatibility and could be potentially used as a biological barrier membrane in surgical operations or artificial organs.

Repositioning of Etravirine as a Potential CK1ε Inhibitor by Virtual Screening.

CK1ε is a key regulator of WNT/β-catenin and other pathways that are linked to tumor progression; thus, CK1ε is considered a target for the development of antineoplastic therapies. In this study, we performed a virtual screening to search for potential CK1ε inhibitors. First, we characterized the dynamic noncovalent interactions profiles for a set of reported CK1ε inhibitors to generate a pharmacophore model, which was used to identify new potential inhibitors among FDA-approved drugs. We found that etravirine and abacavir, two drugs that are approved for HIV infections, can be repurposed as CK1ε inhibitors. The interaction of these drugs with CK1ε was further examined by molecular docking and molecular dynamics. Etravirine and abacavir formed stable complexes with the target, emulating the binding behavior of known inhibitors. However, only etravirine showed high theoretical binding affinity to CK1ε. Our findings provide a new pharmacophore for targeting CK1ε and implicate etravirine as a CK1ε inhibitor and antineoplastic agent.

Mechanical Integrity in a Dynamic Interpenetrating Hydrogel Network of Supramolecular Peptide-Polysaccharide Supports Enhanced Chondrogenesis.

Tissue engineering demands intelligently designed scaffolds that encompass the properties of the target tissues in terms of mechanical and bioactive properties. An ideal scaffold for engineering a cartilage tissue should provide the chondrocytes with a favorable 3D microarchitecture apart from possessing optimal mechanical characteristics such as compressibility, energy dissipation, strain stiffening, etc. Herein, we used a unique design approach to develop a hydrogel having a dynamic interpenetrating network to serve as a framework to support chondrocyte growth and differentiation. An amyloid-inspired peptide amphiphile (1) was self-assembled to furnish kinetically controlled nanofibers and incorporated in a dynamic covalently cross-linked polysaccharide network of carboxymethyl cellulose dialdehyde (CMC-D) and carboxymethyl chitosan (CMCh) using Schiff base chemistry. The dynamic noncovalent interaction played a pivotal role in providing the desired modulation in the structure and mechanical properties of the double-network hydrogels that are imperative for cartilage scaffold design. The adaptable nature supported shear-induced extrusion of the hydrogel and facilitated various cellular functions while maintaining its integrity. The potential of the as-developed hydrogels to support in vitro chondrogenesis was explored using human chondrocytes. Evidence of improved cell growth and cartilage-specific ECM production confirmed the potential of the hydrogel to support cartilage tissue engineering while reaffirming the significance of mimicking the biophysical microenvironment to induce optimal tissue regeneration.