Adaptable Hydrogel Research Articles

Engineering Living Material for Controlled Fragrance Release Utilizing Kluyveromyces marxianus CBS6556 and Adaptive Hydrogel.

The demand for controllable fragrance materials is substantial owing to their potential to impart enduring scents in a variety of applications. However, the practical application of such materials has been limited by challenges in tunable morphogenesis, structural variability, and adaptability to diverse conditions. In our study, we introduce a hybrid living material that integrates a genetically engineered strain of Kluyveromyces marxianus CBS6556 with an adaptive hydrogel. The engineered K. marxianus achieved temperature stability in 2-phenylethanol (2-PE) and 2-phenylethyl acetate (2-PEAc) production by expressing relevant genes in the 2-PE metabolic pathway using the high-temperature preferential promoter SSE1. The enhanced water retention capacity supports the metabolic activities of the encapsulated yeast cells, ensuring their survival and functionality over an extended period. Fragrance-releasing living material (FLM) is designed to controllably emit fragrance 2-PE by adjusting the microbial concentration within the hydrogel matrix. The FLM exhibits versatile adhesion capabilities, effectively binding to a spectrum of surfaces such as wood, textiles, and glass as well as to natural substrates like leaves. This adaptability enhances the material's applicability across various settings. Furthermore, FLM can be crafted into various forms, including microbeads, fibers, and films. This research opens up new horizons for controlled fragrance release of living materials.

Mitigating Critical Peripheral Nerve Deficit Therapy with Reactive Oxygen Species/Ca2+-Responsive Dynamic Hydrogel-Mediated mRNA Delivery.

Critical peripheral nerve deficiencies present as one of the most formidable conundrums in the realm of clinical medicine, frequently culminating in structural degradation and derangement of the neuromuscular apparatus. Engineered extracellular vesicles (EVs) exhibit the potential to ameliorate nerve impairments. However, the advent of Wallerian degeneration (WD), an inexorable phenomenon that ensues post peripheral nerve injury, serves as an insurmountable impediment to the direct therapeutic efficacy of EVs. In this investigation, we have fashioned a dynamic network for the conveyance of PTEN-induced kinase 1 (PINK1) mRNA (E-EV-P@HPCEP) using an adaptive hydrogel with reactive oxygen species (ROS)/Ca2+ responsive ability as the vehicle, bearing dual-targeted, engineered EVs. This intricate system is to precisely deliver PINK1 to senescent Schwann cells (SCs) while concurrently orchestrating a transformation in the inflammatory-senescent milieu following injury, thereby stymying the progression of WD in peripheral nerve fibers through the stimulation of autophagy within the mitochondria of the injured cells and the maintenance of mitochondrial mass equilibrium. WD, conventionally regarded as an inexorable process, E-EV-P@HPCEP achieved functionalized EV targeting, orchestrating a dual-response dynamic release mechanism via boronate ester bonds and calcium chelation, effectuating an enhancement in the inflammatory-senescent microenvironment, which expedites the therapeutic management of nerve deficiencies and augments the overall reparative outcome.

Dynamic adaptive hydrogel facilitates neuroregeneration in segmental nerve deficits via immunomodulation and mitochondrial homeostasis

The clinical management of segmental nerve deficits faces significant challenges, particularly in achieving substantial neural structural reconstruction and functional recovery. Dynamic, adaptive smart hydrogels hold great promise for restoring tissue function by mimicking regenerative microenvironments and cytokine secretion. However, the influence of hydrogel structure on drug release behavior and its role in maintaining nerve bridging during repair remains underexplored and warrants attention. Here, we present a sequentially gel-forming nerve-guiding conduit (NC/DS@HPBGP) composed of bisphosphonates-modified hyaluronic acid (HA-PBA-BP) and Tannic acid-modified GelMA (GelMA-TA), which contains borate ester bonds and metal coordination bonds, allowing for a dual response to ROS and Ca2+ at nerve injury sites. After implantation, the conduit undergoes dynamic gel-sol–gel transitions, including ROS-responsive release of narciclasine (NC) and 5-iodoisoquinoline (DS) and Ca2+ cross-linking-induced 3D structural reorganization, resulting in enhancing nerve regeneration proximally through immunomodulation and ensuring structural integrity distally via mitochondrial autophagy. This multifaceted integration facilitates dynamic remodeling of the nerve regeneration microenvironment, markedly augmenting nerve regeneration and repair efficacy.

Self-regulated reversal deformation and locomotion of structurally homogenous hydrogels subjected to constant light illumination

Environmentally adaptive hydrogels that are capable of reconfiguration in response to external stimuli have shown great potential toward bioinspired actuation and soft robotics. Previous efforts have focused mainly on either the sophisticated design of heterogeneously structured hydrogels or the complex manipulation of external stimuli, and achieving self-regulated reversal shape deformation in homogenous hydrogels under a constant stimulus has been challenging. Here, we report the molecular design of structurally homogenous hydrogels containing simultaneously two spiropyrans that exhibit self-regulated transient deformation reversal when subjected to constant illumination. The deformation reversal mechanism originates from the molecular sequential descending-ascending charge variation of two coexisting spiropyrans upon irradiation, resulting in a macroscale volumetric contraction-expansion of the hydrogels. Hydrogel film actuators were developed to display complex temporary bidirectional shape transformations and self-regulated reversal rolling under constant illumination. Our work represents an innovative strategy for programming complex shape transformations of homogeneous hydrogels using a single constant stimulus.

3D Printable Active Hydrogels with Supramolecular Additive-Driven Adaptiveness.

Smart hydrogels are a promising candidate for the development of next-generation soft materials due to their stimuli-responsiveness, deformability, and biocompatibility. However, it remains challenging to enable hydrogels to actively adapt to various environmental conditions like living organisms. In this work, supramolecular additives are introduced to the hydrogel matrix to confer environmental adaptiveness. Specifically, their microstructures, swelling behaviors, mechanical properties, and transparency can adapt to external environmental conditions. Moreover, the presence of hydrogen bonding provides the hydrogel with applicable rheological properties for 3D extrusion printing, thus allowing for the facile preparation of thickness-dependent camouflage and multistimuli responsive complex. The environmentally adaptive hydrogel developed in this study offers new approaches for manipulating supramolecular interactions and broadens the capability of smart hydrogels in information security and multifunctional integrated actuation.

Highly Strong, Tough, and Cryogenically Adaptive Hydrogel Ionic Conductors via Coordination Interactions.

Despite the promise of high flexibility and conformability of hydrogel ionic conductors, existing polymeric conductive hydrogels have long suffered from compromises in mechanical, electrical, and cryoadaptive properties due to monotonous functional improvement strategies, leading to lingering challenges. Here, we propose an all-in-one strategy for the preparation of poly(acrylic acid)/cellulose (PAA/Cel) hydrogel ionic conductors in a facile yet effective manner combining acrylic acid and salt-dissolved cellulose, in which abundant zinc ions simultaneously form strong coordination interactions with the two polymers, while free solute salts contribute to ionic conductivity and bind water molecules to prevent freezing. Therefore, the developed PAA/Cel hydrogel simultaneously achieved excellent mechanical, conductive, and cryogenically adaptive properties, with performances of 42.5 MPa for compressive strength, 1.6 MPa for tensile strength, 896.9% for stretchability, 9.2 MJ m-3 for toughness, 59.5 kJ m-2 for fracture energy, and 13.9 and 6.2 mS cm-1 for ionic conductivity at 25 and -70 °C, respectively. Enabled by these features, the resultant hydrogel ionic conductor is further demonstrated to be assembled as a self-powered electronic skin (e-skin) with high signal-to-noise ratio for use in monitoring movement and physiological signals regardless of cold temperatures, with hinting that could go beyond high-performance hydrogel ionic conductors.

Advancing neural regeneration via adaptable hydrogels: Enriched with Mg2+ and silk fibroin to facilitate endogenous cell infiltration and macrophage polarization

Peripheral nerve injury is a complex and challenging medical condition due to the limited ability of nerves to regenerate, resulting in the loss of both sensory and motor function. Hydrogels have emerged as a promising biomaterial for promoting peripheral nerve regeneration, while conventional hydrogels are generally unable to support endogenous cell infiltration due to limited network dynamics, thereby compromising the therapeutic outcomes. Herein, we present a cell adaptable hydrogel containing a tissue-mimetic silk fibroin network and a dynamically crosslinked bisphosphonated-alginate network. The dynamic network of this hydrogel can respond to cell-generated forces to undergo the cell-mediated reorganization, thereby effectively facilitating the rapid infiltration of Schwann cells and macrophages, as well as the ingrowth of axons. We further show that the magnesium ions released from the hydrogel not only promote neurite outgrowth but also regulate the polarization of macrophages in a sequential manner, contributing to the formation of a regenerative microenvironment. Therefore, this hydrogel effectively prevents muscle atrophy and promotes the regeneration and functional recovery of nerve defects of up to 10 mm within 8 weeks. The findings from this study demonstrate that adaptable hydrogels are promising inductive biomaterials for enhancing the therapeutic outcomes of peripheral nerve injury treatments.

Bio-Inspired Far-From-Equilibrium Hydrogels: Design Principles and Applications.

Inspired from dynamic living systems that operate under out-of-equilibrium conditions in biology, developing supramolecular hydrogels with self-regulating and autonomously dynamic properties to further advance adaptive hydrogels with life-like behavior is important. This review presents recent progress of bio-inspired supramolecular hydrogels out-of-equilibrium. The principle of out-of-equilibrium self-assembly for creating bio-inspired hydrogels is discussed. Various design strategies have been identified, such as chemical-driven reaction cycles with feedback control and physically oscillatory systems. These strategies can be coupled with hydrogels to achieve temporal and spatial control over structural and mechanical properties as well as programmable lifetime. These studies open up huge opportunities for potential applications, such as fluidic guidance, information storage, drug delivery, actuators and more. Finally, we address the challenges ahead of us in the coming years, and future possibilities and prospects are identified.

Nature‐Inspired Pressure Interactive Alternating Current Electroluminescent for Orientation Indication, Visual Sensing, and Remote Monitoring

AbstractMost current visual pressure sensing devices are greatly limited by less integrated functions. To address this issue, a multi‐dimensional pressure interactive visual monitoring device is proposed based on the temperature and humidity adaptive hydrogel. Specifically, this device is composed of a buffer grid layer that divides it into pressure sensing and luminous display areas. With a double network structure incorporated with a LiBr liquid, the pressure sensing area demonstrates great deformability, resilience, and self‐absorption. In a dynamic mode, the best pressure can be detected at high humidity and low temperature, displaying a range of up to 45 N and offering feedback at a minimum load of 0.25 N. Importantly, the performance of the device remains excellent even after the dynamic compression repeating over 1300 cycles. In static mode, MPI‐ACEL achieves a delay time of up to 390 min. Finally, it is anticipated that this multifunctional device will provide a new, flexible, and effective scheme for visual pressure sensing, environmental adaptive directional indication, and multi‐dimensional remote monitoring.

Hydrogels with Reversible Crosslinks for Improved Localised Stem Cell Retention: A Review.

Successful stem cell applications could have a significant impact on the medical field, where many lives are at stake. However, the translation of stem cells to the clinic could be improved by overcoming challenges in stem cell transplantation and in vivo retention at the site of tissue damage. This review aims to showcase the most recent insights into developing hydrogels that can deliver, retain, and accommodate stem cells for tissue repair. Hydrogels can be used for tissue engineering, as their flexibility and water content makes them excellent substitutes for the native extracellular matrix. Moreover, the mechanical properties of hydrogels are highly tuneable, and recognition moieties to control cell behaviour and fate can quickly be introduced. This review covers the parameters necessary for the physicochemical design of adaptable hydrogels, the variety of (bio)materials that can be used in such hydrogels, their application in stem cell delivery and some recently developed chemistries for reversible crosslinking. Implementing physical and dynamic covalent chemistry has resulted in adaptable hydrogels that can mimic the dynamic nature of the extracellular matrix.

Stable zinc anode interface and environmentally adaptable hydrogel electrolytes for stable operation of zinc-ion hybrid supercapacitors

Hydrogel-based zinc ion hybrid supercapacitors (ZIHS) have stood out from many energy storage device candidates due to their battery-level energy density, inherent flexibility, and safety. Nevertheless, the inevitable dendrite growth of Zn anodes and sharp capacity degradation at low-temperature seriously hinder their practical application. Herein, a dense ZnF2 solid electrolyte interface protective layer was constructed in situ on the Zn electrode surface by a simple chemical deposition method, effectively isolating the water molecules and alleviating the water-induced dendrite growth and parasitic reaction. To achieve the flexible ZIHS with environmental adaptability, a self-adhesion and anti-freezing zwitterionic hydrogel electrolyte was fabricated to afford superior ionic conductivity (97.1 mS cm−1), excellent anti-drying ability, and robust interfacial adhesion. Benefitting from the integrated merits of the as-designed electrolyte and electrode, the ZIHS delivered excellent mechanical adaptability, favorable energy density (103.9 Wh kg−1 at 270.1 W kg−1), broad operating temperature range (−40 to 40 °C), along with long-term cycling stability (12,000 cycles) with 90.3 % capacity retention at −25 °C. Notably, the unencapsulated ZIHS achieved exceptional electrochemical stability in an open environment. This finding provides valuable insights for constructing durable, flexible, and environmentally adaptable zinc-based energy storage systems.

Environmentally Adaptive Polymer Hydrogels: Maintaining Wet‐Soft Features in Extreme Conditions

AbstractHydrogels have been widely explored to adapt to different application circumstances. As typical wet‐soft materials, the high‐water content of hydrogels is beneficial to their wide biomedical applications. Moreover, hydrogels have been displaying considerable application potential in some high‐tech areas, like brain‐computer interface, intelligent actuator, flexible sensor, etc. However, traditional hydrogel is susceptive to freezing below zero, dehydration, performance swelling‐induced deformation, and suffers from mechanical damage in extremely mechanical environments, which result in the loss of wet‐soft peculiarities (e.g., flexibility, structure integrity, transparency), greatly limiting their applications. Therefore, reducing the freezing point, improving the dehydration/solution resistance, and designing mechanical adaptability are effective strategies to endow hydrogels with the extreme environmental adaptability, thus broadening their application fields. This review systematically summarizes research advances of environmentally adaptive hydrogels (EAHs), comprising anti‐freezing, dehydration‐resistant, acid/base/swelling deformation‐resistant, and mechanical environment adaptive hydrogels (MEAHs). Firstly, fabrication methods are presented, including the deep eutectic solvent/ionic liquid substituent, the addition of salts, organogel, polymer network modification, and double network (DN) complex/nanocomposite strategy, etc. Meanwhile, the features of different approaches are overviewed. The mechanisms, properties, and applications (e.g., intelligent actuator, wound dressing, flexible sensor) of EAHs are demonstrated. Finally, the issues and future perspectives for EAHs’ researches are demonstrated.

3D printed heart valve mediated nitric oxide sustained release reduced potential for calcification and inflammatory capacity

Heart valve replacement have numerous problems, such as calcification, inflammation, and limited endothelialization. Herein, we used bio-degradable arginine-modified polylysine and oxidized hyaluronic acid as the substrate, expanding the advantages of rapid Schiff-base reaction of aldehydes and amino groups under physiological conditions to form dynamic acyl-hydrazone bonds. These were used to design dynamic adaptive hydrogels, and a polysaccharide/protein dual-network system that mimicked the extracellular matrix, realizing the excellent mechanical tunability and shear thinning properties of its hydrogel. The dual antibacterial mechanism effectively avoided the occurrence of infection-like inflammation after valve implantation. The hydrogel has great ability in promoting cellular proliferation, and can also promote cell migration through a potential cell recruitment mechanism. The hydrogel dynamically triggers and sustains NO release in vivo, removing highly expressed ROS in inflammatory site as needed. It further promotes angiogenesis, and provides targeted treatment for calcified aortic valve disease caused by oxidative stress signals. Furthermore, it exhibits exceptional anti-calcification properties and can enhance the upregulation of CD31 while suppressing the expression of IL-10 and TNF-α, thereby significantly promoting angiogenesis and reducing inflammation. Additionally, 3D printing technology enables the individualized customization of valves with diverse heterogeneous structures to achieve a high degree of biomimetic tissue.

Enabling glucose adaptive self-healing hydrogel based triboelectric biosensor for tracking a human perspiration

A breakthrough in intelligent healthcare enables the collection of real-time patient data and active diagnosis via the advancement of medical technology. Monitoring glucose levels steady is essential to minimize diabetes-related issues since glucose is used by cells as an essential source of energy. Despite the range of commercially available glucose monitoring devices, the pain of repetitive blood testing and complex power demands has addressed the shortcomings of painless compact glucose biosensors. To address these drawbacks, self-healing glucose adaptive hydrogel based triboelectric biosensors (GAH-TES) are proposed as a biocompatible noninvasive technique for simultaneous glucose monitoring. With the assistance of a -cyclodextrin inclusion complex, glucose-adaptive PVA hydrogels may be utilized as an immobilization matrix for the glucose oxidase enzyme. The modulation of dynamic hydrogel networks in the presence of diversified glucose environments leads in changes in conductivity that boost electrical performance. Introducing glucose-adaptive hydrogel into a triboelectric nanogenerator (TENG) allows for efficient energy conversion from motion-based glucose stimuli in human sweat to electrical output. Higher glucose concentrations were shown to boost TENG production due to the greater conductivity and polarization effect caused by the increased ionic strength carried by the enzymatic activity. Due to its ability to detect high glucose levels autonomously, GAH-TES has broadened the scope of diabetes management by highly selective, flexible, and reliable real-time monitoring of human perspiration.

Nanohybrid Double Network Hydrogels Based on a Platinum Nanozyme Composite for Antimicrobial and Diabetic Wound Healing.

Along with hypoxia, severe bacterial infection, and abnormal pH, continuous inflammatory response hinders diabetic wounds from healing. It leads to the accumulation of large amounts of reactive oxygen species (ROS) and therefore prevents the transition of diabetic wounds from the inflammatory phase to the proliferative phase. In this work, a nanohybrid double network hydrogel with injectable, self-healing, and tissue adhesion properties based on a platinum nanozyme composite (PFOB@PLGA@Pt) was constructed to manage diabetic wound healing. PFOB@PLGA@Pt exhibited oxygen supply capacity and enzyme catalytic performance accompanied by pH self-regulation in the entire phases of wound healing. In the first stage, the oxygen carried by perfluorooctyl bromide (PFOB) can ameliorate the hypoxia and boost the glucose oxidase-like catalyzed reaction of Pt NPs, leading to a lowered pH environment with gluconic acid. As a result, the NADH oxidase-like, peroxidase-like, and oxidase-like multiple enzyme activities were activated successively, leading to synergistic antibacterial effects through the production of ROS. After the bacterial infection had cleared, the catalase-like and superoxide dismutase-like activities of Pt NPs reshaped the redox microenvironment by scavenging the excess ROS, which transitioned the wound from the inflammatory phase to the proliferative phase. The microenvironmentally adaptive hydrogel treatment can cover all phases of wound healing, showing the significant promoting effect in the repair of diabetic infected wounds.

Multileveled Hierarchical Hydrogel with Continuous Biophysical and Biochemical Gradients for Enhanced Repair of Full-Thickness Osteochondral Defect.

The repair of hierarchical osteochondral defect requires sophisticated gradient reestablishment; however, few strategies for continuous gradient casting consider the relevance to clinical practice regarding cell adaptability, multiple gradient elements, and precise gradient mirroring native tissue. Here, a hydrogel with continuous gradients in nano-hydroxyapatite (HA) content, mechanical, and magnetism is developed using synthesized superparamagnetic HA nanorods (MagHA) that easily respond to a brief magnetic field. To precisely reconstruct osteochondral tissue, the optimized gradient mode is calculated according to magnetic resonance imaging (MRI) of healthy rabbit knees. Then, MagHA are patterned to form continuous biophysical and biochemical gradients, consequently generating incremental HA, mechanical, and electromagnetic cues under an external magnetic stimulus. To make such depth-dependent biocues work, an adaptable hydrogel is developed to facilitate cell infiltration. Furthermore, this approach is applied in rabbit full-thickness osteochondral defects equipped with a local magnetic field. Surprisingly, this multileveled gradient composite hydrogel repairs osteochondral unit in a perfect heterogeneous feature, which mimics the gradual cartilage-to-subchondral transition. Collectively, this is the first study that combines an adaptable hydrogel with magneto-driven MagHA gradients to achieve promising outcomes in osteochondral regeneration.

Photoinduced Dithiolane Crosslinking for Multiresponsive Dynamic Hydrogels.

While many hydrogels are elastic networks crosslinked by covalent bonds, viscoelastic hydrogels with adaptable crosslinks are increasingly being developed to better recapitulate time and position-dependent processes found in many tissues. In this work, 1,2-dithiolanes are presented as dynamic covalent photocrosslinkers of hydrogels, resulting in disulfide bonds throughout the hydrogel that respond to multiple stimuli. Using lipoic acid as a model dithiolane, disulfide crosslinks are formed under physiological conditions, enabling cell encapsulation via an initiator-free light-induced dithiolane ring-opening photopolymerization. The resulting hydrogels allow for multiple photoinduced dynamic responses including stress relaxation, stiffening, softening, and network functionalization using a single chemistry, which can be supplemented by permanent reaction with alkenes to further control network properties and connectivity using irreversible thioether crosslinks. Moreover, complementary photochemical approaches are used to achieve rapid and complete sample degradation via radical scission and post-gelation network stiffening when irradiated in the presence of reactive gel precursor. The results herein demonstrate the versatility of this material chemistry to study and direct 2D and 3D cell-material interactions. This work highlights dithiolane-based hydrogel photocrosslinking as a robust method for generating adaptable hydrogels with a range of biologically relevant mechanical and chemical properties that are varied on demand.

Light‐Fueled Nonequilibrium and Adaptable Hydrogels for Highly Tunable Autonomous Self‐Oscillating Functions

AbstractNonequilibrium oscillation fueled by dissipating chemical energy is ubiquitous in living systems for realizing a broad range of complex functions. The design of synthetic materials that can mimic their biological counterparts in the production of dissipative structures and autonomous oscillations is of great interest but remains challenging. Here, a series of environmentally adaptable hydrogels functionalized with photoswitchable spiropyran derivatives that display a tunable equilibrium‐shifting capability, thus endowing those hydrogels with a high degree of freedom and flexibility is reported. Such nonequilibrium hydrogels are able to responsively adapt their shapes under constant light illumination due to asymmetric deswelling, which in turn generates self‐shadowing and consequently creates autonomous self‐oscillating behaviors through a negative feedback process. Diverse oscillation modes including bending, twisting, and snap‐through buckling with tunable frequency and amplitude are widely observed in three different molecular systems. Density functional theory calculations and finite element simulations further demonstrated the robustness of such a photoadaptable self‐oscillation mechanism. This study provides a useful molecular design strategy for construction of highly adaptable hydrogels with potential applications in self‐sustained soft robots and autonomous devices.

Bio-inspired hydrogel actuator with rapid self-strengthening behavior

Inspired by intelligent biomaterials which often have flexible responsiveness to multiple environmental cues and strengthen their mechanical properties by trainings, emerging soft actuators require programmable manipulation. Currently, the integration of such characteristics as rapid self-strengthening, strain-adaptive stiffening and smart actuation, into a single hydrogel actuator is urgently needed. Here, we report a self-strengthened hydrogel actuator based on the semi-interpenetrating polymer network consisting of polyvinyl alcohol (PVA) and poly(N-isopropylacrylamide) (PNIPAm), which can display diverse programmable actuations by responding to temperature/salt stimuli. In the design, the layer of freeze-thawed PNIPAm/PVA (PPGel-F) is assembled with another original PNIPAm/PVA hydrogel layer (PPGel) into one device. By taking advantage of the PVA crystalline nanofibrils in the PPGel-F matrix, the differentiated swelling degree across the bilayer structure gives rise to asymmetric deformations and the resultant shape transformation. Moreover, upon the mechanical training with less than 100 cycles, the anisotropic arrangement of PVA nanofibrils through strong hydrogen bonding interactions can swiftly immobilize the amorphous polymer chains orientation along the tensile direction. This enhances the strain-induced crystallization, thereby generating the rapid self- strengthening behavior. The proposed work provides potential solution for constructing dynamically adaptive hydrogel systems that can mimic biological tissues for more intelligent soft robotics and bionic research.

Bioinspired Oxidation-Resistant Catechol-like Sliding Ring Polyrotaxane Hydrogels

Adaptable hydrogels have been used in the biomedical field to address several pathologies, especially those regarding tissue defects. Here, we describe unprecedented catechol-like functionalized polyrotaxane (PR) polymers able to form hydrogels. PR were functionalized with the incorporation of hydroxypyridinone (HOPO) moieties into the polymer backbone, with a degree of substitution from 4 to 22%, depending on the PR type. The hydrogels form through the functionalized supramolecular systems when in contact with a Fe(III) solution. Despite the hydrogel formation being at physiological pH (7.4), the HOPO derivatives are extremely resistant to oxidation, unlike common catechols; consequently, they prevent the formation of quinones, which can lead to irreversible bounds within the matrix. The resulting hydrogels demonstrated properties lead to unique hydrogels with improved mechanical behavior obtained by metallic coordination crosslinking, due to the synergies of the sliding-ring PR and the non-covalent (reversible) catechol analogues. Following this strategy, we successfully developed innovative, cytocompatible, oxidative-resistant, and reversible crosslinked hydrogels, with the potential of being used as structural self-materials for a variety of applications, including in the biomedical field.