Topologically Entangled Hydrogels with Self-Evolving Ultraplasticity-to-Hyperelasticity

Topologically Entangled Hydrogels with Self-Evolving Ultraplasticity-to-Hyperelasticity | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article Topologically Entangled Hydrogels with Self-Evolving Ultraplasticity-to-Hyperelasticity Yi Chen, Jiawei Lu, Ziguang Zhao, Xizhi Liao, Jiating Liu, Jin Chen, and 7 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7839519/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted You are reading this latest preprint version Abstract Elastoplastic materials with self-evolving ability can exhibit specific elastic or plastic responses to large strains, whereas hydrogels typically behave as elastomers with a low elastic range due to the nonuniform crosslinking structure and restrictions among cross-networks. Achieving both ultraplasticity and hyperelasticity within the same hydrogel has not been previously reported. In this study, a single-component hydrogel is developed that can reversibly transition in situ from ultraplasticity (ultralong plastic deformation, strain (λ) ~ 120000%) to hyperelasticity (λ = 1200%, with full recovery within 2–10 seconds after stretching) by modulating molecular chain conformation and network topology from free to entangled state through differences in electrostatic and hydrophobic interactions. The transformation can be regulated by adjusting internal system parameters, such as the in situ concentrations of polymers and ions. During the transformation process, the hydrogel exhibits a broad range of tuneable mechanical properties, including a modulus (E) ranging from 700 Pa to 2 MPa and a toughness (Γ) varying between 15 and 8000 kJ/m³. Additionally, this hydrogel demonstrated exceptional fatigue resistance and damage tolerance, with a fatigue threshold (Gi) reaching 1050 J/m². The hydrogel with self-evolving ultraplasticity-to-hyperelasticity can provide flexible mechanical responses, and can extensively simulate the mechanical properties of diverse biological tissue matrices, thereby offering a superior option for materials used in cell and tissue engineering. Physical sciences/Chemistry/Materials chemistry/Mechanical properties Physical sciences/Chemistry/Polymer chemistry/Mechanical properties Physical sciences/Materials science/Soft materials/Gels and hydrogels Physical sciences/Materials science/Soft materials/Polymers Physical sciences/Materials science/Biomaterials/Bioinspired materials Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Introduction Hydrogels possess a three-dimensional (3D) structure analogous to that of the extracellular matrix 1 , integrating elasticity and plasticity, and exhibit significant potential in applications such as cell and tissue engineering 2 , 3 , as well as in vitro and in vivo interventional therapies 4 , 5 . However, hydrogels are typically designed as a cross-linked network structure, whether synthetic or natural materials, and thus are restricted to being used only as elastomer materials. In addition, strong cross-linked structures formed by covalent or noncovalent interactions often restrict the conformational changes of polymer chains, leading to brittleness and fixed mechanical properties, whereas weak cross-linking is prone to insufficient strength 6 . Meanwhile, neither of them can achieve an extremely large deformation. In comparison, biological tissues are highly dynamic elastoplastic systems characterized by specific spatial architectures, including reticular elastin, helical collagen fibres, and smooth muscle tissues, all of which contribute to the stabilization of large deformations and special elastoplasticity 7 . Specifically, these tissues exhibit partially elastic “quasi-solid” behavior, undergoing reversible deformation when subjected to an external force, whereas other regions demonstrate fluid-like characteristics, exhibiting irreversible deformation even after the removal of the applied force. The extent of elasticity and plasticity is determined by the tissue's composition and structural organization. Through the synergistic interplay of endogenous and exogenous biological responses within these structural frameworks, biological tissues exhibit a broad spectrum of mechanical behaviours, enabling the maintenance of complex and efficient physiological functions 8 . To match the broad spectrum of mechanical elastoplastic properties exhibited by biological tissues, a variety of sophisticated hydrogel construction strategies have been developed. Typical approaches involve modified macromolecules or biomass materials containing abundant dynamic functionalities, such as proteins, peptides, and polysaccharides, as primary components to fabricate hydrogels 9 , 10 . Through structural design, covalent or noncovalent interactions are utilized to generate dynamic behaviours in response to environmental stimuli (e.g., ions, solvents, pH, and temperature). These features enable the hydrogel to exhibit reversible sol-gel transitions 1 1 , shear thickening or thinning 1 2 , shape memory effects 1 3 , and other mechanical behavior and functionality. However, the aforementioned construction methods and functional characteristics remain structurally constrained because of their inherent network architectures. The network structure cannot fundamentally switch between elastic and plastic states in a reversible manner. If a simple switching mechanism could be integrated to enable in situ reversible switching of both network structures and properties within the same hydrogel system, thereby achieving extensive tunability of elastoplastic mechanical behaviours, it would significantly streamline the structural design efforts required for specific applications and broaden the functional applicability of such materials. In studies of neutral or anionic/cationic hydrogels, various chain conformations induced by intermolecular interactions, such as freely jointed chains (FJCs), pearl-necklace chains (PNCs), and coiled chains (CCs), have been proposed and experimentally validated. Following chemical cross-linking, these conformations can form elastic three-dimensional network structures. However, the cross-linking process simultaneously results in the stabilization, and thus reduced dynamic adaptability, of their mechanical properties. Herein, we propose a novel strategy to achieve self-evolving ultraplasticity to hyperelasticity in single-component hydrogels through reversible transformations of chain conformation and topological structure. This reversibility is driven by the differential electrostatic and hydrophobic interactions among the chains of amphoteric ionic polymers. In the ultraplastic state, the hydrogel achieves an unprecedented stable strain of up to 120000%, upon transition to the hyperelastic state, it maintains a reversible strain of 1200%. Notably, the hydrogel exhibits excellent fatigue resistance and damage tolerance ability throughout the entire elastic-plastic transformation range. The aforementioned characteristics enable the simulation of diverse mechanical properties exhibited by various biological tissues using a single hydrogel system, thereby offering new avenues for the development of advanced hydrogel materials with enhanced mechanical specificity in biomedical engineering applications. Results Topologically free/entangled network In this study, to achieve the self-evolving transformation of hydrogels from ultraplastic to hyperelastic on the basis of mechanical properties, we propose a construction strategy for single-component hydrogels based on a topologically entangled network structure. The amphoteric monomers [2(methacryloyloxy) ethyl] dimethyl-(3-sulfopropyl) (SBMA) are employed to construct unique hydrogels (abbreviated as PSM XM , where x represents the polymer concentration). The monomers undergo radical polymerization through the initiation of C = C double bonds, forming long-chain polymers (with controlled initiation to maintain consistent molecular weights). (Supplementary Figs. 1‒3 and 5)) The key structural features enabling the observed properties are the following. (1) The polymer monomer simultaneously incorporates anionic/cationic groups and hydrophilic/hydrophobic segments. (2) There are no fixed crosslinking points formed by covalent bonds. Consequently, under varying polymer chain concentrations and hydration conditions, the short-range hydrophobic interactions between alkyl chains compete with long-range electrostatic interactions among charged groups (Fig. 1 a). The subtle and antagonistic balance between these forces results in different polymer chain conformations, which are also fully reversible. This mechanism fundamentally differs from the conventional fixed network structures in traditional hydrogels, where the chain conformation is locked to a greater degree. We observe the conformation of the polymer chains using atomic force microscopy (AFM) and perform Gaussian fitting on the -OH peak in the Raman spectrum to validate the extent of the hydration and electrostatic interactions 14 . Gaussian fitting reveals three characteristic hydration peaks. Peak 1 corresponds to free water molecules that exist independently within the system without interacting with the polymer network. Peak 2 represents frozen bound water, which constitutes a secondary hydration shell that plasticizes the polymer chains and enhances the mobility of chain segments. Peak 3 corresponds to nonfrozen bound water, forming the primary hydration shell around the polymer chains and contributing to dipole–dipole interactions. The strength of electrostatic interactions within the system can be quantified through integral analysis by calculating the area ratio between the free water peak and the bound water peaks. At low polymer concentrations (c = 2M), the integral area of the -OH peak and the proportion of free water (Peak 1) are significantly high (Supplementary Fig. 6 and Fig. 1 b), with a free/bound water ratio (Wr) of 32.5% (Fig. 1 c). Under conditions of strong hydration, the hydrophilic charged groups dissociate by releasing counterions into solution and leaving ionized charged groups on the polymer backbone. The electrostatic interactions force the polymer chains to extend because of the electrostatic repulsion between charged monomers, predominantly adopting a freely jointed chain (FJC) conformation with a measured chain size of 0.7 nm (Fig. 1 e). When the polymer concentration is increased to 6M, the free/bound water ratio (Wr) decreases to 14%. With reduced hydration, hydrophobic effects dominate, leading to chain collapse and curling, and the formation of densely packed regions to maximise the number of favourable polymer‒polymer interactions while minimising the number of unfavourable polymer‒solvent contacts 15 . The close entanglement of molecular chains, together with enhanced electrostatic attraction, promotes the formation of helical entangled chains (HECs), increasing the chain size to 3.2 nm. The molecular chain conformations were further validated through molecular dynamics (MD) simulations. Initially, all molecular chains adopt extended, non-crossing linear configurations (Supplementary Fig. 20). The simulation systems at both concentrations were subsequently subjected to NPT equilibration for 200 ns under standard conditions (298.15 K and 1 atm). In the case of PSM 2M , a higher diffusion coefficient (Dc) and greater solvent-accessible surface area (SASA) are observed, leading to the gradual formation of a loose and extended conformation of free chains (Supplementary Figs. 21–23 and 26). In contrast, PSM 6M exhibits a reduced hydration capacity, with approximately one-third of the molecular chains entrapped within the entangled network and inaccessible to solvent molecules, resulting in a highly compact helical entangled structure. This simulation outcome is consistent with the previously described AFM observations and theoretical analyses. We further elucidate the aggregated-state structure of the system. On the basis of the principles of rubber elasticity theory, we conduct a comprehensive calculation of the degree of entanglement (De) and molecular weights of the entanglements (Me) of PSM 2M and PSM 6M by using low-field nuclear magnetic resonance (LF-NMR) and rheological analysis 16 , yielding values of 3.6 and 69, 33663 and 1739 g/mol, respectively. The detailed calculation methods are provided in the Supplementary Information (Supplementary Figs. 31–34). When Me > Mw, a loose and extended topological free network is observed (PSM 2 M), with only a few geometric entanglements formed through chain distortion. In contrast, when Me ≫ Mw, a highly compact topological entangled structure is present (PSM 6 M). (Fig. 1 f and Supplementary Figs. 20 and 21). LF-NMR measurements further quantified the proportion of respective topological structures, by using the XLD 4 model for fitting and calculation, revealing that the topologically entangled content in PSM 6M is approximately 36%, whereas that in PSM 2M is only 18% (Fig. 3 d and Supplementary Figs. 29‒30). With respect to the intermediate concentrations of PSM xM (x = 2 ~ 7), the degree of entanglement is generally positively correlated with the polymer concentration (Fig. 3 e). Furthermore, the averaged mesh size ξ static of PSM network is obtained from the static light scattering (SLS). As shown in Fig. 2 d, the plot of 1/I(q) versus q 2 is linear and the ξ static of PSM 2M is 39.8 nm, which is larger than that of PSM 6M (11.3 nm) (Supplementary Figs. 7‒9). Unlike the fixed three-dimensional network structures of conventional hydrogels, this topological architecture can be continuously tuned by modulating the hydration level or introducing ions to screen for electrostatic interactions. This distinctive feature is further demonstrated and elaborated in the following sections. Ultraplasticity and hyperelasticity Compared with those dominated by topologically entangled networks (PSM 6M ), hydrogels dominated by topologically free networks (PSM 2M ) exhibit significantly distinct elastoplastic properties. PSM 2M exhibits ultraplasticity, with a plasticity ratio of 96% in the system as determined by creep testing (Supplementary Figs. 10‒13) 17 . It can be stretched up to an unprecedented 120000% without breakage (Fig. 2 a), surpassing the previously reported maximum strain (Strain, λ ~ 60000%) 18 , and theoretically allowing for further elongation. Under uniaxial tension, the stress‒strain curve of PSM 2M displays plastic behaviour and strain rate sensitivity (Fig. 2 g). Elastic deformation occurs only within a small strain range (λ = 80%), with a low elastic modulus of 1.1 kPa, during which the polymer chains are primarily extended. Upon entering the yield and plastic deformation regions, the polymer chains undergo slippage and orientation along the tensile direction (Figs. 2 a and c), rapidly transitioning into a new equilibrium state through plastic deformation. This orientation results in a certain degree of stress enhancement, characterized by a plastic hardening index of n = 0.845. The structural evolution of PSM 2M during stretching is observed using X-ray small-angle scattering (SAXS) (Fig. 2 b). In the unstretched state, the 2D SAXS image reveals a circular scattering ring, and the 1D SAXS profile exhibits a broad peak in the low q region, corresponding to an initial interchain distance of 3.21 nm. Upon stretching to λ = 1000%, the scattering rings and peaks shift towards the high q region, indicating a reduction in the interchain spacing to 2.35 nm, which suggests chain slippage and closer proximity. Further stretching to λ = 2000% leads to chain concentration and alignment in the necking region, with the interchain distance decreasing further to 2.08 nm. These plastic slip and orientation processes are irreversible; upon removal of the external force, PSM 2M fails to recover its original shape. For example, at λ = 1000% and λ = 8000%, the recovery ratios λ δ (defined as the ratio of the recovered length to the total stretched length) are only 55% and 36%, respectively (Fig. 2 i). In contrast, PSM 6M exhibits hyperelastic behaviour, with an elasticity ratio exceeding 90% (Supplementary Fig. 12), it can fully recover when it is subjected to a tensile strain of up to 12 times (λ = 1200%) (Fig. 2 d). Under uniaxial stretching, the stress‒strain curve of PSM 6M remains unaffected by the stretching rate (Fig. 2 h), as it displays neither distinct yield points nor significant plastic deformation. The hydrogel possesses an elastic modulus of 77.7 kPa and a toughness of 697 kJ/m³ and is capable of elastic deformation up to λ = 2000%. Unlike PSM 2M , PSM 6M only undergoes elongation of the polymer chains and partial orientation during stretching (Fig. 2 f). In the undeformed state, in situ SAXS measurements reveal circular scattering rings in the 2D SAXS patterns and a broad peak in the 1D SAXS profiles within the high q region (Fig. 2 e), which corresponds to the scatterer of the entangled polymer chain. The radius of gyration (Rg) is calculated as 0.28 nm using the Guinier theoretical model (Supplementary Fig. 28) 19 , with an average distance of 1.83 nm between adjacent entangled scatterer centres. Upon stretching to λ = 5, the high q region features vanish, and new scattering rings and peaks emerge in the low q region, indicating that the entangled structure has been stretched and deformed, with the Rg increasing to 3.79 nm. Upon returning to λ = 0%, the SAXS data closely resemble those of the undeformed state, confirming the excellent structural reversibility of the topological entanglement network in PSM 6M . Furthermore, PSM 6M demonstrates remarkable deformation reversibility. Under a tensile strain of λ = 1000%, the λ δ reaches approximately 92% within 1 second, achieving full recovery within 10 seconds (Fig. 2 i). Under a higher strain (λ = 2000%), λ δ reaches approximately 87% within 1 second and eventually recovers to approximately 94%. The superelasticity of PSM 6M significantly surpasses that of conventional hydrogels, which typically exhibit reversible recovery at λ < 300%, and approaches the performance of the best-reported pearl-chain-structured hyperelastic hydrogels (reversible recovery at λ = 1500%), which rely on the effective unfolding and refolding of subnanometric beads 20 . However, the difference lies in the mechanisms involved. The hyperelastic behaviour of PSM 6M arises partially from the stretching and recoiling of the polymer chains and partially from the topological entanglement network formed through physical constraints. This system relies on polymer chain entanglements to cooperatively transfer tension and dissipate energy along the molecular backbone during deformation. Evolution of mechanical properties over wide ranges This self-evolving capability, spanning a broad range from ultraplasticity to hyperelasticity, represents a significant breakthrough in the modulation of mechanical properties in hydrogels. In this system, the structural and mechanical properties of PSM can be reversibly transformed through processes such as swelling–deswelling or ion incorporation. In the plastic state, the hydrogel is amenable to multiple shaping and reprocessing steps. For example, spherical and cubic hydrogel units can be fused into complex shapes such as a crouching lion, which can subsequently be reshaped into forms such as footballs and basketballs (Fig. 3 a), while retaining their plastic characteristics. Upon swelling to a concentration of c = 6M, the material transitions into an elastic hydrogel. It is capable of fully recovering after bearing a load exceeding 22 kg and can also bounce up and down in a spherical form. When needed, the hydrogel can be further swollen to revert to the plastic state. This feature is particularly advantageous for reshaping via sol-gel transitions, which can be conveniently and efficiently performed in situ under stable conditions. Naturally, the mechanical properties of intermediate polymer concentrations fall between those of the two extreme states, with the degree of elasticity positively correlated with the polymer concentration. Detailed performance characterization results are provided in the Supplementary Information (Supplementary Figs. 46 and 47). The mechanical properties following mutual transformation are evaluated through uniaxial tensile testing. Upon swelling from PSM 2M to PSM 6M , the hydrogel exhibits fully reversible recovery (hyperelasticity) after a tenfold elongation (λ = 1000%). Conversely, when transformed back, it demonstrates an ultraextended stretchability with a strain ratio of λ = 8000% (Supplementary Videos 1 and 2). The corresponding stress‒strain curves closely resemble those of the original PSM 6M and PSM 2M (Figs. 3 b and c). Furthermore, after introducing 5M NaCl into the PSM 6M to shield against electrostatic interactions, the resulting mechanical behaviour becomes comparable to that of PSM 3M (Fig. 3 c). However, after the ions are removed via diffusion, the mechanical performance is largely restored to that of the PSM at the same polymer concentration. Intermediate mechanical properties can be achieved by adjusting either the polymer concentration or the ion concentration. Specifically, the tunable polymer concentration range is 35–75% (Supplementary Fig. 18), while the ion concentration can be modulated between 0 ~ 6M. In this elastoplastic transformation governed by swelling and ion regulation, overall structural reorganization plays a dominant role. Taking PSM 6M as an example, during the swelling process to PSM 2M , the hydration of the entangled regions increases. Some entanglements previously stabilized by hydrophobic interactions become disentangled, leading to an increase in interchain spacing. According to LF-NMR measurements 21 , approximately 32% of the originally entangled chains transition into dangling chains, while 8% become free chains. Consequently, the degree of entanglement decreases from 69 to 4.2 (Figs. 3 d and e). When only 5M NaCl is introduced without altering the swelling state, some of the electrostatic interactions are screened by counterions, resulting in a reduction in the entanglement ratio from 35% to 20%. Approximately 43% of the entangled chains within the entangled domains have one end released, stretching and dangling around the entanglement centre while remaining under certain constraints. Under these conditions, the degree of entanglement is reduced to 11.3 (Fig. 3 e). During the elastoplastic transformation process, the mechanical properties of the hydrogel vary significantly. The average elastic modulus of PSM 2M is approximately 1.5 kPa, with a toughness of 50 kJ/m³, whereas that of PSM 6M is approximately 140 kPa and the toughness is 750 kJ/m³. Upon further swelling to form PSM 12M , the modulus and toughness can reach 2 MPa and 8000 kJ/m³, respectively (the hydrogel is still soft material rather than hard material) (Fig. 3 f). This broad modulus-toughness range not only encompasses the mechanical properties of various natural tissues but also spans the performance spectrum of both conventional and high-performance hydrogels 22 . Such a readily tunable and continuous evolution of mechanical properties facilitates the fabrication of complex-shaped hydrogel materials and enables the simulation of a wide range of biological tissue mechanics which was previously difficult to achieve with conventional hydrogels. Resistance to physical damage On the basis of its topological entanglement network structure, PSM is capable of overcoming the modulus‒fatigue threshold conflict, thereby significantly increasing its damage resistance. The crack resistance of the PSM is evaluated by using a 1/4 shear notch test. Under monotonic loading, when the polymer concentration ranges from 2M to 6M, the PSM can stably achieve large deformations up to a strain of λ = 1500%. The precrack blunts and bifurcates more in the tanglemer network than in the regular network, reducing stress concentration and delaying catastrophic failure (Figs. 4 a and b). In contrast, traditional elastic network hydrogels typically experience rapid nonblunt fracture at strains where λ < 200% 23 . During the shearing process, the amplitude of the energy release rate is known as the fatigue threshold, below which a crack does not grow 24 . For the hyperelastic PSM 6M , only a limited degree of crack blunting occurs at the notch. Under monotonic loading, when λ < 1000%, no crack propagation is observed even after the load is maintained for 10 minutes (Δc < 0.015 mm). As the strain further increases to λ = 1500%, Δc abruptly increases to 0.88 mm (Figs. 4 c and d). Linear regression analysis of the experimental data indicates that the fatigue threshold (Gi) is approximately 1050 J/m², which is the same as that of high-fatigue-resistant hydrogels (800 ~ 1200 J/m²). This increased performance is attributed to the topological entanglement network structure, in which the absence of covalent crosslinking allows relative sliding between polymer chains. Consequently, high stress can be uniformly dispersed along the entire polymer chain, enabling efficient stress transfer throughout the network (Fig. 4 b). In contrast, the crosslinking points in conventional elastic hydrogels restrict the extent of stress dispersion, resulting in localized stress concentration primarily borne by the polymer chains bridging the crack. Naturally, the sliding friction increases with the degree of entanglement. However, in contrast to covalent crosslinking, dense entanglements do not compromise the fatigue threshold. Therefore, PSM 6M not only has a high elastic modulus (140 kPa) and high shear toughness (3615 J/m² at λ = 1500%) (Fig. 4 e) but also maintains a high fatigue threshold. Under cyclic loading conditions, the crack growth rate (dc/dn) per cycle is measured and correlated with the energy release rate amplitude (G) (Figs. 4 f and g). As the number of cycles increases, the cumulative crack propagation progresses at a relatively low rate. The fatigue threshold under cyclic loading, G th , is estimated to be approximately 141 J/m², which is significantly lower than Gi. This discrepancy is primarily due to differences in measurement resolution 25 . In contrast, ultraplastic PSM 2M exhibits a lower degree of entanglement, reduced interchain friction, and a greater tendency for polymer chain sliding, which collectively contribute to enhanced resistance against crack propagation. Consequently, not only is the crack blunting zone broader at the precrack site, but a distinct necking phenomenon is also observed on the opposite side (Fig. 4 a). Although crack propagation under plastic deformation also occurs under small strains, this resistance mechanism enables PSM 2M to be stretched to an exceptionally high strain (λ = 8000%) without fracture. Under cyclic loading conditions, owing to the presence of irreversible plastic deformation, the crack growth rate of the hydrogel increases, with the fatigue threshold G th estimated at approximately 53 J/m². Similarly, the shear toughness is significantly lower, measuring approximately 12 J/m². The resistance mechanism inherent to PSM remains effective across various crack configurations. For example, in the trouser tear test, stress-induced damage is predominantly localized in the trouser legs rather than at the shear crack interface, thereby allowing the hydrogel to sustain high strain without undergoing catastrophic failure (Supplementary Figs. 48‒52). Functions and Applications The self-evolving mechanical behaviour of PSM, which transitions from ultraplasticity to hyperelasticity, significantly increases its potential applications. In this study, we demonstrate its applicability through examples in biomedical fields such as cell engineering and wound treatment. First, PSM was cocultured with human umbilical cord mesenchymal stem cells (UC-MSCs), during which time it exhibited excellent biocompatibility (cell viability reached 96% after 24 hours with PSM 2M ) (Supplementary Figs. 53‒55). Compared with conventional rigid culture surfaces or elastic-based materials 26 , the tunable mechanical elastoplastic properties of PSM significantly influence cell morphology (Figs. 5 a and b). Cells cultured in PSM 2M exhibited a more spread-out growth pattern in all directions, characterized by a larger average cell area (194 µm²) and lower roundness (0.57) (Figs. 5 c and d). In contrast, cells cultured in PSM 6M displayed a more rounded morphology, with a smaller average cell area (58 µm²) and greater roundness (0.69). These findings confirm that the elastoplastic characteristics of the hydrogel network can regulate cell growth, proliferation, and morphological behaviour, phenomena closely related to both passive and actively generated isometric cytoskeletal tension. This mechanism is comparable to that observed in previously reported stress-relaxing hydrogels 27 . However, the wider elastoplastic transition range of PSM offers greater flexibility in tailoring the growth morphology and directing the differentiation of stem cells. Furthermore, we investigate the potential application of PSM loaded with exosomes (Exo) for the in vitro treatment of diabetic wounds. The Exo loading and release capabilities were evaluated using a BCA protein assay kit. PSM interacts with the membrane surface of the Exo through electrostatic binding and demonstrates effective loading (Fig. 5 e). Specifically, PSM 6M has a loading capacity of 103 µg and an encapsulation efficiency of 84%, both of which are higher than those of PSM 2M , which has a loading capacity of 97 µg and an encapsulation efficiency of 77% (Supplementary Fig. 59). This performance surpasses that of conventional hydrogels such as polyacrylamide (PAAm) hydrogels or extracellular matrix (ECM)-based hydrogels 28 , which typically exhibit encapsulation efficiencies ranging from 50% to 70%. Moreover, the release of Exos from PSM is excellent, with a continuous release duration of up to 12 days in a PBS environment. The release profile is characterized by its uniformity and stability, with an average daily release of approximately 6.4 µg and a maximum daily variation of less than 1.2 µg between consecutive days (Supplementary Fig. 60). In comparison, ECM-based hydrogels or dynamically responsive natural hydrogels 29 typically exhibit release durations ranging from 0.5 to 7 days, accompanied by a burst release effect, with up to 80% of the Exo released within the first 24 hours. Compared with hyperelastic PSM 6M , ultraplastic PSM 2M demonstrates superior release performance and a higher total release rate. For instance, the total release rate of PSM 2M reaches 87%, whereas that of PSM 6M is 66% (Fig. 5 f). On the basis of the elastoplastic properties of hydrogels and their impact on Exo loading and release, we can strategically select an optimal mode for wound treatment. Specifically, during the Exo loading process, PSM 6M is selected because of its high loading capacity. After Exo incorporation, the hydrogel can swell and undergo in situ transformation into a more effective plastic PSM. Leveraging its plastic characteristics, the hydrogel can be moulded in situ to conform to the geometry of irregular wounds, thereby achieving better wound surface adaptation. The therapeutic efficacy of PSM-Exo in diabetic wound healing is validated through animal experiments, with a commercially available 3M wound dressing (without Exo loading) serving as the control group. The results demonstrate that on days 7 and 12, the residual wound areas in the PSM-Exo group were reduced to 23% and 11%, respectively, representing a significantly greater reduction than that in the control group, which exhibited residual wound areas of 40% and 28%, respectively (Fig. 5 g). These outcomes also show improved performance relative to previously reported Exo-based hydrogel treatments, which typically achieve residual wound areas of approximately 45% and 23% at the same time points (days 7 and 12, respectively) 30 . Histopathological evaluation and mechanistic analysis further confirms that PSM-Exo promotes epithelial regeneration, collagen deposition, and angiogenesis, indicating its potential as an effective therapeutic strategy for diabetic wound healing (Figs. 5 h and i and Supplementary Fig. 63). Conclusions By constructing reversible topological entanglement networks, we successfully develop a single-component hydrogel capable of reversible self-evolution from ultraplasticity to hyperelasticity. Compared with conventional hydrogels, PSM exhibits a broader elastoplastic range, a tunable modulus, toughness, and superior damage resistance. These properties arise from the reversible conversion between free chains and entangled chains in specially designed amphoteric ionic polymers, driven by electrostatic and hydrophobic interactions, as well as the chain slip orientation and stretch recovery mechanisms under mechanical loading. PSM has overcome the performance limitations of traditional hydrogels in terms of elastoplasticity, demonstrating significant application potential in biomedical fields such as cell and tissue engineering. Moreover, this study establishes a structural design paradigm that provides a straightforward strategy for regulating the structure and performance of hydrogel systems. Declarations Online content Any methods, additional references, Nature Portfolio reporting summaries, source data, extended data, supplementary information, acknowledgements, peer review information; details of author contributions and competing interests; and statements of data and code availability are available. Data availability The data that support the findings of this study are present in the paper and/or in the Supplementary Information. Additional data related to the paper are available from the corresponding author upon request. Source data are provided with this paper. Acknowledgements This work was supported by the National Natural Science Foundation of China (12572286), the Science and Technology Innovation Project of Hunan Province (2023RC1070), the Natural Science Foundation of Hunan Province (2023JJ60447), the Key Research and Development Projects of Hainan Province of China (ZDYF2024SHFZ062), and Scientific research and innovation Foundation of Hunan University of Technology (CX2301). References Wang WK et al (2023) Injectable ECM-mimetic dynamic hydrogels abolish ferroptosis-induced post-discectomy herniation through delivering nucleus pulposus progenitor cell-derived exosomes. 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18:30:15","extension":"html","order_by":14,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":92991,"visible":true,"origin":"","legend":"","description":"","filename":"earlyproof.html","url":"https://assets-eu.researchsquare.com/files/rs-7839519/v1/fa178a3ea1bceeee01b01f12.html"},{"id":99314438,"identity":"5c8629a0-c809-4410-a452-2ca9b869ca6c","added_by":"auto","created_at":"2025-12-31 16:21:28","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":4301188,"visible":true,"origin":"","legend":"\u003cp\u003eTopologically free/entangled network structure of PSM. \u003cstrong\u003ea.\u003c/strong\u003e Monomer structure and polymer chain configurations under different hydration states. \u003cstrong\u003eb.\u003c/strong\u003e Gaussian fitting curve of the -OH peak, along with the corresponding proportions of three kinds of structured water. \u003cstrong\u003ec.\u003c/strong\u003e Ratio of free/bound water (Wr) in PSM. \u003cstrong\u003ed.\u003c/strong\u003e Ornstein-Zernike plot of the inverse average scattering intensity 1/I(q) versus q\u003csup\u003e2\u003c/sup\u003e for the PSM. \u003cstrong\u003ee.\u003c/strong\u003e AFM images of freely jointed chains and helical entangled chains. \u003cstrong\u003ef.\u003c/strong\u003e Schematic illustration and MD simulation results of the monomer polymerization process, the polymer chain morphology (FJC and HEC), and the topological free/entangled network structure.\u003c/p\u003e","description":"","filename":"floatimage1.png","url":"https://assets-eu.researchsquare.com/files/rs-7839519/v1/80e1b8dde539235523ea2faa.png"},{"id":99314184,"identity":"2d5061fe-8403-4109-8054-b6725b651713","added_by":"auto","created_at":"2025-12-31 16:20:58","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":4620864,"visible":true,"origin":"","legend":"\u003cp\u003eUltraplasticity and hyperelasticity of PSM. \u003cstrong\u003ea.\u003c/strong\u003e Photograph of PSM\u003csub\u003e2M\u003c/sub\u003e undergoing plastic deformation under stretching (λ = 120000%), followed by winding into a circular shape, along with schematic illustrations and MD simulation results of polymer chain morphological changes during the stretching process. \u003cstrong\u003eb.\u003c/strong\u003e 1D SAXS profiles and 2D SAXS images of PSM\u003csub\u003e2M\u003c/sub\u003e at various strains.\u003cstrong\u003e c.\u003c/strong\u003e SEM images of PSM\u003csub\u003e2M\u003c/sub\u003e in the unstretched and 20-times-stretched states (λ = 2000%). \u003cstrong\u003ed.\u003c/strong\u003e Photograph of PSM\u003csub\u003e6M\u003c/sub\u003e undergoing elastic stretching (λ = 1200%) and subsequent recovery, accompanied by schematic illustrations and MD simulation results of polymer chain structural evolution during the deformation process. \u003cstrong\u003ee.\u003c/strong\u003e 1D SAXS profiles and 2D SAXS images of PSM\u003csub\u003e6M\u003c/sub\u003e during stretching and recovery. \u003cstrong\u003ef.\u003c/strong\u003e SEM images of PSM\u003csub\u003e6M\u003c/sub\u003e in the unstretched and 20-times-stretched states (λ = 2000%). \u003cstrong\u003eg.\u003c/strong\u003e Stress‒strain curves of PSM\u003csub\u003e2M\u003c/sub\u003e at different strain rates. \u003cstrong\u003eh.\u003c/strong\u003e Stress‒strain curves of PSM\u003csub\u003e6M\u003c/sub\u003e at different strain rates. \u003cstrong\u003ei.\u003c/strong\u003e Tensile recovery ratios of PSM\u003csub\u003e2M\u003c/sub\u003e and PSM\u003csub\u003e6M\u003c/sub\u003e at a strain of λ = 1000%.\u003c/p\u003e","description":"","filename":"floatimage2.png","url":"https://assets-eu.researchsquare.com/files/rs-7839519/v1/d0779ea4abf98b99f71bef21.png"},{"id":99117429,"identity":"2902286b-6060-4627-93cb-72446bf1894a","added_by":"auto","created_at":"2025-12-28 18:30:15","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":2909715,"visible":true,"origin":"","legend":"\u003cp\u003eRegulation of the mechanical properties of PSM over wide ranges. \u003cstrong\u003ea. \u003c/strong\u003eModulation of morphology and elastoplastic behaviour in PSM through swelling and deswelling processes. \u003cstrong\u003eb.\u003c/strong\u003e Stress‒strain curves of PSM\u003csub\u003e2M\u003c/sub\u003e following deswelling transformation into PSM\u003csub\u003e6M\u003c/sub\u003e. \u003cstrong\u003ec.\u003c/strong\u003e Stress‒strain curves of PSM\u003csub\u003e6M\u003c/sub\u003e after swelling to PSM\u003csub\u003e2M\u003c/sub\u003e, full swelling, and introduction of a 5M ionic concentration. \u003cstrong\u003ed.\u003c/strong\u003e Types and proportions of polymer chains in PSM under varying concentrations and after hydration or ion-induced modulation. \u003cstrong\u003ee.\u003c/strong\u003e Schematic illustration of the polymer chain and the degree of entanglement in PSM at different concentrations and following hydration/ion modulation. \u003cstrong\u003ef.\u003c/strong\u003e Comparison of the modulus–toughness performance between PSM and other material systems.\u003c/p\u003e","description":"","filename":"floatimage3.png","url":"https://assets-eu.researchsquare.com/files/rs-7839519/v1/19506b7516a79cbd8bcc137d.png"},{"id":99117430,"identity":"5df15144-a206-45e1-913a-f9b81b010b69","added_by":"auto","created_at":"2025-12-28 18:30:15","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":2485154,"visible":true,"origin":"","legend":"\u003cp\u003ePhysical damage resistance behaviour of PSM. \u003cstrong\u003ea.\u003c/strong\u003e Shear test image and mechanism schematic diagram of PSM\u003csub\u003e2M\u003c/sub\u003e. \u003cstrong\u003eb.\u003c/strong\u003e Shear test image and mechanism schematic diagram of PSM\u003csub\u003e6M\u003c/sub\u003e. \u003cstrong\u003ec.\u003c/strong\u003e Stress‒strain curves for PSM\u003csub\u003e2M\u003c/sub\u003e and PSM\u003csub\u003e6M\u003c/sub\u003e in the uniaxial shear test.\u003cstrong\u003e d.\u003c/strong\u003e Energy release rate‒crack growth curves for PSM\u003csub\u003e2M\u003c/sub\u003e and PSM\u003csub\u003e6M\u003c/sub\u003e in the uniaxial shear test.\u003cstrong\u003e e.\u003c/strong\u003e Shear toughness‒crack growth curves for PSM\u003csub\u003e2M\u003c/sub\u003e and PSM\u003csub\u003e6M\u003c/sub\u003e in the uniaxial shear test. \u003cstrong\u003ef.\u003c/strong\u003e Stress‒strain curves from the cyclic shear tests of PSM\u003csub\u003e2M\u003c/sub\u003e and PSM\u003csub\u003e6M\u003c/sub\u003e. \u003cstrong\u003eg.\u003c/strong\u003e Energy release rate‒crack growth rate curves from the cyclic shear test of PSM\u003csub\u003e2M\u003c/sub\u003e and PSM\u003csub\u003e6M\u003c/sub\u003e. \u003cstrong\u003eh.\u003c/strong\u003e Shear toughness‒crack growth rate curves from the cyclic shear tests of PSM\u003csub\u003e2M\u003c/sub\u003e and PSM\u003csub\u003e6M\u003c/sub\u003e.\u003c/p\u003e","description":"","filename":"floatimage4.png","url":"https://assets-eu.researchsquare.com/files/rs-7839519/v1/b59db445479645f808ea9b8b.png"},{"id":99316123,"identity":"18e7abde-dcb9-4425-b34c-87053f85ba77","added_by":"auto","created_at":"2025-12-31 16:27:46","extension":"png","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":4705804,"visible":true,"origin":"","legend":"\u003cp\u003eEffects of PSM in cell culture and Exo-loaded treatment of diabetic wounds.\u003cstrong\u003e a.\u003c/strong\u003e AO/PI staining images of UC-MSCs cocultured with PSM.\u003cstrong\u003e b.\u003c/strong\u003eSchematic illustration of the mechanism underlying PSM-induced modulation of cell morphology.\u003cstrong\u003e c.\u003c/strong\u003e Quantitative analysis of the cell area. \u003cstrong\u003ed.\u003c/strong\u003eQuantitative analysis of the cell circularity.\u003cstrong\u003e e.\u003c/strong\u003e Schematic diagram of PSM-mediated Exo loading and application in diabetic wound treatment. \u003cstrong\u003ef.\u003c/strong\u003eRelease rate curve of the hydrogels.\u003cstrong\u003e g.\u003c/strong\u003e Residual wound area at different time points during the treatment of diabetic wounds. \u003cstrong\u003eh.\u003c/strong\u003e HE staining images of wound tissue sections on day 12 after treatment. \u003cstrong\u003ei. \u003c/strong\u003eMasson staining images of wound tissue sections on day 12 after treatment.\u003c/p\u003e","description":"","filename":"floatimage5.png","url":"https://assets-eu.researchsquare.com/files/rs-7839519/v1/4feca2e56c4a6565d0c49ac7.png"},{"id":99323559,"identity":"ff04198d-386d-4b6a-b1d7-8c8ba8781aad","added_by":"auto","created_at":"2025-12-31 16:45:36","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":19601058,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7839519/v1/53d52173-a784-41a3-a38a-2f24c7093407.pdf"},{"id":99117440,"identity":"a7652aff-cd7b-4571-a3fe-051a0b43a943","added_by":"auto","created_at":"2025-12-28 18:30:15","extension":"docx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":64028749,"visible":true,"origin":"","legend":"Supplementary Information","description":"","filename":"RevisedSupplementaryInformation.docx","url":"https://assets-eu.researchsquare.com/files/rs-7839519/v1/f39749e99fb2cdda093fd24c.docx"},{"id":99117444,"identity":"7edea5c1-d04a-4184-9472-01f040b428b4","added_by":"auto","created_at":"2025-12-28 18:30:16","extension":"rar","order_by":2,"title":"","display":"","copyAsset":false,"role":"supplement","size":165116469,"visible":true,"origin":"","legend":"Supplementary Videos","description":"","filename":"SupplementaryVideos.rar","url":"https://assets-eu.researchsquare.com/files/rs-7839519/v1/944cfd5c1d8212a5030e8527.rar"}],"financialInterests":"There is \u003cb\u003eNO\u003c/b\u003e Competing Interest.","formattedTitle":"Topologically Entangled Hydrogels with Self-Evolving Ultraplasticity-to-Hyperelasticity","fulltext":[{"header":"Introduction","content":"\u003cp\u003eHydrogels possess a three-dimensional (3D) structure analogous to\u0026nbsp;that of\u0026nbsp;the extracellular matrix\u003csup\u003e1\u003c/sup\u003e, integrating elasticity and plasticity, and exhibit significant potential in applications such as cell and tissue engineering\u003csup\u003e2\u003c/sup\u003e\u003csup\u003e,\u003c/sup\u003e\u003csup\u003e3\u003c/sup\u003e, as well as in vitro and in vivo interventional therapies\u003csup\u003e4\u003c/sup\u003e\u003csup\u003e,\u003c/sup\u003e\u003csup\u003e5\u003c/sup\u003e. However, hydrogels are typically designed as a cross-linked network structure, whether synthetic or natural materials, and thus are restricted to being used only as elastomer materials. In addition, strong cross-linked structures formed by covalent or\u0026nbsp;noncovalent interactions\u0026nbsp;often restrict the conformational changes of polymer chains, leading to brittleness and fixed mechanical properties,\u0026nbsp;whereas\u0026nbsp;weak cross-linking is prone to insufficient strength\u003csup\u003e6\u003c/sup\u003e. Meanwhile, neither of them can achieve an extremely large deformation. In comparison, biological tissues are highly dynamic elastoplastic systems characterized by specific spatial architectures, including reticular elastin, helical collagen fibres, and smooth muscle tissues, all of which contribute to the stabilization of large deformations and special elastoplasticity\u003csup\u003e7\u003c/sup\u003e. Specifically, these tissues exhibit partially elastic \u0026ldquo;quasi-solid\u0026rdquo;\u0026nbsp;behavior, undergoing reversible deformation when subjected to an external force, whereas other regions demonstrate fluid-like characteristics, exhibiting irreversible deformation even after the removal of the applied force. The extent of elasticity and plasticity is determined by the tissue\u0026apos;s composition and structural organization.\u0026nbsp;Through the synergistic interplay of endogenous and exogenous biological responses within these structural frameworks, biological tissues exhibit a broad spectrum of mechanical behaviours, enabling the maintenance of complex and efficient physiological functions\u003csup\u003e8\u003c/sup\u003e.\u003c/p\u003e\n\u003cp\u003eTo match the broad spectrum of mechanical elastoplastic properties exhibited by biological tissues, a variety of sophisticated hydrogel construction strategies have been developed. Typical approaches involve modified macromolecules or biomass materials containing abundant dynamic functionalities, such as proteins, peptides, and polysaccharides, as primary components to fabricate hydrogels\u003csup\u003e9\u003c/sup\u003e\u003csup\u003e,\u003c/sup\u003e\u003csup\u003e10\u003c/sup\u003e. Through structural design, covalent or\u0026nbsp;noncovalent\u0026nbsp;interactions are utilized to generate dynamic behaviours\u0026nbsp;in response to\u0026nbsp;environmental stimuli (e.g., ions, solvents, pH, and temperature). These features enable the hydrogel to exhibit reversible sol-gel transitions\u003csup\u003e1\u003c/sup\u003e\u003csup\u003e1\u003c/sup\u003e, shear thickening or thinning\u003csup\u003e1\u003c/sup\u003e\u003csup\u003e2\u003c/sup\u003e, shape memory effects\u003csup\u003e1\u003c/sup\u003e\u003csup\u003e3\u003c/sup\u003e, and other mechanical behavior and functionality. However, the aforementioned construction methods and functional characteristics remain structurally constrained\u0026nbsp;because of\u0026nbsp;their inherent network architectures. The network structure cannot fundamentally switch between elastic and plastic states in a reversible manner. If a simple switching mechanism could be integrated to enable in\u0026nbsp;situ reversible switching of both network structures and properties within the same hydrogel system, thereby achieving extensive tunability\u0026nbsp;of elastoplastic\u0026nbsp;mechanical behaviours, it would significantly streamline\u0026nbsp;the\u0026nbsp;structural design efforts required for specific applications and broaden the functional applicability of such materials.\u003c/p\u003e\n\u003cp\u003eIn studies of neutral or anionic/cationic hydrogels, various chain conformations induced by intermolecular interactions, such as freely jointed chains (FJCs), pearl-necklace chains (PNCs), and coiled chains (CCs), have been proposed and experimentally validated. Following chemical cross-linking, these conformations can form elastic three-dimensional network structures. However, the cross-linking process simultaneously results in the stabilization, and thus reduced dynamic adaptability, of their mechanical properties. Herein, we propose a novel strategy to achieve self-evolving ultraplasticity to hyperelasticity in single-component hydrogels through reversible transformations of chain conformation and topological structure. This reversibility is driven by the differential electrostatic and hydrophobic interactions among the chains of amphoteric ionic polymers. In the ultraplastic state, the hydrogel achieves an unprecedented stable strain of up to 120000%, upon transition to the hyperelastic state, it maintains a reversible strain of 1200%. Notably, the hydrogel exhibits excellent fatigue resistance and damage tolerance ability throughout the entire elastic-plastic transformation range. The aforementioned characteristics enable the simulation of diverse mechanical properties exhibited by various biological tissues using a single hydrogel system, thereby offering new avenues for the development of advanced hydrogel materials with enhanced mechanical specificity in biomedical engineering applications.\u003c/p\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec2\" class=\"Section2\"\u003e \u003ch2\u003eTopologically free/entangled network\u003c/h2\u003e \u003cp\u003eIn this study, to achieve the self-evolving transformation of hydrogels from ultraplastic to hyperelastic on the basis of mechanical properties, we propose a construction strategy for single-component hydrogels based on a topologically entangled network structure. The amphoteric monomers [2(methacryloyloxy) ethyl] dimethyl-(3-sulfopropyl) (SBMA) are employed to construct unique hydrogels (abbreviated as PSM\u003csub\u003eXM\u003c/sub\u003e, where x represents the polymer concentration). The monomers undergo radical polymerization through the initiation of C\u0026thinsp;=\u0026thinsp;C double bonds, forming long-chain polymers (with controlled initiation to maintain consistent molecular weights). (Supplementary Figs.\u0026nbsp;1‒3 and 5)) The key structural features enabling the observed properties are the following. (1) The polymer monomer simultaneously incorporates anionic/cationic groups and hydrophilic/hydrophobic segments. (2) There are no fixed crosslinking points formed by covalent bonds. Consequently, under varying polymer chain concentrations and hydration conditions, the short-range hydrophobic interactions between alkyl chains compete with long-range electrostatic interactions among charged groups (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003ea). The subtle and antagonistic balance between these forces results in different polymer chain conformations, which are also fully reversible. This mechanism fundamentally differs from the conventional fixed network structures in traditional hydrogels, where the chain conformation is locked to a greater degree.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eWe observe the conformation of the polymer chains using atomic force microscopy (AFM) and perform Gaussian fitting on the -OH peak in the Raman spectrum to validate the extent of the hydration and electrostatic interactions\u003csup\u003e\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e\u003c/sup\u003e. Gaussian fitting reveals three characteristic hydration peaks. Peak 1 corresponds to free water molecules that exist independently within the system without interacting with the polymer network. Peak 2 represents frozen bound water, which constitutes a secondary hydration shell that plasticizes the polymer chains and enhances the mobility of chain segments. Peak 3 corresponds to nonfrozen bound water, forming the primary hydration shell around the polymer chains and contributing to dipole\u0026ndash;dipole interactions. The strength of electrostatic interactions within the system can be quantified through integral analysis by calculating the area ratio between the free water peak and the bound water peaks. At low polymer concentrations (c\u0026thinsp;=\u0026thinsp;2M), the integral area of the -OH peak and the proportion of free water (Peak 1) are significantly high (Supplementary Fig.\u0026nbsp;6 and Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eb), with a free/bound water ratio (Wr) of 32.5% (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003ec). Under conditions of strong hydration, the hydrophilic charged groups dissociate by releasing counterions into solution and leaving ionized charged groups on the polymer backbone. The electrostatic interactions force the polymer chains to extend because of the electrostatic repulsion between charged monomers, predominantly adopting a freely jointed chain (FJC) conformation with a measured chain size of 0.7 nm (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003ee). When the polymer concentration is increased to 6M, the free/bound water ratio (Wr) decreases to 14%. With reduced hydration, hydrophobic effects dominate, leading to chain collapse and curling, and the formation of densely packed regions to maximise the number of favourable polymer‒polymer interactions while minimising the number of unfavourable polymer‒solvent contacts\u003csup\u003e\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e\u003c/sup\u003e. The close entanglement of molecular chains, together with enhanced electrostatic attraction, promotes the formation of helical entangled chains (HECs), increasing the chain size to 3.2 nm. The molecular chain conformations were further validated through molecular dynamics (MD) simulations. Initially, all molecular chains adopt extended, non-crossing linear configurations (Supplementary Fig.\u0026nbsp;20). The simulation systems at both concentrations were subsequently subjected to NPT equilibration for 200 ns under standard conditions (298.15 K and 1 atm). In the case of PSM\u003csub\u003e2M\u003c/sub\u003e, a higher diffusion coefficient (Dc) and greater solvent-accessible surface area (SASA) are observed, leading to the gradual formation of a loose and extended conformation of free chains (Supplementary Figs.\u0026nbsp;21\u0026ndash;23 and 26). In contrast, PSM\u003csub\u003e6M\u003c/sub\u003e exhibits a reduced hydration capacity, with approximately one-third of the molecular chains entrapped within the entangled network and inaccessible to solvent molecules, resulting in a highly compact helical entangled structure. This simulation outcome is consistent with the previously described AFM observations and theoretical analyses.\u003c/p\u003e \u003cp\u003eWe further elucidate the aggregated-state structure of the system. On the basis of the principles of rubber elasticity theory, we conduct a comprehensive calculation of the degree of entanglement (De) and molecular weights of the entanglements (Me) of PSM\u003csub\u003e2M\u003c/sub\u003e and PSM\u003csub\u003e6M\u003c/sub\u003e by using low-field nuclear magnetic resonance (LF-NMR) and rheological analysis\u003csup\u003e\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e\u003c/sup\u003e, yielding values of 3.6 and 69, 33663 and 1739 g/mol, respectively. The detailed calculation methods are provided in the Supplementary Information (Supplementary Figs.\u0026nbsp;31\u0026ndash;34). When Me\u0026thinsp;\u0026gt;\u0026thinsp;Mw, a loose and extended topological free network is observed (PSM\u003csub\u003e2\u003c/sub\u003eM), with only a few geometric entanglements formed through chain distortion. In contrast, when Me ≫ Mw, a highly compact topological entangled structure is present (PSM\u003csub\u003e6\u003c/sub\u003eM). (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003ef and Supplementary Figs.\u0026nbsp;20 and 21). LF-NMR measurements further quantified the proportion of respective topological structures, by using the XLD 4 model for fitting and calculation, revealing that the topologically entangled content in PSM\u003csub\u003e6M\u003c/sub\u003e is approximately 36%, whereas that in PSM\u003csub\u003e2M\u003c/sub\u003e is only 18% (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003ed and Supplementary Figs.\u0026nbsp;29‒30). With respect to the intermediate concentrations of PSM\u003csub\u003exM\u003c/sub\u003e (x\u0026thinsp;=\u0026thinsp;2\u0026thinsp;~\u0026thinsp;7), the degree of entanglement is generally positively correlated with the polymer concentration (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003ee). Furthermore, the averaged mesh size ξ\u003csub\u003estatic\u003c/sub\u003e of PSM network is obtained from the static light scattering (SLS). As shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003ed, the plot of 1/I(q) versus q\u003csup\u003e2\u003c/sup\u003e is linear and the ξ\u003csub\u003estatic\u003c/sub\u003e of PSM\u003csub\u003e2M\u003c/sub\u003e is 39.8 nm, which is larger than that of PSM\u003csub\u003e6M\u003c/sub\u003e (11.3 nm) (Supplementary Figs.\u0026nbsp;7‒9). Unlike the fixed three-dimensional network structures of conventional hydrogels, this topological architecture can be continuously tuned by modulating the hydration level or introducing ions to screen for electrostatic interactions. This distinctive feature is further demonstrated and elaborated in the following sections.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eUltraplasticity and hyperelasticity\u003c/h2\u003e \u003cp\u003eCompared with those dominated by topologically entangled networks (PSM\u003csub\u003e6M\u003c/sub\u003e), hydrogels dominated by topologically free networks (PSM\u003csub\u003e2M\u003c/sub\u003e) exhibit significantly distinct elastoplastic properties. PSM\u003csub\u003e2M\u003c/sub\u003e exhibits ultraplasticity, with a plasticity ratio of 96% in the system as determined by creep testing (Supplementary Figs.\u0026nbsp;10‒13)\u003csup\u003e\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e\u003c/sup\u003e. It can be stretched up to an unprecedented 120000% without breakage (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003ea), surpassing the previously reported maximum strain (Strain, λ\u0026thinsp;~\u0026thinsp;60000%)\u003csup\u003e18\u003c/sup\u003e, and theoretically allowing for further elongation. Under uniaxial tension, the stress‒strain curve of PSM\u003csub\u003e2M\u003c/sub\u003e displays plastic behaviour and strain rate sensitivity (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eg). Elastic deformation occurs only within a small strain range (λ\u0026thinsp;=\u0026thinsp;80%), with a low elastic modulus of 1.1 kPa, during which the polymer chains are primarily extended. Upon entering the yield and plastic deformation regions, the polymer chains undergo slippage and orientation along the tensile direction (Figs.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003ea and c), rapidly transitioning into a new equilibrium state through plastic deformation. This orientation results in a certain degree of stress enhancement, characterized by a plastic hardening index of n\u0026thinsp;=\u0026thinsp;0.845. The structural evolution of PSM\u003csub\u003e2M\u003c/sub\u003e during stretching is observed using X-ray small-angle scattering (SAXS) (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eb). In the unstretched state, the 2D SAXS image reveals a circular scattering ring, and the 1D SAXS profile exhibits a broad peak in the low q region, corresponding to an initial interchain distance of 3.21 nm. Upon stretching to λ\u0026thinsp;=\u0026thinsp;1000%, the scattering rings and peaks shift towards the high q region, indicating a reduction in the interchain spacing to 2.35 nm, which suggests chain slippage and closer proximity. Further stretching to λ\u0026thinsp;=\u0026thinsp;2000% leads to chain concentration and alignment in the necking region, with the interchain distance decreasing further to 2.08 nm. These plastic slip and orientation processes are irreversible; upon removal of the external force, PSM\u003csub\u003e2M\u003c/sub\u003e fails to recover its original shape. For example, at λ\u0026thinsp;=\u0026thinsp;1000% and λ\u0026thinsp;=\u0026thinsp;8000%, the recovery ratios λ\u003csub\u003eδ\u003c/sub\u003e (defined as the ratio of the recovered length to the total stretched length) are only 55% and 36%, respectively (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003ei).\u003c/p\u003e \u003cp\u003eIn contrast, PSM\u003csub\u003e6M\u003c/sub\u003e exhibits hyperelastic behaviour, with an elasticity ratio exceeding 90% (Supplementary Fig.\u0026nbsp;12), it can fully recover when it is subjected to a tensile strain of up to 12 times (λ\u0026thinsp;=\u0026thinsp;1200%) (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003ed). Under uniaxial stretching, the stress‒strain curve of PSM\u003csub\u003e6M\u003c/sub\u003e remains unaffected by the stretching rate (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eh), as it displays neither distinct yield points nor significant plastic deformation. The hydrogel possesses an elastic modulus of 77.7 kPa and a toughness of 697 kJ/m\u0026sup3; and is capable of elastic deformation up to λ\u0026thinsp;=\u0026thinsp;2000%. Unlike PSM\u003csub\u003e2M\u003c/sub\u003e, PSM\u003csub\u003e6M\u003c/sub\u003e only undergoes elongation of the polymer chains and partial orientation during stretching (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003ef). In the undeformed state, in situ SAXS measurements reveal circular scattering rings in the 2D SAXS patterns and a broad peak in the 1D SAXS profiles within the high q region (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003ee), which corresponds to the scatterer of the entangled polymer chain. The radius of gyration (Rg) is calculated as 0.28 nm using the Guinier theoretical model (Supplementary Fig.\u0026nbsp;28)\u003csup\u003e\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e\u003c/sup\u003e, with an average distance of 1.83 nm between adjacent entangled scatterer centres. Upon stretching to λ\u0026thinsp;=\u0026thinsp;5, the high q region features vanish, and new scattering rings and peaks emerge in the low q region, indicating that the entangled structure has been stretched and deformed, with the Rg increasing to 3.79 nm. Upon returning to λ\u0026thinsp;=\u0026thinsp;0%, the SAXS data closely resemble those of the undeformed state, confirming the excellent structural reversibility of the topological entanglement network in PSM\u003csub\u003e6M\u003c/sub\u003e. Furthermore, PSM\u003csub\u003e6M\u003c/sub\u003e demonstrates remarkable deformation reversibility. Under a tensile strain of λ\u0026thinsp;=\u0026thinsp;1000%, the λ\u003csub\u003eδ\u003c/sub\u003e reaches approximately 92% within 1 second, achieving full recovery within 10 seconds (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003ei). Under a higher strain (λ\u0026thinsp;=\u0026thinsp;2000%), λ\u003csub\u003eδ\u003c/sub\u003e reaches approximately 87% within 1 second and eventually recovers to approximately 94%. The superelasticity of PSM\u003csub\u003e6M\u003c/sub\u003e significantly surpasses that of conventional hydrogels, which typically exhibit reversible recovery at λ\u0026thinsp;\u0026lt;\u0026thinsp;300%, and approaches the performance of the best-reported pearl-chain-structured hyperelastic hydrogels (reversible recovery at λ\u0026thinsp;=\u0026thinsp;1500%), which rely on the effective unfolding and refolding of subnanometric beads\u003csup\u003e\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e\u003c/sup\u003e. However, the difference lies in the mechanisms involved. The hyperelastic behaviour of PSM\u003csub\u003e6M\u003c/sub\u003e arises partially from the stretching and recoiling of the polymer chains and partially from the topological entanglement network formed through physical constraints. This system relies on polymer chain entanglements to cooperatively transfer tension and dissipate energy along the molecular backbone during deformation.\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eEvolution of mechanical properties over wide ranges\u003c/h3\u003e\n\u003cp\u003eThis self-evolving capability, spanning a broad range from ultraplasticity to hyperelasticity, represents a significant breakthrough in the modulation of mechanical properties in hydrogels. In this system, the structural and mechanical properties of PSM can be reversibly transformed through processes such as swelling\u0026ndash;deswelling or ion incorporation. In the plastic state, the hydrogel is amenable to multiple shaping and reprocessing steps. For example, spherical and cubic hydrogel units can be fused into complex shapes such as a crouching lion, which can subsequently be reshaped into forms such as footballs and basketballs (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003ea), while retaining their plastic characteristics. Upon swelling to a concentration of \u003cem\u003ec\u0026thinsp;=\u003c/em\u003e\u0026thinsp;6M, the material transitions into an elastic hydrogel. It is capable of fully recovering after bearing a load exceeding 22 kg and can also bounce up and down in a spherical form. When needed, the hydrogel can be further swollen to revert to the plastic state. This feature is particularly advantageous for reshaping via sol-gel transitions, which can be conveniently and efficiently performed in situ under stable conditions. Naturally, the mechanical properties of intermediate polymer concentrations fall between those of the two extreme states, with the degree of elasticity positively correlated with the polymer concentration. Detailed performance characterization results are provided in the Supplementary Information (Supplementary Figs.\u0026nbsp;46 and 47).\u003c/p\u003e \u003cp\u003eThe mechanical properties following mutual transformation are evaluated through uniaxial tensile testing. Upon swelling from PSM\u003csub\u003e2M\u003c/sub\u003e to PSM\u003csub\u003e6M\u003c/sub\u003e, the hydrogel exhibits fully reversible recovery (hyperelasticity) after a tenfold elongation (λ\u0026thinsp;=\u0026thinsp;1000%). Conversely, when transformed back, it demonstrates an ultraextended stretchability with a strain ratio of λ\u0026thinsp;=\u0026thinsp;8000% (Supplementary Videos 1 and 2). The corresponding stress‒strain curves closely resemble those of the original PSM\u003csub\u003e6M\u003c/sub\u003e and PSM\u003csub\u003e2M\u003c/sub\u003e (Figs.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003eb and c). Furthermore, after introducing 5M NaCl into the PSM\u003csub\u003e6M\u003c/sub\u003e to shield against electrostatic interactions, the resulting mechanical behaviour becomes comparable to that of PSM\u003csub\u003e3M\u003c/sub\u003e (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003ec). However, after the ions are removed via diffusion, the mechanical performance is largely restored to that of the PSM at the same polymer concentration. Intermediate mechanical properties can be achieved by adjusting either the polymer concentration or the ion concentration. Specifically, the tunable polymer concentration range is 35\u0026ndash;75% (Supplementary Fig.\u0026nbsp;18), while the ion concentration can be modulated between 0\u0026thinsp;~\u0026thinsp;6M. In this elastoplastic transformation governed by swelling and ion regulation, overall structural reorganization plays a dominant role. Taking PSM\u003csub\u003e6M\u003c/sub\u003e as an example, during the swelling process to PSM\u003csub\u003e2M\u003c/sub\u003e, the hydration of the entangled regions increases. Some entanglements previously stabilized by hydrophobic interactions become disentangled, leading to an increase in interchain spacing. According to LF-NMR measurements\u003csup\u003e\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e\u003c/sup\u003e, approximately 32% of the originally entangled chains transition into dangling chains, while 8% become free chains. Consequently, the degree of entanglement decreases from 69 to 4.2 (Figs.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003ed and e). When only 5M NaCl is introduced without altering the swelling state, some of the electrostatic interactions are screened by counterions, resulting in a reduction in the entanglement ratio from 35% to 20%. Approximately 43% of the entangled chains within the entangled domains have one end released, stretching and dangling around the entanglement centre while remaining under certain constraints. Under these conditions, the degree of entanglement is reduced to 11.3 (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003ee).\u003c/p\u003e \u003cp\u003eDuring the elastoplastic transformation process, the mechanical properties of the hydrogel vary significantly. The average elastic modulus of PSM\u003csub\u003e2M\u003c/sub\u003e is approximately 1.5 kPa, with a toughness of 50 kJ/m\u0026sup3;, whereas that of PSM\u003csub\u003e6M\u003c/sub\u003e is approximately 140 kPa and the toughness is 750 kJ/m\u0026sup3;. Upon further swelling to form PSM\u003csub\u003e12M\u003c/sub\u003e, the modulus and toughness can reach 2 MPa and 8000 kJ/m\u0026sup3;, respectively (the hydrogel is still soft material rather than hard material) (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003ef). This broad modulus-toughness range not only encompasses the mechanical properties of various natural tissues but also spans the performance spectrum of both conventional and high-performance hydrogels\u003csup\u003e\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e\u003c/sup\u003e. Such a readily tunable and continuous evolution of mechanical properties facilitates the fabrication of complex-shaped hydrogel materials and enables the simulation of a wide range of biological tissue mechanics which was previously difficult to achieve with conventional hydrogels.\u003c/p\u003e\n\u003ch3\u003eResistance to physical damage\u003c/h3\u003e\n\u003cp\u003eOn the basis of its topological entanglement network structure, PSM is capable of overcoming the modulus‒fatigue threshold conflict, thereby significantly increasing its damage resistance. The crack resistance of the PSM is evaluated by using a 1/4 shear notch test. Under monotonic loading, when the polymer concentration ranges from 2M to 6M, the PSM can stably achieve large deformations up to a strain of λ\u0026thinsp;=\u0026thinsp;1500%. The precrack blunts and bifurcates more in the tanglemer network than in the regular network, reducing stress concentration and delaying catastrophic failure (Figs.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003ea and b). In contrast, traditional elastic network hydrogels typically experience rapid nonblunt fracture at strains where λ\u0026thinsp;\u0026lt;\u0026thinsp;200%\u003csup\u003e23\u003c/sup\u003e. During the shearing process, the amplitude of the energy release rate is known as the fatigue threshold, below which a crack does not grow\u003csup\u003e\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eFor the hyperelastic PSM\u003csub\u003e6M\u003c/sub\u003e, only a limited degree of crack blunting occurs at the notch. Under monotonic loading, when λ\u0026thinsp;\u0026lt;\u0026thinsp;1000%, no crack propagation is observed even after the load is maintained for 10 minutes (Δc\u0026thinsp;\u0026lt;\u0026thinsp;0.015 mm). As the strain further increases to λ\u0026thinsp;=\u0026thinsp;1500%, Δc abruptly increases to 0.88 mm (Figs.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003ec and d). Linear regression analysis of the experimental data indicates that the fatigue threshold (Gi) is approximately 1050 J/m\u0026sup2;, which is the same as that of high-fatigue-resistant hydrogels (800\u0026thinsp;~\u0026thinsp;1200 J/m\u0026sup2;). This increased performance is attributed to the topological entanglement network structure, in which the absence of covalent crosslinking allows relative sliding between polymer chains. Consequently, high stress can be uniformly dispersed along the entire polymer chain, enabling efficient stress transfer throughout the network (Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003eb). In contrast, the crosslinking points in conventional elastic hydrogels restrict the extent of stress dispersion, resulting in localized stress concentration primarily borne by the polymer chains bridging the crack. Naturally, the sliding friction increases with the degree of entanglement. However, in contrast to covalent crosslinking, dense entanglements do not compromise the fatigue threshold. Therefore, PSM\u003csub\u003e6M\u003c/sub\u003e not only has a high elastic modulus (140 kPa) and high shear toughness (3615 J/m\u0026sup2; at λ\u0026thinsp;=\u0026thinsp;1500%) (Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003ee) but also maintains a high fatigue threshold. Under cyclic loading conditions, the crack growth rate (dc/dn) per cycle is measured and correlated with the energy release rate amplitude (G) (Figs.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003ef and g). As the number of cycles increases, the cumulative crack propagation progresses at a relatively low rate. The fatigue threshold under cyclic loading, G\u003csub\u003eth\u003c/sub\u003e, is estimated to be approximately 141 J/m\u0026sup2;, which is significantly lower than Gi. This discrepancy is primarily due to differences in measurement resolution\u003csup\u003e\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eIn contrast, ultraplastic PSM\u003csub\u003e2M\u003c/sub\u003e exhibits a lower degree of entanglement, reduced interchain friction, and a greater tendency for polymer chain sliding, which collectively contribute to enhanced resistance against crack propagation. Consequently, not only is the crack blunting zone broader at the precrack site, but a distinct necking phenomenon is also observed on the opposite side (Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003ea). Although crack propagation under plastic deformation also occurs under small strains, this resistance mechanism enables PSM\u003csub\u003e2M\u003c/sub\u003e to be stretched to an exceptionally high strain (λ\u0026thinsp;=\u0026thinsp;8000%) without fracture. Under cyclic loading conditions, owing to the presence of irreversible plastic deformation, the crack growth rate of the hydrogel increases, with the fatigue threshold G\u003csub\u003eth\u003c/sub\u003e estimated at approximately 53 J/m\u0026sup2;. Similarly, the shear toughness is significantly lower, measuring approximately 12 J/m\u0026sup2;. The resistance mechanism inherent to PSM remains effective across various crack configurations. For example, in the trouser tear test, stress-induced damage is predominantly localized in the trouser legs rather than at the shear crack interface, thereby allowing the hydrogel to sustain high strain without undergoing catastrophic failure (Supplementary Figs.\u0026nbsp;48‒52).\u003c/p\u003e\n\u003ch3\u003eFunctions and Applications\u003c/h3\u003e\n\u003cp\u003eThe self-evolving mechanical behaviour of PSM, which transitions from ultraplasticity to hyperelasticity, significantly increases its potential applications. In this study, we demonstrate its applicability through examples in biomedical fields such as cell engineering and wound treatment. First, PSM was cocultured with human umbilical cord mesenchymal stem cells (UC-MSCs), during which time it exhibited excellent biocompatibility (cell viability reached 96% after 24 hours with PSM\u003csub\u003e2M\u003c/sub\u003e) (Supplementary Figs.\u0026nbsp;53‒55). Compared with conventional rigid culture surfaces or elastic-based materials\u003csup\u003e\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e\u003c/sup\u003e, the tunable mechanical elastoplastic properties of PSM significantly influence cell morphology (Figs.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e5\u003c/span\u003ea and b). Cells cultured in PSM\u003csub\u003e2M\u003c/sub\u003e exhibited a more spread-out growth pattern in all directions, characterized by a larger average cell area (194 \u0026micro;m\u0026sup2;) and lower roundness (0.57) (Figs.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e5\u003c/span\u003ec and d). In contrast, cells cultured in PSM\u003csub\u003e6M\u003c/sub\u003e displayed a more rounded morphology, with a smaller average cell area (58 \u0026micro;m\u0026sup2;) and greater roundness (0.69). These findings confirm that the elastoplastic characteristics of the hydrogel network can regulate cell growth, proliferation, and morphological behaviour, phenomena closely related to both passive and actively generated isometric cytoskeletal tension. This mechanism is comparable to that observed in previously reported stress-relaxing hydrogels\u003csup\u003e\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e\u003c/sup\u003e. However, the wider elastoplastic transition range of PSM offers greater flexibility in tailoring the growth morphology and directing the differentiation of stem cells.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eFurthermore, we investigate the potential application of PSM loaded with exosomes (Exo) for the in vitro treatment of diabetic wounds. The Exo loading and release capabilities were evaluated using a BCA protein assay kit. PSM interacts with the membrane surface of the Exo through electrostatic binding and demonstrates effective loading (Fig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e5\u003c/span\u003ee). Specifically, PSM\u003csub\u003e6M\u003c/sub\u003e has a loading capacity of 103 \u0026micro;g and an encapsulation efficiency of 84%, both of which are higher than those of PSM\u003csub\u003e2M\u003c/sub\u003e, which has a loading capacity of 97 \u0026micro;g and an encapsulation efficiency of 77% (Supplementary Fig.\u0026nbsp;59). This performance surpasses that of conventional hydrogels such as polyacrylamide (PAAm) hydrogels or extracellular matrix (ECM)-based hydrogels\u003csup\u003e\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e\u003c/sup\u003e, which typically exhibit encapsulation efficiencies ranging from 50% to 70%. Moreover, the release of Exos from PSM is excellent, with a continuous release duration of up to 12 days in a PBS environment. The release profile is characterized by its uniformity and stability, with an average daily release of approximately 6.4 \u0026micro;g and a maximum daily variation of less than 1.2 \u0026micro;g between consecutive days (Supplementary Fig.\u0026nbsp;60). In comparison, ECM-based hydrogels or dynamically responsive natural hydrogels\u003csup\u003e\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e\u003c/sup\u003e typically exhibit release durations ranging from 0.5 to 7 days, accompanied by a burst release effect, with up to 80% of the Exo released within the first 24 hours. Compared with hyperelastic PSM\u003csub\u003e6M\u003c/sub\u003e, ultraplastic PSM\u003csub\u003e2M\u003c/sub\u003e demonstrates superior release performance and a higher total release rate. For instance, the total release rate of PSM\u003csub\u003e2M\u003c/sub\u003e reaches 87%, whereas that of PSM\u003csub\u003e6M\u003c/sub\u003e is 66% (Fig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e5\u003c/span\u003ef).\u003c/p\u003e \u003cp\u003eOn the basis of the elastoplastic properties of hydrogels and their impact on Exo loading and release, we can strategically select an optimal mode for wound treatment. Specifically, during the Exo loading process, PSM\u003csub\u003e6M\u003c/sub\u003e is selected because of its high loading capacity. After Exo incorporation, the hydrogel can swell and undergo in situ transformation into a more effective plastic PSM. Leveraging its plastic characteristics, the hydrogel can be moulded in situ to conform to the geometry of irregular wounds, thereby achieving better wound surface adaptation. The therapeutic efficacy of PSM-Exo in diabetic wound healing is validated through animal experiments, with a commercially available 3M wound dressing (without Exo loading) serving as the control group. The results demonstrate that on days 7 and 12, the residual wound areas in the PSM-Exo group were reduced to 23% and 11%, respectively, representing a significantly greater reduction than that in the control group, which exhibited residual wound areas of 40% and 28%, respectively (Fig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e5\u003c/span\u003eg). These outcomes also show improved performance relative to previously reported Exo-based hydrogel treatments, which typically achieve residual wound areas of approximately 45% and 23% at the same time points (days 7 and 12, respectively)\u003csup\u003e\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e\u003c/sup\u003e. Histopathological evaluation and mechanistic analysis further confirms that PSM-Exo promotes epithelial regeneration, collagen deposition, and angiogenesis, indicating its potential as an effective therapeutic strategy for diabetic wound healing (Figs.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e5\u003c/span\u003eh and i and Supplementary Fig.\u0026nbsp;63).\u003c/p\u003e"},{"header":"Conclusions","content":"\u003cp\u003eBy constructing reversible topological entanglement networks, we successfully develop a single-component hydrogel capable of reversible self-evolution from ultraplasticity to hyperelasticity. Compared with conventional hydrogels, PSM exhibits a broader elastoplastic range, a tunable modulus, toughness, and superior damage resistance. These properties arise from the reversible conversion between free chains and entangled chains in specially designed amphoteric ionic polymers, driven by electrostatic and hydrophobic interactions, as well as the chain slip orientation and stretch recovery mechanisms under mechanical loading. PSM has overcome the performance limitations of traditional hydrogels in terms of elastoplasticity, demonstrating significant application potential in biomedical fields such as cell and tissue engineering. Moreover, this study establishes a structural design paradigm that provides a straightforward strategy for regulating the structure and performance of hydrogel systems.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eOnline content\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAny methods, additional references, Nature Portfolio reporting summaries, source data, extended data, supplementary information, acknowledgements, peer review information; details of author contributions and competing interests; and statements of data and code availability are available.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData availability\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe data that support the findings of this study are present in the paper and/or in the Supplementary Information. Additional data related to the paper are available from the corresponding author upon request. Source data are provided with this paper.\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis work was supported by the National Natural Science Foundation of China (12572286), the Science and Technology Innovation Project of Hunan Province (2023RC1070), the Natural Science Foundation of Hunan Province (2023JJ60447), the Key Research and Development Projects of Hainan Province of China (ZDYF2024SHFZ062), and Scientific research and innovation Foundation of Hunan University of Technology (CX2301).\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eWang WK et al (2023) Injectable ECM-mimetic dynamic hydrogels abolish ferroptosis-induced post-discectomy herniation through delivering nucleus pulposus progenitor cell-derived exosomes. 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Adv Healthc Mater 14:2404966\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"nature-portfolio","isNatureJournal":true,"hasQc":false,"allowDirectSubmit":false,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"","title":"Nature Portfolio","twitterHandle":"","acdcEnabled":false,"dfaEnabled":false,"editorialSystem":"ejp","reportingPortfolio":"","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"","lastPublishedDoi":"10.21203/rs.3.rs-7839519/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7839519/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eElastoplastic materials with self-evolving ability can exhibit specific elastic or plastic responses to large strains, whereas hydrogels typically behave as elastomers with a low elastic range due to the nonuniform crosslinking structure and restrictions among cross-networks. Achieving both ultraplasticity and hyperelasticity within the same hydrogel has not been previously reported. In this study, a single-component hydrogel is developed that can reversibly transition in situ from ultraplasticity (ultralong plastic deformation, strain (λ) ~ 120000%) to hyperelasticity (λ = 1200%, with full recovery within 2–10 seconds after stretching) by modulating molecular chain conformation and network topology from free to entangled state through differences in electrostatic and hydrophobic interactions. The transformation can be regulated by adjusting internal system parameters, such as the in situ concentrations of polymers and ions. During the transformation process, the hydrogel exhibits a broad range of tuneable mechanical properties, including a modulus (E) ranging from 700 Pa to 2 MPa and a toughness (Γ) varying between 15 and 8000 kJ/m³. Additionally, this hydrogel demonstrated exceptional fatigue resistance and damage tolerance, with a fatigue threshold (Gi) reaching 1050 J/m². The hydrogel with self-evolving ultraplasticity-to-hyperelasticity can provide flexible mechanical responses, and can extensively simulate the mechanical properties of diverse biological tissue matrices, thereby offering a superior option for materials used in cell and tissue engineering.\u003c/p\u003e","manuscriptTitle":"Topologically Entangled Hydrogels with Self-Evolving Ultraplasticity-to-Hyperelasticity","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-12-28 18:30:08","doi":"10.21203/rs.3.rs-7839519/v1","editorialEvents":[],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"nature-communications","isNatureJournal":true,"hasQc":false,"allowDirectSubmit":false,"externalIdentity":"NCOMMS","sideBox":"Learn more about [Nature Communications](http://www.nature.com/ncomms/)","snPcode":"","submissionUrl":"https://mts-ncomms.nature.com/","title":"Nature Communications","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"ejp","reportingPortfolio":"Nature Communications","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"602cc893-4ab9-4dab-924c-4bda5cdbbf0c","owner":[],"postedDate":"December 28th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[{"id":59966820,"name":"Physical sciences/Chemistry/Materials chemistry/Mechanical properties"},{"id":59966821,"name":"Physical sciences/Chemistry/Polymer chemistry/Mechanical properties"},{"id":59966822,"name":"Physical sciences/Materials science/Soft materials/Gels and hydrogels"},{"id":59966823,"name":"Physical sciences/Materials science/Soft materials/Polymers"},{"id":59966824,"name":"Physical sciences/Materials science/Biomaterials/Bioinspired materials"}],"tags":[],"updatedAt":"2025-12-29T12:05:45+00:00","versionOfRecord":[],"versionCreatedAt":"2025-12-28 18:30:08","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-7839519","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7839519","identity":"rs-7839519","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}