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This review critically evaluates advancements in multifunctional hydrogels, particularly focusing on their applications in osteoarthritis (OA) therapy. As research evolves from traditional natural materials, there is a significant shift towards synthetic and composite hydrogels, known for their superior mechanical properties and enhanced biodegradability. This review spotlights novel applications such as injectable hydrogels, microneedle technology, and responsive hydrogels, which have revolutionized OA treatment through targeted and efficient therapeutic delivery. Moreover, it discusses innovative hydrogel materials, including protein-based and superlubricating hydrogels, for their potential to reduce joint friction and inflammation. The integration of bioactive compounds within hydrogels to augment therapeutic efficacy is also examined. Furthermore, the review anticipates continued technological advancements and a deeper understanding of hydrogel-based OA therapies. It emphasizes the potential of hydrogels to provide tailored, minimally invasive treatments, thus highlighting their critical role in advancing the dynamic field of biomaterial science for OA management.

Shape-shifting polymers are widely used in various fields such as intelligent switches, soft robots and sensors, which require both multiple stimulus-response functions and qualified mechanical strength. In this study, a novel near-infrared-light (NIR)-responsible shape-shifting hydrogel system was designed and fabricated through embedding vinylsilane-modified carbon nanotubes (CNTs) into particle double-network (P-DN) hydrogels by micellar copolymerisation. The dispersed brittle Poly(sodium 2-acrylamido-2-methylpropane-1-sulfonate) (PNaAMPS) network of the microgels can serve as sacrificial bonds to toughen the hydrogels, and the CNTs endow it with NIR photothermal conversion ability. The results show that the CNTs embedded in the P-DN hydrogels present excellent mechanical strength, i.e., a fracture strength of 312 kPa and a fracture strain of 357%. Moreover, an asymmetric bilayer hydrogel, where the active layer contains CNTs, can achieve 0°-110° bending deformation within 10 min under NIR irradiation and can realise complex deformation movement. This study provides a theoretical and experimental basis for the design and manufacture of photoresponsive soft actuators.

Shape-shifting polymers usually require not only reversible stimuli-responsive ability, but also strong mechanical properties. A novel shape-shifting photochromic hydrogel system was designed and fabricated by embedding hydrophobic spiropyran (SP) into double polymeric network (DN) through micellar copolymerisation. Here, sodium alginate (Alg) and poly acrylate-co-methyl acrylate-co-spiropyran (P(SA- co -MA- co -SPMA)) were employed as the first network and the second network, respectively, to realise high mechanical strength. After being soaked in the CaCl 2 solution, the carboxyl groups in the system underwent metal complexation with Ca 2+ to enhance the hydrogel. Moreover, after the hydrogel was exposed to UV-light, the closed isomer of spiropyran in the hydrogel network could be converted into an open zwitterionic isomer merocyanine (MC), which was considered to interact with Ca 2+ ions. Interestingly, Ca 2+ and UV-light responsive programmable shape of the copolymer hydrogel could recover to its original form via immersion in pure water. Given its excellent metal ion and UV light stimuli-responsive and mechanical properties, the hydrogel has potential applications in the field of soft actuators.

This study combined inorganic α-hemihydrate gypsum ( α -HHG) with organic polyacrylamide (PAM) hydrogel to create a novel α -HHG/PAM composite material. Through this facile composite strategy, this fabricated material exhibited a significantly longer initial setting time and higher mechanical strength compared to α -HHG. The effects of the addition amount and the concentration of PAM precursor solution on the flowability of the α -HHG/PAM composite material slurry, initial setting time, and mechanical properties of the hardened specimens were investigated. The structural characteristics of the composite material were examined using XRD, FE-SEM, and TGA. The results showed that the initial setting time of the α -HHG/PAM composite material was 25.7 min, which is an extension of 127.43% compared to that of α -HHG. The flexural strength and compressive strength of the oven-dried specimens were 23.4 MPa and 58.6 MPa, respectively, representing increases of 34.73% and 84.86% over values for α -HHG. The XRD, FE-SEM, and TGA results all indicated that the hydration of α -HHG in the composite material was incomplete. The incompleteness is caused by the competition between the hydration process of inorganic α -HHG and the gelation process of the acrylamide molecules for water, which hinders some α -HHG from entirely reacting with water. The enhanced mechanical strength of the α -HHG/PAM composite material results from the tight interweaving and integrating of organic and inorganic networks. This study provides a concise and efficient approach to the modification research of hemihydrate gypsum., Competing Interests: The authors declare no conflicts of interest.

Hydrogels usually are fabricated by using monomers or preexisting polymers in precursor solutions. Here, a polyelectrolyte complex biohydrogel (Bio-PEC hydrogel) made from a precursor dough, by kneading, annealing, and crosslinking the dough of two oppositely charged polysaccharides, cationic chitosan quaternary ammonium salt (HACC) and anionic sodium hyaluronate (HA), photoinitiator (α-ketoglutaric acid), crosslinker glycidyl methacrylate (GMA), and water of very small quantity is reported. Controlled kneading and annealing homogenized the dough with respect to transforming randomly distributed, individual polymer chains into tightly wound double-stranded structures, which, upon UV irradiation, covalently sparsely crosslinked into a highly entangled network and subsequently, upon fully swollen in water, results in Bio-PEC hydrogel, HACC/HA, exhibiting near-perfect elasticity, high tensile strength, and high swelling resistance. Via the same kneading and annealing, tetracarboxyphenylporphyrin iron (Fe-TCPP) metal nanoclusters are incorporated into HACC/HA to obtain photocatalytic, antibacterial, and biocompatible Bio-PEC hydrogel composite, Fe-TCPP@HACC/HA. Using SD rat models, the efficacy of Fe-TCPP@HACC/HA in inhibiting Escherichia coli (E. coli) growth in vitro and the ability to promote wound healing and scar-free skin regeneration in vivo, or its high potential as a wound dressing material for biomedical applications are demonstrated., (© 2023 Wiley‐VCH GmbH.)

Polyampholyte (PA) hydrogels are randomly copolymerized from anionic and cationic monomers, showing good mechanical properties owing to the existence of numerous ionic bonds in the networks. However, relatively tough PA gels can be synthesized successfully only at high monomer concentrations ( C M ), where relatively strong chain entanglements exist to stabilize the primary supramolecular networks. This study aims to toughen weak PA gels with relatively weak primary topological entanglements (at relatively low C M ) via a secondary equilibrium approach. According to this approach, an as-prepared PA gel is first dialyzed in a FeCl 3 solution to reach a swelling equilibrium and then dialyzed in sufficient deionized water to remove excess free ions to achieve a new equilibrium, resulting in the modified PA gels. It is proved that the modified PA gels are eventually constructed by both ionic and metal coordination bonds, which could synergistically enhance the chain interactions and enable the network toughening. Systematic studies indicate that both C M and FeCl 3 concentration (CFeCl3) influence the enhancement effectiveness of the modified PA gels, although all the gels could be dramatically enhanced. The mechanical properties of the modified PA gel could be optimized at C M = 2.0 M and CFeCl3 = 0.3 M, where the Young's modulus, tensile fracture strength, and work of tension are improved by 1800%, 600%, and 820%, respectively, comparing to these of the original PA gel. By selecting a different PA gel system and diverse metal ions (i.e., Al 3+ , Mg 2+ , Ca 2+ ), we further prove that the proposed approach is generally appliable. A theoretical model is used to understand the toughening mechanism. This work well extends the simple yet general approach for the toughening of weak PA gels with relatively weak chain entanglements.

Stimuli-responsive hydrogel actuators have attracted tremendous interest in switches and microrobots. Based on N -isopropylacrylamide (NIPAM) monomers with LCST phase separation and photochromic molecule spiropyran which can respond to ultraviolet light and H+, we develop a novel multistimuli-responsive co-polymer anisotropic bilayer hydrogel, which can undergo complex deformation behavior under environmental stimuli. Diverse bending angles were achieved based on inhomogeneous swelling. By controlling the environmental temperature, the bilayer hydrogels achieved bending angles of 83.4° and -162.4° below and above the critical temperature of PNIPAM. Stimulated by ultraviolet light and H+, the bilayer hydrogels showed bending angles of -19.4° and -17.3°, respectively. In addition, we designed a strategy to enhance the mechanical properties of the hydrogel via double network (DN). The mechanical properties and microscopic Fourier transform infrared (micro-FTIR) spectrum showed that the bilayer hydrogel can be well bonded at the interfaces of such bilayers. This work will inspire the design and fabrication of novel soft actuators with synergistic functions.

Hydrogels with high mechanical strength, good crack resistance, and good adhesion are highly desirable in various areas, such as soft electronics and wound dressing. Yet, these properties are usually mutually exclusive, so achieving such hydrogels is difficult. Herein, we fabricate a series of strong, tough, and adhesive composite hydrogels from polyampholyte (PA) gel reinforced by nonwoven cellulose-based fiber fabric (CF) via a simple composite strategy. In this strategy, CF could form a good interface with the relatively tough PA gel matrix, providing high load-bearing capability and good crack resistance for the composite gels. The relatively soft, sticky PA gel matrix could also provide a large effective contact area to achieve good adhesion. The effect of CF content on the mechanical and adhesion properties of composite gels is systematically studied. The optimized composite gel possesses 35.2 MPa of Young's modulus, 4.3 MPa of tensile strength, 8.1 kJ m -2 of tearing energy, 943 kPa of self-adhesive strength, and 1.4 kJ m -2 of self-adhesive energy, which is 22.1, 2.3, 1.8, 6.0, and 4.2 times those of the gel matrix, respectively. The samples could also form good adhesion to diverse substrates. This work opens a simple route for fabricating strong, tough, and adhesive hydrogels.

The poor adhesion performance of typical gels still remains a challenge to find a simple method to achieve strong and reversible adhesion with the existence of water. Here, a poly(acryloyloxyethyl trimethyl ammonium chloride-co-2-vinyl-4-6-diamino-1,3,5-triazine) (P(DAC-co-VDT)) gel with high and adjustable interfacial adhesion is fabricated by combining cation-triazine π interaction and multiple hydrogen bonding and through a one-pot route. Characterization of the gels reveals that the two types of interactions are introduced into the gel network and that the gel-gel and gel-glass interfacial adhesion can be readily adjusted in a wide range from 15.98 to 123.60 kPa. This approach enables the creation of high-strength composites using P(DAC-co-VDT) gel as matrix, anionic monomer sodium p-styrene sulfonate as ion concentration adjustor, and discrete quartz sands as filler with easy and repeated moldability and self-healing capability., (© 2022 Wiley-VCH GmbH.)

The structure, morphology, fracture toughness and flaw sensitivity length scale of chain-extended poly(butylene succinate) with various pre-stretch ratios were studied. PBS modification adopted from a multifunctional, commercially available chain-extension containing nine epoxy groups (ADR9) as the first step chain extension and hydroxyl addition modified dioxazoline (BOZ) as the second step. Time-temperature superposition (TTS) studies show that the viscosity increased sharply and the degree of molecular branching increased. Fourier transform infrared spectroscopy (FT-IR) confirm successful chain extension reactions. The orientation of the polymer in the pre-stretch state is such that spherulites deformation along the stretching direction was observed by polarized light optical microscopy (PLOM). The fracture toughness of sample ( λ fix = 5) is Γ ≈ 10 6 J m -2 and its critical flaw sensitivity length scale is Γ / W c ≈ 0.01 m, approximately 5 times higher than PBS without chain-extension ( Γ ≈ 2 × 10 5 J m -2 and Γ / W c ≈ 0.002 m, respectively). The notch sensitivity of chain-extended PBS is significantly reduced, which is due to the orientation of spherulites more effectively preventing crack propagation. The principle can be generalized to other high toughness material systems.

Herein, we report a method of fabricating strong and thermosensitive double network (T-DN) poly(N-isopropyl acrylamide) (PNIPAM)-based hydrogels, i.e. rigid and brittle poly(2-acrylamido-2-methylpropanesulfonic acid sodium salt) (PNaAMPS) as the first and soft and ductile poly(N-isopropyl acrylamide-co-acrylamide) (P(NIPAM-co-AAm)) as the second interpenetrating each other. In particular, NIPAM was deliberately integrated into the double network as an adjustor of elastic modulus and hydrophilicity, besides thermosensitivity. Such double network construction strategy resulted in PNaAMPS/P(NIPAM-co-AAm) T-DN hydrogels of excellent mechanical properties (0.83-1.37 MPa) and desirable temperature-dependent swellabilities. Besides, T-DN hydrogels with various NIPAM contents exhibited good biocompatibility with high cell survival rates around normal body temperatures. Furthermore, crystal violet (CV) could be readily loaded to impart antibacterial functionality to the T-DN hydrogels against E. coli. The double network construction strategy could be adapted to fabricating high-strength antibacterial hydrogels for a broad range of biomedical applications.

Rewritable information record materials usually demand not only reversibly stimuli-responsive ability, but also strong mechanical properties. To achieve one photochromic hydrogel with super-strong mechanical strength, hydrophobic molecule spiropyran (SP) has been introduced into a copolymer based on ion-hybrid crosslink. The hydrogels exhibit both photoinduced reversible color changes and excellent mechanical properties, i.e., the tensile stress of 3.22 MPa, work of tension of 12.8 MJ m -3 , and modulus of elasticity of 8.6 MPa. Moreover, the SP-based Ca 2+ crosslinked hydrogels can be enhanced further when exposed to UV-light via ionic interaction coordination between Ca 2+ , merocyanine (MC) with polar copolymer chain. In particular, hydrogels have excellent reversible conversion behavior, which can be used to realize repeatable writing of optical information. Thus, the novel design is demonstrated to support future applications in writing repeatable optical information, optical displays, information storage, artificial intelligence systems, and flexible wearable devices., (© 2021 Wiley-VCH GmbH.)

Soft fiber-reinforced polymers (FRPs), consisting of rubbery matrices and rigid fabrics, are widely utilized in industry because they possess high specific strength in tension while allowing flexural deformation under bending or twisting. Nevertheless, existing soft FRPs are relatively weak against crack propagation due to interfacial delamination, which substantially increases their risk of failure during use. In this work, a class of soft FRPs that possess high specific strength while simultaneously showing extraordinary crack resistance are developed. The strategy is to synthesize tough viscoelastic matrices from acrylate monomers in the presence of woven fabrics, which generates soft composites with a strong interface and interlocking structure. Such composites exhibit fracture energy, Γ, of up to 2500 kJ m -2 , exceeding the toughest existing materials. Experimental elucidation shows that the fracture energy obeys a simple relation, Γ = W · l T , where W is the volume-weighted average of work of extension at fracture of the two components and l T is the force transfer length that scales with the square root of fiber/matrix modulus ratio. Superior Γ is achieved through a combination of extraordinarily large l T (10-100 mm), resulting from the extremely high fiber/matrix modulus ratios (10 4 -10 5 ), and the maximized energy dissipation density, W. The elucidated quantitative relationship provides guidance toward the design of extremely tough soft composites., (© 2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

The research on multiple hydrogen bonds (H-bonds) hydrogels have gradually aroused wide interest. In this paper, a multiple H-bonds-reinforced poly(acrylamide-co-2-vinyl-4,6-diamino-2-vinyl-1,3,5-triazine)/tannic acid (P(Am-co-VDT)/TA) hydrogels are prepared. The results suggest that the prepared hydrogel has two types of H-bonds crosslinking regions: A "soft" region of H-bonds between the diaminotriazine (DAT) moieties on the polymer chains and the TA pyrogallol/catechol groups, and a "hard" region of H-bonds forming by DAT moieties with itself. The hard crosslinking region exhibits significantly higher activation energy than the soft region. Such soft and hard dual physically crosslinked networks dramatically enhance the mechanical properties of P(Am-co-VDT)/TA hydrogels in a synergistic manner (tensile strength is 2.34 MPa, elongation at break is 410%). Due to the multiple hydrogen bonds, the hydrogel has good pH sensitivity and rapid response to shape memory within a few minutes. In addition, the hydrogels have the capacity of physical adsorption of the anti-inflammatory drug diclofenac sodium and other molecules with a specific spatially arranged chemical composition. These hydrogels with high mechanical strength, excellent shape memory behavior, and capacity of adsorption of anti-inflammatory drug could be attractive candidates for applications in the fields of biomedicine, tissue engineering, and medical materials., (© 2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

A versatile ionic crosslink lithography (ICL) approach is reported to achieve geometry transitions of strong polyvinyl alcohol/sodium alginate (PVA/SA) hydrogels in a controllable and programmable manner. Specifically, localized PVA/SA and PVA/SA/Fe 3+ hydrogel domains of significantly different swellabilities (i.e., in-plane gradient) are created by patterning and selective ionic crosslinking of one single type of PVA/SA hydrogel. A simple two-step sequential pre- and free-swelling, or each alone, directs the patterned, inhomogeneous hydrogel to transform in various programmable and quasi-quantitative ways through local bulging and/or global buckling. All types of shape changing are reversible and repeatable due to the reversible nature of ionic coordination in the hydrogel networks. The flexibility and versatility of 3D printing is also demonstrated in creating through-thickness gradient in PVA and PVA/SA hydrogel assemblies with similar morphing capability. The ICL approach developed in this work may help shed some light on developing strong and shape morphing hydrogels as soft sensors and actuators and for potentially biomimetic transformations. The ICL approach may also be transferable to fabrication of many other types of hydrogel materials for similar applications., (© 2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

We report a simple and facile self-assembly approach to fabricate polyelectrolyte complex (PEC) hydrogel films with positively charged chitosan (CS) and negatively charged heparin sodium (HS) by combining hydrogen bonding and electrostatic interactions. The CS/HS hydrogel films exhibited excellent tensile strength and toughness, good self-recovery ability, superior water absorbency, and pH-dependent surface charge characteristics. The gelation mechanism was investigated by zeta potential measurements. The CS/HS hydrogel films exhibited high antibacterial efficacy against E. coli at selected pHs or when coordinated with various metal ions and a significant effect on accelerating wound healing. The self-assembly approach presented in this work may serve as a generic strategy for the fabrication of novel multi-functional PEC hydrogels for broad biomedical applications.