Responsive Hydrogels Research Articles

Clickable, Thermally Responsive Hydrogels Enabled by Recombinant Spider Silk Protein and Spy Chemistry for Sustained Neurotrophin Delivery.

The ability to deliver protein therapeutics in a minimally invasive, safe, and sustained manner, without resorting to viral delivery systems, will be crucial for treating a wide range of chronic injuries and diseases. Among these challenges, achieving axon regeneration and functional recovery post-injury or disease in the central nervous system remains elusive to most clinical interventions, constantly calling for innovative solutions. Here, a thermally responsive hydrogel system utilizing recombinant spider silk protein (spidroin) is developed. The protein solution undergoes rapid sol-gel transition at an elevated temperature (37°C) following brief sonication. This thermally triggered gelation confers injectability to the system. Leveraging SpyTag/SpyCatcher chemistry, the hydrogel, composed of SpyTag-fusion spidroin, can be functionalized with diverse SpyCatcher-fusion bioactive motifs, such as neurotrophic factors (e.g., ciliary neurotrophic factor) and cell-binding ligands (e.g., laminin), rendering it well-suited for neuronal culturing. More importantly, the intravitreous injection of the protein materials decorated with SpyCatcher-fusion CNTF into the vitreous body after optic nerve injury leads to prolonged JAK/STAT3 signaling, increased neuronal survival, and enhanced axon regeneration. This study illustrates a generalizable material system for injectable and sustained delivery of protein therapeutics for neuroprotection and regeneration, with the potential for extension to other chronic diseases and injuries.

Injectable responsive chemodynamic hydrogel for the sustained and localized delivery of a ferroptosis inducer to improve anticancer therapy

Injectable responsive chemodynamic hydrogel for the sustained and localized delivery of a ferroptosis inducer to improve anticancer therapy

Beeswax-based nanoconstructs enriched dual responsive hydrogel for diabetic foot ulcers in streptozotocin-induced diabetic rats.

Diabetic foot ulcer (DFU) is a complicated pathophysiological process, and there is now no recognized treatment. Hyperglycemia, neuropathy, impaired angiogenesis, reactive oxygen species, and advanced glycation end products construct the distinctive wound environment of diabetic wounds. This study aimed to develop naringenin-ferulic acid beeswax-based nanoconstructs enriched dual-responsive hydrogel (NAR-FA NLC HG) for topical application for DFU. The pH- and temperature-responsive hydrogel was formulated via a chemical cross-linking reaction of carboxymethyl chitosan and poloxamer 407 and loaded with NAR-FA NLC using the swelling-loading method. SEM, FTIR, and XRD observed the morphology and characterization of the prepared hydrogel. The in vitro release study showed controlled release during 48 h. Antibacterial activity significantly inhibits B. subtilis and E. coli compared to NLC and control groups (p < 0.05). Cell line studies show that hydrogel is compatible with HaCaT cells and 92.4 ± 4.9 % of wound contraction after 48 h of scratch wound assay. The wound closure rate with NAR FA NLC HG in STZ-induced diabetic rats reached 93.2 ± 3.4 % by day 15 with significant (p < 0.001) increases in the VEGF level and decreasing ICAM-1 level. Hence, the smart hydrogel established in this study has the potential to serve as a promising topical therapy for DFU with inherent antimicrobial activity components, including beeswax, NAR, and FA.

UV-induced coumarin-based spiropyran gradient photodimerization and photoisomerization to construct near-infrared responsive gradient hydrogel actuators in one-step

In recent years, the fabrication process of near-infrared (NIR) light-driven gradient hydrogels remains complex. Furthermore, NIR light-driven hydrogels based on the photothermal conversion mechanism have continued to face challenges in achieving spatio-temporal control of the internal structure due to the diffusive nature of heat. Therefore, it is sensible to develop NIR light-driven gradient hydrogels based on the near-infrared upconversion luminescence mechanism through a simple method. In this study, a novel photoresponsive coumarin-based spiropyran monomer (SPCMA) was designed and synthesized, followed by the fabrication of a series of double gradient hydrogels (MHMs) with rapid NIR light-driven capability and reusability through fast in situ photopolymerization of the precursor comprising SPCMA, upconversion nanoparticles (MUCNPs), and hydroxyethyl acrylate (HEA). MHMs exhibit excellent mechanical properties with fracture stress of 4.4 MPa and fracture elongation of 1282 %. Compared with hydrogel using N, N′-Methylenebis(2-propenamide) as a crosslinker, MHMs possess outstanding NIR light-driven capability and reversible cycling characteristics. MHMs rapidly transform from a three-dimensional spiral tubular to a sheet-like morphology within 30 s of NIR light irradiation and achieve a larger actuating angle of 450° within 120 s. Additionally, MHMs maintain similar driveability to the original samples after 10 cycles of NIR light-driven and UV light-recovery processes. More importantly, cargoes with seven times the mass of the "gripper" are firmly grasped and easily lifted by the "gripper" prepared using MHMs within 60 s of NIR light irradiation, demonstrating its powerful gripping ability. This work offers a new strategy for the development of biomimetic smart gradient materials.

Matrix Metalloproteinase-Responsive Controlled Release of Self-Assembly Nanoparticles Accelerates Heart Valve Regeneration In Situ by Orchestrating Immunomodulation.

In situ tissue engineering heart valves (TEHVs) are the most promising way to overcome the defects of existing valve prostheses. Despite their promising prospects, the clinical translation of TEHVs remains a formidable challenge, mainly due to unpredictable host interactions post-implantation. An immunomodulatory idea based on hydrogel encapsulation of nanoparticle-coated heart valve scaffolds is introduced. Specifically, galactose-modified human serum albumin nanoparticles (miR-93@HSA NPs) to deliver microRNA-93 mimics are utilized, which target macrophages and induce their differentiation into the anti-inflammatory M2 subtype, fostering a conducive immune microenvironment. Matrix metalloproteinase (MMP)-responsive hydrogel is used to encapsulate the nanoparticles, enabling targeted and sustained release. Results show that the miR-93@HSA NPs exhibit excellent ability to induce macrophage polarization toward the M2 phenotype. A decellularized valve modified with hydrogel reveals MMP-response release of the miR-93@HSA NPs. In vitro, the immunomodulatory heart valve possesses good endocytocompatibility and effectively reprograms macrophages when cocultured with HUVECs or RAW264.7 macrophages. In vivo, this valve scaffold promises to mitigate early inflammatory damage and provide a pro-endothelialization niche for scaffolds' constructive remodeling. With the use of cell coculture systems and transcriptome sequencing, the mechanism of immune-modulating scaffold accelerating endothelialization is being elucidated. The immunomodulatory heart valve scaffold holds promising potential for clinical translation.

Inflammation-Responsive Functional Core-Shell Micro-Hydrogels Promote Rotator Cuff Tendon-To-Bone Healing by Recruiting MSCs and Immuno-Modulating Macrophages in Rats.

Rotator cuff injuries often necessitate surgical intervention, but the outcomes are often unsatisfactory. The underlying reasons can be attributed to multiple factors, with the intricate inflammatory activities and insufficient presence of stem cells being particularly significant. In this study, an innovative inflammation-responsive core-shell micro-hydrogel is designed for independent release of SDF-1 and IL-4 within a single delivery system to promote tendon-to-bone healing by recruiting MSCs and modulating M2 macrophages polarization. First, a MMP-2 responsive hydrogel loaded with IL-4 (GelMA-MMP/IL-4) is synthesized by cross-linking gelatin methacrylate (GelMA) with MMP-2 substrate peptide. Then, the resulting core particles are coated with a shell of chitosan /SDF-1/hyaluronic acid (CS/HA/SDF-1) using the layer-by-layer electrostatic deposition method to form a core-shell micro-hydrogel composite. The core-shell micro-hydrogel shows sustained release of SDF-1 and MMP-2-responsive release of IL-4 associated in situ MSCs homing and smart inflammation regulation by promoting M2 macrophages polarization. Additionally, by injecting these micro-hydrogels into a rat rotator cuff tear and repair model, notable improvements of fibrocartilage layer are observed between tendon and bone. Notably, this study presents a new and potentially powerful environment-responsive drug delivery strategy that offers valuable insights for regulating the intricate micro-environment associated with tissue regeneration.

A functional dual responsive CMC/OHA/SA/TOB hydrogel as wound dressing to enhance wound healing.

Within the clinical realm, the complexities of wound healing have consistently presented formidable challenges. Recent advancements, notably in hydrogel technologies, have broadened the therapeutic spectrum. This study focuses on investigating a novel dual responsive composite hydrogel for wound healing. This hydrogel is ingeniously designed to maintain an optimal moist environment, expedite healing, and combat bacterial infection during wound recovery. This study combining carboxymethyl chitosan (CMC), oxidized hyaluronic acid (OHA), and sodium alginate (SA), in addition, tobramycin (TOB) was incorporated to create a CMC/OHA/SA/TOB hydrogel. Hydrogel cross-linking was verified by infrared spectroscopy, and the microstructure was examined with scanning electron microscopy. We explored its swelling and degradation behaviors in different pH environments. The drug release profile and biocompatibility was evaluated via cytotoxicity and hemolysis assays. The antibacterial efficacy of hydrogel was tested in both solid and liquid media. Additionally, the wound models in Sprague-Dawley (SD) rat was employed to investigate the hydrogel's wound healing capabilities in vivo. Results showed that CMCOHA/SA/TOB hydrogel was effectively cross-linked with a network structure. The hydrogel exhibited pronounced responsiveness in its swelling and degradation characteristics, which was significantly influenced by different levels of pH. In vitro results demonstrated that the CMC/OHA/SA/TOB hydrogel exhibits limited cytotoxicity and hemolysis, coupled with a drug release profile of dual responsive characteristics. Antibacterial activity of the hydrogel against Staphylococcus aureus, Pseudomonas aeruginosa, and Escherichia coli was confirmed. Furthermore, in vivo experiments underscored the hydrogel's proficiency in promoting wound healing, highlighting its potential for clinical applications. The CMC/OHA/SA/TOB hydrogel not only fosters a moist environment essential for wound healing and enhances structural stability, but it also exhibits functional dual responsive capabilities in swelling and degradation. These distinctive abilities enable the precise release of TOB, thereby optimizing wound healing.

Endogenous/exogenous stimuli‐responsive smart hydrogels for diabetic wound healing

AbstractDiabetes significantly impairs the body's wound‐healing capabilities, leading to chronic, infection‐prone wounds. These wounds are characterized by hyperglycemia, inflammation, hypoxia, variable pH levels, increased matrix metalloproteinase activity, oxidative stress, and bacterial colonization. These complex conditions complicate effective wound management, prompting the development of advanced diabetic wound care strategies that exploit specific wound characteristics such as acidic pH, high glucose levels, and oxidative stress to trigger controlled drug release, thereby enhancing the therapeutic effects of the dressings. Among the solutions, hydrogels emerge as promising due to their stimuli‐responsive nature, making them highly effective for managing these wounds. The latest advancements in mono/multi‐stimuli‐responsive smart hydrogels showcase their superiority and potential as healthcare materials, as highlighted by relevant case studies. However, traditional wound dressings fall short of meeting the nuanced needs of these wounds, such as adjustable adhesion, easy removal, real‐time wound status monitoring, and dynamic drug release adjustment according to the wound's specific conditions. Responsive hydrogels represent a significant leap forward as advanced dressings proficient in sensing and responding to the wound environment, offering a more targeted approach to diabetic wound treatment. This review highlights recent advancements in smart hydrogels for wound dressing, monitoring, and drug delivery, emphasizing their role in improving diabetic wound healing. It addresses ongoing challenges and future directions, aiming to guide their clinical adoption.

Retraction Note: A pH/enzyme dual responsive PMB spatiotemporal release hydrogel promoting chronic wound repair

Retraction Note: A pH/enzyme dual responsive PMB spatiotemporal release hydrogel promoting chronic wound repair

An advanced hydrogel dressing system with progressive delivery and layer-to-layer response for diabetic wound healing

Wound healing in diabetic patients presents a significant challenge due to delayed inflammatory responses, which obstruct subsequent healing stages. In response, we have developed a progressive, layer-by-layer responsive hydrogel, specifically designed to meet the dynamic requirements of diabetic wounds throughout different healing phases. This hydrogel initiates with a glucose-responsive layer formed by boronate ester bonds between 4-arm-poly (ethylene glycol) succinimidyl glutarate (4arm-PEG-SG) and 3-aminophenylboronic acid. This configuration ensures precise control over the physicochemical properties, facilitating accurate drug release during the healing process. Furthermore, we have incorporated an active pharmaceutical ingredient ionic liquid (API) composed of diclofenac and L-carnitine. This combination effectively tackles the solubility and stability issues commonly associated with anti-inflammatory drugs. To further refine drug release, we integrated matrix metalloproteinase-9 (MMP-9)-sensitive gelatin microcapsules, ensuring a controlled release and preventing the abrupt, uneven drug distribution often seen in other systems. Our hydrogel's rheological properties closely resemble human skin, offering a more harmonious approach to diabetic wound healing. Overall, this progressive layer-by-layer responsive wound management system, which is a safe, efficient, and intelligent approach, holds significant potential for the clinical treatment of diabetic wounds. Statement of significanceThe two main problems of diabetic wounds are the long-term infiltration of inflammation and the delayed repair process. In this experiment, a glucose-responsive hierarchical drug delivery system was designed to intelligently adjust gel properties to meet the needs of inflammation and repair stage of wound healing, accelerate the transformation of inflammation and repair stage, and accelerate the process of repair stage. In addition, in order to achieve accurate drug release in anti-inflammatory layer hydrogels and avoid sudden drug release due to poor solubility of anti-inflammatory small molecule drugs, we constructed a ionic liquid of active pharmaceutical ingredients (API-ILs) using diclofenac and L-carnitine as raw materials. It was wrapped in MMP-9 enzyme active gelatin microcapsule to construct a double-reaction anti-inflammatory layer gel to achieve accurate drug release. These findings highlight the potential of our system in treating diabetic wounds, providing a significant advance in wound treatment.

Exos-Loaded Gox-Modified Smart-Response Self-Healing Hydrogel Improves the Microenvironment and Promotes Wound Healing in Diabetic Wounds.

Wound management has always been a challenge in the clinical treatment of diabetes. In this study, glucose oxidase (GOx) is grafted onto natural pullulan polysaccharides, and oxidization is carried out to form a self-healing hydrogel using carboxymethyl chitosan by means of reversible Schiff base covalent bonding. The smart-response drug release properties of this natural self-healing hydrogel are demonstrated in diabetic wounds by taking advantage of two key factors, namely the pH-responsive nature of Schiff base bonding and the fact that GOx reduces the pH in diabetic wounds. To further enhance the biological functions of the hydrogel dressing, exosomes (Exos) are introduced into the hydrogel system. The GOx present in the hydrogel system improves the high-glucose microenvironment of diabetic wounds, releasing H2O2 to impart antimicrobial effects, and ensuring that the hydrogel realizes a smart-response function. The carboxymethyl chitosan component used to construct the hydrogel plays an effective antibacterial role. Moreover, the Exos loaded into the hydrogel effectively promotes neovascularization of the wound. The Exos also regulates macrophage polarization and reduces the levels of persistent inflammation in diabetic wounds. These results suggest that this smart responsive, multifunctional, and self-healing hydrogel dressing is ideal for the management of diabetic wounds.

Responsive Hydrogel-Based Drug Delivery Platform for Osteoarthritis Treatment.

Osteoarthritis (OA) is the most prevalent chronic joint disorder and is a major cause of disability among the elderly population. The degeneration and damage of articular cartilage associated with OA can result in a diminished range of motion in joints, subsequently impacting fundamental activities such as ambulation, standing, and grasping objects. In severe cases, it may culminate in disability. Traditional pharmacological treatments are often accompanied by various side effects, while invasive surgical procedures increase the risk of infection and thrombosis. Consequently, identifying alternative new methods for OA treatment remains a formidable challenge. With advancements in responsive hydrogel drug delivery platforms, an increasing number of strategies have emerged to enhance OA treatment protocols. Injectable response hydrogel drug delivery platforms show many advantages in treating OA, including improved biocompatibility, prolonged drug release duration, elevated drug loading capacity and enhanced sensitivity. This article reviews the recent progress of injectable responsive hydrogel drug delivery platform for OA treatment over the past few years. These innovative methodologies present new strategies and directions for future OA treatment while summarizing a series of challenges faced during the clinical transformation of injectable response hydrogel drug delivery platforms. Overall, injectable responsive hydrogel drug delivery platforms show great potential in treating OA, especially regarding improving drug retention time and stimulus-responsive release at the lesion sites. These innovative methods provide new hope for future OA treatment and point the way for clinical applications.

Solvent-adaptive hydrogels with lamellar confinement cellular structure for programmable multimodal locomotion

Biological organisms can perform flexible and controllable multimodal motion under external stimuli owing to the hierarchical assembly of anisotropic structures across multiple length scales. However, artificial soft actuators exhibit the limited response speed, deformation programmability and movement capability especially in harsh environments because of insufficient anisotropic hierarchy and precision in structural design. Here, we report a programmed assembly directed confinement polymerization method for the fabrication of environmentally tolerant and fast responsive hydrogels with lamellar assembly-confined cellular structure interpenetrated with highly aligned nanopillars by the directional freezing-assisted polymerization in the predesigned anisotropic laminar scaffold. The obtained hydrogel exhibits ultrafast responsiveness and anisotropic deformation exposed to temperature/light/solvent stimulation, maintaining highly consistent responsive deformation capability in all-polarity solvents over 100 days of soaking. Moreover, the hydrogels implement photoactive programmable multi-gait locomotion whose amplitude and directionality are precisely regulated by the intrinsic structure, including controlled crawling and rotation in water and non-polar solvents, and 3D self-propulsion floating and swimming in polar solvents. Thus, this hydrogel with hierarchically ordered structure and dexterous locomotion may be suitable for flexible intelligent actuators serving in harsh solvent environments.

Arginine-Biofunctionalized Ternary Hydrogel Scaffolds of Carboxymethyl Cellulose-Chitosan-Polyvinyl Alcohol to Deliver Cell Therapy for Wound Healing.

Wound healing is important for skin after deep injuries or burns, which can lead to hospitalization, long-term morbidity, and mortality. In this field, tissue-engineered skin substitutes have therapy potential to assist in the treatment of acute and chronic skin wounds, where many requirements are still unmet. Hence, in this study, a novel type of biocompatible ternary polymer hybrid hydrogel scaffold was designed and produced through an entirely eco-friendly aqueous process composed of carboxymethyl cellulose, chitosan, and polyvinyl alcohol and chemically cross-linked by citric acid, forming three-dimensional (3D) matrices, which were biofunctionalized with L-arginine (L-Arg) to enhance cellular adhesion. They were applied as bilayer skin biomimetic substitutes based on human-derived cell cultures of fibroblasts and keratinocytes were seeded and grown into their 3D porous structures, producing cell-based bio-responsive hybrid hydrogel scaffolds to assist the wound healing process. The results demonstrated that hydrophilic hybrid cross-linked networks were formed via esterification reactions with the 3D porous microarchitecture promoted by foam templating and freeze-drying. These hybrids presented chemical stability, physicochemical properties, high moisture adsorption capacity, surface properties, and a highly interconnected 3D porous structure well suited for use as a skin substitute in wound healing. Additionally, the surface biofunctionalization of these 3D hydrogel scaffolds with L-arginine through amide bonds had significantly enhanced cellular attachment and proliferation of fibroblast and keratinocyte cultures. Hence, the in vivo results using Hairless mouse models (an immunocompromised strain) confirmed that these responsive bio-hybrid hydrogel scaffolds possess hemocompatibility, bioadhesion, biocompatibility, adhesiveness, biodegradability, and non-inflammatory behavior and are capable of assisting the skin wound healing process.

A Multi-Responsive Hydrogel Combined With Mild Heat Stimulation Promotes Diabetic Wound Healing by Regulating Inflammatory and Enhancing Angiogenesis.

The repair of diabetic wound still encounters huge challenges, such as disordered inflammatory regulation and impaired neovascularization. Here, a pH/ROS/glucose responsive and photothermal hydrogel is developed for diabetic wound healing. The hydrogel is formed through cross-linkage between phenylboronic acid-modified carboxymethyl chitosan (CMCS-PBA) and oxide dextran (OXD), utilizing Schiff base and phenylboronate ester bonds. Additionally, insulin-like growth factor 1 C domain (IGF-1C) and deferoxamine-loaded polydopamine nanoparticles (D@P) are incorporated into the hydrogel. The hydrogel demonstrates sustained drug release, excellent photo thermal effect, prominent antioxidant, antibacterial and anti-inflammatory activities, desirable mechanical and tissue adhesive properties, enhanced tube formation, and cell migration. Furthermore, the hydrogel combined with mild heat treatment can regulate chronic inflammation by promoting the transformation of macrophages from M1 phenotype to M2 phenotype and enhance angiogenesis by up-regulating the expression levels of angiogenesis-related factors such as hypoxia-inducible factor-1 alpha (HIF-1α), vascular endothelial growth factor (VEGF), CD31, and α-SMA, thus greatly accelerates the wound healing in streptozotocin (STZ)-induced diabetic mice. Therefore, this multi-responsive and multifunctional hydrogel holds potential as a therapeutic strategy for diabetic wounds.

Injectable hydrogel microsphere-bomb for MRSA-infected chronic osteomyelitis

Biofilm and bone tissue defect induced by the bacterial infection severely impede chronic osteomyelitis treatment. It is critical to break though the densely and obstinate biofilm so that the target drugs can deliver to the infected bone more effectively. Herein, an acoustically responsive multifunctional hydrogel microsphere-bomb (EMgel) was designed and prepared by microfluidic technology, which could be injected to the focus of bone infection, and blasted into the nidus deeply to destroy the bacterial biofilm matrix barrier under penetrating ultrasound, so the encapsulated natural polyphenolic EGCG and bioactive MoS2 released to repair the damaged bone. The results proved the hydrogel microsphere-bomb exhibited controlling drug release, favorable antibacterial (as high as 99 %), high biofilm resistance, fascinating antioxidation, good cytocompatibility, and osteogenic differentiation. The acoustically responsive microsphere-bomb further proved their fantastic ability to eradicate biofilm and promote bone regeneration in the Methicillin-resistant Staphylococcus aureus (MRSA) infected chronic osteomyelitis model due to the synergy effects of EGCG and bioactive MoS2. Especially, immunohistochemical staining showed lower inflammatory reaction and higher expression of OCN in EMgel group treated with ultrasound wave. This study presents a new design of hydrogel microsphere-based intelligence drug delivery for osteomyelitis treatment, which exhibit great promising potential for dealing with chronic orthopedic infections, drug delivery system and tissue engineering.

Kinetic and thermodynamic analysis of engineered alginate–chitosan hydrogel based scaffolds for drug delivery applications

The synthesis of stimulus–responsive hydrogel–based scaffolds has been extensively investigated for controlled drug delivery applications. This study focused on synthesizing alginate and chitosan–based scaffolds for potential use in releasing antibiotic antimycotic solution (AAS) drugs. The controlled release of AAS from AAS–loaded alginate–chitosan scaffolds was investigated under distinct temperatures viz. 37 °C, 25 °C, and 10 °C, labeled as scaffolds A, B, and C, respectively. Porosity assessment revealed consistent and substantial mean porosity percentage of 95.06 ± 2.01 % across all scaffolds. The lower temperature of 10 °C significantly contributed to a gradual and consistent cumulative release of 91.67 ± 1.47 %, compared to 37 °C (94.07 ± 1.89 %) and 25 °C (92.75 ± 1.51 %). The Korsmeyer–Peppas model exhibited high R2 values (0.98, 0.97 to 0.99) for scaffolds A, B, and C, indicating its suitability for describing the in–vitro release of AAS. Furthermore, the obtained release exponent values (0.60, 0.65, and 0.72 for scaffolds A, B, and C, respectively) suggest non–Fickian diffusion as the primary mechanism governing drug release. The release was also pH–dependent, with slower release at acidic (pH 3) and faster release under basic conditions (pH 8) due to varying swelling ratios. Evaluation of thermodynamic parameters viz. Ea, ΔG, ΔH and ΔS, using the rate constant of the Korsmeyer–Peppas model, revealed positive values of ΔH > 0 and ΔS > 0, indicating the prevalence of hydrophobic interactions in the release process.

Multiresponsive Color-Changing and Tough Hydrogels Enabled by Self-Assembled Epoxy Oligomer Microspheres.

The fabrication process of hydrogels often incorporates various strategies to achieve multiple responses and enhance strength, which always make the procedure complex and even hinder the incorporation. Here, we develop a facile and flexible method to simultaneously achieve multiresponsive color-changing and tough properties in hydrogels by introducing epoxy oligomer microspheres (DEPMS) to hydrophobic association (HA) hydrogels. DEPMS is responsive to both pH and solvents, showing color changes due to conversion to a conjugated structure. The obtained DEPMS composite hydrogels could demonstrate diverse color-changing patterns by simply adjusting the components and pH of the solvents. Meanwhile, amphiphilic DEPMS helps to disperse hydrophobic regions of the HA hydrogel, resulting in more uniform cross-linking and thereby contributing to the enhanced mechanical properties. The tensile strength and toughness of the composite hydrogels could be easily adjusted and reach 1.00 MPa and 11.18 MJ m-3, respectively. This work provides an approach to the design of multiple responsive and tough hydrogels while offering insights into the recycling of waste epoxy resins.

Green synthesis of multifunctional responsive hydrogel embedded with silver, based on xanthan gum, N-isopropylacrylamide, vinyl imidazole, and Luffa cylindrica for wound healing

In this study, a pH- and temperature-responsive smart hydrogel was developed by utilizing Xanthan Gum (XG), N-Isopropylacrylamide (NIPAM), Vinyl Imidazole (VI), and Luffa cylindrical (LC). Semi-interpenetrating polymer networks (semi-IPNs) were created using free radical polymerization with N,N′-methylenebisacrylamide (MBA) as the cross-linker and ammonium persulfate (APS) as the initiator. Silver nanoparticles (AgNPs) were synthesized within semi-IPN hydrogel network structures to impart antibacterial properties. Malva sylvestris (MS) aqueous leaf extract was used as a reducing and stabilizing agent for the green synthesis of the AgNPs. The semi-IPN hydrogels exhibited pH- and temperature-responsive swelling behavior, which also enabled the controlled release of the drug. After 11 h, the cumulative release reached approximately 73% at pH 7.2 and 87% at pH 8.3. Additionally, the sustained release mechanism of the Trimethoprim drug was described using the Korsmeyer-Peppas model and was governed by Fickian diffusion. The drug-loaded semi-IPN@Ag nanocomposite hydrogel has demonstrated effective antibacterial activity against various Gram-negative and Gram-positive bacteria, indicating its promising potential as a wound dressing material for reducing infection risk.

Double Enzyme Active Hydrogel Program Regulates the Microenvironment of Staphylococcus aureus-Infected Pressure Ulcers.

The treatment of infected pressure ulcers (IUPs) requires addressing diverse microenvironments. A pressing challenge is to effectively enhance the regenerative microenvironment at different stages of the healing process, tailoring interventions as needed. Here, a dual enzyme mimetic and bacterial responsive self-activating antimicrobial hydrogel designed to enhance IPUs healing is introduced. This hydrogel incorporates pH-responsive dual enzyme-active nanoplatforms (HNTs-Fe-Ag) encapsulated within a methacrylate-modified silk fibroin (SFMA) and dopamine methacrylamide (DMA) matrix. This composite hydrogel exhibits adaptive microenvironment regulation capabilities. Under the low pH microenvironment of bacterial infection, it has excellent antimicrobial activity by self-activating the •OH generation in conjunction with photothermal effects. Under the neutral and alkaline microenvironment of chronic inflammation, it catalyzes the decomposition of hydrogen peroxide (H2O2) to produce oxygen (O2), thereby alleviating hypoxia and scavenging reactive oxygen species (ROS), which in turn remodulates the phenotype of macrophages. The composite hydrogel demonstrates on-demand therapeutic effects in the microenvironment of infected wounds, significantly enhancing the regenerative microenvironment of IUPs by promoting wound closure, inflammation regulation, and collagen deposition through self-activated antimicrobial action during infection and adaptive hypoxia relief during recovery. This approach offers a novel strategy for developing smart wound dressings.