Responsive Hydrogels Research Articles

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.

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.

Optically Responsive Hydrogel with Rapid Deformation for Motion Regulation of Magnetic Actuators.

Optically and magnetically responsive soft actuators are gaining attention for their noncontact actuation, flexibility, and remote control capabilities. However, they face challenges in rapidly switching motion postures and modes, which limits their performance in complex environments. We developed bilayer hydrogel actuators based on poly(N-isopropylacrylamide) (PNIPAm) using an ice-templating method combined with free radical polymerization. This approach results in the formation of large, interconnected pores within the hydrogel. Under near-infrared light (27 W/cm2), the actuation speed of the actuator reached 38.5°/s, with complete recovery to the original shape 8 s after light cessation. In addition, the reversible changes in stiffness and volume enable the actuators to lock and dynamically adjust their magnetization curve, allowing for the decoupling of deformation and movement as well as the regulation of motion postures and modes. This work opens new pathways for multigait robots and shows promising applications in environmental monitoring and underwater exploration.

Emerging magnetic-responsive hydrogel actuators with anisotropic shape for intracardiovascular directional motion

A magnetically responsive valve actuator inspired by the starfish shape and fabricated with hydrophilic and hydrophobic surfaces was developed. The surface morphology and wettability of the magnetically responsive colloidal crystal hydrogel actuator were characterized using scanning electron microscopy and contact angle measurements. The actuator, resembling a flower, consists of Poly(HEMA-co-AAm)/Fe3O4/PDMS, exhibiting distinct Janus wettability with hydrophobic Fe3O4/PDMS and hydrophilic Poly(HEMA-co-AAm) surfaces. The directional movement of water droplets on the V-shaped structured film confirmed the anisotropic wetting behavior, influenced by the film’s wettability and structural dimensions. Moreover, the actuator demonstrated responsive angular and positional adjustments under varying magnetic fields, facilitated by embedded Fe3O4 particles aligning with magnetic lines of force. In experimental setups simulating intravascular applications, the actuator exhibited controlled movement within tubes and demonstrated effective adhesion to heart valve injuries under magnetic guidance. Additionally, a layered inverse opal film within the actuator showed promising capabilities for unidirectional fluid permeation, enhancing its functional versatility. These findings underscore the potential of the magnetically responsive colloidal crystal hydrogel actuator for biomedical applications, particularly in minimally invasive cardiac interventions requiring precise actuation and adhesive functionalities.

Injectable Magnetic Hydrogel Incorporated with Anti-Inflammatory Peptide for Efficient Magnetothermal Treatment of Endometriosis.

Endometriosis is a prevalent gynecological condition characterized by chronic pelvic pain, dysmenorrhea, and infertility, affecting ≈176 million women of reproductive age worldwide. Current treatments, including pharmacological and surgical interventions, are often associated with significant side effects and high recurrence rates. Consequently, there is an urgent need for innovative and safer therapeutic approaches. In this study, an injectable magnetic hydrogel nanosystem is developed designed for the dual-purpose magnetothermal and anti-inflammatory treatment of endometriosis. This hydrogel incorporates Fe3O4 nanoparticles alongside an anti-inflammatory peptide. Upon magnetic activation, the Fe3O4 nanoparticles induce a localized hyperthermic response, raising the temperature of endometriotic lesions to 63.3°C, effectively destroying endometriotic cells. Concurrently, the thermally responsive hydrogel facilitates the controlled release of the anti-inflammatory peptide, thus modulating the inflammatory milieu. The biocompatibility and complete in vivo degradability of the hydrogel further enhance its therapeutic potential. The in vivo studies demonstrated that this injectable magnetic hydrogel system achieved a 90% reduction in the volume of endometriotic lesions and significantly decreased inflammatory markers, offering a promising non-invasive treatment modality for endometriosis. By integrating precise lesion ablation with the modulation of the inflammatory microenvironment, this system represents a novel approach to the clinical management of endometriosis.

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.

Magnetic augmentation through multi-gradient coupling enables direct and programmable profiling of circulating biomarkers

Conventional magnetic biosensing technologies have reduced analytical capacity for magnetic field dimensionality and require extensive sample processing. To address these challenges, we spatially engineer 3D magnetic response gradients for direct and programmable molecular detection in native biofluids. Named magnetic augmentation through triple-gradient coupling for high-performance detection (MATCH), the technology comprises gradient-distributed magnetic nanoparticles encapsulated within responsive hydrogel pillars and suspended above a magnetic sensor array. This configuration enables multi-gradient matching to achieve optimal magnetic activation, response and transduction, respectively. Through focused activation by target biomarkers, the platform preferentially releases sensor-proximal nanoparticles, generating response gradients that complement the sensor’s intrinsic detection capability. By implementing an upstream module that recognizes different biomarkers and releases universal activation molecules, the technology achieves programmable detection of various circulating biomarkers in native plasma. It bypasses conventional magnetic labeling, completes in <60 minutes and achieves sensitive detection (down to 10 RNA and 1000 protein copies). We apply the MATCH to measure RNAs and proteins directly in patient plasma, achieving accurate cancer classification.

Reversible fluorescence/photochromic switching of repeated-response cellulose-based hydrogels for information encryption

The rapid development of anti-counterfeiting technology has brought new challenges to the repeatability and stability of reversible fluorescence/photochromic switching hydrogels. To address this issue, a series of chemical cross-linked cellulose-based intelligent responsive hydrogels were synthesized by free-radical graft copolymerization in a hydrothermal process. This strategy allows for the creation of a chemical cross-linked three-dimensional structure that anchors photochromic ammonium molybdate and fluorescent carbon dots together, resulting in enhanced stability and mechanical properties. Especially, the tensile and compressive strength of hydrogel reached a maximum value of 280 kPa and 560 kPa, respectively, which far exceeds that of some reported hydrogels. The resultant hydrogels exhibited desired reversible fluorescence/photochromic switching, reversible printing and erasing of patterns, and information encryption/decryption. Notably, the change of photochromism from yellow to green can be realized, and the self-fading process can be shortened to 25 min at 60 °C instead of 6 h at room temperature. More importantly, the fluorescence quenching phenomenon of the hydrogel occurs gradually after 2 min of continuous irradiation, and it can be recovered by selective treatment with ethanol. Overall, this study provides a simple strategy for the preparation of environmentally friendly reversible fluorescence/photochromic switching cellulose-based hydrogels for information encryption.

Advancement in Soft Hydrogel Grippers: Comprehensive Insights into Materials, Fabrication Strategies, Grasping Mechanism, and Applications.

Soft hydrogel grippers have attracted considerable attention due to their flexible/elastic bodies, stimuli-responsive grasping and releasing capacity, and novel applications in specific task fields. To create soft hydrogel grippers with robust grasping of various types of objects, high load capability, fast grab response, and long-time service life, researchers delve deeper into hydrogel materials, fabrication strategies, and underlying actuation mechanisms. This article provides a systematic overview of hydrogel materials used in soft grippers, focusing on materials composition, chemical functional groups, and characteristics and the strategies for integrating these responsive hydrogel materials into soft grippers, including one-step polymerization, additive manufacturing, and structural modification are reviewed in detail. Moreover, ongoing research about actuating mechanisms (e.g., thermal/electrical/magnetic/chemical) and grasping applications of soft hydrogel grippers is summarized. Some remaining challenges and future perspectives in soft hydrogel grippers are also provided. This work highlights the recent advances of soft hydrogel grippers, which provides useful insights into the development of the new generation of functional soft hydrogel grippers.

Self-cleavage of genetically encoded Zn2+-dependent deoxyribozymes for low-cost biotechnological production of programable responsive DNA hydrogels

Despite the emergence of sequence-programable responsive DNA hydrogels, their further development is still hampered by the limited availability of chemically synthesized nucleic acid constituents. We herein developed a cost-efficient biotechnological approach for general production of programable responsive DNA hydrogels by harnessing bacteria as cell factories. Programmable pseudogenes of responsive DNA hydrogels were designed by interleaving Y-unit strand sequences with Zn2+-dependent self-cleaving deoxyribozymes. After in vivo amplification, self-cleavage of these deoxyribozymes in extracted precursor ssDNAs were systematically investigated. The versatility of this approach was demonstrated by preparing a unitary Y-unit system of pH-responsive DNA hydrogel and a binary Y-unit system of Cas12a-responsive hydrogel. This low-cost biotechnological approach requires only standard molecular biology equipment and inexpensive consumables, which may encourage further exploration of responsive DNA hydrogels.

PNIPAAm-based temperature responsive ionic conductive hydrogels for flexible strain and temperature sensing

Conductive hydrogels have received much attention in the field of flexible wearable sensors due to their outstanding flexibility, conductivity, sensitivity and excellent compatibility. However, most conductive hydrogels mainly focus on strain sensors to detect human motion and lack other features such as temperature response. Herein, we prepared a strain and temperature dual responsive ionic conductive hydrogel (PPPNV) with an interpenetrating network structure by introducing a covalent crosslinked network of N-isopropylacrylamide (NIPAAm) and 1-vinyl-3-butylimidazolium bromide (VBIMBr) into the skeleton of the hydrogel composed of polyvinylalcohol (PVA) and polyvinylpyrrolidone (PVP). The PPPNV hydrogel exhibited excellent anti-freezing properties (−37.34 °C) and water retention with high stretchability (∼930 %) and excellent adhesion. As a wearable strain sensor, the PPPNV hydrogel has good responsiveness and stability to a wide range of deformations and exhibits high strain sensitivity (GF=2.6) as well as fast response time. It can detect large and subtle body movements with good signal stability. As wearable temperature sensors, PPPNV hydrogels can detect human physiological signals and respond to temperature changes, and the volumetric phase transition temperature (VPTT) can be easily controlled by adjusting the molar ratio of NIPAAm to VBIMBr. In addition, a bilayer temperature-sensitive hydrogel was prepared with the temperature responsive hydrogel by two-step synthesis, which shows great promising applications in temperature actuators.

Responsive DNA hydrogels: design strategies and prospects for biosensing.

Hydrogels, water-filled networks that can adapt to external stimuli by altering their volume, are known for their high flexibility and biocompatibility. DNA, a critical biomolecule renowned for its exceptional characteristics including information transmission, molecular recognition, and editability, has found widespread applications in the biosensing field as well. The integration of these two biomaterials offers promising opportunities for the development of novel biosensors with enhanced sensitivity, specificity, and adaptability. Therefore, by virtue of the collective features, researchers have recently focused on the construction of responsive DNA hydrogel systems. This feature article describes recent developments in fabricating DNA hydrogels and their applications in the biosensing area. Initially, it focuses on the design strategies employed in preparing DNA hydrogels, encompassing both pure DNA hydrogels and hybridized DNA hydrogels. Subsequently, it summarizes the use of DNA hydrogels in biosensing applications, highlighting their applications in visual detection, electrochemical sensing, and optical biosensing analyses. Furthermore, the underlying responsive mechanisms within these biosensing systems are also described. Lastly, this article presents a comprehensive discussion on the existing challenges and prospects of responsive DNA hydrogels, offering insights into their potential to revolutionize the field of biosensing.

Self-assembled ROS-triggered Bletilla striata polysaccharide-releasing hydrogel dressing for inflammation-regulation and enhanced tissue-healing

The antimicrobial and pro-healing properties remain critical clinical objectives for skin wound management. However, the escalating problem of antibiotic overuse and the corresponding rise in bacterial resistance necessitates an urgent shift towards an antibiotic-free approach to antibacterial treatment. The quest for antimicrobial efficacy while accelerating wound healing without antibiotic treatment have emerged as innovative strategies in skin wound treatment. Here, a dual-function hydrogel with antimicrobial and enhanced tissue-healing properties was developed by utilizing cyclodextrin, ferrocene, polyethyleneimine (PEI), and Bletilla striata polysaccharide (BSP), through multiple non-covalent interactions, which can intelligently release BSP by recognizing the wound inflammatory microenvironment through the cyclodextrin-ferrocene unit. Moreover, the porosity (65 % - 85 %), Young's modulus (400 KPa - 140 KPa), and DPPH scavenge rate (18 % - 40 %) of the hydrogel are modulated by varying the BSP content. The hydrogel exhibits outstanding antibacterial properties (98.3 % reduction of Escherichia coli observed after exposure to HTFC@BSP-20 for 24 h) and favorable biocompatibility. Furthermore, in a rat full-thickness skin wound model, the dual-function hydrogel significantly accelerates wound healing, increased CD31 expression promotes vascular regeneration, reduced TNF-α express and inhibited the inflammation. This multifunctional ROS responsive hydrogel provides a new perspective for antibiotics-free treatment of skin injuries.

Ultrasound-Responsive HBD Peptide Hydrogel with Antibiofilm Capability for Fast Diabetic Wound Healing.

Despite advancements in therapeutic agents for diabetic chronic wounds, challenges such as suboptimal bioavailability, intricate disease milieus, and inadequate delivery efficacy have impeded treatment outcomes. Here, ultrasound-responsive hydrogel incorporated with heparin-binding domain (HBD) peptide nanoparticles is developed to promote diabetic wound healing. HBD peptide, derived from von Willebrand Factor with angiogenic activity, are first engineered to self-assemble into nanoparticles with enhanced biostability and bioavailability. Ultrasound responsive cargo release and hydrogel collapses are first verified through breakage of crosslinking. In addition, desired antioxidant and antibacterial activity of such hydrogel is observed. Moreover, the degradation of hydrogel under ultrasound stimulation into smaller fragments facilitated the deeper wound penetration of ≈400 µm depth. Complete wound closure is observed from diabetic mice with chronic wounds after being treated with the proposed hydrogel. In detail, in vivo studies revealed that hydrogels loaded with HBD peptide nanoparticles increased the levels of angiogenesis-related growth factors (VEGF-A, CD31, and α-SMA) to effectively accelerate wound repair. Overall, this study demonstrates that ultrasound-responsive HBD peptide hydrogel provides a synergistic therapeutic strategy for external biofilm elimination and internal effective delivery for diabetic wounds with biofilm infection.

Novel Supramolecular Hydrogel for Infected Diabetic Foot Ulcer Treatment.

Multifunctional responsive hydrogels hold significant promise for diabetic foot ulcer (DFU) treatment, though their complex design and manufacturing present challenges. This study introduces a novel supramolecular guanosine-phenylboronic-chlorogenic acid (GBC) hydrogel developed using a dynamic covalent strategy. The hydrogel forms through guanosine quadruplex assembly in the presence of potassium ions and chlorogenic acid (CA) linkage via dynamic borate bonds. GBC hydrogels exhibit pH and glucose responsiveness, releasing more chlorogenic acid under acidic and high glucose conditions due to borate bond dissociation and G-quadruplex (G4)hydrogel disintegration. Experimental results indicate that GBC hydrogels exhibit good self-healing, shear-thinning, injectability, and swelling properties. Both in vitro and in vivo studies demonstrate the GBC hydrogel's good biocompatibility, ability to eliminate bacteria and reactive oxygen species (ROS), facilitate macrophage polarization from the M1 phenotype to the M2 phenotype (decreasing CD86 expression and increasing CD206 expression), exhibit anti-inflammatory effects (reducing TNF-α expression and increasing IL-10 expression), and promote angiogenesis (increasing VEGF, CD31, and α-SMA expression). Thus, GBC hydrogels accelerate DFU healing and enhance tissue remodeling and collagen deposition. This work provides a new approach to developing responsive hydrogels to expedite DFU healing.