Pharmacokinetics of a Natural Self-emulsifying Reversible Hybrid-Hydrogel (N'SERH) Formulation of Full-Spectrum Boswellia serrata Oleo-Gum Resin Extract: Randomised Double-Blinded Placebo-Controlled Crossover Study.

The oleo-gum-resin of Boswellia serrata, an Ayurvedic herb for the treatment of chronic inflammatory diseases, contains both volatile (terpenes) and nonvolatile (boswellic acids) molecules as responsible for its bioactivity. The present randomized, double-blinded, placebo-controlled, crossover study evaluated the human pharmacokinetics of a 'natural' hybrid-hydrogel formulation of a unique full-spectrum boswellia extract (BFQ-20) (standardized for both volatile and nonvolatile bioactives) in comparison with unformulated extract (U-BE), for the first time. Mass spectrometry coupled with LC (UPLC-MS/MS) and gas chromatography (GC-MS/MS) measurements of the plasma concentration of boswellic acids and α-thujene at different post-administration time points followed by a single dose (400 mg) of U-BE and BFQ-20, to healthy volunteers (n = 16), offered 4-fold enhancement in the overall bioavailability of boswellic acids from BFQ-20, [area under the curve (AUC) (BFQ-20) = 9484.17 ± 767.82 ng * h/mL vs. AUC (U-BE) = 2365.87 ± 346.89 ng * h/mL], with the absorption maximum (Tmax) at 6.3 h post-administration and elimination half-life (T1/2) of 15.5 h (p < 0.001). While plasma α-thujene was not detectable upon U-BE administration, BFQ-20 provided significant absorption, [AUC (BFQ-20): 298.60 ± 35.48 ng * h/mL; Cmax: 68.80 ± 18.60 ng/mL; Tmax: 4.12 ± 0.38 h; T1/2: 16.24 ± 1.12 h]. Further investigation of the anti-inflammatory effect revealed 70.5% inhibition of paw edema in rats compared to 38.0% for U-BE. In summary, the natural self-emulsifying reversible hybrid-hydrogel (N'SERH) formulation of boswellia extract using fenugreek mucilage (FenuMat®) significantly increased the solubility (58-fold), stability, and bioavailability of both the volatile and non-volatile bioactives which in turn improved the anti-inflammatory efficacy of Boswellia extract.

PDI-Based Organic Small Molecule Regulated by Inter/Intramolecular Interactions for Efficient Solar Vapor Generation.

Organic small molecules with processing feasibility, structural diversity, and fine-tuned properties have the potential applications in solar vapor generation. However, the common defects of narrow solar absorption, low photothermal conversion efficiency, and photobleaching result in limited materials available and unsatisfactory evaporation performance. Herein, the perylene diimide (PDI) derivatives are exploited as stable sunlight absorbers for solar vapor generation. Particularly, the N,N'-bis(3,4,5-trimethoxyphenyl)-3,4,9,10-perylenetetracarboxylic diimide (PDI-DTMA) is well-designed with donor-acceptor-donor configuration based on plane rigid PDI core. The efficient photothermal conversion is enabled through strong intermolecular π-π stacking and intramolecular charge transfer, as revealed by experimental demonstration and theoretical calculation. The PDI-DTMA with a narrow band gap of 1.17 eV exhibits expanded absorption spectrum and enhanced nonradiative transition capability. The 3D hybrid hydrogels (PPHs) combining PDI-DTMA and polyvinyl alcohol are constructed. With the synergistic effect of solar-to-heat conversion, thermal localization management, water activation, and unobstructed water transmission of PPHs, the high water evaporation rates can reach 3.61-10.07 kg m-2 h-1 under one sun. The hydrogels also possess great potential in seawater desalination and sewage treatment. Overall, this work provides valuable insights into the design of photothermal organic small molecules and demonstrates their potentials in solar water evaporation.

In situ forming ROS-scavenging hybrid hydrogel loaded with polydopamine-modified fullerene nanocomposites for promoting skin wound healing.

BACKGROUND: Excessive oxidative stress at the wound sites always leads to a prolonged healing and even causes chronic inflammatory wounds. Therefore, antioxidative dressings with multiple features are desired to improve wound healing performance. Herein, we fabricated a ROS-scavenging hybrid hydrogel by incorporating mussel-inspired fullerene nanocomposites (C60@PDA) into gelatin methacryloyl (GelMA) hydrogel. RESULTS: The developed C60@PDA/GelMA hydrogel showed a sustainable free radical scavenging ability, and eliminated ROS to protect cells against external oxidative stress damage. Besides, the hydrogel presented favorable cytocompatibility, hemocompatibility, and antibacterial ability in vitro. Furthermore, in a mouse full-thickness wound defect model, the in situ forming hybrid hydrogel accelerated wound closure by 38.5% and 42.9% on day 3 and day 7 over the control. Histological results demonstrated that hybrid hydrogels effectively enhanced wound healing on re-epithelialization, collagen deposition and angiogenesis. CONCLUSION: Collectively, the C60@PDA/GelMA hydrogel could be a promising dressing for promoting cutaneous wound repair.

Facile and eco-friendly fabrication of biocompatible hydrogel containing CuS@Ser NPs with mechanical flexibility and photothermal antibacterial activity to promote infected wound healing.

Bacterial infections can significantly impede wound healing and pose a serious threat to the patient's life. The excessive use of antibiotics to combat bacterial infections has led to the emergence of multi-drug-resistant bacteria. Therefore, there is a pressing need for alternative approaches, such as photothermal therapy (PTT), to address this issue. In this study, for the first time, CuS NPs with photothermal properties were synthesized using sericin as a biological template, named CuS@Ser NPs. This method is simple, green, and does not produce toxic and harmful by-products. These nanoparticles were incorporated into a mixture (XK) of xanthan gum and konjac glucomannan (KGM) to obtain XK/CuS NPs composite hydrogel, which could overcome the limitations of current wound dressings. The composite hydrogel exhibited excellent mechanical flexibility, photothermal response, and biocompatibility. It also demonstrated potent antibacterial properties against both Gram-positive and negative bacteria via antibacterial experiments and accelerated wound healing in animal models. Additionally, it is proved that the hydrogel promoted tissue regeneration by stimulating collagen deposition, angiogenesis, and reducing inflammation. In summary, the XK/CuS NPs composite hydrogel presents a promising alternative for the clinical management of infected wounds, offering a new approach to promote infected wound healing.

Engineering Hydrogels for the Development of Three-Dimensional In Vitro Models.

The superiority of in vitro 3D cultures over conventional 2D cell cultures is well recognized by the scientific community for its relevance in mimicking the native tissue architecture and functionality. The recent paradigm shift in the field of tissue engineering toward the development of 3D in vitro models can be realized with its myriad of applications, including drug screening, developing alternative diagnostics, and regenerative medicine. Hydrogels are considered the most suitable biomaterial for developing an in vitro model owing to their similarity in features to the extracellular microenvironment of native tissue. In this review article, recent progress in the use of hydrogel-based biomaterial for the development of 3D in vitro biomimetic tissue models is highlighted. Discussions of hydrogel sources and the latest hybrid system with different combinations of biopolymers are also presented. The hydrogel crosslinking mechanism and design consideration are summarized, followed by different types of available hydrogel module systems along with recent microfabrication technologies. We also present the latest developments in engineering hydrogel-based 3D in vitro models targeting specific tissues. Finally, we discuss the challenges surrounding current in vitro platforms and 3D models in the light of future perspectives for an improved biomimetic in vitro organ system.

Conductive single-wall carbon nanotubes/extracellular matrix hybrid hydrogels promote the lineage-specific development of seeding cells for tissue repair through reconstructing an integrin-dependent niche.

BACKGROUND: The niche of tissue development in vivo involves the growth matrix, biophysical cues and cell-cell interactions. Although natural extracellular matrixes may provide good supporting for seeding cells in vitro, it is evitable to destroy biophysical cues during decellularization. Reconstructing the bioactivities of extracellular matrix-based scaffolds is essential for their usage in tissue repair. RESULTS: In the study, a hybrid hydrogel was developed by incorporating single-wall carbon nanotubes (SWCNTs) into heart-derived extracellular matrixes. Interestingly, insoluble SWCNTs were well dispersed in hybrid hydrogel solution via the interaction with extracellular matrix proteins. Importantly, an augmented integrin-dependent niche was reconstructed in the hybrid hydrogel, which could work like biophysical cues to activate integrin-related pathway of seeding cells. As supporting scaffolds in vitro, the hybrid hydrogels were observed to significantly promote seeding cell adhesion, differentiation, as well as structural and functional development towards mature cardiac tissues. As injectable carrier scaffolds in vivo, the hybrid hydrogels were then used to delivery stem cells for myocardial repair in rats. Similarly, significantly enhanced cardiac differentiation and maturation(12.5 ± 2.3% VS 32.8 ± 5%) of stem cells were detected in vivo, resulting in improved myocardial regeneration and repair. CONCLUSIONS: The study represented a simple and powerful approach for exploring bioactive scaffold to promote stem cell-based tissue repair.

3D Bio-Printability of Hybrid Pre-Crosslinked Hydrogels.

Maintaining shape fidelity of 3D bio-printed scaffolds with soft biomaterials is an ongoing challenge. Here, a rheological investigation focusing on identifying useful physical and mechanical properties directly related to the geometric fidelity of 3D bio-printed scaffolds is presented. To ensure during- and post-printing shape fidelity of the scaffolds, various percentages of Carboxymethyl Cellulose (CMC) (viscosity enhancer) and different calcium salts (CaCl2 and CaSO4, physical cross-linkers) were mixed into alginate before extrusion to realize shape fidelity. The overall solid content of Alginate-Carboxymethyl Cellulose (CMC) was limited to 6%. A set of rheological tests, e.g., flow curves, amplitude tests, and three interval thixotropic tests, were performed to identify and compare the shear-thinning capacity, gelation points, and recovery rate of various compositions. The geometrical fidelity of the fabricated scaffolds was defined by printability and collapse tests. The effect of using multiple cross-linkers simultaneously was assessed. Various large-scale scaffolds were fabricated (up to 5.0 cm) using a pre-crosslinked hybrid. Scaffolds were assessed for the ability to support the growth of Escherichia coli using the Most Probable Number technique to quantify bacteria immediately after inoculation and 24 h later. This pre-crosslinking-based rheological property controlling technique can open a new avenue for 3D bio-fabrication of scaffolds, ensuring proper geometry.

Novel Chitosan-Silica Hybrid Hydrogels for Cell Encapsulation and Drug Delivery.

Hydrogels constructed from naturally derived polymers provide an aqueous environment that encourages cell growth, however, mechanical properties are poor and degradation can be difficult to predict. Whilst, synthetic hydrogels exhibit some improved mechanical properties, these materials lack biochemical cues for cells growing and have limited biodegradation. To produce hydrogels that support 3D cell cultures to form tissue mimics, materials must exhibit appropriate biological and mechanical properties. In this study, novel organic-inorganic hybrid hydrogels based on chitosan and silica were prepared using the sol-gel technique. The chemical, physical and biological properties of the hydrogels were assessed. Statistical analysis was performed using One-Way ANOVAs and independent-sample t-tests. Fourier transform infrared spectroscopy showed characteristic absorption bands including amide II, Si-O and Si-O-Si confirming formation of hybrid networks. Oscillatory rheometry was used to characterise the sol to gel transition and viscoelastic behaviour of hydrogels. Furthermore, in vitro degradation revealed both chitosan and silica were released over 21 days. The hydrogels exhibited high loading efficiency as total protein loading was released in a week. There were significant differences between TC2G and C2G at all-time points (p < 0.05). The viability of osteoblasts seeded on, and encapsulated within, the hydrogels was >70% over 168 h culture and antimicrobial activity was demonstrated against Pseudomonas aeruginosa and Enterococcus faecalis. The hydrogels developed here offer alternatives for biopolymer hydrogels for biomedical use, including for application in drug/cell delivery and for bone tissue engineering.

Carbon Nanotubes Hybrid Hydrogels for Environmental Remediation: Evaluation of Adsorption Efficiency under Electric Field.

The performance of Carbon Nanotubes hybrid hydrogels for environmental remediation was investigated using Methylene Blue (MB), Rhodamine B (RD), and Bengal Rose (BR) as model contaminating dyes. An acrylate hydrogel network with incorporated CNT was synthesized by photo-polymerization without any preliminary derivatization of CNT surface. Thermodynamics, isothermal and kinetic studies showed favorable sorption processes with the application of an external 12 V electric field found to be able to influence the amount of adsorbed dyes: stronger interactions with cationic MB molecules (qexp and qexp12 of 19.72 and 33.45 mg g-1, respectively) and reduced affinity for anionic RD (qexp and qexp12 of 28.93 and 13.06 mg g-1, respectively) and neutral BR (qexp and qexp12 of 36.75 and 15.85 mg g-1, respectively) molecules were recorded. The influence of pH variation on dyes adsorption was finally highlighted by reusability studies, with the negligible variation of adsorption capacity after five repeated sorption cycles claiming for the suitability of the proposed systems as effective sorbent for wastewater treatment.

Incorporation of dumbbell-shaped and Y-shaped cross-linkers in adjustable pullulan/polydopamine hydrogels for selective adsorption of cationic dyes.

Hydrogel adsorbents have attracted considerable attention due to their sludge minimization, good water permeability and renewable performance. Here, a promising strategy for the one-step preparation of pullulan/polydopamine hybird hydrogels (PPGels) was presented. Dumbbell-shaped cross-linker neopentyl glycol diglycidyl ether (NGDE, 2 arms) and Y-shaped cross-linker trimethylolpropane triglycidyl ether (TTE, 3 arms) were selected to study the relationship between cross-linker structure and hydrogel performances. The NGDE possessing less molecular repulsive force and higher reactivity demonstrated more effective cross-linking with the pullulan, which leaded to a decrease in pore size of the hydrogel. Meanwhile, the introduction of polydopamine significantly enhanced the adsorption ability and gave the resulting hybrid gel the specific selectivity toward cationic dyes (96 mg/g for crystal violet, 25.8 mg/g for methylene blue and barely not adsorption for azophloxine). Our data suggested that the electrostatic interaction played a vital role in the dye adsorption process, and the adsorption data could be explained by pseudo-second-order model and Langmuir isotherm model. Furthermore, the obtained PPGel could be easily separated after adsorption. This study describes the relationship between cross-linker structure and properties of pullulan/polydopamine hybrid gels, which provides a new strategy to create polysaccharide-based adsorbents for wastewater remediation.

Construction of Super-Hydrophobic Lignocellulosic Nanofibrils Aerogels as Speedy Oil Absorbents.

Lignocellulosic nanofibrils (LCNF) aerogels have a three-dimensional structure, with large specific surface area, low density, which is promising to be developed into a new type of adsorbent with high absorption capacity. However, LCNF aerogels have the problem of simultaneous oil and water adsorption. This high hydrophilicity directly leads to low adsorption efficiency in oil-water systems. This paper suggests a facile and economical method for the synthesis of biocompatible CE-LCNF aerogels using LCNF and Castor oil triglycidyl ether (CE) was successfully established. The use of LCNF enabled aerogels to possess remarkably uniform pore size and structural integrity, while the introduction of hydrophobic silica produced stable superhydrophobicity for more than 50 days at room temperature. These aerogels presented desirable hydrophobicity (131.6°), excellent oil adsorption capacity (62.5 g/g) and excellent selective sorption property, making them ideal absorbents for oil spill cleaning. The effects of ratios of LCNF to CE composition, temperatures and oil viscosity on the oil adsorption performance of aerogels were estimated. The results displayed that the aerogels had the maximum adsorption capacity at 25 °C. The pseudo-secondary model had higher validity in oil adsorption kinetic theories compared to the pseudo-first-order model. The CE-LCNF aerogels were excellent super-absorbents for oil removal. Moreover, the LCNF was renewable and nontoxic, which has the potential to promote environmental applications.

Effective removal and adsorption mechanism of fluoride from water by biochar-based Ce(III)-La(III)-crosslinked sodium alginate hybrid hydrogel.

An eco-friendly macroparticle biochar (BC)-based Ce(III)-La(III) crosslinked sodium alginate (SA) hybrid hydrogel (BC/Ce-SA-La) was synthesized by droplet polymerization and characterized by SEM-EDS, XRD, FTIR, UV-Vis and XPS. The effects of dosage, pH, contact time, temperature and coexisting ions on the F- ions removal by hybrid hydrogel, and the adsorption performance, interaction mechanism and reusability were investigated. The results demonstrate that the composite has a fancy wrinkle structure with a particle size of about 1.8 mm and abundant porosity on the surface. The removal rate of F- ions by BC/Ce-SA-La reached 90.2 % under the conditions of pH 2.0, 200 min of contact time and 298 K. The adsorption behavior was perfectly explained by Langmuir model, and the maximum adsorption capacity reached 129 mg/g. The adsorption process was an endothermic spontaneous reaction and followed Pseudo-second-order rate model. The strong adsorption was attributed to multi-interactions including complexation, hydrogen bonding and electrostatic adsorption between the composite and F- ions. Coexisting ions hardly interfered with the adsorption of F- ions by BC/Ce-SA-La except for a slight effect of phosphate. The composite after F- ion adsorption was easily separated and could be reused at least three times. BC/Ce-SA-La is a cost-effective and promising granular biosorbent.

Adhesive polydopamine-based photothermal hybrid hydrogel for on-demand lidocaine delivery, effective anti-bacteria, and prolonged local long-lasting analgesia.

Considering the astonishing prevalence of localized pain affecting billions of patients worldwide, the development of advanced analgesic formulations or delivery systems to achieve clinical applicability is of great significance. In this study, an integrated PDA-based LiH@PDA@Ag@PAA@Gelatin system was designed for sustained delivery of lidocaine hydrochloride (LiH). By optimizing the preparation process and formulation of the hydrogel, the hydrogel exhibited superior mechanical properties, reversibility, adhesion strength, and self-healing attributes. Moreover, PDA@Ag nanoparticles were evenly dispersed within the hydrogel, and the optimized PDA@Ag@PAA@Gelatin showed a higher photothermal conversion efficiency than that of pure PDA. Importantly, LiH@PDA@Ag@PAA@Gelatin could effectively capture and eradicate bacteria through the synergistic interaction between near-infrared (NIR), PDA, Ag and LiH. In vitro and in vivo tests demonstrated that LiH@PDA@Ag@PAA@Gelatin exhibited higher drug delivery efficiency compared to commercial lidocaine patches. By evaluating the mechanical pain withdrawal threshold of the spared nerve injury (SNI) model in rats, it was proven that LiH@PDA@Ag@PAA@Gelatin enhanced and prolonged the analgesic effect of LiH. Furthermore, LiH@PDA@Ag@PAA@Gelatin induced by NIR possessed excellent on-demand photothermal analgesic ability. Therefore, this study develops a convenient method for preparing localized analgesic hydrogel patches, providing an important step towards advancing PDA-based on-demand pain relief applications.

Supramolecular Polymer Co-Assembled Multifunctional Chiral Hybrid Hydrogels with Adhesive, Self-Healing and Antibacterial Properties.

Amino acid-derived self-assembled nanofibers comprising supramolecular chiral hydrogels with unique physiochemical characteristics are highly demanded biomaterials for various biological applications. However, their narrow functionality often limits practical use, necessitating the development of biomaterials with multiple features within a single system. Herein, chiral co-assembled hybrid hydrogel systems termed LPH-EGCG and DPH-EGCG were constructed by co-assembling L/DPFEG gelators with epigallocatechin gallate (EGCG) followed by cross-linking with polyvinyl alcohol (PVA) and hyaluronic acid (HA). The developed hybrid hydrogels exhibit superior mechanical strength, self-healing capabilities, and adhesive properties, owing to synergistic non-covalent interactions. Integrating hydrophilic polymers enhances the system's capacity to demonstrate favorable swelling characteristics. Furthermore, the introduction of EGCG facilitated the hybrid gels to display notable antibacterial properties against both Gram-positive and Gram-negative bacterial strains, alongside showcasing strong antioxidant capabilities. In vitro investigation demonstrated enhanced cell adhesion and migration with the LPH-EGCG system in comparison to DPH-EGCG, thus emphasizing the promising prospects of these hybrid hydrogels in advanced tissue engineering applications.

Versatile and durable polyvinyl alcohol/alginate/gelatin/quaternary ammonium chitosan/Fe3O4 particles hybrid hydrogel beads: adsorption capabilities for cleaning pollutants.

A novel hybrid hydrogel bead (HHBFe) composed of polyvinyl alcohol/sodium alginate/gelatin/quaternary ammonium chitosan (PVA/GA/SA/QCS) and Fe3O4 magnetic nanoparticles was developed through green cross-linking of Ca2+ and tannic acid (TA) combined freeze-thaw method. HHBFe exhibited a good spherical shape, porosity, magnetic properties, and excellent mechanical properties and durability. The adsorption capacity of HHB and HHBFe towards methyl orange (MO), tetracycline (Tc), and Cr (VI) was systematically studied and compared. Results revealed similar adsorption capacities for MO and Cr (VI) between HHB and HHBFe, while the presence of Fe3O4 significantly enhanced Tc adsorption, indicating the versatile adsorption functions of HHBFe. Adsorption kinetic followed the pseudo-second-order model, with external diffusion and intra-particle diffusion controlling process. The adsorption data were consistent with the Langmuir isothermal adsorption model, indicating predominantly monolayer adsorption of pollutants by beads. Notably, the beads exhibited easily regenerated, maintaining 60 % of initial adsorption capacity after 5 cycles, particularly for Tc and Cr (VI). The good adsorption performance of HHBFe can be attributed to the strong interaction between their multi-functional groups including phenolic hydroxyl groups, carboxyl groups, amino groups, etc., and pollutant molecules. The multifunctional HHBFe beads prepared in this study and the results obtained with three completely different types of pollutants provide reliability support for their use in different wastewater treatment fields and even in the field of drug carriers.

3D matrix stiffness modulation unveils cardiac fibroblast phenotypic switching.

This study investigates how dynamic fluctuations in matrix stiffness affect the behavior of cardiac fibroblasts (CFs) within a three-dimensional (3D) hydrogel environment. Using hybrid hydrogels with tunable stiffness, we created an in vitro model to mimic the varying stiffness of the cardiac microenvironment. By manipulating hydrogel stiffness, we examined CF responses, particularly the expression of α-smooth muscle actin (α-SMA), a marker of myofibroblast differentiation. Our findings reveal that increased matrix stiffness promotes the differentiation of CFs into myofibroblasts, while matrix softening reverses this process. Additionally, we identified the role of focal adhesions and integrin ß1 in mediating stiffness-induced phenotypic switching. This study provides significant insights into the mechanobiology of cardiac fibrosis and suggests that modulating matrix stiffness could be a potential therapeutic strategy for treating cardiovascular diseases.

Alginate-CaCO3 hybrid colloidal hydrogel with tunable physicochemical properties for cell growth.

Biomaterials composed of food polysaccharides are of great interest for future biomedical applications due to their great biocompatibility, tunable mechanical properties, and complex architectural designs that play a crucial role in the modulation of cell adhesion and proliferation. In this work, a facile approach was designed to obtain novel 3D alginate-CaCO3 hybrid hydrogel particles in situ. Controlling the gel concentration from 3 to 20 mg·mL-1 allows us to control the alginate-CaCO3 hydrogel particles' size and density (size variation from 1.86 to 2.34 mm and density from 1.22 to 1.29 mg/mm3). This variable also has a considerable influence on the mineralization process resulting in CaCO3 particles with varied sizes and amounts within the hydrogel beads. The measurements of Young's modulus showed that the inclusion of CaCO3 particles into the alginate hydrogel improved its mechanical properties, and Young's modulus of these hybrid hydrogel particles had a linear relationship with alginate content and hydrogel particle size. Cell experiments indicated that alginate-CaCO3 hybrid hydrogel particles can support osteoblastic cell proliferation and growth. In particular, the amount of hydroxyapatite deposition on the cell membrane significantly increased after the treatment of cells with hybrid hydrogel particles, up to 20-fold. This work offers a strategy for constructing inorganic particle-doped polysaccharide hybrid hydrogel scaffolds that provide the potential to support cell growth.

Metal-amplified sonodynamic therapy of Ti-based chitosan-polyvinyl alcohol hybrid hydrogel dressing against subcutaneous Staphylococcus aureus infection.

Ultrasound (US)-mediated sonodynamic therapy (SDT) has received extensive attention in pathogen elimination for non-invasiveness and high spatial and temporal accuracy. Considering that hydrogel can provide a healing-friendly environment for wounds, in this work, hybrid hydrogels are constructed by embedding Ag doped TiO2 nanoparticles in chitosan-polyvinyl alcohol hydrogels for enhanced sonodynamic antibacterial therapy. With metal silver doped, TiO2 nanoparticles sonosensitivity is improved to generate more reactive oxygen species (ROS), which endows hybrid hydrogels with high-efficient antibacterial properties. In vivo results show that hybrid hydrogel dressing can prevent infection and promote wound closure within 2 days. The healing ratio excess 95 % with no pus produced at the end of treatment. The therapeutic mechanism was identified that heterojunction formed in Ag doped TiO2 facilitates the separation of charge carriers under US irradiation, leading to elevating ROS generation. The generated ROS promote hybrid hydrogels sonodynamic antibacterial therapeutic efficacy to thoroughly eliminate pathogen via disrupting bacterial cell membrane integrity, decreasing membrane fluidity and increasing membrane permeability. Besides, biofilm formation could be effectively inhibited. This work developed a hybrid hydrogel with amplified SDT effect for wound healing, which is expected to provide inspiration of hybrid hydrogels design and Ti-based nanomaterials sonosensitivity enhancement.

Hybrid gelatin-ascorbyl phosphate scaffolds accelerate diabetic wound healing via ROS scavenging, angiogenesis and collagen remodeling.

Skin wound healing, particularly diabetic wound healing, is challenging in clinical management. Impaired wound healing is associated with persistent oxidative stress, altered inflammatory responses, unsatisfactory angiogenesis and epithelialization. Magnesium ascorbyl phosphate (MAP), which is an ascorbic acid derivative and active ingredient in cosmetics, has been reported to scavenge reactive oxygen species (ROS), and is considered a potential therapeutic agent for diabetic wounds. Herein, we report a hybrid gelatin-MAP scaffolds that can reduces oxidative stress damage, enhances angiogenesis and collagen remodeling to accelerate diabetic wound repair. Preliminary insights based on network pharmacology indicate that MAP may accelerate wound repair through multiple biological pathways, including extracellular matrix remodeling and anti-apoptosis. In vitro studies showed that the hybrid hydrogel scaffold had suitable mechanical properties, excellent biocompatibility and bioactivity. Further animal experiments demonstrated that the hydrogel accelerated full-thickness wound repair in diabetic mice (repair rate MAP vs Control=91.791±3.306 % vs 62.962±6.758 %) through antioxidant, neuroangiogenesis, collagen remodeling, and up-regulated the expression of the related factors COL-1, CD31, VEGF, and CGRP. Overall, we developed a bioactive hybrid hydrogel encapsulating MAP that synergistically promotes diabetic wound repair through multiple biological effects. This potentially integrated therapeutic scaffold may enrich future surgical approaches for treating diabetic wounds.

A Cellulose/Chitosan Dual Cross-Linked Multifunctional and Resilient Hydrogel for Emergent Open Wound Management.

Adhesive hydrogel holds huge potential in biomedical applications, such as hemostasis and emergent wound management during outpatient treatment or surgery. However, most adhesive hydrogels underperform to offer robust adhesions on the wet tissue, increasing the risk of hemorrhage and reducing the fault tolerance of surgery. To address this issue, this work develops a polysaccharide-based bioadhesive hydrogel tape (ACAN) consisting of dual cross-linking of allyl cellulose (AC) and carboxymethyl chitosan (CMCS). The hygroscopicity of AC and CMCS networks enables ACAN to remove interfacial water from the tissue surface and initializes a physical cross-link instantly. Subsequently, covalent cross-links are developed with amine moieties to sustain long-term and robust adhesion. The dual cross-linked ACAN also has good cytocompatibility with controllable mechanical properties matching to the tissue, where the addition of CMCS provides remarkable antibacterial properties and hemostatic capability. Moreover, compared with commercially available 3 M film, ACAN provides an ultrafast wound healing on tissue. The ACAN hybrid hydrogels have advantages such as biocompatibility and antibacterial, hemostatic, and wound healing properties, shedding new light on first-aid tape design and advancing the cellulose-based materials technology for high-performance biomedical applications.