Bacteria-responsive programmed self-activating antibacterial hydrogel to remodel regeneration microenvironment for infected wound healing.

There is still an urgent need to develop hydrogels with intelligent antibacterial ability to achieve on-demand treatment of infected wounds and accelerate wound healing by improving the regeneration microenvironment. We proposed a strategy of hydrogel wound dressing with bacteria-responsive self-activating antibacterial property and multiple nanozyme activities to remodel the regeneration microenvironment in order to significantly promote infected wound healing. Specifically, pH-responsive H2O2 self-supplying composite nanozyme (MSCO) and pH/enzyme-sensitive bacteria-responsive triblock micelles encapsulated with lactate oxidase (PPEL) were prepared and encapsulated in hydrogels composed of L-arginine-modified chitosan (CA) and phenylboronic acid-modified oxidized dextran (ODP) to form a cascade bacteria-responsive self-activating antibacterial composite hydrogel platform. The hydrogels respond to multifactorial changes of the bacterial metabolic microenvironment to achieve on-demand antibacterial and biofilm eradication through transformation of bacterial metabolites, and chemodynamic therapy enhanced by nanozyme activity in conjunction with self-driven nitric oxide (NO) release. The composite hydrogel showed 'self-diagnostic' treatment for changes in the wound microenvironment. Through self-activating antibacterial therapy in the infection stage to self-adaptive oxidative stress relief and angiogenesis in the post-infection stage, it promotes wound closure, accelerates wound collagen deposition and angiogenesis, and completely improves the microenvironment of infected wound regeneration, which provides a new method for the design of intelligent wound dressings.

Multifunctional On-Demand Removability Hydrogel Dressing Based on in Situ Formed AgNPs, Silk Microfibers and Hydrazide Hyaluronic Acid for Burn Wound Healing.

Elevated temperatures can deactivate tissues in the burn wound area, allowing pathogenic bacteria to multiply on the wound surface, ultimately leading to local or systemic infection. An ideal burn dressing should provide antibacterial properties and facilitate painless dressing changes. Silk microfibers coated with poly (2, 3, 4-trihydroxybenzaldehyde) (referred to as mSF@PTHB) to in situ reduce AgNO3 to silver nanoparticles (AgNPs) in a hydrazide hyaluronic acid-based hydrogel are utilized. The findings indicate a more homogeneous distribution of the silver elements compared to directly doped AgNPs, which also conferred antioxidant and antibacterial properties to the hydrogel. Moreover, hydrogels containing pH-responsive dynamic acylhydrazone bonds can undergo a gel-sol transition in a weak acid environment, leading to the painless removal of adhesive hydrogel dressings. Notably, the on-demand replaceable self-healing antioxidant hydrogel dressing exhibits antibacterial effects and cytocompatibility in vitro, and the wound-healing performance of the hydrogel is validated by treating a burn mouse model with full-thickness skin defects. It is demonstrated that hydrogel dressings offer a viable therapeutic approach to prevent infection and facilitate the healing of burn wounds.

Injectable Self-Expanding/Self-Propelling Hydrogel Adhesive with Procoagulant Activity and Rapid Gelation for Lethal Massive Hemorrhage Management.

Developing hydrogels that can quickly reach deep bleeding sites, adhere to wounds, and expand to stop lethal and/or noncompressible bleeding in civil and battlefield environments remains a challenge. Herein, an injectable, antibacterial, self-expanding, and self-propelling hydrogel bioadhesive with procoagulant activity and rapid gelation is reported. This hydrogel combines spontaneous gas foaming and rapid Schiff base crosslinking for lethal massive hemorrhage. Hydrogels have rapid gelation and expansion rate, high self-expanding ratio, excellent antibacterial activity, antioxidant efficiency, and tissue adhesion capacity. In addition, hydrogels have good cytocompatibility, procoagulant ability, and higher blood cell/platelet adhesion activity than commercial combat gauze and gelatin sponge. The optimized hydrogel (OD-C/QGQL-A30) exhibits better hemostatic ability than combat gauze and gelatin sponge in rat liver and femoral artery bleeding models, rabbit volumetric liver loss massive bleeding models with/without anticoagulant, and rabbit liver and kidney incision bleeding models with bleeding site not visible. Especially, OD-C/QGQL-A30 rapidly stops the bleedings from pelvic area of rabbit, and swine subclavian artery vein transection. Furthermore, OD-C/QGQL-A30 has biodegradability and biocompatibility, and accelerates Methicillin-resistant S. aureus (MRSA)-infected skin wound healing. This injectable, antibacterial, self-expanding, and self-propelling hydrogel opens up a new avenue to develop hemostats for lethal massive bleeding, abdominal organ bleeding, and bleeding from coagulation lesions.

Injectable Antiswelling and High-Strength Bioactive Hydrogels with a Wet Adhesion and Rapid Gelling Process to Promote Sutureless Wound Closure and Scar-free Repair of Infectious Wounds.

Developing injectable antiswelling and high-strength bioactive hydrogels with wet tissue adhesiveness and a rapid gelling process to meet the requirements for rapid hemostasis, sutureless wound closure, and scar-free repair of infected skin wounds continues to have ongoing challenges. Herein, injectable, antibacterial, and antioxidant hydrogel adhesives based on poly(citric acid-co-polyethylene glycol)-g-dopamine and amino-terminated Pluronic F127 (APF) micelles loaded with astragaloside IV (AS) are prepared. The H2O2/horseradish peroxidase (HRP) system is used to cause cross-linking of the hydrogel network through oxidative coupling between catechol groups and chemical cross-linking between the catechol group and the amino group. The hydrogels exhibit a rapid gelling process, high mechanical strength, an antiswelling effect, good antioxidant property, H2O2 release behavior, and degradability. In addition, the hydrogels present good wet tissue adhesiveness, high bursting pressure, excellent antibacterial activity, long-term sustained release of AS, and good biocompatibility. The hydrogels perform good hemostasis on mouse liver, rat liver, and rabbit femoral vein bleeding models and achieve much better closure and healing of skin incisions than biomedical glue and surgical sutures. Furthermore, the hydrogel dressing significantly improved the scar-free repair of MRSA-infected full thickness skin defect wounds by modulating inflammation, regulating the ratio of collagen I/III, and improving the vascularization and granulation tissue formation. Thus, AS-loaded hydrogels show huge potential as multifunctional dressings for in vivo hemostasis, sutureless wound closure, and scar-free repair of infected skin wounds.

Antibacterial conductive self-healing hydrogel wound dressing with dual dynamic bonds promotes infected wound healing.

In clinical applications, there is a lack of wound dressings that combine efficient resistance to drug-resistant bacteria with good self-healing properties. In this study, a series of adhesive self-healing conductive antibacterial hydrogel dressings based on oxidized sodium alginate-grafted dopamine/carboxymethyl chitosan/Fe3+ (OSD/CMC/Fe hydrogel)/polydopamine-encapsulated poly(thiophene-3-acetic acid) (OSD/CMC/Fe/PA hydrogel) were prepared for the repair of infected wound. The Schiff base and Fe3+ coordination bonds of the hydrogel structure are dynamic bonds that can be repaired automatically after the hydrogel network is disrupted. Macroscopically, the hydrogel exhibits self-healing properties, allowing the hydrogel dressing to adapt to complex wound surfaces. The OSD/CMC/Fe/PA hydrogel showed good conductivity and photothermal antibacterial properties under near-infrared (NIR) light irradiation. In addition, the hydrogels exhibit tunable rheological properties, suitable mechanical properties, antioxidant properties, tissue adhesion properties and hemostatic properties. Furthermore, all hydrogel dressings improved wound healing in the infected full-thickness defect skin wound repair test in mice. The wound size repaired by OSD/CMC/Fe/PA3 hydrogel + NIR was much smaller (12%) than the control group treated with Tegaderm™ film after 14 days. In conclusion, the hydrogels have high antibacterial efficiency, suitable conductivity, great self-healing properties, good biocompatibility, hemostasis and antioxidant properties, making them promising candidates for wound healing dressings for the treatment of infected skin wounds.

Hypnotizability and Disordered Personality Styles in Cluster A Personality Disorders.

AIM: Interpersonal sensitivity and mistrust are the main characteristics of cluster A personality disorders (CAPD) which might be due to the high accessibility to negative suggestions from environments. Yet the exact associations between hypnotic suggestibility and their personality disorder functioning styles remain unclear. METHODS: We invited 36 patients with CAPD and 115 healthy volunteers to undergo the Stanford Hypnotic Susceptibility Scale: Form C (SHSS:C) and Parker Personality Measure (PERM). RESULTS: Compared to controls; patients scored higher on PERM paranoid; schizoid; schizotypal; borderline; avoidant; and dependent styles; on the SHSS:C total and "challenge suggestions", and the passing rates of "hand lowering", "arm rigidity", "dream", and "arm immobilization". In patients, "dream" negatively predicted the schizoid; "hallucinated voice" negatively the schizotypal; "mosquito hallucination" positively the histrionic and dependent; and "arm immobilization" negatively the avoidant style. CONCLUSIONS: Our results suggested that the insusceptibility to perceptual suggestions from others and the high control over body contribute to the paranoid attitude and interpersonal avoidance in CAPD. These findings help to understand the cause of interpersonal problems in these patients and suggest the trial of hypnotherapy for them.

Antibacterial adhesive self-healing hydrogels to promote diabetic wound healing.

The development of compressible, stretchable and self-healing hydrogel dressings with good adhesive, antibacterial and angiogenesis properties is needed to promote the regeneration of diabetic wounds in clinical applications. In this work, a series of self-healing, adhesive and antibacterial hydrogels based on gelatin methacrylate (GelMA), adenine acrylate (AA), and CuCl2 were designed through covalent bonding, coordination complexation of Cu2+ and carboxyl groups and hydrogen bonding to promote diabetic wound healing. These hydrogels exhibit efficient self-healing properties, remarkable fatigue resistance, and good adhesive properties due to the hydrogen bond and the metal-ligand coordination provided by the Cu2+ and the carboxyl group. The GelMA/AA/Cu1.0 hydrogel (containing 1.0 mg/mL Cu2+) with well-balanced biocompatibility and antibacterial properties exhibited efficient hemostatic performance in a mouse liver trauma model and significantly promoted the healing process in a full-thickness skin diabetic wound model. The immunohistochemistry results showed that the GelMA/AA/Cu1.0 hydrogel can promote regular epithelialization and collagen deposition when compared to the TegadermTM Film, GelMA hydrogel, and GelMA/AA/Cu0 hydrogel. The immunofluorescence results confirmed that the GelMA/AA/Cu1.0 hydrogel can reduce the expression of proinflammatory factors and promote angiogenesis. In conclusion, the GelMA/AA/Cu hydrogel is an effective wound dressing to promote the healing process of diabetic skin wounds. STATEMENT OF SIGNIFICANCE: Diabetic wounds exhibit an extremely high risk of bacterial infection and poor angiogenesis in a high-sugar environment, hindering their healing process. Hydrogel wound dressings are a promising wound care material that need to have stable and long-lasting adhesive properties, avoid shedding, provide lasting protection to wounds, antibacterial properties and promote angiogenesis. In this study, a series of self-healing, adhesive, and antibacterial hydrogels based on gelatin methacrylate (GelMA), acrylated adenine (AA), and CuCl2 were designed and synthesized via free radical polymerization, hydrogen bond, and ionic bond to promote diabetic wound healing. Overall, GelMA/AA/Cu hydrogels are promising materials to promote diabetic wound healing.

Mussel-inspired adhesive antioxidant antibacterial hemostatic composite hydrogel wound dressing via photo-polymerization for infected skin wound healing.

With the increasing prevalence of drug-resistant bacterial infections and the slow healing of chronically infected wounds, the development of new antibacterial and accelerated wound healing dressings has become a serious challenge. In order to solve this problem, we developed photo-crosslinked multifunctional antibacterial adhesive anti-oxidant hemostatic hydrogel dressings based on polyethylene glycol monomethyl ether modified glycidyl methacrylate functionalized chitosan (CSG-PEG), methacrylamide dopamine (DMA) and zinc ion for disinfection of drug-resistant bacteria and promoting wound healing. The mechanical properties, rheological properties and morphology of hydrogels were characterized, and the biocompatibility of these hydrogels was studied through cell compatibility and blood compatibility tests. These hydrogels were tested for the in vitro blood-clotting ability of whole blood and showed good hemostatic ability in the mouse liver hemorrhage model and the mouse-tail amputation model. In addition, it has been confirmed that the multifunctional hydrogels have good inherent antibacterial properties against Methicillin-resistant Staphylococcus aureus (MRSA). In the full-thickness skin defect model infected with MRSA, the wound closure ratio, thickness of granulation tissue, number of collagen deposition, regeneration of blood vessels and hair follicles were measured. The inflammation-related cytokines (CD68) and angiogenesis-related cytokines (CD31) expressed during skin regeneration were studied. All results indicate that these multifunctional antibacterial adhesive hemostatic hydrogels have better healing effects than commercially available Tegaderm™ Film, revealing that they have become promising alternative in the healing of infected wounds.

The Effects of Dexmedetomidine in a Rat Model of Sepsis-Induced Lung Injury are Mediated Through the Adenosine Monophosphate-Activated Protein Kinase (AMPK)/Silent Information Regulator 1 (SIRT1) Pathway.

BACKGROUND This study aimed to investigate the effects of dexmedetomidine in a rat model of sepsis-induced lung injury and the role of the adenosine monophosphate-activated protein kinase (AMPK) gene and silent information regulator 1 (SIRT1) gene signaling pathway. MATERIAL AND METHODS Sixty 28-week-old healthy male Sprague-Dawley rats were randomly divided into three groups, the sham group, the model group, and the dexmedetomidine-treated group. The rat model of sepsis-induced lung injury was developed by surgical cecal ligation and puncture. Lung tissues examined histologically in the three study groups. Cell apoptosis was measured using the TUNEL assay, and the expression of inflammatory cytokines, tumor necrosis factor-alpha (TNF-alpha), interleukin-1ß (IL-1ß), and IL-10 were measured in rat lung tissue by enzyme-linked immunosorbent assay (ELISA). Apoptosis-associated proteins and AMPK/SIRT1 pathway-associated protein expression levels were detected using Western blot. RESULTS Dexmedetomidine significantly increased the survival rate and reduced the body temperature of rats in the model group with sepsis-induced lung injury, reduced lung injury, significantly reduced apoptosis in lung tissues, and reduced the expression levels of TNF-alpha, and IL-1ß, and increased the levels of IL-10. Dexmedetomidine significantly reduced the expression of caspase-3 in the rat lung tissue (P<0.01), and significantly increased the expression of Bcl-2/Bax and the phosphorylation levels of AMPK, SIRT1, nuclear factor-kappaB (NF-kappaB), and forkhead box class O 3a (FOXO3a). CONCLUSIONS In a rat model of sepsis-induced lung injury, dexmedetomidine reduced lung damage by activating the AMPK/SIRT1 signaling pathway and reduced the expression of inflammatory cytokines and cell apoptosis.