ROS-responsive hydrogels with spatiotemporally sequential delivery of antibacterial and anti-inflammatory drugs for the repair of MRSA-infected wounds.

For the treatment of MRSA-infected wounds, the spatiotemporally sequential delivery of antibacterial and anti-inflammatory drugs is a promising strategy. In this study, ROS-responsive HA-PBA/PVA (HPA) hydrogel was prepared by phenylborate ester bond cross-linking between hyaluronic acid-grafted 3-amino phenylboronic acid (HA-PBA) and polyvinyl alcohol (PVA) to achieve spatiotemporally controlled release of two kinds of drug to treat MRSA-infected wound. The hydrophilic antibiotic moxifloxacin (M) was directly loaded in the hydrogel. And hydrophobic curcumin (Cur) with anti-inflammatory function was first mixed with Pluronic F127 (PF) to form Cur-encapsulated PF micelles (Cur-PF), and then loaded into the HPA hydrogel. Due to the different hydrophilic and hydrophobic nature of moxifloxacin and Cur and their different existing forms in the HPA hydrogel, the final HPA/M&Cur-PF hydrogel can achieve different spatiotemporally sequential delivery of the two drugs. In addition, the swelling, degradation, self-healing, antibacterial, anti-inflammatory, antioxidant property, and biocompatibility of hydrogels were tested. Finally, in the MRSA-infected mouse skin wound, the hydrogel-treated group showed faster wound closure, less inflammation and more collagen deposition. Immunofluorescence experiments further confirmed that the hydrogel promoted better repair by reducing inflammation (TNF-α) and promoting vascular (VEGF) regeneration. In conclusion, this HPA/M&Cur-PF hydrogel that can spatiotemporally sequential deliver antibacterial and anti-inflammatory drugs showed great potential for the repair of MRSA-infected skin wounds.

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.

In-Depth Characterization of Sphingoid Bases via Radical-Directed Dissociation Tandem Mass Spectrometry.

Sphingoid base (SPH) is a basic structural unit of all classes of sphingolipids. A sphingoid base typically consists of an aliphatic chain that may be desaturated between C4 and C5, an amine group at C2, and a variable number of OH groups located at C1, C3, and C4. Variations in the chain length and the occurrence of chemical modifications, such as methyl branching, desaturation, and hydroxylation, lead to a large structural diversity and distinct functional properties of sphingoid bases. However, conventional tandem mass spectrometry (MS/MS) via collision-induced dissociation (CID) faces challenges in characterizing these modifications. Herein, we developed an MS/MS method based on CID-triggered radical-directed dissociation (RDD) for in-depth characterization of sphingoid bases. The method involves derivatizing the sphingoid amine with 3-(2,2,6,6-tetramethylpiperidin-1-yloxymethyl)-picolinic acid 2,5-dioxopyrrolidin-1-yl ester (TPN), followed by MS2 CID to unleash the pyridine methyl radical moiety for subsequent RDD. This MS/MS method was integrated on a reversed-phase liquid chromatography-mass spectrometry workflow and further applied for in-depth profiling of total sphingoid bases in bovine heart and Caenorhabditis elegans. Notably, we identified and relatively quantified a series of unusual sphingoid bases, including SPH id17:2 (4,13) and SPH it19:0 in C. elegans, revealing that the metabolic pathways of sphingolipids are more diverse than previously known.

Conductive hydrogels for tissue repair.

Conductive hydrogels (CHs) combine the biomimetic properties of hydrogels with the physiological and electrochemical properties of conductive materials, and have attracted extensive attention in the past few years. In addition, CHs have high conductivity and electrochemical redox properties and can be used to detect electrical signals generated in biological systems and conduct electrical stimulation to regulate the activities and functions of cells including cell migration, cell proliferation, and cell differentiation. These properties give CHs unique advantages in tissue repair. However, the current review of CHs is mostly focused on their applications as biosensors. Therefore, this article reviewed the new progress of CHs in tissue repair including nerve tissue regeneration, muscle tissue regeneration, skin tissue regeneration and bone tissue regeneration in the past five years. We first introduced the design and synthesis of different types of CHs such as carbon-based CHs, conductive polymer-based CHs, metal-based CHs, ionic CHs, and composite CHs, and the types and mechanisms of tissue repair promoted by CHs including anti-bacterial, antioxidant and anti-inflammatory properties, stimulus response and intelligent delivery, real-time monitoring, and promoted cell proliferation and tissue repair related pathway activation, which provides a useful reference for further preparation of bio-safer and more efficient CHs used in tissue regeneration.

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.

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.

pH/Glucose Dual Responsive Metformin Release Hydrogel Dressings with Adhesion and Self-Healing via Dual-Dynamic Bonding for Athletic Diabetic Foot Wound Healing.

In view of the lack of a specific drug-sustained release system that is responsive to chronic wounds of the type II diabetic foot, and the demands for frequent movement at the foot wound, pH/glucose dual-responsive metformin-released adhesion-enhanced self-healing easy-removable antibacterial antioxidant conductive hemostasis multifunctional phenylboronic acid and benzaldehyde bifunctional polyethylene glycol-co-poly(glycerol sebacic acid)/dihydrocaffeic acid and l-arginine cografted chitosan (PEGS-PBA-BA/CS-DA-LAG, denoted as PC) hydrogel dressings were constructed based on the double dynamic bond of the Schiff-base and phenylboronate ester. It was further demonstrated that the PC hydrogel promotes wound healing by reducing inflammation and enhancing angiogenesis in a rat type II diabetic foot model. In addition, the addition of metformin (Met) and graphene oxide (GO), as well as their synergy, were confirmed to better promote wound repair in vivo. In summary, adhesion-enhanced self-healing multifunctional PC/GO/Met hydrogels with stimuli-responsive metformin release ability and easy removability have shown a promoting effect on the healing of chronic athletic diabetic wounds and provide a local-specific drug dual-response release strategy for the treatment of type II diabetic feet.