ABSTRACT
In this study, we developed a tissue-adhesive and long-term antibacterial hydrogel consisting of protamine (PRTM) grafted carboxymethyl chitosan (CMC) (PCMC), catechol groups modified CMC (DCMC), and oxidized hyaluronic acid (OHA), named DCMC-OHA-PCMC. According to the antibacterial experiments, the PCMC-treated groups showed obvious and long-lasting inhibition zones against E. coli (and S. aureus), and the corresponding diameters varied from 10.1 mm (and 15.3 mm) on day 1 to 9.8 mm (and 15.3 mm) on day 7. The DCMC-OHA-PCMC hydrogel treated groups also exhibited durable antibacterial ability against E. coli (and S. aureus), and the antibacterial rates changed from 99.3 ± 0.21 % (and 99.6 ± 0.36 %) on day 1 to 76.2 ± 1.74 % (and 84.2 ± 1.11 %) on day 5. Apart from good mechanical and tissue adhesion properties, the hydrogel had excellent hemostatic ability mainly because of the grafted positive-charged PRTM. As the animal assay results showed, the hydrogel was conducive to promoting the deposition of new collagen (0.84 ± 0.03), the regeneration of epidermis (98.91 ± 6.99 µm) and wound closure in the process of wound repairing. In conclusion, the presented outcomes underline the prospective potential of the multifunctional CMC-based hydrogel for applications in wound dressings.
Subject(s)
Anti-Bacterial Agents , Chitosan , Chitosan/analogs & derivatives , Escherichia coli , Hemostasis , Hydrogels , Protamines , Skin , Staphylococcus aureus , Wound Healing , Chitosan/chemistry , Chitosan/pharmacology , Wound Healing/drug effects , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Hydrogels/chemistry , Hydrogels/pharmacology , Animals , Escherichia coli/drug effects , Staphylococcus aureus/drug effects , Protamines/chemistry , Protamines/pharmacology , Hemostasis/drug effects , Skin/drug effects , Mice , Male , Rats , Hemostatics/pharmacology , Hemostatics/chemistry , Tissue Adhesives/pharmacology , Tissue Adhesives/chemistryABSTRACT
Multifunctional hydrogels have been developed to meet the various requirements of wound healing. Herein, an innovative hydrogel (QCMC-HA-PEG) was formed through the Schiff base reaction, composed of quaternary ammonium-modified carboxymethyl chitosan (QCMC), hyaluronic acid (HA), and 8-arms Polyethylene Glycol aldehyde (8-ARM-PEG-CHO). The resulting hydrogels exhibited good mechanical and adhesive properties with improved antibacterial efficacy against both Gram-positive and Gram-negative bacteria compared to CMC hydrogels. QCMC-HA-PEG hydrogels demonstrated remarkable adhesive ability in lap-shear test. Furthermore, the incorporation of MnO2 nanosheets into the hydrogel significantly enhanced its reactive oxygen species (ROS) scavenging and oxygen generation capabilities. Finally, experimental results from a full-thickness skin wound model revealed that the QCMC-HA-PEG@MnO2 hydrogel promoted skin epithelization, collagen deposition, and inflammatory regulation significantly accelerated the wound healing process. Therefore, QCMC-HA-PEG@MnO2 hydrogel could be a promising wound dressing to promote wound healing.
Subject(s)
Anti-Bacterial Agents , Antioxidants , Chitosan , Hydrogels , Quaternary Ammonium Compounds , Wound Healing , Chitosan/chemistry , Chitosan/analogs & derivatives , Chitosan/pharmacology , Wound Healing/drug effects , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Hydrogels/chemistry , Hydrogels/pharmacology , Animals , Quaternary Ammonium Compounds/chemistry , Quaternary Ammonium Compounds/pharmacology , Antioxidants/pharmacology , Antioxidants/chemistry , Reactive Oxygen Species/metabolism , Mice , Polyethylene Glycols/chemistry , Polyethylene Glycols/pharmacology , Manganese Compounds/chemistry , Manganese Compounds/pharmacology , Oxides/chemistry , Oxides/pharmacology , Hyaluronic Acid/chemistry , Hyaluronic Acid/pharmacology , Skin/drug effectsABSTRACT
The infected wounds pose one of the major threats to human health today. To address this issue, it is necessary to develop innovative wound dressings with superior antibacterial activity and other properties. Due to its potent antibacterial, antioxidant, and immune-boosting properties, epigallocatechin gallate (EGCG) has been widely utilized. In this study, a multifunctional curdlan hydrogel loading EGCG (Cur-EGCGH3) was designed. Cur-EGCGH3 exhibited excellent physicochemical properties, good biocompatibility, hemostatic, antibacterial, and antioxidant activities. Also, ELISA data showed that Cur-EGCGH3 stimulated macrophages to secrete pro-inflammatory and pro-regenerative cytokines. Cell scratch results indicated that Cur-EGCGH3 promoted the migration of NIH3T3 and HUVECs. In vivo experiments confirmed that Cur-EGCGH3 could inhibit bacterial infection of the infected wounds, accelerate hemostasis, and promote epithelial regeneration and collagen deposition. These results demonstrated that Cur-EGCGH3 holds promise for promoting healing of the infected wounds.
Subject(s)
Anti-Bacterial Agents , Catechin , Catechin/analogs & derivatives , Hemostatics , Hydrogels , Wound Healing , beta-Glucans , Catechin/pharmacology , Catechin/chemistry , Animals , Wound Healing/drug effects , Mice , beta-Glucans/chemistry , beta-Glucans/pharmacology , Hydrogels/chemistry , Hydrogels/pharmacology , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Humans , NIH 3T3 Cells , Hemostatics/pharmacology , Hemostatics/chemistry , Wound Infection/drug therapy , Wound Infection/microbiology , Antioxidants/pharmacology , Antioxidants/chemistry , Human Umbilical Vein Endothelial Cells/drug effectsABSTRACT
Chitosan-based hydrogels are considered to be ideal materials for promoting wound healing due to their nontoxic, biodegradable, and biocompatible properties. However, the weak mechanical strength, hemostatic properties, and adhesive properties of chitosan hydrogels limit their potential applications. In this study, we synthesized methacrylimide-chitosan (MAC)-4-arm polyethylene glycol (PEG)-dopamine (DMA) (MAC-PEG-DMA) hybrid hydrogels containing A-chain homodimers of platelet-derived growth factor (PDGF-AA) through one-pot photo-crosslinking. The resulting hydrogel exhibited improved mechanical strength and hemostatic properties as demonstrated by both in vitro blood clotting assay and rat liver hemorrhage assay. Furthermore, The PDGF-AA loaded hydrogel was also able to accelerate cell migration and proliferation. Data from skin wounds treated with this hybrid hydrogel showed faster wound closure and collagen maturation. Therefore, MAC-PEG-DMA (PDGF-AA) has great potential as a dressing to promote wound healing.
Subject(s)
Chitosan , Hemostatics , Methacrylates , Polyethylene Glycols , Rats , Animals , Hydrogels , Wound Healing , Platelet-Derived Growth Factor , Anti-Bacterial AgentsABSTRACT
The introduction of antibacterial and hemostatic hydrogels with good mechanical properties that display desirable impacts on wound healing process is still an unmet essential for clinical wound dressings. Herein, a multifunctional hydrogel PEG-CMC-THB-PRTM was fabricated via a one-pot method combining carboxymethyl chitosan (CMC), 2,3,4-trihydroxybenzaldehyde (THB), protamine (PRTM) and 4-arm polyethylene glycol aldehyde (PEG). The hydrogel was formed by the dynamic Schiff base reaction between amino groups of carboxymethyl chitosan and aldehyde groups of 4-arm polyethylene glycol aldehyde and exhibited excellent mechanical properties. The developed hydrogel also showed outstanding effects on anti-bacteria and hemostasis through the release of PRTM. Moreover, the hydrogel could promote extracellular matrix formation and wound closure in vivo, thereby accelerating the healing of skin wound. These results suggested that the multifunctional PEG-CMC-THB-PRTM hydrogel is a promising candidate for the clinical treatment of full-thickness wounds.
