Preparation and Application of Quaternized Chitosan- and AgNPs-Base Synergistic Antibacterial Hydrogel for Burn Wound Healing.
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ABSTRACT:
SUBMITTER: Chen X
PROVIDER: S-EPMC8271850 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Overexpression of reactive oxygen species (ROS) can lead to chronic inflammation, which limits skin wound healing. Therefore, it is of great significance to develop materials that can locally control the adverse reactions caused by excessive ROS. In this research, an ROS-sensitive hydrogel with strong free radical scavenging ability was prepared by introducing the thione (Tk) group into carboxymethyl chitosan (CMCTS) hydrogel. CMCTS hydrogel was cross-linked by NH2-Tk-NH2 agent and loaded curcumin (Cur), which possessed favorable nontoxicity, water absorption, mechanical property, biodegradability, drug release behavior, the M2 phenotype, and inflammatory factor regulating the capacity of macrophages. It is worth noting that Cur@CMCTS-Tk hydrogel can significantly inhibit oxidative damage of human fibroblasts in the H2O2-induced microenvironment and protect their viability by reducing the production of intracellular ROS. In vivo, ROS-removing hydrogel effectively accelerated the process of wound healing and possessed good regenerative properties, including hair follicle formation, promotion of new blood vessel formation, and highly orderly arrangement of collagen fibers in the full-thickness skin burn defect rat model. Hence, we expect that the Cur@CMCTS-Tk hydrogel could be used for wound treatment and tissue regeneration due to the ability to scavenge excess ROS.
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Project description:BackgroundPolysaccharide-based hydrogels have been developed for many years to treat burn wounds. Essential oils extracted from aromatic plants generally exhibit superior biological activity, especially antibacterial properties. Studies have shown that antibacterial hydrogels mixed with essential oils have great potential for burn wound healing. This study aimed to develop an antibacterial polysaccharide-based hydrogel with essential oil for burn skin repair.MethodsEucalyptus essential oil (EEO), ginger essential oil (GEO) and cumin essential oil (CEO) were employed for the preparation of effective antibacterial hydrogels physically crosslinked by carboxymethyl chitosan (CMC) and carbomer 940 (CBM). Composite hydrogels were prepared and characterized using antimicrobial activity studies, Fourier-transform infrared spectroscopy, X-ray diffraction, scanning electron microscopy, gas chromatography-mass spectrometery, rheological analysis, viscosity, swelling, water loss rate and water vapor transmission rate studies. In addition, the biocompatibility of hydrogels was evaluated in vivo by cytotoxicity and cell migration assays and the burn healing ability of hydrogels was tested in vivo using burn-induced wounds in mice.ResultsThe different essential oils exhibited different mixing abilities with the hydrogel matrix (CMC and CBM), which caused varying levels of reduction in essential oil hydrogel viscosity, swelling and water vapor transmission. Among the developed hydrogels, the CBM/CMC/EEO hydrogel exhibited optimal antibacterial activities of 46.26 ± 2.22% and 63.05 ± 0.99% against Staphylococcus aureus and Escherichia coli, respectively, along with cell viability (>92.37%) and migration activity. Furthermore, the CBM/CMC/EEO hydrogel accelerated wound healing in mouse burn models by promoting the recovery of dermis and epidermis as observed using a hematoxylin-eosin and Masson's trichrome staining assay. The findings from an enzyme-linked immunosorbent assay demonstrated that the CBM/CMC/EEO hydrogel could repair wounds through interleukin-6 and tumor necrosis factor-α downregulation and transforming growth factor-β, vascular endothelial growth factor (VEGF) and epidermal growth factor upregulation.ConclusionsThis study successfully prepared a porous CBM/CMC/EEO hydrogel with high antibacterial activity, favorable swelling, optimal rheological properties, superior water retention and water vapor transmission performance and a significant effect on skin repair in vitro and in vivo. The results indicate that the CBM/CMC/EEO hydrogel has the potential for use as a promising burn dressing material for skin burn repair.
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Project description:BackgroundClinic treatment of diabetic foot ulcers (DFUs) is considerably challenging. Impaired wound healing may be caused by poor vascularization and dysfunction of the extracellular matrix, which leads to poor re-epithelialization and increased risk of infection. In this study, we evaluated the treatment potential of a functional dressing comprising quaternized chitosan (hydroxypropyltrimethyl ammonium chloride chitosan) and magnesium (Mg) on DFUs.MethodsDressings were prepared by vacuum freeze-drying. The cellular proliferation, migration, and angiogenesis potential of the functional dressings were determined in vitro. Methicillin-resistant Staphylococcus aureus (MRSA, ATCC43300) and methicillin-resistant Staphylococcus epidermidis 287 (MRSE287) were used to evaluate the antibacterial efficiency of the dressings. Finally, a diabetic rat model with infected wounds was used to further evaluate the effects of functional dressings on the healing of DFUs.ResultsFunctional dressings facilitated the migration of human dermal fibroblasts and human umbilical vein endothelial cells (HUVECs), while also stimulating angiogenesis in HUVECs. Additionally, the functional dressing could effectively eradicate MRSA and MRSE, exhibiting excellent antibacterial ability against drug-resistant bacteria. The results of in vivo microbiological and histological tests demonstrated effective anti-infection ability and wound-healing potential of this functional dressing.ConclusionsThe dual-functional dressing exhibited wound-healing ability and anti-infection efficiency, demonstrating potential application prospects in DFU treatment.Translational potential of this articleAs one of the common and serious complications of diabetes, DFUs do not heal easily, causing great suffering to patients. Therefore, improvement in the prognosis of DFUs is a crucial clinical need. The dual-functional dressing prepared in this study was proven to improve the treatment of DFUs, both in vitro and in vivo. Considering its urgent clinical necessity and good biocompatibility of its raw materials, such as alginate, Mg, and chitosan derivatives, this dual-functional dressing presents good prospects for clinical translation.
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Project description:Wound immersion in seawater with high salt, high sodium, and a high abundance of pathogenic bacteria, especially gram-negative bacteria, can cause serious infections and difficulties in wound repair. The present study aimed to prepare a composite hydrogel composed of hyaluronic acid (HA) and quaternized chitosan (QCS) that may promote wound healing of seawater-immersed wounds and prevent bacterial infection. Based on dynamic Schiff base linkage, hydrogel was prepared by mixing oxidized hyaluronic acid (OHA) and hyaluronic acid-hydrazide (HA-ADH) under physiological conditions. With the addition of quaternized chitosan, oxidized hyaluronic acid/hyaluronic acid-hydrazide/quaternized chitosan (OHA/HA-ADH/O-HACC and OHA/HA-ADH/N-HACC) composite hydrogels with good swelling properties and mechanical properties, appropriate water vapor transmission rates (WVTR), and excellent stability were prepared. The biocompatibility of the hydrogels was demonstrated by in vitro fibroblast L929 cell culture study. The results of in vitro and in vivo studies revealed that the prepared antibacterial hydrogels could largely inhibit bacterial growth. The in vivo study further demonstrated that the antibacterial hydrogels exhibited high repair efficiencies in a seawater-immersed wound defect model. In addition, the antibacterial hydrogels decreased pro-inflammatory factors (TNF-α, IL-1β, and IL-6) but enhanced anti-inflammatory factors (TGF-β1) in wound. This work indicates that the prepared antibacterial composite hydrogels have great potential in chronic wound healing applications, such as severe wound cure and treatment of open trauma infections.
| S-EPMC6914676 | biostudies-literature
Project description:Background: The repair of wounds usually caused by trauma or other chronic diseases remained challenging in clinics due to the potential risk of inflammation and inadequate tissue regenerative properties. Among them, the behaviour of immune cells, such as macrophages, is critical in tissue repair. Materials and methods: In this study, a water-soluble phosphocreatine-grafted methacryloyl chitosan (CSMP) was synthesized with a one-step lyophilization method, followed by the fabrication of CSMP hydrogel with a photocrosslinked method. The microstructure, water absorption and mechanical properties for the hydrogels were investigated. Then, the macrophages were co-cultured with hydrogels and the pro-inflammatory factors and polarization markers for these macrophages were detected through real-time quantitative polymerase chain reaction (RT-qPCR), Western blot (WB), and flow cytometry methods. Finally, the CSMP hydrogel was implanted in a wound defect area in mice to test its ability to promote wound healing. Results: The lyophilized CSMP hydrogel had a porous structure with pores ranging in size from 200 to 400 μm, which was larger than the CSM hydrogel’s. The lyophilized CSMP hydrogel possessed a higher water absorption rate compared with the CSM hydrogel. The compressive stress and modulus of these hydrogels were increased in the initial 7 days immersion and then gradually decreased during the in vitro immersion in PBS solution up to 21 days; the CSMP hydrogel showed a higher value in these parameters versus the CSM hydrogel. The CSMP hydrogel inhibited the expression of inflammatory factors such as interleukin-1β (IL-1β), IL-6, IL-12, and tumor necrosis factor-α (TNF-α) in an in vitro study cocultured with pro-inflammatory factors in pre-treated bone marrow-derived macrophages (BMM). The mRNA sequencing results showed that the CSMP hydrogel might inhibit the macrophages’ M1 type polarization through the NF-κB signaling pathway. Furthermore, when compared to the control group, the CSMP hydrogel promoted more skin area repair in the mouse wound defect area, and inflammatory factors such as IL-1β, IL-6, and TNF-α were lower in the repaired tissue for the CSMP group. Conclusion: This phosphate-grafted chitosan hydrogel showed great promise for wound healing through regulating the macrophage’s phenotype via the NF-κB signaling pathway.
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Project description:The presence of bacteria directly affects wound healing. Chitosan-based hydrogel biomaterials are a solution as they offer advantages for wound-healing applications due to their strong antimicrobial properties. Here, a double-cross-linking chitosan-based hydrogel with antibacterial, self-healing, and injectable properties is reported. Thiolated chitosan was successfully prepared, and the thiolated chitosan molecules were cross-linked by Ag-S coordination to form a supramolecular hydrogel. Subsequently, the amine groups in the thiolated chitosan covalently cross-linked with genipin to further promote hydrogel formation. In vitro experimental results indicate that hydrogel can release Ag+ over an extended time, achieving an antibacterial rate of over 99% against Escherichia coli and Staphylococcus aureus. Due to the reversible and dynamic feature of Ag-S coordination, an antibacterial hydrogel exhibited injectable and self-healing capabilities. Additionally, the hydrogel showed excellent biocompatibility and biodegradability.Supplementary informationThe online version contains supplementary material available at 10.1007/s42995-023-00211-z.
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Project description:A patch with the capability of avoiding wound infection and promoting tissue remolding is of great value for wound healing. In this paper, we develop a biomass chitosan microneedle array (CSMNA) patch integrated with smart responsive drug delivery for promoting wound healing. Chitosan possesses many outstanding features such as the natural antibacterial property and has been widely utilized for wound healing. Besides, the microstructure of microneedles enables the effective delivery of loaded drugs into the target area and avoids the excessive adhesion between the skin and the patch. Also, vascular endothelial growth factor (VEGF) is encapsulated in the micropores of CSMNA by temperature sensitive hydrogel. Therefore, the smart release of the drugs can be controllably realized via the temperature rising induced by the inflammation response at the site of wounds. It is demonstrated that the biomass CSMNA patch can promote inflammatory inhibition, collagen deposition, angiogenesis, and tissue regeneration during the wound closure. Thus, this versatile CSMNA patch is potentially valuable for wound healing in clinical applications.
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Project description:Treatment of wounds in special areas is challenging due to inevitable movements and difficult fixation. Common cotton gauze suffers from incomplete joint surface coverage, confinement of joint movement, lack of antibacterial function, and frequent replacements. Hydrogels have been considered as good candidates for wound dressing because of their good flexibility and biocompatibility. Nevertheless, the adhesive, mechanical, and antibacterial properties of conventional hydrogels are not satisfactory. Herein, cationic polyelectrolyte brushes grafted from bacterial cellulose (BC) nanofibers are introduced into polydopamine/polyacrylamide hydrogels. The 1D polymer brushes have rigid BC backbones to enhance mechanical property of hydrogels, realizing high tensile strength (21-51 kPa), large tensile strain (899-1047%), and ideal compressive property. Positively charged quaternary ammonium groups of tethered polymer brushes provide long-lasting antibacterial property to hydrogels and promote crawling and proliferation of negatively charged epidermis cells. Moreover, the hydrogels are rich in catechol groups and capable of adhering to various surfaces, meeting adhesive demand of large movement for special areas. With the above merits, the hydrogels demonstrate less inflammatory response and faster healing speed for in vivo wound healing on rats. Therefore, the multifunctional hydrogels show stable covering, little displacement, long-lasting antibacteria, and fast wound healing, demonstrating promise in wound dressing.
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Project description:Severe burns are challenging to heal and result in significant death throughout the world. Adipose-derived mesenchymal stem cells (ADSCs) have emerged as a promising treatment for full-thickness burn healing but are impeded by their low viability and efficiency after grafting in vivo. Nitric oxide (NO) is beneficial in promoting stem cell bioactivity, but whether it can function effectively in vivo is still largely unknown. In this study, we bioprinted an efficient biological scaffold loaded with ADSCs and NO (3D-ADSCs/NO) to evaluate its biological efficacy in promoting severe burn wound healing. The integral 3D-ADSCs/NO hydrogel scaffolds were constructed via 3D bioprinting. Our results shown that 3D-ADSCs/NO can enhance the migration and angiogenesis of Human Umbilical Vein Endothelial Cells (HUVECs). Burn wound healing experiments in mice revealed that 3D-ADSCs/NO accelerated the wound healing by promoting faster epithelialization and collagen deposition. Notably, immunohistochemistry of CD31 suggested an increase in neovascularization, supported by the upregulation of vascular endothelial growth factor (VEGF) mRNA in ADSCs in the 3D biosystem. These findings indicated that 3D-ADSC/NO hydrogel scaffold can promote severe burn wound healing through increased neovascularization via the VEGF signalling pathway. This scaffold may be considered a promising strategy for healing severe burns.
| S-EPMC8071097 | biostudies-literature
Project description:Adipose mesenchymal stem cell (ADMSC)-derived exosomes (ADMSC-Exos) have shown great potential in regenerative medicine and been evidenced benefiting wound repair such as burns. However, the low yield, easy loss after direct coating, and no suitable loading system to improve their availability and efficacy hinder their clinical application for wound healing. And few studies focused on the comparison of biological functions between exosomes derived from different culture techniques, especially in exosome-releasing hydrogel system. Therefore, we designed a high-performance exosome controllable releasing hydrogel system for burn wound healing, namely loading 3D-printed microfiber culture-derived exosomes in a highly biocompatible hyaluronic acid (HA). In this project, we compared the biological functions in vitro and in a burn model among exosomes derived from the conventional two-dimensional (2D) plate culture (2D-Exos), microcarrier culture (2.5D-Exos), and 3D-printed microfiber culture (3D-Exos). Results showed that compared with 2D-Exos and 2.5D-Exos, 3D-Exos promoted HACATs and HUVECs cell proliferation and migration more significantly. Additionally, 3D-Exos had stronger angiogenesis-promoting effects in tube formation of (HUVECs) cells. Moreover, we found HA-loaded 3D-Exos showed better burn wound healing promotion compared to 2D-Exos and 2.5D-Exos, including accelerated burn wound healing rate and better collagen remodeling. The study findings reveal that the HA-loaded, controllable-release 3D-Exos repair system distinctly augments therapeutic efficacy in terms of wound healing, while concurrently introducing a facile application approach. This system markedly bolsters the exosomal loading efficiency, provides a robust protective milieu, and potentiates the inherent biological functionalities of the exosomes. Our findings provide a rationale for more efficient utilization of high-quality and high-yield 3D exosomes in the future, and a novel strategy for healing severe burns.
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