ROS-Eliminating Carboxymethyl Chitosan Hydrogel to Enhance Burn Wound-Healing Efficacy.
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ABSTRACT:
SUBMITTER: Yang C
PROVIDER: S-EPMC8238405 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Wound healing involves multiple interrelated processes required to lead to successful healing outcomes. Phagocytosis, inflammation, cell proliferation, angiogenesis, energy production, and collagen synthesis are all directly or indirectly dependent on oxygen. Along with other critical factors, such as nutrition and comorbidities, availability of oxygen is a key determinant of healing success. Previously, we have presented a novel oxygenated hydrogel material that can be made into dressings for continuous localized oxygen delivery to wounds. In this study, an acute porcine wound model was used to test the healing benefits of these oxygenated MACF (MACF + O2) hydrogel dressings compared to controls, which included commercial Derma-GelTM hydrogel dressings. Wound closure and histological analyses were performed to assess re-epithelialization, collagen synthesis, angiogenesis, and keratinocyte maturation. Results from these assays revealed that wounds treated with MACF + O2 hydrogel dressings closed faster as compared to Derma-Gel (p<0.05). Targeted metabolomics via liquid chromatography separation and mass spectrometric detection (LC-MS/MS) and a biochemical assay determined the concentration of hydroxyproline in wound samples at days 14 and 21, showing that MACF + O2 hydrogel dressings improved wound healing via an upregulated collagen synthesis pathway as compared to Derma-Gel (p<0.05). Histological evidence showed that MACF + O2 hydrogel dressings improve new blood vessel formation and keratinocyte maturation over all other treatments.
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Project description:Hydrogels have various applications in medicine, for example, in systems for controlled drug release or as wound dressings, where they provide an appropriate environment for healing and constitute a barrier to microorganisms. The aim of this study was to evaluate the action of carboxymethyl chitosan (CMCS) hydrogels in wound healing therapy in vivo using a laboratory rat model. The hydrogels were formed from aqueous solutions of a CMCS biopolymer via electron beam irradiation, with the presence of a crosslinking agent of poly(ethylene glycol) diacrylate. A histopathological examination of injured tissue, using a model of a hard-to-heal wound, indicated that the CMCS hydrogel supported healing. The new gel dressing, being noncytotoxic, presents great potential in wound treatment, with positive effects on the amount of inflammatory infiltration, young collagen formation, and the degree of epidermalization. A key advantage of the current approach (i.e., using competitive radiation technology for synthesis) is that it includes only one step, with the product being sterilized as it is synthesized. The hydrogel effectively supports wound healing and can serve as a bio-based and biodegradable platform for other medical applications.
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Project description:Infection is the major reason that people die from burns; however, traditional medical dressings such as gauze cannot restrain bacterial growth and enhance the healing process. Herein, an organic- and inorganic-base hydrogel with antibacterial activities was designed and prepared to treat burn wounds. Oxidized dextran (ODex) and adipic dihydrazide grafted hyaluronic acid (HA-ADH) were prepared, mixed with quaternized chitosan (HACC) and silver nanoparticles to fabricate Ag@ODex/HA-ADH/HACC hydrogel. The hydrogel, composed of nature biomaterials, has a good cytocompatibility and biodegradability. Moreover, the hydrogel has an excellent antibacterial ability and presents fast healing for burn wounds compared with commercial Ag dressings. The Ag@ODex/HA-ADH/HACC hydrogel will be a promising wound dressing to repair burn wounds and will significantly decrease the possibility of bacterial infection.
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Project description:Neovascularization is a critical determinant of wound-healing outcomes for deep burn injuries. We hypothesize that dextran-based hydrogels can serve as instructive scaffolds to promote neovascularization and skin regeneration in third-degree burn wounds. Dextran hydrogels are soft and pliable, offering opportunities to improve the management of burn wound treatment. We first developed a procedure to treat burn wounds on mice with dextran hydrogels. In this procedure, we followed clinical practice of wound excision to remove full-thickness burned skin, and then covered the wound with the dextran hydrogel and a dressing layer. Our procedure allows the hydrogel to remain intact and securely in place during the entire healing period, thus offering opportunities to simplify the management of burn wound treatment. A 3-week comparative study indicated that dextran hydrogel promoted dermal regeneration with complete skin appendages. The hydrogel scaffold facilitated early inflammatory cell infiltration that led to its rapid degradation, promoting the infiltration of angiogenic cells into the healing wounds. Endothelial cells homed into the hydrogel scaffolds to enable neovascularization by day 7, resulting in an increased blood flow significantly greater than treated and untreated controls. By day 21, burn wounds treated with hydrogel developed a mature epithelial structure with hair follicles and sebaceous glands. After 5 weeks of treatment, the hydrogel scaffolds promoted new hair growth and epidermal morphology and thickness similar to normal mouse skin. Collectively, our evidence shows that customized dextran-based hydrogel alone, with no additional growth factors, cytokines, or cells, promoted remarkable neovascularization and skin regeneration and may lead to novel treatments for dermal wounds.
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Project description:BackgroundNonscar wound healing is a desirable treatment for cutaneous wounds worldwide. Peptide OH-CATH30 (OH30) from king cobra can selectively regulate the innate immunity and create an anti-inflammatory micro-environment which might benefit nonscar wound healing.PurposeTo overcome the enzymatic digestion and control release of OH30, OH30 encapsulated in carboxymethyl chitosan nanoparticles (CMCS-OH30 NP) were prepared and their effects on wound healing were evaluated.MethodsCMCS-OH30 NP were prepared by mild ionic gelation method and properties of the prepared CMCS-OH30 NP were determined by dynamic light scattering. Encapsulation efficiency, stability and release profile of OH30 from prepared CMCS-OH30 NP were determined by HPLC. Cytotoxicity, cell migration and cellular uptake of CMCS-OH30 NP were determined by conventional methods. The effects of prepared CMCS-OH30 NP on the wound healing was investigated by full-thickness excision animal models.ResultsThe release of encapsulated OH30 from prepared CMCS-OH30 NP was maintained for at least 24 h in a controlled manner. CMCSOH30 NP enhanced the cell migration but had no effects on the metabolism and proliferation of keratinocytes. In the full-thickness excision animal models, the CMCS-OH30 NP treatment significantly accelerated the wound healing compared with CMCS or OH30 administration alone. Histopathological examination suggested that CMCS-OH30 NP promoted wound healing by enhancing the granulation tissue formation through the re-epithelialized and neovascularized composition. CMCS-OH30 NP induced a steady anti-inflammatory cytokine IL10 expression but downregulated the expressions of several pro-inflammatory cytokines.ConclusionThe prepared biodegradable drug delivery system accelerates the healing and shows better prognosis because of the combined effects of OH30 released from the nanoparticles.
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Project description:Low availability of oxygen can lead to stalled wound healing processes and chronic wounds. To address local hypoxia and to better understand direct cellular benefits, a perfluorocarbon conjugated chitosan (MACF) hydrogel that delivers oxygen was created and applied for the first time to in vitro cultures of human dermal fibroblasts and human epidermal keratinocytes under both normoxic (21% O2) and hypoxic (1% O2) environments. Results revealed that local application of MACF provided 233.8 ± 9.9 mmHg oxygen partial pressure at 2 h and maintained equilibrium oxygen levels that were approximately 17 mmHg partial pressure greater than untreated controls. Cell culture experiments showed that MACF oxygenating gels improved cellular functions involved in wound healing such as cell metabolism, total DNA synthesis and cell migration under hypoxia in both fibroblasts and keratinocytes. Adenosine triphosphate (ATP) quantification also revealed that MACF treatments improved cellular ATP levels significantly over controls under both normoxia and hypoxia (p < 0.005). In total, these studies provide new data to indicate that supplying local oxygen via MACF hydrogels under hypoxic environments improves key wound healing cellular functions.
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Project description:At present, silk fibroin (SF) hydrogel can be prepared by means of electrodeposition at 25 V in direct current (DC) mode. Reducing the applied voltage would provide benefits, including lower fabrication costs, less risk of high voltage shocks, and better stability of devices. Here, a simple but uncommon strategy for SF-based hydrogel preparation using 4 V in DC mode is discussed. SF was mixed and cross-linked with carboxymethyl chitosan (CMCS) through hydrogen bonding, then co-deposited on the graphite electrode. The thickness, mass, and shape of the SF/CMCS hydrogel were easily controlled by adjusting the electrodeposition parameters. Morphological characterization of the prepared hydrogel via SEM revealed a porous network within the fabricated hydrogel. This structure was due to intermolecular hydrogen bonding between SF and CMCS, according to the results of thermogravimetric analysis and rheological measurements. As a potential wound dressing, SF/CMCS hydrogel maintained a suitable moisture environment for wound healing and demonstrated distinct properties in terms of promoting the proliferation of HEK-293 cells and antibacterial activity against Escherichia coli and Staphylococcus aureus. Furthermore, histological studies were conducted on a full-thickness skin wound in rats covered with the SF/CMCS hydrogel, with results indicating that this hydrogel can promote wound re-epithelization and enhance granulation tissue formation. These results illustrate the feasibility of using the developed strategy for SF-based hydrogel fabrication in practice for wound dressing.
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Project description:Improving the degree of vascularization through the regulation of wound microenvironment is crucial for wound repair. Gene activated matrix (GAM) technology provides a new approach for skin regeneration. It is a local gene delivery system that can not only maintain a moist environment, but also increase the concentration of local active factors. For this purpose, we fabricated the mVEGF165/TGF-β1 gene-loaded N-carboxymethyl chitosan/sodium alginate hydrogel and studied its effect on promoting deep second degree burn wound repair. The average diameter of the hydrogel pores was 100 μm and the porosity was calculated as 50.9%. SEM and CLSM images showed that the hydrogel was suitable for cell adhesion and growth. The NS-GAM could maintain continuous expression for at least 9 days in vitro, showing long-term gene release and expression effect. Deep second-degree burn wound model was made on the backs of Wistar rats to evaluate the healing effect. The wounds were healed by day 22 in NS-GAM group with the prolonged high expression of VEGF and TGF-β1 protein. A high degree of neovascularization and high expression level of CD34 were observed in NS-GAM group in 21 days. The histological results showed that NS-GAM had good tissue safety and could effectively promote epithelialization and collagen regeneration. These results indicated that the NS-GAM could be applied as a promising local gene delivery system for the repair of deep second-degree burn wounds.
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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.
| S-EPMC10213409 | biostudies-literature
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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