Hypericum Perforatum Callus Extract-Loaded Composite Hydrogel with Diverse Bioactivities for Enhanced Wound Healing and Fibrosis Prevention.

Plant Callus are a valuable source of pluripotent stem cells and bioactive phytochemicals. Meanwhile, the Hypericum perforatum callus extract (HPCE) is particularly rich in compounds such as hyperforin, hypericin, quercetin, and other phenolic and flavonoid derivatives. These phytochemicals exhibit strong antibacterial, antioxidant, anti-inflammatory, and anti-fibrotic properties, making them promising for wound healing. One of the most critical challenges following wound healing is the formation of fibrosis, which can compromise the complex structural integrity of skin. To address this issue, a poly(vinyl alcohol)/chitosan/alginate (PCA) wound dressing loaded with HPCE is developed. This hydrogel dressing features a porous structure with suitable mechanical properties and a high swelling capacity, potentially enhancing its effectiveness in promoting tissue regeneration and wound healing. In vitro studies have confirmed its biocompatibility, cell proliferation, and cell adhesion properties. Additionally, the dressing has demonstrated the ability to inhibit the proliferation of certain antibiotic-resistant bacteria. The in vivo studies revealed the anti-inflammatory properties, promotion of angiogenesis, facilitation of re-epithelialization, and stimulation of collagen deposition of the dressing under investigation. Moreover, the immunohistochemistry analysis of the two key markers, p16 and p53, has shown that the application of the dressing helps prevent fibrosis after wound healing.

The effects of bioactive glass hydrogel coated with hyaluronic acid-Pluronic F-127 conjugates containing silver nanoparticles for accelerating of infected wounds healing.

Antimicrobial resistance has forced researchers to produce new dressings for the treatment of infected wounds. Tissue engineering based on biomaterials is used to accelerate the wound healing process. The purpose of this study was to examine the effects of bioactive glass (BG) hydrogel coated with hyaluronic acid (HA)-Pluronic F-127 (PLF-127) conjugates containing silver nanoparticles (AgNPs) for healing the infected wounds. HA/BG, PL&HA/BG and PL&HA/BG-AgNPs formulations were designed and their properties were evaluated for application in the wound healing process. Safety and antibacterial properties of formulations were also evaluated. These were applied for the treatment of infected wounds and their efficiencies were assessed by measuring wound contraction, total bacterial count, pathological parameters and the expression of positive cells of cyclin-D1, c-Myc, WNT-1, B-Catenin, and COL-1A. The synthesized thermally reversible hydrogels demonstrated sol-gel transition, indicating the gels' potential as injectable hydrogels. These exhibited antibacterial properties and safety. The PL&HA/BG-AgNPs, PL&HA/BG and HA/BG hydrogels showed greatest wound healing activities, respectively and could compete with Polysporin® due to their effects on total bacterial count and modulation in increasing the expressions of B-Catenin, COL-1A, cyclin-D1 and c-Myc. In sum, PL&HA/BG-AgNP hydrogels are good candidate for accelerating the wound healing process and as alternatives for antibiotics in the treatment of infected wounds.

The navel nanoethosomal formulation of gamma-oryzanol attenuates testicular ischemia/reperfusion damages.

Testicular torsion reduces blood flow to testes and induces tissue ischemia. Antioxidant can have pivotal roles in alleviation of the effects of torsion/reperfusion. Gamma-oryzanol (γ-Oryzanol) has several pharmacological properties such as antioxidant and anti-apoptosis that can be used in this way. This study was conducted to evaluate the effects of nanoethosomal formulation of gamma-oryzanol (γ-Oryzanol-NEs) on testicular damages in a mouse model of ischemia/reperfusion damage. Following induction of ischemia/reperfusion, the mice were treated with γ-Oryzanol and γ-Oryzanol-NEs (6 mg/kg) in times of 3 h and 6 h. The expression of positive cells of TUNEL, superoxide dismutase (SOD), glutathione peroxidase (GPx), heat shock protein-70 (HSP70) and caspase 3 and histopathological parameters were assessed. The results showed higher expression of positive cells of TUNEL, HSP70 and caspase 3 and lower expressions of SOD and GPx in control mice compared with those treated with γ-Oryzanol-NEs (P = 0.001). The treatment with γ-Oryzanol-NEs could decrease pathological damages and the expression of positive cells of TUNEL, HSP70 and caspase 3 and increase the expressions of SOD and GPx. In conclusion, γ-Oryzanol-NEs could have the protective effects on torsion/reperfusion by decreasing apoptosis and increasing antioxidant status in a mouse model.

Facile synthesis of 2-hydroxy-ß-cyclodextrin/polyacrylamide/carbazole hydrogel and its application for the treatment of infected wounds in a murine model.

This work aimed to synthesize hydrogels by combining carbazole (Carb) with 2-hydroxy, ß-cyclodextrin (HPßCD)/polyacrylamide (PAA) hybrid complexes. The hydrogels were then evaluated for their potential use in treating infected wounds. The physicochemical structures of the preparations were evaluated using several characterization methods including FTIR, FESEM, EDX, XRD, pH sensitivity, and TGA. Moreover, In vitro release, toxicity, antibacterial activity and in vivo infected wound healing activity were evaluated. Physicochemical testing verified the effective synthesis of the preparations and the timely release of Carb. The P(AA-co-AM)/HPßCD material exhibited an open structure characterized by macroscopic voids, whereas the hydrogels displayed surfaces that were not uniform. The FTIR analysis revealed the creation of a novel polymeric hydrogel composed of HPßCD as the main polymer structure. The hydrogels exhibited good reversible swelling and recoverable deformation, with an optimal swelling ratio of 30.12 achieved at pH 7.4. The antibacterial and safety of the formulations were validated by in vitro studies. ß.Dex/PAA/Carb hydrogels have been shown to effectively expedite the healing of infected wounds by promoting the production of CD31, FGF-2, and COL1A, while reducing the levels of ROS, CD68, COX-2, and NF-κB. Overall, the combination of Carb, ß.Dex, and PAA molecules had a synergistic impact on the healing process of infected wounds.

Accelerative effects of alginate-chitosan/titanium oxide@geraniol nanosphere hydrogels on the healing process of wounds infected with Acinetobacter baumannii and Streptococcus pyogenes bacteria.

This study was conducted to evaluate the effects of alginate-chitosan/titanium oxide/geraniol (Alg-Csn/TiO2@GRL nanosphere) nanospheres hydrogels on the healing process of the wounds infected with Acinetobacter baumannii and Streptococcus pyogenes bacteria. The nanospheres were successfully synthesized and their physicochemical properties such as DLS, FTIR, FE-SEM, TEM, XRD and also their safety and in-vitro antibacterial activity were assessed and confirmed. Following induction of the infected wounds, the mice were treated with s base ointment (Control), mupirocin® as standard control group and also hydrogels prepared from Alg-Csn@GRL, Alg-Csn/TiO2 and Alg-Csn/TiO2@GRL. Wound contraction, total bacterial count, expression of bFGF, VEGF, IGF-1, CD68 and COL-1 A, iNOS and eNOS were measured. The results showed the treatment of wounds with Alg-Csn/TiO2@GRL hydrogels significantly accelerated wound contraction, decreased total bacterial count and reduced the expressions of CD68, iNOS and eNOS and increased the expressions of VEGF, bFGF, IGF-1 and COL-1 A compared with other groups. It can be concluded that Alg-Csn/TiO2@GRL hydrogels expedite the wound healing process by their effects on bacteria and subsequently inflammation and increasing the expression of proliferative genes. The Alg-Csn/TiO2@GRL hydrogel can be utilized in combination with other agents for the treatment of infected wounds after future clinical studies.

Fabrication of geraniol nanophytosomes loaded into polyvinyl alcohol: A new product for the treatment of wounds infected with methicillin-resistant Staphylococcusaureus.

The current study was conducted to evaluate the effectiveness of geraniol nanophytosomes in accelerating the healing process of wounds infected with Methicillin-resistant Staphylococcus aureus (MRSA) in a mouse model. The physicochemical properties confirmed physical properties and successful synthesis of the nanophytosomes. Wounds were induced and mice (n = 90) were treated with a base ointment (negative control group) and/or mupirocin (positive control) and also formulations prepared from geraniol (GNL), geraniol nanophytosomes (NPhs-GNL), and PVA/NPhs-GNL. Wound contraction, total bacterial count, pathological parameters and the expressions of bFGF, CD31 and COL1A were also assessed. The results showed that topical administration of mupirocin and PVA/NPhs/GNL increased wound contraction, fibroblast and epithelization and also the expressions of bFGF, CD31 and COL1A while decreased the expression of total bacterial count and edema compared with negative control mice (P = 0.001). The results also showed that PVA/NPhs-GNL and mupirocin could compete and PVA/NPhs-GNL formulation was safe. In conclusion, the prepared formulations accelerated the wound healing process by modulation in proliferative genes. Geraniol nanophytosomes loaded into PVA could improve the healing in infected full-thickness wounds healing process and can be used for the treatment of infected wounds after future clinical studies.

Wound Healing: A Brief Look at the Inflammatory Stage and Role of Medicinal Plants and Their Derivations on Modulating the Inflammatory Responses: A Systematic Review.

Aims: Wound is believed to be a major disorder in certain organs and/or tissues, which could be transmitted to other tissues. Skin is constantly exposed to infections, injuries, scratches, and burns. Wound dressings are commonly utilized for the treatment of wound site and protect it from external contamination. The biological importance of natural agents, such as herbal medicines and their derivations including extracts, essential oils and active compounds in the wound healing process has attracted the attention of researchers and also some manufacturers of wound dressings. Such natural agents improve wound healing by their antioxidant and antibacterial properties. This novel review article was conducted to evaluate the effects of medicinal plants and their derivations on inflammatory responses in surgical wound infection. Methods: The data were collected from various databases using specific keywords. Results: The results revealed that different medicinal plants and their derivations decrease the inflammation in the wound healing process by modulating in gene expression of inflammatory cytokines and immune cells. Conclusion: Active compounds of medicinal plants can alleviate inflammation in the wound healing process, which must be taken into consideration in pharmaceutical industries.

Facile fabrication of carboxymethylcellulose/ZnO/g-C3N4 containing nutmeg extract with photocatalytic performance for infected wound healing.

New topical antibacterial agents are required to inhibit and development of bacteria and also promoting the wound healing process. This study was evaluating the healing effect of Myristica fragrans extract coated with carboxymethyl cellulose, zinc oxide and graphite carbon nitride (CMC/ZnO/g-C3N4/MyR) by photocatalytic process on the healing process of full-thickness infectious excision wounds in mice. Nanosheets were prepared and physicochemical properties were evaluated. Safety, in vitro release, antibacterial activities under in vitro and in vivo condition, wound contraction, histopathological properties and the protein expressions of tumor necrosis factor-α (TNF-α), collagen 1A (COL1A) and CD31 were also evaluated. Physicochemical properties confirmed their successful synthesis. Nanosheets exhibited antibacterial activity under in vitro and in vivo conditions. The formulations containing CMC/ZnO/g-C3N4/MyR, significantly (P < 0.05) competed with standard ointment of mupirocin for accelerating the wound healing process due to their effects on bacterial count and the expression of TNF-α and also accelerating the proliferative phase. This structure can be used as a safe structure in combination with other agents for accelerating the wound healing process following future clinical studies.

Carboxymethyl chitosan-gelatin-mesoporous silica nanoparticles containing Myrtus communis L. extract as a novel transparent film wound dressing.

Wound healing and health care requirements have attracted more attention, and the need to develop new drug-containing dressings to accelerate wound healing is required. Carboxymethyl chitosan (CMCS)/gelatin-based films with mesoporous silica nanoparticles (MSNs) containing the Myrtus communis L. (Myrtle) aqueous extract were designed to answer this demand. Myrtle aqueous extract included total phenolic content and good free radical scavenging ability in vitro assay. The infrared spectroscopy characterized the functional groups of myrtle extract and biocomposite films. It was found that mesoporous silica nanoparticles increased the tensile strength of the flexible dressings, which is essential in therapeutic uses. MSNs influenced swelling ratio, oxygen, and water vapor permeability that indicates the CMCS/Gelatin/Myrtle/5 % MSNs wound dressing can absorb wound exudates and preserve skin moisture. Also, these biocompatible nanoparticles reduced the cytotoxicity of fibroblast cells due to the decelerated drug release. Correspondingly, silica nanoparticles affected the extract release rate and could accumulate and release the extract prolonged in CMCS/Gelatin/Myrtle/5 % MSNs models. Finally, histological analysis showed collagen growth and fibroblast migration in wounds treated with CMCS/Gelatin/Myrtle/5 % MSNs, causing proper wound contraction and accelerating wound healing in mice models. The results suggest that CMCS/Gelatin/Myrtle/5 % MSNs films have a beneficial application as wound dressings.

Effectiveness of topical administration of platelet-rich plasma on the healing of methicillin-resistant Staphylococcus aureus-infected full-thickness wound model.

This study aimed to investigate the wound-healing activity of animal platelet-rich plasma (PRP) in wounds infected with methicillin-resistant Staphylococcus aureus (MRSA) in rats. After wound induction, the rats were divided into three groups: noninfected animals treated with PRP (PRP group), MRSA-infected animals treated with mupirocin (standard control group), and MRSA-infected animals treated with PRP (MRSA+PRP group). Scratch assays, MTT test, and live/dead cells were also investigated. Total bacterial count, parameters of wound area, histopathological assessment, and expressions of IL-1ß, TNF-α, iNOS, PDGF, FGF-2, and TGF-ß mRNA levels and immunofluorescent staining of CD31 and collagen type 1 were assessed. The results showed that culture with PRP increased migration. PRP only showed cytotoxicity in a concentration of 100%. Topical application of PRP (50 µL) reduced the wound area and total bacterial count compared with the control group (P<0.05). The mRNA levels of IL-1ß, TNF-α, and iNOS expression on days 7 and 14 (P<0.05) decreased in the treated groups compared with control rats. The mRNA levels of PDGF and TGF-ß expression (P<0.05) increased in the treatment groups compared with control rats on days 3 and 7 (P<0.05). FGF-2 expression was significantly higher in the treated groups compared with the control group on days 7 and 14 (P<0.05). Moreover, positive expressions of macrophage colony-stimulating factor (M-CSF), CD31, collagen type 1 and cytokeratin proteins keratinocyte proliferation, and re-epithelization were significantly (P<0.05) increased in both PRP and MRSA+PRP-treated groups compared with the control groups on days 7 and 14. Topical administration of PRP accelerated the wound healing in MRSA-infected wound by decreasing the inflammation and improving the proliferative phase.

Acceleration in healing of infected full-thickness wound with novel antibacterial γ-AlOOH-based nanocomposites.

This study was conducted to synthesize γ-AlOOH (bohemite)-based nanocomposites (NCs) of Au/γ-AlOOH-NC and its functionalized derivative using chitosan (Au/γ-AlOOH/Ctn-NC) and with the help of one-step Mentha piperita. The physicochemical characteristics of the NCs were investigated. In addition, biomedical properties, such as antibacterial activity under in vitro and in vivo conditions, and cell viability were assessed. Wound healing activity on infected wounds and histological parameters were assessed. The gene expressions of TNF-α, Capase 3, Bcl-2, Cyclin-D1 and FGF-2 were investigated. The TEM and FESEM images showed the sheet-like structure for bohemite in Au/γ-AlOOH-NC with Au nanoparticles in a range of 14-15 nm. The elemental analysis revealed the presence of carbon, oxygen, aluminum, and Au elements in the as-synthesized Au/γ-AlOOH. The results for toxicity showed that the produced nanocomposites did not show any cytotoxicity. Biomedical studies confirmed that Au/γ-AlOOH-NC and Au/γ-AlOOH/Ctn-NC have anti-bacterial properties and could expedite the wound healing process in infected wounds by an increase in collagen biosynthesis. The administration of ointment containing Au/γ-AlOOH-NC and Au/γ-AlOOH/Ctn-NC decreased the expressions of TNF-α, and increased the expressions of Capase 3, Bcl-2, Cyclin-D1 and FGF-2. The novelty of this study was that bohemite and Au nanoparticles can be used as a dressing to accelerate the wound healing process. In green synthesis of Au/γ-AlOOH-NC, phytochemical compounds of the plant extract are appropriate reagents for stabilization and the production of Au/γ-AlOOH-NC. Therefore, the new bohemite-based NCs can be considered as candidate for treatment of infected wounds after future clinical studies.

Accelerative effect of nanohydrogels based on chitosan/ZnO incorporated with citral to heal the infected full-thickness wounds; an experimental study.

Antimicrobial-resistant is a major challenge in to treat infected wounds, and new formulations should be produced. Citral (Citl), chitosan (Chsn), and zinc oxide (ZnO) nanoparticles may accelerate the wound healing process in terms of their antibacterial properties. This new study aimed to investigate the effects of ointments produced from ZnO/Chsn/Citl nanoparticles (NPs) to treat the infected wounds. Following the preparation of ZnO/Chsn/Citl-NPs, swelling behavior, the release of citral, toxicity, and antibacterial properties were evaluated. Base ointment, mupirocin, and ointments made from Chsn-NPs, Chsn/Citl-NPs, and ZnO/Chsn/Citl-NPs were used to treat the mice. The ointments' effects on wound contraction, total bacterial count, and immunofluorescence staining for TNF-α, TGF-ß, and bFGF were tested. The synthesis of ZnO/Chsn/Citl-NPs was validated by XRD, FT-IR, DLS, and TEM findings. In higher dilutions, chitosan/citral and ZnO/Chsn/Citl-NPs indicated better antibacterial activity. Nanoparticles were safe up to concentration of the 0.5 mg/mL. The mice in Chsn/Citl and ZnO/Chsn/Citl-NPs treated groups showed higher (P < 0.05) wound contraction ratio and expressions for bFGF, and lower total bacterial count and expressions for TGF-ß and TNF-α compared to control mice. Ointments prepared from ZnO/Chsn/Citl-NPs could compete with the commercial ointment of mupirocin and can be used to treat infected wounds after clinical studies.

Biofabrication of ZnO/Malachite nanocomposite and its coating with chitosan to heal infectious wounds.

Recently, nanocomposites produced from clays and metals coated with chitosan have shown wound healing activity. This study aimed to synthesize the zinc oxide/malachite nanocomposite (ZnO/Mlt-NC) and its coating form with chitosan (ZnO/Mlt/Chsn-NC). Physicochemical characterization of the produced nanocomposites was investigated. Biomedical effects of nanocomposites, such as in vivo and in vitro antibacterial activity, antioxidant properties, cytotoxicity, and modulation in the gene expressions of interleukin-1ß (IL-1ß), interleukin-6 (IL-6), interleukin-10 (IL-10), and transforming growth factor-ß (TGF-ß) and histopathological parameters, were also investigated. Expression intensities of basic fibroblast growth factor (bFGF) and tumor necrosis factor alpha (TNF-α) were also investigated by immunofluorescence staining. To investigate biomedical effects under in vivo conditions, infected wounds were induced and inoculated with Staphylococcus aureus (ATCC 25923), and Pseudomonas aeruginosa (ATCC 27853). The results indicated spherical ZnO nanoparticles on the surface of malachite and strong antibacterial activity and antioxidant properties. The ointments produced from the nanocomposites also exhibited wound healing activity. The administration of the ointments prepared from ZnO/Mlt, and ZnO/Mlt/Chsn NCs decreased the expressions of IL-1ß, IL-6, and TNF-α, while it increased the expressions of IL-10, TGF-ß and bFGF. In sum, the nanocomposites produced from ZnO, malachite, and chitosan had better biological activity than ZnO/Malachite nanocomposites. We suggest applying ZnO/Mlt/Chsn nanocomposites in the structure of ointments to treat infected wounds after future clinical studies.

Accelerated wound healing and its promoting effects of topical codeine on the healing of full-thickness cutaneous wound, evidences for modulating cytokines involved in pain, inflammation and collagen biosynthesis.

INTRODUCTION: The inflammation and pain occur in all the wounds. Opioids drugs decrease pain and may act as an anti-inflammation. The current study was conducted to investigate the efficiency of the topical uses of Codeine on full-thickness excision wound models by focusing on relationship between pain mediators, inflammation and wound healing rate. METHODS: Following the induction of anesthesia, a skin wound with a size of 7-mm punch was induced on the dorsal surfaces of each mouse. The mice were divided into five categories: groups I-III were daily administered 2.5%, 5%, and 10% Codeine gel; those in group IV were administered phenytoin cream, and group V (controls) received base ointment. To assess the effects of Codeine gel on the wound healing process, the wound area, histological parameters, and the relative protein expression of CXCR1, CXCR2, IL-6, IL-6R, PDGF, PDGFR, and COL1A along with the plasma concentrations of IL-1ß, IL-10, and TNF-α were investigated on days 3, 7, and 14. RESULTS: On days 7 and 14, the wound area was significantly lower in the treated mice compared to the controls (P < 0.05). Angiogenesis, collagen deposition, and epithelium thickness were significantly higher in the treatment groups compared to the control group (P < 0.05). The relative protein expressions of CXCR1, CXCR2, IL-6, and IL-6R and the plasma concentrations of IL-1ß and TNF-α were significantly lower in the treated groups. Meanwhile, the relative protein expressions of PDGF, PDGFR, and COL1A and the plasma concentration of IL-10 were significantly higher in the treated mice (P < 0.05). CONCLUSION: Administration of Codeine gel accelerated wound healing through decreasing the pain mediators, inflammation and promoting proliferative phase.

Effectiveness of Gamma Oryzanol on prevention of surgical induced endometriosis development in rat model.

Infertility is believed to be triggered by endometriosis whose pathophysiology and the etiology is still unknown. Certain genes play pivotal roles in pathogenesis of endometriosis. Natural products and plants are used as important sources for production of new drugs. The current study assesses the effects of gamma-oryzanol (GO) in a rat model with surgically induced endometriosis. The experimental endometriosis was induced in 24 wistar rats, and the animals were subsequently subdivided into endometriosis-sole (endom group), 3000 and 6000 µg/kg GO (GO-3000 and GO-6000) and Vit C groups. The protein levels of estrogen receptor-alpha (ER-α), Steroidogenic factor 1 (SF1), Sirtuin 1 (SIRT1), heme oxygenase 1 (HO1), light chain 3 (LC3B) and Beclin1 (BECN1) were assessed. TUNEL staining was used for detecting the apoptosis rate. The results revealed that protein levels of SF1, HO1, and total LC3B significantly (P < 0.05) decreased in GO-6000-treated groups compared to endom group. Moreover, the protein level of BECN1 and SIRT-1 significantly (P < 0.05) increased in GO-6000-treated groups compared to endom group. GO treatment did not imply any significant difference (P > 0.05) concerning the protein levels of ER-α. The TUNEL staining results showed higher TUNEL-positive cells reactions in the rats treated with GO-6000 and Vit C. Thus, GO is involved in improving condition rats involved with endometriosis through modulation in the protein levels of some molecules and also induction of apoptosis.

Comparison effects of platelet-rich plasma on healing of infected and non-infected excision wounds by the modulation of the expression of inflammatory mediators: experimental research.

INTRODUCTION: Microbial invasion in soft tissue is believed to cause infectious wounds and increase healthcare costs, anxiety, and distress. The current study was conducted to evaluate the effects of topical use of platelet-rich plasma (PRP) on infected wound-healing process in rats. METHODS: Following the induction of a circular wound, the animals were divided into three groups, including (1) standard control: infected wounds treated with mupirocin (SDCL), (2) non-infected wounds treated with PRP (PRP), and (3) infected group in which the rats were infected with Staphylococcus epidermidis and Pseudomonas aeruginosa and treated with PRP (INF + PRP). To evaluate the effects of PRP on the wound-healing rate, total bacterial count, histopathological assessment, the serum concentrations of sialic acid, C-reactive protein, haptoglobin, and fibrinogen were assessed. Additionally, IL-1ß, IL-6, TNF-α, IL-3, NF-κB, iNOS, PDGF, and EGF mRNA level expressions were assessed employing the qRT-PCR method. RESULTS: The results indicated that topical application of PRP could significantly decrease total bacterial count, the level of C-reactive protein, and pro-inflammatory cytokines (IL-1ß, IL-6, and TNF-α) compared to the SDCL group. The administration of PRP also promoted re-epithelization rate by increasing the expression of EGF mRNA level. CONCLUSION: We could recommend the use of PRP for the treatment of infected wounds owing to its efficiency in decreasing colonization of tissue bacteria, tissue inflammation, and stimulating wound heal-up.

Topical Administration of an Ointment Prepared From Satureja sahendica Essential Oil Accelerated Infected Full-Thickness Wound Healing by Modulating Inflammatory Response in a Mouse Model.

INTRODUCTION: Satureja sahendica has antibacterial and anti-inflammatory properties that can have beneficial effects for decreasing inflammation in infected wounds. OBJECTIVE: This study was conducted to evaluate the effects of an ointment prepared from S sahendica essential oil (SSO) on an infected wound model in BALB/c mice. MATERIALS AND METHODS: One full-thickness excisional skin wound was surgically created per animal and inoculated with 5 × 107 colony-forming units of Pseudomonas aeruginosa and Staphylococcus aureus. Following induction of the wound, the mice (N = 90) were treated with soft yellow paraffin (negative control, n = 18), mupirocin (positive control, n = 18) and 1%, 2%, and 4% SSO (n = 18 in each of the 3 groups). To determine the effect of the treatments on healing of an infected wound, the following factors were assessed: rate of the wound area, tissue bacterial count, histopathology, collagen biosynthesis, immunohistochemistry, and the expressions of insulin-like growth factor (IGF)-1, fibroblast growth factor (FGF)-2, vascular endothelial growth factor (VEGF), interleukin (IL)-1ß, IL-4, transforming growth factor beta (TGF-ß), and chemokine (CXC motif) ligand 1 (CXCL-1) on days 3, 7, and 14 after induction of the wound. RESULTS: Topical administration of SSO shortened the inflammatory phase, accelerated cellular proliferation, and increased fibroblast distribution per 1 mm2, collagen deposition, and rapid reepithelialization in comparison with control animals (P <.05). The messenger RNA levels of IGF-1, IL-10, FGF-2, VEGF, TGF-ß1, and CXCL-1 were remarkably increased, and IL-1ß level decreased (P <.05) in the treated animals compared with the control group (P <.05). The immunohistochemical analyses showed topical administration of SSO increased collagen biosynthesis in the treated group (P <.05). CONCLUSIONS: Topical administration of SSO shows evidence of accelerating wound healing by upregulating the expression of IGF-1, IL-10, FGF-2, VEGF, TGF-ß, and CXCL-1; shortening the inflammatory stage; and promoting the proliferative phase.

Biological fabrication and electrostatic attractions of new layered silver/talc nanocomposite using Lawsonia inermis L. and its chitosan-capped inorganic/organic hybrid: Investigation on acceleration of Staphylococcus aureus and Pseudomonas aeruginosa infected wound healing.

In the present study, new-layered inorganic/organic hybrid of silver/talc nanocomposites (Ag/Tlc-NPs) and its chitosan-capped derivative (Ag/Tlc/Csn NCs) were biochemically synthesized utilizing Lawsonia inermis L. extract. The silver nanoparticles (Ag NPs) were synthesized employing green method on the exterior surface layer of talc mineral as a solid substrate. The negatively charged surface layer of talc might function as templates and can attract the chitosan cations from a solution to yield a layered hybrid structure, whose inorganic phase is formed by Si-O-Ag bonds. Our results revealed that Ag NPs were formed on the exterior surface of talc with a diameter with size of 124-215 nm. In addition, cytotoxicity, in vitro antibacterial activity, and clinical effects of wound-healing ointments containing talc were investigated. The results implied the successful synthesis of Ag/Tlc/Csn NCs using the extract. The structures were safe up to 0.50 mg/mL. In vitro studies confirmed antioxidant and antibacterial properties of Ag/Tlc/Csn NCs. In sum, our findings showed that the ointments improve wound healing process by inducing an anti-inflammatory M2 phenotype and bFGF, CD206, collagen1A, and IL-10 production that causes fibroblast migration and wound closure through influencing M2 macrophage. Ag/Tlc/Csn is suggested to be taken into consideration as a medical combination for improving infected wound healing and as a promising agent for clinical administration.

Quercus infectoria gall extract aids wound healing in a streptozocin-induced diabetic mouse model.

OBJECTIVE: Quercus infectoria galls have commonly been used for different therapeutic purposes. This study was conducted to investigate the effects of topical application of an ointment prepared from Quercus infectoria gall hydroethanolic extract on open wound healing in a streptozocin-induced diabetic BALB/c mouse model. METHOD: After induction of diabetes, two circular wounds (5mm) were created on the dorsum of the mice which were then divided into three groups. The mice were treated with soft yellow paraffin (control-sham group) and therapeutic doses of 5% and 10% of an ointment prepared from Quercus infectoria, respectively. To evaluate the effects of the therapeutic ointment on the wound healing process, wound area, histological parameters, mRNA levels of vascular endothelial growth factor (VEGF), Bcl-2 and p53, plasma levels of interleukin-6 (IL-6) and tumour necrosis factor (TNF)-α, and tissue antioxidant capacity were investigated. RESULTS: The mice (n=54) were divided into three equal groups. Wound area and concentrations of IL-6 and TNF-α were significantly decreased in both ointment-treated groups compared to the control group (p<0.05). Moreover, angiogenesis, fibroblast distribution per mm2 of wound tissue, collagen deposition, rapid re-epithelialisation, and the expression of VEGF, Bcl-2 and p53 mRNA, were significantly increased (p<0.05). The administration of the ointment reduced malondialdehyde concentration and increased total antioxidant capacity compared with the control group (p<0.05). CONCLUSION: Our study suggests that an ointment prepared from Quercus infectoria gall hydroethanolic extract accelerated open wound healing in a diabetic animal model by shortening the inflammatory phase, inducing apoptosis, up-regulating the expression of Bcl-2 and p53 mRNA, antioxidant properties and cellular proliferation.

Effectiveness of Green Synthesis of Silver/Kaolinite Nanocomposite Using Quercus infectoria Galls Aqueous Extract and Its Chitosan-Capped Derivative on the Healing of Infected Wound.

Kaolinite nanocomposites (NCs) could be utilized as agents for wound healing owing to their efficiency and low toxicity. The present study was conducted to synthesize a novel silver/kaolinite NCs (Ag/Kaol NCs) and investigate their chitosan derivation (Ag/Kaol/Chit NCs) using oak extract. XRD, SEM, EDX, FT-IR, and DLS were employed for the investigation of structural and physio-chemical properties of the synthesized NCs. The obtained results revealed that synthesized Ag/Kaol NCs were mesoporous and spherical with sizes ranging from 7-11 nm. They also demonstrated successful synthesis between silver and kaolinite using the extract. Cytotoxicity and in vitro antibacterial activity were also investigated. The clinical effects of ointments containing the NCs for improving wound healing were studied on the wound area, total bacterial count, histological parameters, and protein expression of some genes. Nanocomposites were safe up to 0.50 mg/mL. The results of in vivo and in vitro antibacterial activity showed that Ag/Kaol NCs, were of antibacterial activity ( ). The results of antioxidant activity indicated that Ag/Kaol NCs have antioxidant structures. Our findings concerning molecular mechanism implied that Ag/Kaol/Chit increased the expression of Wnt/ ß -catenin and collagen ( ). In sum, Ag/Kaol/Chit showed antibacterial activity and improved wound healing by decreasing the inflammation and promoting the proliferative phase. The novel NCs showed wound healing properties by decreasing inflammation and total bacterial count and increasing proliferative phase. The application of Ag/Kaol/Chit was suggested as a green agent for improving infected wound healing.