Healing Of Infected Skin Wounds Research Articles

A Hydrogel Dressing Comprised of Silk Fibroin, Ag Nanoparticles, and Reduced Graphene Oxide for NIR Photothermal-Enhanced Antibacterial Efficiency and Skin Regeneration.

Bacterial infection, inflammation, and excessive oxidative stress are the primary factors that contribute to delayed healing of skin wounds. In this study, a multifunctional wound dressing (SF/Ag@rGO hydrogel) is developed to promote the healing of infected skin wounds by combining the inherent antibacterial activity of Ag nanoparticles (NPs) with near-infrared (NIR)-assisted antibacterial therapy. Initially, L-ascorbic acid is used as a reducing agent and PVP-K17 as a stabilizer and dispersant, this facilitates the synthesis of reduced graphene oxide loaded with Ag NPs (Ag@rGO). Ag@rGO is then blended with a silk fibroin (SF) solution to form an instantly gelling SF/Ag@rGO hydrogel that exhibits rapid self-healing, injectability, shape adaptability, NIR responsiveness, antioxidant, high tissue adhesion, and robust mechanical properties. In vitro and in vivo experiments show that the SF/Ag@rGO hydrogel demonstrates strong antioxidant and photothermal antibacterial capabilities, promoting wound healing through angiogenesis, stimulating collagen generation, alleviating inflammation, antioxidant, and promoting cell proliferation, indicating that the SF/Ag@rGO hydrogel dressing is an ideal candidate for clinical treatment of full-thickness bacterial-stained wounds.

Enhancing Infected Wound Healing Through Scavenging Reactive Oxygen Species Using Synergetic Composites of Sub‐Nanoscale TiO2 with DNA

AbstractOxidative stress (OS) resulting from excessive reactive oxygen species (ROS) is the initial pathogenesis of many diseases, thus various pharmaceutical materials are explored to scavenge ROS. However, the medical applications of most ROS‐scavenging materials are limited due to side effects and low bio‐stability. DNA has emerged as a promising ROS‐scavenging material with excellent biosafety and programmability, but the efficiency needs to be improved by developing new fabrication methods. Here, a sub‐nanoscale TiO2 composite modified with DNA with excellent biostability, biocompatibility, and enhanced ROS‐scavenging efficiency for medical applications is presented. The sub‐nanoscale TiO2‐DNA (SNTD) composite exhibits higher scavenging capacities for multiple ROS including ·OH, H2O2, and O2•−. Additionally, it can regulate macrophages from pro‐inflammatory to anti‐inflammatory phenotype. In vivo experiments show that the nanocomposites reduce ROS concentration, decrease inflammatory cell infiltration, accelerate re‐epithelization, and promote collagen regeneration, thereby enhancing the healing of infected skin wounds.

Natural self-healing injectable hydrogels loaded with exosomes and berberine for infected wound healing

Complete and rapid healing of infected skin wounds remains a challenge in current clinical treatment. In this study, we prepared a self-healing injectable CK hydrogel by crosslinking two natural polysaccharides, carboxymethyl chitosan and oxidized konjac glucomannan, based on the Schiff base bond. To enhance the biological function of the hydrogel, we multi-functionalized hydrogen by loading it with berberine (BBR) and stem cell-derived exosomes (Exo), forming a composite hydrogel, CK@BBR&Exo, which could be injected directly into the wound through a needle and adhered to the wound. Furthermore, the self-healing properties of CK@BBR&Exo increased its usefulness and service life. Additionally, the drug-loaded CK@BBR&Exo hydrogel was versatile, inhibiting bacterial growth, regulating the inflammatory response, and promoting neovascularization in infected skin wounds, thus achieving the rapid healing of infected skin wounds. These results suggest that the CK@BBR&Exo-injectable self-healing hydrogel is an ideal dressing for treating infected skin wounds.

Dietary nitrate accelerates the healing of infected skin wounds in mice by increasing microvascular density

As skin injuries resulting from acute trauma, burns, and chronic diseases present significant challenges to healthcare systems worldwide, the promotion of skin wound healing remains an unmet therapeutic area. Dietary nitrate serves as a crucial pathway for the production of nitric oxide, which plays various physiological roles in the body, including vasodilation, increased blood flow, and antioxidant activity. However, the impact of dietary nitrate on skin wound healing remains uncertain. This study aimed to investigate the role of dietary nitrate in infected skin wound healing using a mouse model. We created a full-thickness wound infection model in mice and examine the effects of dietary nitrate (0.5 mmol/kg/d and 1 mmol/kg/d) on wound healing. The results demonstrated that dietary nitrate significantly increased serum nitrate and nitrite levels, leading to accelerated wound healing by increasing microvascular density, promoting collagen deposition and re-epithelialization. Moreover, nitrate supplementation exhibited a certain degree of reduction in inflammatory factors within the body. Our study also found that 1 mmol/kg/d nitrate has a more effective therapeutic effect and can increase blood perfusion and expedite the formation of new blood vessels, thereby promoting skin wound healing. These results indicate that dietary nitrate presents a novel therapeutic approach for infected skin wound healing.

Bioinspired multifunctional injectable hydrogel for hemostasis and infected wound management.

Routine wound management faces significant challenges including rebleeding and bacterial infection that affect millions of people each year. However, conventional wound dressings (e.g., gauze, bandage) are limited to simply cover the injured surfaces and rarely show special functionality to promote the wound recovery. Currently, injectable hydrogels have been widely designed as multifunctional wound dressings to manage the hemostatic and wound healing process. Nevertheless, the integration of multiple functions through simple composition and easy construction is still difficult and hardly achieved. Herein, we reported a bioinspired multifunctional injectable hydrogel (CQCS@gel) consisted of only two components, catechol-functionalized quaternized chitosan (CQCS) and dibenzaldehyde-terminated poly(ethylene glycol) (DB-PEG2000). The building blocks endowed CQCS@gel with tissue-adhesive, antibacterial, antioxidant, self-healing and pH-responsive properties. Based on the in vivo hemostatic study, quick hemostasis for acute tissue injuries such as liver and carotid wounds was realized owing to the rapid gelation rate and strong tissue-adhesiveness of CQCS@gel. Moreover, CQCS@gel remarkably boosted the chronic recovery process of MRSA-infected cutaneous wounds by promoting collagen deposition, hair follicles regeneration and angiogenesis. Overall, this multifunctional injectable hydrogel shows potentials as a universal wound dressing in clinical applications, enabling both hemostasis and infected wound management. STATEMENT OF SIGNIFICANCE: This is the first report showing the multifunctional injectable hydrogel (CQCS@gel) consisted of catechol-functionalized quaternized chitosan and dibenzaldehyde-terminated poly(ethylene glycol). The incorporation of quaternary ammonium groups imparted the CQCS@gel with outstanding contact-active bacterial killing efficiency and the catechol moieties enhanced its tissue adhesive and antioxidant properties. Moreover, the reversible imine crosslinks endowed the CQCS@gel with self-healing and pH-responsive drug release capabilities. These multiple functions were integrated into a single injectable hydrogel system with easy availability and low cost. In vitro and in vivo results showed that the newly designed hydrogel was biocompatible, realized successful sealing hemostasis under multiple bleeding scenarios and enabled accelerated healing of infected skin wounds.

Glucose Oxidase-Integrated Metal-Polyphenolic Network as a Microenvironment-Activated Cascade Nanozyme for Hyperglycemic Wound Disinfection.

The high systemic blood glucose concentration of hyperglycemic wound microenvironment (WME) severely impedes the disinfection and healing of infected skin wounds. Herein, a WME-activated smart natural product, integrated GOx-GA-Fe nanozyme (GGFzyme), is engineered, which combines a nanozyme and natural enzyme to promote reactive oxygen species (ROS) generation in situ for hyperglycemic wound disinfection. GGFzyme can consume a high concentration of glucose in hyperglycemia wounds and generate H2O2. The conversion of glucose into gluconic acid not avails starvation treatment but reduces the pH of WME to elevate the catalytic activities of both the nanozyme (GA-Fe) and natural enzyme (GOx). And H2O2 is then high efficiently catalyzed into •OH and O2•- in situ to combat pathogenic bacteria and promote wound disinfection. The high catalytic antibacterial capacity and superior biosafety, combined with beneficial WME modulation, demonstrate that GGFzyme is a promising therapeutic agent for hyperglycemic wounds.

Effect of platelet-rich fibrin (PRF) membranes on the healing of infected skin wounds.

Tissue engineering focuses on wound healing and tissue regeneration. Platelet-rich fibrin (PRF) is a fibrin matrix containing cytokines, growth factors and cells that are gradually released into the wound over time. This study aimed to evaluate the effect of PRF membranes on wound repair and microbial control in infected wounds. Skin wounds were performed on the dorsum of rats using a 6mm diameter metal punch. The defects were randomly assigned into four groups (n = 12/each) accordingly to the treatment: G1, noninfected wound filled only with clot; G2, noninfected wound with PRF; G3, infected wound (S. aureus) without PRF; G4, infected wound (S. aureus) with PRF. After 7 and 14days, macroscopic and histological analyses of the wounds were performed. Furthermore, the quantification of β-defensin in PRF was measured by ELISA. At 14days, the groups with PRF (G2 and G4) had wound sizes significantly smaller than the original defects (6mm) (p < 0.05) and significantly smaller than those not treated with PRF, in both the infected and noninfected groups (p < 0.05). Furthermore, the groups with infected wounds (G3 and G4) demonstrated a significantly lower inflammation score in the PRF group than in the noninfected groups (p < 0.05). In vitro analysis of β-defensin was performed in all PRF membrane groups, and the median value was 1.444pg/mL. PRF in the wounds of both control and infected rats played an important role in the modulation of tissue healing, most notably in infected sites.

Регенеративные эффекты пептидов Gly-His-Lys и Gly-His-Lys-D-Ala при кожной инфицированной ране

Skin wound healing mechanisms and new ways of improving their efficiency represent an important focus in medicine. In this regard, regulatory peptides, which exhibit physiological polyfunctionality and modulate cell growth and differentiation, are of special interest. This study evaluates the effects of Gly-His-Lys (GHK) and Gly-His-Lys-D-Ala (GHK-D-Ala) peptides in the infected skin wound healing. The wounds were modeled in rats (n=150) by full-thickness dorsal skin defects. The peptides were administered intracutaneously at daily doses of 0.5 or 1.5 µg/kg. The healing was assessed on days 3, 7, and 10 by histomorphometric examination of the wounds with adjacent intact skin. GHK-D-Ala administered at daily doses of 0.5 µg/kg had pronounced positive effect on regeneration processes in the wound, as indicated by significantly reduced numbers of granulocytes and lymphocytes with increased representation of fibroblastic lineages and macrophages, and the resulting higher cellular index (p &lt; 0.05–0.001). At higher doses of GHK-D-Ala (1.5 µg/kg), the beneficial effects were less pronounced. According to the comparative morphological examination, the highest positive effect was achieved with 0.5 µg/kg of GHK-D-Ala. Thus, local administration of the GHK peptide with extra D-alanine at carboxy-terminus significantly mitigated the inflammatory reaction and facilitated the healing of infected skin wounds in rat model.

PEGylated Graphene Oxide Carried OH-CATH30 to Accelerate the Healing of Infected Skin Wounds.

BackgroundThe treatment of Staphylococcus aureus (S. aureus)-infected wounds is difficult. It causes extreme pain to tens of thousands of patients and increases the cost of medical care. The antimicrobial peptide OH-CATH30 (OH30) has a good killing activity against S. aureus and can play a role in accelerating wound healing and immune regulation. Therefore, it shows great potential for wound healing.PurposeThe aim of this study was to overcome the short half-life and easy enzymolysis of OH30 by using graphene oxide conjugated with polyethylene glycol to load OH30 (denoted as PGO-OH30), as well as to evaluate its effect on wounds infected by S. aureus.MethodsPGO-OH30 nanoparticles were prepared by π–π conjugation and characterized. Their cell cytotoxicity, cell migration, infectious full-thickness dermotomy models, and histopathology were evaluated.ResultsCharacterization and cytotoxicity experiments revealed that the PGO-OH30 drug-delivery system had good biocompatibility and excellent drug-delivery ability. Cell-migration experiments showed that PGO-OH30 could promote the migration of human immortalized keratinocytes (HaCaT) cells compared with the control group (P<0.05). In a mouse model of skin wound infection, PGO-OH30 accelerated skin-wound healing and reduced the amount of S. aureus in wounds compared with the control group (P<0.05). In particular, on day 7, the number of S. aureus was 100 times lower in the PGO-OH30 group than in the control group.ConclusionThe PGO-OH30 drug-delivery system had good biocompatibility and excellent drug-delivery ability, indicating its good therapeutic effect on a skin wound-infection model.

Therapeutic activity of chlorhexidine-poloxamer antiseptic gel on wound healing in rats: a preclinical study.

Despite the progress in curative and preventive medicine, skin lesions after injuries or surgical interventions are still a big problem. The aim of wound care is to get damaged tissues to heal as soon as possible. A gel-forming material helps to maintain proper humidity in the wound and promotes the healing process. For this purpose, a healing gel containing the active substance chlorhexidine based on poloxamer was prepared. The aim of this study was to assess in vivo the therapeutic efficacy of chlorhexidine-poloxamer gel in treatment of wounds caused experimentally and inoculated with bacteria, and the effect of an antiseptic gel applied on a healthy rat skin. Wistar albino rats were selected for these studies. The effect of an antiseptic gel on the healing excision and incision wounds, as well as the irritating effect on the healthy skin were assessed. Cross-sectional full-thickness specimens from each group were collected at the end of the experiment to assess the histopathological alterations. Chlorhexidine-poloxamer gels accelerate the healing of infected skin wounds because the active ingredient chlorhexidine remains at the application site, and systemic effects are avoided. Moreover, chlorhexidine-poloxamer gels are easy to use because they can be easily washed off from the wound surface by water. The present study has revealed that chlorhexidine-poloxamer gels promote healing of full-thickness skin wounds without skin irritation. This makes it possible to plan further clinical trials in the target species.

Exploring simvastatin, an antihyperlipidemic drug, as a potential topical antibacterial agent.

The rapid rise of bacterial resistance to traditional antibiotics combined with the decline in discovery of novel antibacterial agents has created a global public health crisis. Repurposing existing drugs presents an alternative strategy to potentially expedite the discovery of new antimicrobial drugs. The present study demonstrates that simvastatin, an antihyperlipidemic drug exhibited broad-spectrum antibacterial activity against important Gram-positive (including methicillin-resistant Staphylococcus aureus (MRSA)) and Gram-negative pathogens (once the barrier imposed by the outer membrane was permeabilized). Proteomics and macromolecular synthesis analyses revealed that simvastatin inhibits multiple biosynthetic pathways and cellular processes in bacteria, including selective interference of bacterial protein synthesis. This property appears to assist in simvastatin’s ability to suppress production of key MRSA toxins (α-hemolysin and Panton-Valentine leucocidin) that impair healing of infected skin wounds. A murine MRSA skin infection experiment confirmed that simvastatin significantly reduces the bacterial burden and inflammatory cytokines in the infected wounds. Additionally, simvastatin exhibits excellent anti-biofilm activity against established staphylococcal biofilms and demonstrates the ability to be combined with topical antimicrobials currently used to treat MRSA skin infections. Collectively the present study lays the foundation for further investigation of repurposing simvastatin as a topical antibacterial agent to treat skin infections.

Efficacy of Some Antibiotics in Curing Resistant &amp;lt;i&amp;gt;Escherichia coli&amp;lt;/i&amp;gt; Infection

There is growing interest in re-evaluation of older antibiotics with the wide spread of pathogen resistance, especially gram negative bacteria, which impair treatment of some infections. In contrast various studies have reported that some antibiotics have efficacy in clearing resistant bacterial infections. On account of that it was interesting to evaluate the efficacy of erythromycin, chloramphenicol and/or tenoxicam in curing and/or relieving wound infection of highly resistant Escherichia coli and investigate the possible mechanisms beyond their antibacterial activity. This was achieved through evaluating highly resistant E. coli strains in vitro using agar dilution and in vivo rat models of E. coli infected wound and acute inflammation by carrageenin, where possible mechanisms were evaluated through measuring immunological mediators and histopathological examination. This study revealed that in vivo, erythromycin alone or in combination with tenoxicam significantly improved the healing of infected skin wounds with E. coli irresspective of resistancy in vitro. In addition to the improvement of immunological mediators involved in inflammatory reaction, oxidative stress and in cytokines expression as response to the bacterial infection in vivo. On the other hand chloramphenicol neither alone nor in combination with tenoxicam, achieved any significant effect. Tenoxicam didn’t show antimicrobial activity alone nor in combination with tested antibiotics in vitro, but it has shown synergestic activity in combination with tested antibiotics in vivo. Thus we concluded that immunomodulatory activity of erythromycin through anti-inflammatory and antioxidant effects was the possible mechanisms by which this antibiotic had healed infection with resistant E. coli in vivo, despite its resistancy to this antibiotic in vitro.

Effects of low intensity laser irradiation during healing of infected skin wounds in the rat

Low intensity laser irradiation remains a controversial treatment for non-healing wounds. This study examines the effect of low intensity light on healing of infected skin wounds in the rat. Wounds on the rat dorsum were inoculated with Pseudomonas aeruginosa. Wounds were irradiated or sham-irradiated three times weekly from day 1 to 19 using 635-nm or 808-nm diode lasers delivering continuous wave (CW) or intensity modulated (3800 Hz) laser radiation, all at radiant exposures of 1 and 20 J/cm2. Wound area and bacterial growth on the wound surface were evaluated three times a week. Histological and immunohistochemical analyses were performed at day 8 and 19. Wounds that were irradiated using a wavelength of 635 nm (1 and 20 J/cm2) or intensity modulated 808-nm laser light at 20 J/cm2 were smaller in area at day 19 than the sham-irradiated controls (achieved significance level=0.0105-0.0208) and were similar to controls in respect of bacterial growth. The remaining light protocols had no effect on wound area at day 19 although they increased Staphylococcus aureus growth across the time line compared with controls (p<0.0001 to p<0.004). CW 808-nm light at 20 J/cm2 significantly delayed half-heal time. Histological and immunohistochemical analyses supported wound closure findings: improved healing was associated with faster resolution of inflammation during the acute phase and increased signs of late repair at day 19. Significant inflammation was seen at day 19 in all irradiated groups regardless of radiant exposure, except when using 635 nm at 1 J/cm2. Red light improved healing of wounds. Only one 808-nm light protocol enhanced healing; lack of benefit using the remaining 808-nm light protocols may have been due to stimulatory effects of the light on S. aureus growth.

Simvastatin improves the healing of infected skin wounds of rats

PURPOSE: This study explores the potential of the simvastatin to ameliorate inflammation and infection in open infected skin wounds of rats. METHODS: Fourteen Wistar rats weighing 285±12g were used. The study was done in a group whose open infected skin wounds were treated with topical application of sinvastatina microemulsion (SIM, n=7) and a second group with wounds treated with saline 0.9 % (SAL, n=7). A bacteriological exam of the wounds fluid for gram positive and gram negative bacteria, the tecidual expression of TNFá and IL-1â by imunohistochemical technique, and histological analysis by HE stain were performed. RESULTS: The expression of TNFa could be clearly demonstrated in lower degree in skin wounds treated with simvastatin (668.6 ± 74.7 ìm²) than in saline (2120.0 ± 327.1 ìm²). In comparison, wound tissue from SIM group displayed leukocyte infiltration significantly lower than that observed in SAL group (p&lt;0.05). Culture results of the samples taken from wound fluid on fourth post treatment day revealed wound infection in only one rat of group simvastatin (SIM), where Proteus mirabilis, Escherchia coli and Enterobacter sp were isolated. In the rats whose wounds were treated with saline (SAL), polymicrobial infection with more than 100,000 CFU/g was detected in all the wounds. CONCLUSION: In addition to its antiinflammatory properties, the protective effects of simvastatin in infected open skin wounds is able to reduce infection and probably has antibacterial action. The potential to treat these wounds with statins to ameliorate inflammation and infection is promising.

Efficiency of magnesium-containing preparation polykatan in therapy of purulent wounds.

Local treatment with polykatan, a magnesium-containing drug based on bischofite mineral, promoted healing of infected skin wounds. Wound cleansing from bacteria was due to a direct antibacterial effect of the drug.