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1.
PLoS One ; 19(5): e0301201, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38743750

RESUMEN

With the rise of AMR the management of wound infections are becoming a big challenge. This has been attributed to the fact that most wound bacterial isolates have been found to possess various virulence factors like enzymes, toxins & biofilms production. Therefore, need for discovery of new lead compounds is paramount as such factors make these microbes to be resistant to already existing arsenal of antibiotics or even the immune system. This study aimed at documenting the nutritional, physicochemical, phytochemical and antibacterial properties of stingless bee honey. Isolation and characterization of bacterial isolates from 34 samples obtained from wounds of outpatients and surgical wards of Nakuru County Referral Hospital, Kenya was done. Various bacterial isolates (43) were isolated Staphylococcus aureus (34.8%) being predominant, followed by Pseudomonas aeruginosa (27.9%), Klebsiella pneumoniae (23.3%) and Escherichia coli (14.0%). A total of 36 out of the total isolates were genotypically characterized using molecular techniques detecting the prevalence of the following virulence genes; 16 srRNA (756 bp), hla (229 bp), cnf1 (426 bp), cnf2 (543 bp), hlyA (1011 bp), rmpA (461 bp), lasL (600 bp), gyrB (411 bp), khe (77 bp) and magA (128 bp). An assessment of the in vitro antibacterial activity of 26 stingless bee honey samples collected from their cerumen egg-shaped pots in Marigat sub-County, Baringo County, Kenya was done. Antibacterial properties of the stingless bee honey was done with varying susceptibility patterns being observed at different concentrations of honey impregnated discs (10x104, 20x104, 50x104 and 75x104 ml µg/ ml) giving mean inhibition diameters of 18.23 ± 0.4 mm (Staphylococcus aureus), 17.49 ± 0.3 mm (Pseudomonas aeruginosa), 16.05 ± 0.6 mm (Klebsiella pneumoniae) and 10.19 ± 0.5 mm (Escherichia coli) with a mean range of 14.54 ± 2.0 mm to 17.58 ± 3 mm. Higher susceptibility to honey was recorded across all the bacterial isolates compared to conventional antibiotics while the mean MIC and MBC of the honey were recorded at 62.5 ml µg/ ml and 250 ml µg/ ml respectively. Control bacterial isolates Staphylococcus aureus ATCC 25923, Escherichia coli ATCC 25922, Klebsiella pneumoniae ATCC 27736 and Pseudomonas aeruginosa ATCC 27858 were used in the analysis. The stingless bee honey was found to be rich in various nutritive components like sugar (89.85 ± 5.07 g/100 g) and moisture (81.75 ± 10.35 mg/g) with a significant difference of P <0.05 as the main antibacterial components. Additionally, the stingless honey did possess water soluble vitamins, proteins and minerals of which potassium was the most dominant one. In regard to phytochemicals, on our preliminary analysis phenolic, flavonoid and carotenoid compounds were found to be present with phenolic compounds being the most dominant one. Stingless bee honey from Marigat, has antimicrobial properties which could be attributed to the rich phytochemicals it possesses and its physicochemical properties in addition to its high nutritive value.


Asunto(s)
Antibacterianos , Miel , Pruebas de Sensibilidad Microbiana , Miel/análisis , Antibacterianos/farmacología , Animales , Abejas/microbiología , Humanos , Bacterias/efectos de los fármacos , Bacterias/aislamiento & purificación , Fitoquímicos/farmacología , Infección de Heridas/microbiología , Infección de Heridas/prevención & control , Infección de Heridas/tratamiento farmacológico , Factores de Virulencia
2.
Wounds ; 36(4): 108-114, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38743855

RESUMEN

BACKGROUND: HOCl (eg, pHAp) preserved solutions have antimicrobial properties and are considered safe and effective for wound management. NPWTi-d (or NPWTi) is an established adjunctive wound modality for a variety of wound etiologies in various anatomic locations in which an instillate solution dwells on the surface of the wound to assist in wound bed preparation. A variety of solutions have been used, including 0.9% normal saline wound cleansers and antiseptics. pHAp is growing in popularity as the solution of choice for NPWTi-d. OBJECTIVE: To evaluate consensus statements on the use of NPWTi-d with pHAp. METHODS: A 15-member multidisciplinary panel of expert clinicians in the United States, Canada, and France convened in person in April 2023 in Washington, D.C. and/or corresponded later to discuss 10 statements on the use of pHAp with NPWTi-d. The panelists then replied "agree" or "disagree" to each statement and had the option to provide comments. RESULTS: Ten consensus statements are presented, along with the proportion of agreement or disagreement and summary comments. Although agreement with the statements on NPWTi-d with pHAp varied, the statements appear to reflect individual preferences for use rather than concerns about safety or efficacy. CONCLUSION: The consensus indicates that NPWTi-d with pHAp can have a beneficial effect in wound care.


Asunto(s)
Consenso , Ácido Hipocloroso , Terapia de Presión Negativa para Heridas , Cicatrización de Heridas , Humanos , Terapia de Presión Negativa para Heridas/métodos , Ácido Hipocloroso/uso terapéutico , Cicatrización de Heridas/efectos de los fármacos , Heridas y Lesiones/terapia , Irrigación Terapéutica/métodos , Canadá , Infección de Heridas/prevención & control , Infección de Heridas/tratamiento farmacológico , Estados Unidos
3.
Carbohydr Polym ; 337: 122147, 2024 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-38710554

RESUMEN

Treatment of infected wound by simultaneously eliminating bacteria and inducing angiogenesis to promote wound tissue regeneration remains a clinical challenge. Dynamic and reversable hydrogels can adapt to irregular wound beds, which have raised great attention as wound dressings. Herein, a sprayable chitosan-based hydrogel (HPC/CCS/ODex-IGF1) was developed using hydroxypropyl chitosan (HPC), caffeic acid functionalized chitosan (CCS), oxidized dextran (ODex) to crosslink through the dynamic imine bond, which was pH-responsive to the acidic microenvironment and could controllably release insulin growth factor-1 (IGF1). The HPC/CCS/ODex-IGF1 hydrogels not only showed self-healing, self-adaptable and sprayable properties, but also exhibited excellent antibacterial ability, antioxidant property, low-cytotoxicity and angiogenetic activity. In vivo experiments demonstrated that hydrogels promoted tissue regeneration and healing of bacteria-infected wound with a rate of approximately 98.4 % on day 11 by eliminating bacteria, reducing inflammatory and facilitating angiogenesis, demonstrating its great potential for wound dressing.


Asunto(s)
Antibacterianos , Quitosano , Hidrogeles , Neovascularización Fisiológica , Cicatrización de Heridas , Quitosano/química , Quitosano/farmacología , Hidrogeles/química , Hidrogeles/farmacología , Cicatrización de Heridas/efectos de los fármacos , Animales , Antibacterianos/farmacología , Antibacterianos/química , Ratones , Neovascularización Fisiológica/efectos de los fármacos , Antiinflamatorios/farmacología , Antiinflamatorios/química , Antiinflamatorios/uso terapéutico , Humanos , Masculino , Factor I del Crecimiento Similar a la Insulina , Staphylococcus aureus/efectos de los fármacos , Vendajes , Infección de Heridas/tratamiento farmacológico , Infección de Heridas/microbiología , Dextranos/química , Dextranos/farmacología , Angiogénesis
4.
AAPS PharmSciTech ; 25(5): 110, 2024 May 13.
Artículo en Inglés | MEDLINE | ID: mdl-38740721

RESUMEN

Antimicrobial peptide LL37 is a promising antibacterial candidate due to its potent antimicrobial activity with no known bacterial resistance. However, intrinsically LL37 is susceptible to degradation in wound fluids limits its effectiveness. Bacterial toxins which are released after cell lysis are found to hinder wound healing. To address these challenges, encapsulating LL37 in microspheres (MS) and loading the MS onto activated carbon (AC)-chitosan (CS) hydrogel. This advanced wound dressing not only protects LL37 from degradation but also targets bacterial toxins, aiding in the healing of chronic wound infections. First, LL37 MS and LL37-AC-CS hydrogel were prepared and characterised in terms of physicochemical properties, drug release, and peptide-polymer compatibility. Antibacterial and antibiofilm activity, bacterial toxin elimination, cell migration, and cell cytotoxicity activities were investigated. LL37-AC-CS hydrogel was effective against Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus. LL37-AC-CS hydrogel bound more endotoxin than AC with CS hydrogel alone. The hydrogel also induced cell migration after 72 h and showed no cytotoxicity towards NHDF after 72 h of treatment. In conclusion, the LL37-AC-CS hydrogel was shown to be a stable, non-toxic advanced wound dressing method with enhanced antimicrobial and antitoxin activity, and it can potentially be applied to chronic wound infections to accelerate wound healing.


Asunto(s)
Antibacterianos , Vendajes , Quitosano , Escherichia coli , Hidrogeles , Microesferas , Pseudomonas aeruginosa , Staphylococcus aureus , Quitosano/química , Antibacterianos/farmacología , Antibacterianos/administración & dosificación , Antibacterianos/química , Hidrogeles/química , Hidrogeles/farmacología , Staphylococcus aureus/efectos de los fármacos , Humanos , Pseudomonas aeruginosa/efectos de los fármacos , Escherichia coli/efectos de los fármacos , Cicatrización de Heridas/efectos de los fármacos , Infección de Heridas/tratamiento farmacológico , Infección de Heridas/microbiología , Infección de Heridas/prevención & control , Péptidos Catiónicos Antimicrobianos/farmacología , Péptidos Catiónicos Antimicrobianos/química , Péptidos Catiónicos Antimicrobianos/administración & dosificación , Catelicidinas , Pruebas de Sensibilidad Microbiana/métodos , Toxinas Bacterianas , Liberación de Fármacos , Movimiento Celular/efectos de los fármacos , Carbono/química , Biopelículas/efectos de los fármacos
5.
Int J Biol Macromol ; 267(Pt 1): 131575, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38614178

RESUMEN

Wound healing is a dynamic and complex process, it's urgent to develop new wound dressings with excellent performance to promote wound healing at the different stages. Here, a novel composite hydrogel dressing composed by silver nanoparticles (AgNPs) impregnated adenine-modified chitosan (CS-A) and octafunctionalized polyhedral oligomeric silsesquioxane (POSS) of benzaldehyde-terminated polyethylene glycol (POSS-PEG-CHO) solution was presented to solve the problem of wound infection. Modification of chitosan with adenine, not only can improve the water solubility of chitosan, but also introduce bioactive substances to promote cell proliferation. CS-A and POSS-PEG-CHO were cross-linked by Schiff-base reaction to form the injectable self-healing hydrogel. On this basis, AgNPs were added into the hydrogel, which endows the hydrogel with better antibacterial activity. Moreover, this kind of hydrogel exhibits excellent cell proliferation properties. Studies demonstrated that the hydrogel can significantly accelerate the closure of infected wounds. The histological analysis and immunofluorescence staining demonstrated that the wounds treated with the composite hydrogel exhibited fewer inflammatory cells, more collagen deposition and angiogenesis, faster regeneration of epithelial tissue. Above all, adenine-modified chitosan composite hydrogel with AgNPs loaded was considered as a dressing material with great application potential for promoting the healing of infected wounds.


Asunto(s)
Adenina , Antibacterianos , Proliferación Celular , Quitosano , Hidrogeles , Nanopartículas del Metal , Polietilenglicoles , Plata , Cicatrización de Heridas , Quitosano/química , Quitosano/farmacología , Cicatrización de Heridas/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Antibacterianos/farmacología , Antibacterianos/química , Polietilenglicoles/química , Plata/química , Plata/farmacología , Hidrogeles/química , Hidrogeles/farmacología , Animales , Nanopartículas del Metal/química , Adenina/farmacología , Adenina/química , Ratones , Compuestos de Organosilicio/química , Compuestos de Organosilicio/farmacología , Ratas , Humanos , Infección de Heridas/tratamiento farmacológico
6.
Carbohydr Polym ; 336: 122102, 2024 Jul 15.
Artículo en Inglés | MEDLINE | ID: mdl-38670773

RESUMEN

Skin wounds are susceptible to infection, leading to severe inflammatory reactions that can progress to chronic wounds, ultimately causing significant physical and mental distress to the patient. In this study, we propose an injectable composite hydrogel achieved through one-pot gelation of oxidized xyloglucan (OXG), cationic polyamide ε-poly-l-lysine (EPL), and surface amino-rich silicon nanoparticles (SiNPs). OXG exhibits commendable anti-inflammatory properties and provides crosslinking sites. SiNPs serve as mechanically reinforced crosslinkers, facilitating the construction of a dynamic Schiff base network. SiNPs significantly reduced the gelation time to 3 s and tripled the storage modulus of the hydrogels. Additionally, the combination of EPL and SiNPs demonstrated synergistic antimicrobial activity against both S. aureus and E. coli. Notably, the hydrogel effectively halted liver bleeding within 30 s. The hydrogel demonstrated outstanding shear-thinning and self-healing properties, crucial considerations for the design of injectable hydrogels. Furthermore, its efficacy was evaluated as a wound dressing in a mouse model with S. aureus infection. The results indicated that, compared to commercial products, the hydrogel exhibited a shorter wound healing time, decreased inflammation, thinner epithelium, increased hair follicles, enhanced neovascularization, and more substantial collagen deposition. These findings strongly suggest the promising potential of the proposed hydrogel as an effective wound dressing for the treatment of infected wounds.


Asunto(s)
Antibacterianos , Escherichia coli , Glucanos , Hidrogeles , Nanopartículas , Polilisina , Staphylococcus aureus , Cicatrización de Heridas , Xilanos , Glucanos/química , Glucanos/farmacología , Animales , Cicatrización de Heridas/efectos de los fármacos , Xilanos/química , Xilanos/farmacología , Hidrogeles/química , Hidrogeles/farmacología , Polilisina/química , Polilisina/farmacología , Ratones , Nanopartículas/química , Escherichia coli/efectos de los fármacos , Staphylococcus aureus/efectos de los fármacos , Antibacterianos/farmacología , Antibacterianos/química , Antibacterianos/administración & dosificación , Infecciones Estafilocócicas/tratamiento farmacológico , Reactivos de Enlaces Cruzados/química , Infección de Heridas/tratamiento farmacológico , Masculino
7.
Int Wound J ; 21(5): e14878, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38682897

RESUMEN

The primary objective of this study was to develop a carboxymethyl cellulose (CMC) and carboxymethyl chitosan (CMCS) hydrogel containing ethylene diamine tetra acetic acid (EDTA) as the materials for wound healing. CMC and CMCS solutions were prepared with a concentration of 4% (w/v). These solutions were made using normal saline serum with a concentration of 0.5% (v/v). Additionally, EDTA with the concentrations of 0.01%, 0.05%, 0.1%, 0.5%, 1%, and 2% (w/v) was included in the prepared polymer solution. The analysis of the hydrogels revealed that they possess porous structures with interconnected pores, with average in size 88.71 ± 5.93 µm. The hydrogels exhibited a swelling capacity of up to 60% of their initial weight within 24 h, as indicated by the weight loss and swelling measurements. The antibacterial experiments showed that the formulated CMC/CMCS/EDTA 0.5% hydrogel inhibited the growth of Staphylococcus aureus and Pseudomonas aeruginosa. Moreover, the produced hydrogels were haemocompatible and biocompatible. At the last stage, the evaluation of wound healing in the animal model demonstrated that the use of the produced hydrogels significantly improved the process of wound healing. Finally, the findings substantiated the effectiveness of the formulated hydrogels as the materials for promoting wound healing and antibacterial agents.


Asunto(s)
Biopelículas , Carboximetilcelulosa de Sodio , Quitosano , Quitosano/análogos & derivados , Ácido Edético , Hidrogeles , Pseudomonas aeruginosa , Staphylococcus aureus , Cicatrización de Heridas , Animales , Quitosano/farmacología , Ratas , Ácido Edético/farmacología , Ácido Edético/uso terapéutico , Staphylococcus aureus/efectos de los fármacos , Pseudomonas aeruginosa/efectos de los fármacos , Carboximetilcelulosa de Sodio/farmacología , Cicatrización de Heridas/efectos de los fármacos , Biopelículas/efectos de los fármacos , Hidrogeles/farmacología , Modelos Animales de Enfermedad , Masculino , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Ratas Wistar , Infecciones Estafilocócicas/tratamiento farmacológico , Infección de Heridas/tratamiento farmacológico , Infecciones por Pseudomonas/tratamiento farmacológico
8.
J Wound Care ; 33(5): 335-347, 2024 May 02.
Artículo en Inglés | MEDLINE | ID: mdl-38683776

RESUMEN

OBJECTIVE: Burn injuries pose a heightened risk of infection, which is primarily responsible for increased morbidity and mortality. Factors such as extensive skin damage and compromised immunity exacerbate this vulnerability. Pseudomonas aeruginosa and Staphylococcus aureus are frequently identified in burns, with Gram-negative Pseudomonas aeruginosa often resistant to antibacterial agents. While Flaminal, an alginate-based wound dressing (Flen Health, Belgium), aids wound healing, its antibacterial effects are limited compared with 1% silver sulfadiazine (1% SSD). In contrast, Prontosan Wound Gel X, a betaine and polyhexanide-based hydrogel (B. Braun Medical AG, Switzerland), has been shown to effectively combat various microbes and promotes wound healing. METHOD: In this study, two research cohorts were retrospectively established (control group: patients receiving standard of care with the alginate-based wound dressing; intervention group: patients receiving the polyhexanide hydrogel wound dressing), comprising patients admitted to a burn centre between 2019 and 2022. Patients were eligible when continuous wound treatment with either of the two wound dressings was performed. Laser Doppler imaging (LDI) scans were conducted. Regions of interest (ROIs) were selected based on LDI scans and divided into healing time categories. Wound swabs were collected and the presence of Pseudomonas aeruginosa and Staphylococcus aureus was documented. Bacterial load was evaluated using a semiquantitative scale. Wound healing was recorded. RESULTS: The control group consisted of 31 patients with 93 ROIs, while the intervention group had 67 ROIs involving 29 patients. Both groups exhibited similar proportions of healing time categories (p>0.05). The polyhexanide hydrogel dressing outperformed the alginate-based dressing in antiseptic efficacy by significantly reducing the incidence of Pseudomonas aeruginosa- and Staphylococcus aureus-positive cultures in patients' wounds. Wound healing time for conservative treatment was comparable between groups. CONCLUSION: In this study, the polyhexanide hydrogel dressing minimised Pseudomonas aeruginosa and Staphylococcus aureus colonisation in burn wounds, demonstrating strong antibacterial properties, emphasising its potential to minimise infections in burn injuries.


Asunto(s)
Alginatos , Antibacterianos , Biguanidas , Quemaduras , Cicatrización de Heridas , Humanos , Alginatos/uso terapéutico , Biguanidas/uso terapéutico , Quemaduras/terapia , Masculino , Femenino , Estudios Retrospectivos , Adulto , Antibacterianos/uso terapéutico , Antibacterianos/administración & dosificación , Persona de Mediana Edad , Cicatrización de Heridas/efectos de los fármacos , Pseudomonas aeruginosa/efectos de los fármacos , Vendajes , Infección de Heridas/tratamiento farmacológico , Staphylococcus aureus/efectos de los fármacos , Hidrogeles
9.
J Wound Care ; 33(5): 290-296, 2024 May 02.
Artículo en Inglés | MEDLINE | ID: mdl-38683781

RESUMEN

OBJECTIVE: To assess the clinical impact and acceptance of an infection management (IM) pathway, designed to improve the consistency of care of wound infection when introduced, and supported by an educational programme. METHOD: An education and evaluation programme (T3 programme) was-conducted in Portugal, Spain and Italy. This consisted of a two-hour educational, virtual seminar, followed by a four-week evaluation of an IM pathway during which survey data were collected on the impact of this pathway on clinician-selected patients. Finally, all participants reconvened for a virtual meeting during which the combined results were disseminated. The pathway provided guidance to clinicians regarding the targeted use of antimicrobial wound dressings according to the presence and absence of signs and symptoms of wound infection. RESULTS: Responses relating to 259 patients treated according to the IM pathway, 139 (53.7%) of whom had received previous antimicrobial treatment, were captured. Signs and symptoms of infection resolved within four weeks of treatment in >90% of patients. All 25 patients who had received prior antimicrobial treatment for ≥3 months experienced a resolution in the signs and symptoms of infection within four weeks. The majority of participating clinicians agreed that the IM pathway improved decision-making (94.9%) and confidence (97.3%), and helped to determine the correct antimicrobial treatment (91.4%) in the context of wound infection. CONCLUSION: The T3 programme was an efficient way to deliver a structured educational programme. The use of the IM pathway resulted in >90% of patients achieving resolution of their signs and symptoms of wound infection.


Asunto(s)
Infección de Heridas , Humanos , Infección de Heridas/tratamiento farmacológico , Infección de Heridas/terapia , Italia , Vías Clínicas , Portugal , España , Femenino , Masculino , Antibacterianos/uso terapéutico , Vendajes , Persona de Mediana Edad
10.
J Nanobiotechnology ; 22(1): 152, 2024 Apr 04.
Artículo en Inglés | MEDLINE | ID: mdl-38575979

RESUMEN

Infected wound healing remains a challenging task in clinical practice due to several factors: (I) drug-resistant infections caused by various pathogens, (II) persistent inflammation that hinders tissue regeneration and (III) the ability of pathogens to persist intracellularly and evade antibiotic treatment. Microneedle patches (MNs), recognized for their effecacious and painless subcutaneous drug delivery, could greatly enhance wound healing if integrated with antibacterial functionality and tissue regenerative potential. A multifunctional agent with subcellular targeting capability and contained novel antibacterial components, upon loading onto MNs, could yield excellent therapeutic effects on wound infections. In this study, we sythesised a zeolitic imidazolate framework-8 nanoparticles (ZIF-8 NPs) loaded with low molecular weight fucoidan (Fu) and further coating by hyaluronic acid (HA), obtained a multifunctional HAZ@Fu NPs, which could hinders Methicillin-resistant Staphylococcus aureus (MRSA) growth and promotes M2 polarization in macrophages. We mixed HAZ@Fu NPs with photocrosslinked gelatin methacryloyl (GelMA) and loaded it into the tips of the MNs (HAZ@Fu MNs), administered to mice model with MRSA-infected full-thickness cutaneous wounds. MNs are able to penetrate the skin barrier, delivering HAZ@Fu NPs into the dermal layer. Since cells within infected tissues extensively express the HA receptor CD44, we also confirmed the HA endows the nanoparticles with the ability to target MRSA in subcellular level. In vitro and in vivo murine studies have demonstrated that MNs are capable of delivering HAZ@Fu NPs deep into the dermal layers. And facilitated by the HA coating, HAZ@Fu NPs could target MRSA surviving at the subcellular level. The effective components, such as zinc ions, Fu, and hyaluronic acid could sustainably released, which contributes to antibacterial activity, mitigates inflammation, promotes epithelial regeneration and fosters neovascularization. Through the RNA sequencing of macrophages post co-culture with HAZ@Fu, the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis reveals that the biological functionalities associated with wound healing could potentially be facilitated through the PI3K-Akt pathway. The results indicate that the synergistic application of HAZ@Fu NPs with biodegradable MNs may serve as a significant adjunct in the treatment of infected wounds. The intricate mechanisms driving its biological effects merit further investigation.


Asunto(s)
Antiinfecciosos , Staphylococcus aureus Resistente a Meticilina , Polisacáridos , Infección de Heridas , Ratones , Animales , Ácido Hialurónico/farmacología , Fosfatidilinositol 3-Quinasas , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Cicatrización de Heridas , Antiinfecciosos/farmacología , Infección de Heridas/tratamiento farmacológico , Inflamación
11.
J Wound Care ; 33(Sup4a): xcix-cx, 2024 Apr 02.
Artículo en Inglés | MEDLINE | ID: mdl-38588056

RESUMEN

Metal-based nanoparticles (MNPs) are promoted as effective compounds in the treatment of bacterial infections and as possible alternatives to antibiotics. These MNPs are known to affect a broad spectrum of microorganisms using a multitude of strategies, including the induction of reactive oxygen species and interaction with the inner structures of the bacterial cells. The aim of this review was to summarise the latest studies about the effect of metal-based nanoparticles on pathogenic bacterial biofilm formed in wounds, using the examples of Gram-positive bacterium Staphylococcus aureus and Gram-negative bacterium Pseudomonas aeruginosa, as well as provide an overview of possible clinical applications.


Asunto(s)
Nanopartículas , Infecciones Estafilocócicas , Infección de Heridas , Humanos , Biopelículas , Staphylococcus aureus , Antibacterianos/uso terapéutico , Antibacterianos/farmacología , Pseudomonas aeruginosa , Nanopartículas/uso terapéutico , Infección de Heridas/tratamiento farmacológico , Infección de Heridas/microbiología
12.
Acta Biomater ; 179: 284-299, 2024 Apr 15.
Artículo en Inglés | MEDLINE | ID: mdl-38494084

RESUMEN

Methicillin-resistant Staphylococcus aureus (MRSA) is the primary pathogenic agent responsible for epidermal wound infection and suppuration, seriously threatening the life and health of human beings. To address this fundamental challenge, we propose a heterojunction nanocomposite (Ca-CN/MnS) comprised of Ca-doped g-C3N4 and MnS for the therapy of MRSA-accompanied wounds. The Ca doping leads to a reduction in both the bandgap and the singlet state S1-triplet state T2 energy gap (ΔEST). The Ca doping also facilitates the two-photon excitation, thus remarkably promoting the separation and transfer of 808 nm near-infrared (NIR) light-triggered electron-hole pairs together with the built-in electric field. Thereby, the production of reactive oxygen species and heat are substantially augmented nearby the nanocomposite under 808 nm NIR light irradiation. Consequently, an impressive photocatalytic MRSA bactericidal efficiency of 99.98 ± 0.02 % is achieved following exposure to NIR light for 20 min. The introduction of biologically functional elements (Ca and Mn) can up-regulate proteins such as pyruvate kinase (PKM), L-lactate dehydrogenase (LDHA), and calcium/calmodulin-dependent protein kinase (CAMKII), trigger the glycolysis and calcium signaling pathway, promote cell proliferation, cellular metabolism, and angiogenesis, thereby expediting the wound-healing process. This heterojunction nanocomposite, with its precise charge-transfer pathway, represents a highly effective bactericidal and bioactive system for treating multidrug-resistant bacterial infections and accelerating tissue repair. STATEMENT OF SIGNIFICANCE: Due to the bacterial resistance, developing an antibiotic-free and highly effective bactericidal strategy to treat bacteria-infected wounds is critical. We have designed a heterojunction consisting of calcium doped g-C3N4 and MnS (Ca-CN/MnS) that can rapidly kill methicillin-resistant Staphylococcus aureus (MRSA) without damaging normal tissue through a synergistic effect of two-photon stimulated photothermal and photodynamic therapy. In addition, the release of trace amounts of biofunctional elements Mn and Ca triggers glycolysis and calcium signaling pathways that promote cellular metabolism and cell proliferation, contributing to tissue repair and wound healing.


Asunto(s)
Calcio , Glucólisis , Staphylococcus aureus Resistente a Meticilina , Staphylococcus aureus Resistente a Meticilina/efectos de los fármacos , Glucólisis/efectos de los fármacos , Animales , Calcio/metabolismo , Infecciones Estafilocócicas/tratamiento farmacológico , Fototerapia , Infección de Heridas/microbiología , Infección de Heridas/patología , Infección de Heridas/tratamiento farmacológico , Humanos , Nanocompuestos/química , Cicatrización de Heridas/efectos de los fármacos , Ratones , Rayos Infrarrojos
13.
Acta Biomater ; 178: 147-159, 2024 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-38447811

RESUMEN

Wound infection commonly causes delayed healing, especially in the setting of chronic wounds. Local release of antibiotics is considered a viable approach to treat chronic wounds. We have developed a versatile telodendrimer (TD) platform for efficient loading of charged antibiotic molecules via a combination of multivalent and synergistic charge and hydrophobic interactions. The conjugation of TD in biocompatible hydrogel allows for topical application to provide sustained antibiotic release. Notably, a drug loading capacity as high as 20 % of the drug-to-resin dry weight ratio can be achieved. The payload content (PC) and release profile of the various antibiotics can be optimized by fine-tuning TD density and valency in hydrogel based on the charge and hydrophobic features of the drug, e.g., polymyxin B (PMB), gentamycin (GM), and daptomycin (Dap), for effective infection control. We have shown that hydrogel with moderately reduced TD density demonstrates a more favorable release profile than hydrogel with higher TD density. Antibiotics loaded in TD hydrogel have comparable antimicrobial potency and reduced cytotoxicity compared to the free antibiotics due to a prolonged, controlled drug release profile. In a mouse model of skin and soft tissue infection, the subcutaneous administration of PMB-loaded TD hydrogel effectively eliminated the bacterial burden. Overall, these results suggest that engineerable TD hydrogels have great potential as a topical treatment to control infection for wound healing. STATEMENT OF SIGNIFICANCE: Wound infection causes a significant delay in the wound healing process, which results in a significant financial and resource burden to the healthcare system. PEGA-telodendrimer (TD) resin hydrogel is an innovative and versatile platform that can be fine-tuned to efficiently encapsulate different antibiotics by altering charged and hydrophobic structural moieties. Additionally, this platform is advantageous as the TD density in the resin can also be fine-tuned to provide the desired antibiotic payload release profile. Sustained antibiotics release through optimization of TD density provides a prolonged therapeutic window and reduces burst release-induced cytotoxicity compared to conventional antibiotics application. Studies in a preclinical mouse model of bacteria-induced skin and soft tissue infection demonstrated promising therapeutic efficacy as evidenced by effective infection control and prolonged antibacterial efficacy of antibiotics-loaded PEGA-TD resin. In conclusion, the PEGA-TD resin platform provides a highly customizable approach for effective antibiotics release with significant potential for topical application to treat various bacterial wound infections to promote wound healing.


Asunto(s)
Resinas Acrílicas , Polietilenglicoles , Infecciones de los Tejidos Blandos , Infección de Heridas , Ratones , Animales , Antibacterianos/uso terapéutico , Hidrogeles/química , Infecciones de los Tejidos Blandos/tratamiento farmacológico , Infección de Heridas/tratamiento farmacológico , Control de Infecciones
14.
Int Wound J ; 21(3): e14747, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38445778

RESUMEN

The purpose of the meta-analysis was to evaluate and compare the photodynamic therapy's effectiveness in treating infected skin wounds. The results of this meta-analysis were analysed, and the odds ratio (OR) and mean difference (MD) with 95% confidence intervals (CIs) were calculated using dichotomous or contentious random- or fixed-effect models. For the current meta-analysis, 6 examinations spanning from 2013 to 2021 were included, encompassing 154 patients with infected skin wounds were the used studies' starting point. Photodynamic therapy had a significantly lower wound ulcer size (MD, -4.42; 95% CI, -7.56--1.28, p = 0.006), better tissue repair (MD, -8.62; 95% CI, -16.76--0.48, p = 0.04) and lower microbial cell viability (OR, 0.13; 95% CI, 0.04-0.42, p < 0.001) compared with red light exposure in subjects with infected skin wounds. The examined data revealed that photodynamic therapy had a significantly lower wound ulcer size, better tissue repair and lower microbial cell viability compared with red light exposure in subjects with infected skin wounds. However, given that all examinations had a small sample size, consideration should be given to their values.


Asunto(s)
Fotoquimioterapia , Enfermedades Cutáneas Infecciosas , Úlcera Cutánea , Traumatismos de los Tejidos Blandos , Infección de Heridas , Humanos , Úlcera , Úlcera Cutánea/tratamiento farmacológico , Piel , Infección de Heridas/tratamiento farmacológico
15.
BMC Biotechnol ; 24(1): 10, 2024 Mar 04.
Artículo en Inglés | MEDLINE | ID: mdl-38439037

RESUMEN

Polymicrobial communities lead to worsen the wound infections, due to mixed biofilms, increased antibiotic resistance, and altered virulence production. Promising approaches, including enzymes, may overcome the complicated condition of polymicrobial infections. Therefore, this study aimed to investigate Staphopain A-mediated virulence and resistance alteration in an animal model of Staphylococcus aureus and Pseudomonas aeruginosa co-infection. S. aureus and P. aeruginosa were co-cultured on the L-929 cell line and wound infection in an animal model. Then, recombinant staphopain A was purified and used to treat mono- and co-infections. Following the treatment, changes in virulence factors and resistance were investigated through phenotypic methods and RT-PCR. Staphopain A resulted in a notable reduction in the viability of S. aureus and P. aeruginosa. The biofilm formed in the wound infection in both animal model and cell culture was disrupted remarkably. Moreover, the biofilm-encoding genes, quorum sensing regulating genes, and virulence factors (hemolysin and pyocyanin) controlled by QS were down-regulated in both microorganisms. Furthermore, the resistance to vancomycin and doripenem decreased following treatment with staphopain A. According to this study, staphopain A might promote wound healing and cure co-infection. It seems to be a promising agent to combine with antibiotics to overcome hard-to-cure infections.


Asunto(s)
Coinfección , Infección de Heridas , Animales , Virulencia , Pseudomonas aeruginosa/genética , Staphylococcus aureus/genética , Coinfección/tratamiento farmacológico , Factores de Virulencia/genética , Modelos Animales , Farmacorresistencia Microbiana , Infección de Heridas/tratamiento farmacológico
16.
Int J Biol Macromol ; 267(Pt 1): 131252, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38554897

RESUMEN

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.


Asunto(s)
Resinas Acrílicas , Antibacterianos , Carbazoles , Hidrogeles , Cicatrización de Heridas , beta-Ciclodextrinas , Animales , Resinas Acrílicas/química , Hidrogeles/química , Hidrogeles/síntesis química , Hidrogeles/farmacología , Ratones , beta-Ciclodextrinas/química , Carbazoles/química , Carbazoles/farmacología , Carbazoles/síntesis química , Cicatrización de Heridas/efectos de los fármacos , Antibacterianos/farmacología , Antibacterianos/química , Antibacterianos/síntesis química , Infección de Heridas/tratamiento farmacológico , Infección de Heridas/microbiología , Modelos Animales de Enfermedad , Liberación de Fármacos
17.
Biomaterials ; 308: 122548, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38554642

RESUMEN

The treatment of infected wounds poses a formidable challenge in clinical practice due to the detrimental effects of uncontrolled bacterial infection and excessive oxidative stress, resulting in prolonged inflammation and impaired wound healing. In this study, we presented a MXene@TiO2 (MT) nanosheets loaded composite hydrogel named as GA/OKGM/MT hydrogel, which was formed based on the Schiff base reaction between adipic dihydrazide modified gelatin (GA)and Oxidized Konjac Glucomannan (OKGM), as the wound dressing. During the hemostasis phase, the GA/OKGM/MT hydrogel demonstrated effective adherence to the skin, facilitating rapid hemostasis. In the subsequent inflammation phase, the GA/OKGM/MT hydrogel effectively eradicated bacteria through MXene@TiO2-induced photothermal therapy (PTT) and eliminated excessive reactive oxygen species (ROS), thereby facilitating the transition from the inflammation phase to the proliferation phase. During the proliferation phase, the combined application of GA/OKGM/MT hydrogel with electrical stimulation (ES) promoted fibroblast proliferation and migration, leading to accelerated collagen deposition and angiogenesis at the wound site. Overall, the comprehensive repair strategy based on the GA/OKGM/MT hydrogel demonstrated both safety and reliability. It expedited the progression through the hemostasis, inflammation, and proliferation phases of wound healing, showcasing significant potential for the treatment of infected wounds.


Asunto(s)
Proliferación Celular , Gelatina , Hemostasis , Hidrogeles , Mananos , Titanio , Cicatrización de Heridas , Cicatrización de Heridas/efectos de los fármacos , Titanio/química , Hidrogeles/química , Animales , Proliferación Celular/efectos de los fármacos , Ratones , Hemostasis/efectos de los fármacos , Gelatina/química , Mananos/química , Masculino , Terapia Fototérmica , Nanoestructuras/química , Especies Reactivas de Oxígeno/metabolismo , Infección de Heridas/tratamiento farmacológico , Infección de Heridas/terapia , Humanos
18.
Int J Biol Macromol ; 266(Pt 1): 131257, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38554908

RESUMEN

The infected wounds pose one of the major threats to human health today. To address this issue, it is necessary to develop innovative wound dressings with superior antibacterial activity and other properties. Due to its potent antibacterial, antioxidant, and immune-boosting properties, epigallocatechin gallate (EGCG) has been widely utilized. In this study, a multifunctional curdlan hydrogel loading EGCG (Cur-EGCGH3) was designed. Cur-EGCGH3 exhibited excellent physicochemical properties, good biocompatibility, hemostatic, antibacterial, and antioxidant activities. Also, ELISA data showed that Cur-EGCGH3 stimulated macrophages to secrete pro-inflammatory and pro-regenerative cytokines. Cell scratch results indicated that Cur-EGCGH3 promoted the migration of NIH3T3 and HUVECs. In vivo experiments confirmed that Cur-EGCGH3 could inhibit bacterial infection of the infected wounds, accelerate hemostasis, and promote epithelial regeneration and collagen deposition. These results demonstrated that Cur-EGCGH3 holds promise for promoting healing of the infected wounds.


Asunto(s)
Antibacterianos , Catequina , Catequina/análogos & derivados , Hemostáticos , Hidrogeles , Cicatrización de Heridas , beta-Glucanos , Catequina/farmacología , Catequina/química , Animales , Cicatrización de Heridas/efectos de los fármacos , Ratones , beta-Glucanos/química , beta-Glucanos/farmacología , Hidrogeles/química , Hidrogeles/farmacología , Antibacterianos/farmacología , Antibacterianos/química , Humanos , Células 3T3 NIH , Hemostáticos/farmacología , Hemostáticos/química , Infección de Heridas/tratamiento farmacológico , Infección de Heridas/microbiología , Antioxidantes/farmacología , Antioxidantes/química , Células Endoteliales de la Vena Umbilical Humana/efectos de los fármacos
19.
Int J Biol Macromol ; 263(Pt 2): 129887, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38383251

RESUMEN

Infected wound management is a great challenge to healthcare, especially in emergencies such as accidents or battlefields. Hydrogels as wound dressings can replace or supplement traditional wound treatment strategies, such as bandages or sutures. It is significant to develop novel hydrogel-based wound dressings with simple operation, inexpensive, easy debridement, effective antibacterial, biocompatibility, etc. Here, we designed a novel gelatin-based hydrogel wound dressing Gel-TA-Fe3+. The hydrogels used tannic-modified gelatin as the main body and Fe3+ as the crosslinking agent to achieve a controllable rapid sol-gel transition. The hydrogels exhibited tough mechanical properties, excellent antibacterial ability, biocompatibility and an acceptable temperature response to near-infrared light (NIR). Moreover, the hydrogels could promote the healing process of MRSA-infected skin wound in rats. This multifunctional hydrogel was thought to have potential for emergency treatment of bacterial infected wound.


Asunto(s)
Staphylococcus aureus Resistente a Meticilina , Infección de Heridas , Animales , Ratas , Gelatina/farmacología , Cicatrización de Heridas , Suplementos Dietéticos , Antibacterianos/farmacología , Hidrogeles/farmacología , Infección de Heridas/tratamiento farmacológico
20.
J Appl Microbiol ; 135(3)2024 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-38366933

RESUMEN

Chronic wound infections are generally of polymicrobial nature with aerobic and anaerobic bacteria, as well as fungi frequently observed in them. Wound treatment involves a series of steps, including debridement of the wound, flushing, and often the use of multiple wound dressings many of which are antimicrobial. Yet, many wound dressings are tested versus single species of planktonic microbes, which fails to mirror the real-life presence of biofilms. AIMS: Simple biofilm models are the first step to testing of any antimicrobial and wound dressing; therefore, the aim of this study was to develop and validate a simple polymicrobial colony biofilm wound model comprised of Pseudomonas aeruginosa, Staphylococcus aureus, and Candida albicans on RPMI-1640 agar. The model was then used to evaluate the topical disinfectant chlorohexidine and four commercially available wound dressings using the polymicrobial model. The model used was as a starting point to mimic debridement in clinical care of wounds and the effectiveness of wound dressings evaluated afterwards. METHODS AND RESULTS: Planktonic assessment using AATCC100-2004 demonstrated that all antimicrobial wound dressings reduced the planktonic microbial burden below the limit of detection; however, when challenged with polymicrobial colony biofilms, silver wound dressings showed limited effectiveness (1-2 log CFU reductions). In contrast, a single iodine releasing wound dressing showed potent antibiofilm activity reducing all species CFUs below the limit of detection (>6-10 log) depending on the species. A disrupted biofilm model challenge was performed to represent the debridement of a wound and wound silver-based wound dressings were found to be marginally more effective than in whole colony biofilm challenges while the iodine containing wound dressing reduced microbial recovery below the limit of detection. CONCLUSIONS: In this model, silver dressings were ineffective versus the whole colony biofilms but showed some recovery of activity versus the disrupted colony biofilm. The iodine wound dressing reduced the viability of all species below the level of detection. This suggests that mode of action of wound dressing should be considered for the type of biofilm challenge as should the clinical use, e.g. debridement.


Asunto(s)
Antiinfecciosos , Yodo , Infección de Heridas , Humanos , Plata , Antiinfecciosos/farmacología , Vendajes , Yodo/farmacología , Yodo/uso terapéutico , Biopelículas , Infección de Heridas/prevención & control , Infección de Heridas/tratamiento farmacológico , Pseudomonas aeruginosa
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