RESUMEN

Infected wounds produce pus and heal slowly. To address this issue, we developed a rapid-setting SP/SA@BP-C hydrogel by combining sodium alginate (SA) and soy protein (SP) with black phosphorus (BP) grafted with clarithromycin (Cla) and incorporating Ca2+ for chelation. This hydrogel dressing exhibits excellent photothermal (PT) and photodynamic (PD) bacteriostatic effects without biotoxicity, making it suitable for treating infected wounds. Characterization confirmed its successful fabrication, and the bacteriostatic effect demonstrated over 99 % efficacy through the synergistic effects of PT, PD, and Cla. Cellular studies indicated nontoxicity and a promoting effect on cell proliferation (121.6 %). In the mouse-infected wound model, the hydrogel led to complete healing in 12 days, with good recovery of the skin's superficial dermal layer and appendages. Consequently, SP/SA@BP-C is a natural hydrogel dressing with promising properties.

RESUMEN

The treatment of infected wounds relies on antibiotics; however, increasing drug resistance has made therapeutic processes more difficult. Activating self-innate immune abilities may provide a promising alternative to treat wounds with bacterial infections. In this work, we constructed an immunogenic injectable hydrogel crosslinked by the Schiff base reaction of carboxymethyl chitosan (NOCC) and aldehyde hyaluronic acid (AHA) and encapsulated with stimulator of interferon genes (STING) agonist c-di-GMP loaded ZIF-8 nanoparticles (c-di-GMP@ZIF-8). Nanocubic ZIF-8 was screened as the most efficient intracellular drug delivery vector from five differently-shaped morphologies. The NOCC/AHA hydrogel released c-di-GMP@ZIF-8 more quickly (43 %) in acidic environment (pH = 5.5) of infected wounds compared with 34 % in non-infected wound environment (pH = 7.4) at 96 h due to pH-responsive degradation performance. The released c-di-GMP@ZIF-8 was found to activate the STING signaling of macrophages and enhance the secretion of IFN-ß, CCL2, and CXCL12 5.8-7.6 times compared with phosphate buffer saline control, which effectively inhibited S. aureus growth and promoted fibroblast migration. In rat models with infected wounds, the c-di-GMP@ZIF-8 nanocomposite hydrogels improved infected wound healing by promoting granulation tissue regeneration, alleviating S. aureus-induced inflammation, and improving angiogenesis. Altogether, this study demonstrated a feasible strategy using STING-targeted and pH-responsive hydrogels for infected wound management.

RESUMEN

Infected wounds pose a significant clinical challenge due to bacterial resistance, recurrent infections, and impaired healing. Reactive oxygen species (ROS)-based strategies have shown promise in eradicating bacterial infections. However, the excess ROS in the infection site after treatments may cause irreversible damage to healthy tissues. To address this issue, we developed bovine serum albumin-iridium oxide nanoclusters (BSA-IrOx NCs) which enable photo-regulated ROS generation and scavenging using near infrared (NIR) laser. Upon NIR laser irradiation, BSA-IrOx NCs exhibit enhanced photodynamic therapy, destroying biofilms and killing bacteria. When the NIR laser is off, the nanoclusters' antioxidant enzyme-like activities prevent inflammation and repair damaged tissue through ROS clearance. Transcriptomic and metabolomic analyses revealed that BSA-IrOx NCs inhibit bacterial nitric oxide synthase, blocking bacterial growth and biofilm formation. Furthermore, the nanoclusters repair impaired skin by strengthening cell junctions and reducing mitochondrial damage in a fibroblast model. In vivo studies using rat infected wound models confirmed the efficacy of BSA-IrOx NCs. This study presents a promising strategy for treating biofilm-induced infected wounds by regulating the ROS microenvironment, addressing the challenges associated with current ROS-based antibacterial approaches.

RESUMEN

Wound healing is a complex process that is critical for maintaining the barrier function of the skin. However, when a large quantity of microorganisms invade damaged skin for an extended period, they can cause local and systemic inflammatory responses. If left untreated, this condition may lead to chronic infected wounds. Infected wounds significantly escalate wound management costs worldwide and impose a substantial burden on patients and healthcare systems. Recent clinical trial results suggest that the utilization of effective antimicrobial wound dressing could represent the simplest and most cost-effective strategy for treating infected wounds, but there has hitherto been no comprehensive evaluation reported on the efficacy of antimicrobial wound dressings in promoting wound healing. Therefore, this review aims to systematically summarize the various types of antimicrobial wound dressings and the current research on antimicrobial agents, thereby providing new insights for the innovative treatment of infected wounds.

RESUMEN

Regulating macrophage phenotypes to reconcile the conflict between bacterial suppression and tissue regeneration is ideal for treating infectious skin wounds. Here, an injectable immunoregulatory hydrogel (SrmE20) that sequentially drives macrophage phenotypic polarization (M0 to M1, then to M2) was constructed by integrating anti-inflammatory components and proinflammatory solvents. In vitro experiments demonstrated that the proinflammatory solvent ethanol stabilized the hydrogel structure, maintained the phenolic hydroxyl group activity, and achieved macrophages' proinflammatory transition (M0 to M1) to enhance antibacterial effects. With ethanol depletion, the hydrogel's cations and phenolic hydroxyl groups synergistically regulated macrophages' anti-inflammatory transition (M1 to M2) to initiate regeneration. In the anti-contraction full-thickness wound model with infection, this hydrogel effectively eliminated bacteria and even achieved anti-inflammatory M2 macrophage accumulation at three days post-surgery, accelerated angiogenesis and collagen deposition. By sequentially driving macrophage phenotypic polarization, this injectable immunoregulatory hydrogel will bring new guidance for the care and treatment of infected wounds.

RESUMEN

Treatment of multiple bacterial infected wounds by eliminating bacteria and promoting tissue regeneration remains a clinical challenge. Herein, dual-network hydrogels (CS-GA/A-ß-CD) with snap-structure were designed to achieve curcumin immobilization, using gallic acid-grafted chitosan (CS-GA) and aldehyde-ß-cyclodextrin (A-ß-CD) crosslinked. A-ß-CD were able to achieve rapid dissolution (≥222.35 mg/mL H2O), and helped CS-GA/A-ß-CD achieve rapid gelation (≤66.23 s). By adjusting the ratio of aldehyde groups of A-ß-CD, mechanical properties and drug release can be controlled. CS-GA/A-ß-CD/Cur exhibited excellent antimicrobial properties against S. aureus, E. coli, and P. aeruginosa. In vivo experiments demonstrated that CS-GA/A-ß-CD/Cur achieved acute bacterial infection wound healing after 20th days, proving its great potential for wound dressing.

Asunto(s)

Antibacterianos , Quitosano , Hidrogeles , Cicatrización de Heridas , Infección de Heridas , beta-Ciclodextrinas , Quitosano/química , Hidrogeles/química , Hidrogeles/farmacología , beta-Ciclodextrinas/química , Animales , Cicatrización de Heridas/efectos de los fármacos , Infección de Heridas/tratamiento farmacológico , Infección de Heridas/microbiología , Antibacterianos/farmacología , Antibacterianos/química , Polifenoles/química , Polifenoles/farmacología , Liberación de Fármacos , Ratones , Staphylococcus aureus/efectos de los fármacos , Aldehídos/química , Escherichia coli/efectos de los fármacos , Curcumina/química , Curcumina/farmacología , Vendajes

RESUMEN

Interruption of wound healing by multi-drug resistant-bacterial infection is a harmful issue for the worldwide health care system, and conventional treatment approaches may not resolve this issue due to antimicrobial resistance. So, there is an unmet need to develop scaffolds with intrinsic wound healing properties to combat bacterial-infected wounds. Inspired by the α-lactalbumin's (Lalb's) ability to promote collagen synthesis, we herein electrospun Lalb with cephalexin (CPL) and epigallocatechin (EP) to produce nanofibers (CE-Lalb NFs) to solve this issue. The CE-Lalb NFs were prepared using the electrospinning technique and subjected to physicochemical characterizations, in vitro, and in vivo assessments. The CE-Lalb NFs promoted fibroblast migration, proliferation, and collagen synthesis, while CPL/EP annihilated MRSA and E. coli infections. Physicochemical characterizations proved the successful fabrication and doping of CE-Lalb NFs. Antimicrobial assays and fractional inhibitory concentration index (FICI) declared synergistic antibacterial activity of CE-Lalb NFs against MRSA and E. coli. The in vivo and immunohistochemical data evidenced its exceptional potential for wound healing, promoting growth factor, collagen synthesis, and reduced scar formation. The presence of mature collagen, fewer inflammatory cytokines, increased expression of blood vessels, and low expression of IL-6 at the wound site support in vitro and in vivo results. In our view, the tailored scaffold is the next step for personalized wound dressings that could meet patients with infected wounds' unmet needs by the subscription of noninvasive and easily navigable therapeutic options.

Asunto(s)

Antibacterianos , Lactalbúmina , Cicatrización de Heridas , Cicatrización de Heridas/efectos de los fármacos , Animales , Antibacterianos/farmacología , Antibacterianos/química , Antibacterianos/administración & dosificación , Lactalbúmina/química , Lactalbúmina/farmacología , Andamios del Tejido/química , Escherichia coli/efectos de los fármacos , Ratones , Nanofibras/química , Staphylococcus aureus Resistente a Meticilina/efectos de los fármacos , Colágeno , Catequina/análogos & derivados , Catequina/química , Catequina/farmacología , Catequina/administración & dosificación , Masculino , Cefalexina/farmacología , Cefalexina/química , Cefalexina/administración & dosificación , Fibroblastos/efectos de los fármacos , Regeneración/efectos de los fármacos , Humanos , Proliferación Celular/efectos de los fármacos , Infecciones por Escherichia coli/tratamiento farmacológico , Infecciones Estafilocócicas/tratamiento farmacológico , Movimiento Celular/efectos de los fármacos , Ratas

RESUMEN

Better infection control will accelerate wound healing and alleviate associated healthcare burdens. Traditional antibacterial dressings often inadequately control infections, inadvertently promoting antibacterial resistance. Our research unveils a novel, dual-functional living dressing that autonomously generates antibacterial agents and delivers electrical stimulation, harnessing the power of spore-forming Bacillus subtilis. This dressing is built on an innovative wearable microbial fuel cell (MFC) framework, using B. subtilis endospores as a powerful, dormant biocatalyst. The endospores are resilient, reactivating in nutrient-rich wound exudate to produce electricity and antibacterial compounds. The combination allows B. subtilis to outcompete pathogens for food and other resources, thus fighting infections. The strategy is enhanced by the extracellular synthesis of tin oxide and copper oxide nanoparticles on the endospore surface, boosting antibacterial action, and electrical stimulation. Moreover, the MFC framework introduces a pioneering dressing design featuring a conductive hydrogel embedded within a paper-based substrate. The arrangement ensures cell stability and sustains a healing-friendly moist environment. Our approach has proven very effective against three key pathogens in biofilms: Pseudomonas aeruginosa, Escherichia coli, and Staphylococcus aureus demonstrating exceptional capabilities in both in vitro and ex vivo models. Our innovation marks a significant leap forward in wearable MFC-based wound care, offering a potent solution for treating infected wounds.

Asunto(s)

Antibacterianos , Bacillus subtilis , Fuentes de Energía Bioeléctrica , Biopelículas , Escherichia coli , Pseudomonas aeruginosa , Staphylococcus aureus , Infección de Heridas , Antibacterianos/farmacología , Antibacterianos/química , Staphylococcus aureus/efectos de los fármacos , Humanos , Pseudomonas aeruginosa/efectos de los fármacos , Infección de Heridas/tratamiento farmacológico , Infección de Heridas/microbiología , Bacillus subtilis/efectos de los fármacos , Biopelículas/efectos de los fármacos , Escherichia coli/efectos de los fármacos , Dispositivos Electrónicos Vestibles , Vendajes , Cobre/química , Cobre/farmacología , Cicatrización de Heridas/efectos de los fármacos , Hidrogeles/química , Hidrogeles/farmacología

RESUMEN

Wound healing is a critical but complex biological process of skin tissue repair and regeneration resulting from various systems working together at the cellular and molecular levels. Quick wound healing and the problems associated with traditional wound repair techniques are being overcome with multifunctional materials. Over time, this research area has drawn significant attention. Metal-organic frameworks (MOFs), owning to their peculiar physicochemical characteristics, are now considered a promising class of well-suited porous materials for wound healing in addition to their other biological applications. This detailed literature review provides an overview of the latest developments in MOFs for wound healing applications. We have discussed the synthesis, essential biomedical properties, wound-healing mechanism, MOF-based dressing materials, and their wound-healing applications. The possible major challenges and limitations of MOFs have been discussed, along with conclusions and future perspectives. This overview of the literature review addresses MOFs-based wound healing from several angles and covers the most current developments in the subject. The readers may discover how the MOFs advanced this discipline by producing more inventive, useful, and successful dressings. It influences the development of future generations of biomaterials for the healing and regeneration of skin wounds.

Asunto(s)

Vendajes , Materiales Biocompatibles , Estructuras Metalorgánicas , Piel , Cicatrización de Heridas , Estructuras Metalorgánicas/química , Humanos , Materiales Biocompatibles/química , Animales , Porosidad

RESUMEN

Aim: Here, an innovative kind of antibacterial nanocomposite film is developed by incorporating graphene oxide and zinc oxide into chitosan matrix. Materials & methods: Our dressing was fabricated using the solution casting method. Fourier transform infrared spectra and TGA-DTG clearly confirmed the structure of film dressing. Results & conclusion: Our results showed the tensile strength and elongation at the break of the films were 20.1 ± 0.7 MPa and 36 ± 10%, respectively. Our fabricated film could absorb at least three-times the fluid of its dry weight while being biocompatible, antibacterial, non-irritant and non-allergic. In addition, it accelerated the healing process of infected wounds by regulating epithelium thickness and the number of inflammatory cells, thus it may be useful for direct application to damaged infected wounds.

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In this study, an innovative kind of antibacterial nanocomposite film is developed by incorporating graphene oxide and zinc oxide into chitosan matrix. Our antibacterial wound dressing was fabricated using the solution casting method. Our fabricated film could absorb at least three-times the fluid of its dry weight while being biocompatible, antibacterial, non-irritant and non-allergic. In addition, our film accelerated the healing process of infected wounds by regulating epithelium thickness and the number of inflammatory cells. thus it may be useful for direct application to damaged infected wounds.

RESUMEN

Staphylococcus aureus is a pathogen widely involved in wound infection due to its ability to release several virulence factors that impair the skin healing process, as well as its mechanism of drug resistance. Herein, sodium alginate and chitosan were combined to produce a hydrogel for topical delivery of neomycin to combat S. aureus associated with skin complications. The hydrogel was formulated by combining sodium alginate (50 mg/mL) and chitosan (50 mg/mL) solutions in a ratio of 9:1 (HBase). Neomycin was added to HBase to achieve a concentration of 0.4 mg/mL (HNeo). The incorporation of neomycin into the product was confirmed by scanning electron microscopy, FTIR and TGA analysis. The hydrogels produced are homogeneous, have a high swelling capacity, and show biocompatibility using erythrocytes and fibroblasts as models. The formulations showed physicochemical and pharmacological stability for 60 days at 4 ± 2 °C. HNeo totally inhibited the growth of S. aureus after 4 h. The antimicrobial effects were confirmed using ex vivo (porcine skin) and in vivo (murine) wound infection models. Furthermore, the HNeo-treated mice showed lower severity scores than those treated with HBase. Taken together, the obtained results present a new low-cost bioproduct with promising applications in treating infected wounds.

Asunto(s)

Alginatos , Antibacterianos , Quitosano , Hidrogeles , Neomicina , Staphylococcus aureus , Quitosano/química , Quitosano/farmacología , Alginatos/química , Alginatos/farmacología , Hidrogeles/química , Hidrogeles/farmacología , Staphylococcus aureus/efectos de los fármacos , Animales , Ratones , Neomicina/farmacología , Neomicina/química , Neomicina/administración & dosificación , Antibacterianos/farmacología , Antibacterianos/química , Infecciones Estafilocócicas/tratamiento farmacológico , Infecciones Cutáneas Estafilocócicas/tratamiento farmacológico , Infecciones Cutáneas Estafilocócicas/microbiología , Infecciones Cutáneas Estafilocócicas/patología , Portadores de Fármacos/química , Piel/efectos de los fármacos , Piel/microbiología

RESUMEN

Wounds infected with bacteria, if left untreated, have the potential to escalate into life-threatening conditions, such as sepsis, which is characterized by widespread inflammation and organ damage. A comprehensive approach to treating bacterial-infected wounds, encompassing the control of bacterial infection, biofilm eradication, and inflammation regulation, holds significant importance. Herein, a microneedle (MN) patch (FM@ST MN) has been developed, with silk fibroin (SF) and tannic acid-based hydrogel serving as the matrix. Encapsulated within the MNs are the AIEgen-based activatable probe (FQ-H2O2) and the NLRP3 inhibitor MCC950, serving as the optical reporter/antibacterial agent and the inflammation regulator, respectively. When applied onto bacterial-infected wounds, the MNs in FM@ST MN penetrate bacterial biofilms and gradually degrade, releasing FQ-H2O2 and MCC950. The released FQ-H2O2 responds to endogenously overexpressed reactive oxygen species (H2O2) at the wound site, generating a chromophore FQ-OH which emits noticeable NIR-II fluorescence and optoacoustic signals, enabling real-time imaging for outcome monitoring; and this chromophore also exhibits potent antibacterial capability due to its dual positive charges and shows negligible antibacterial resistance. However, the NLRP3 inhibitor MCC950, upon release, suppresses the activation of NLRP3 inflammasomes, thereby mitigating the inflammation triggered by bacterial infections and facilitating wound healing. Furthermore, SF in FM@ST MN aids in tissue repair and regeneration by promoting the proliferation of epidermal cells and fibroblasts and collagen synthesis. This MN system, free from antibiotics, holds promise as a solution for treating and monitoring bacterially infected wounds without the associated risk of antimicrobial resistance.

RESUMEN

Bacterial-infected wounds present a significant challenge in the medical field, posing a severe threat to public health. Traditional wound dressings have limited efficacy in treating bacterial-infected wounds, and antibiotics suffer from cytotoxicity and drug resistance. Consequently, an urgent requirement exists for developing multifunctional wound dressings capable of providing superior antimicrobial activity and expediting wound repair. In recent years, chitosan-based natural polysaccharide hydrogels have garnered attention for their biocompatibility, antimicrobial properties, and ability to aid in hemostasis. This study presents the development of a multi-functional, bi-dynamic network hydrogel for the treatment of wounds infected with bacteria. The hydrogel consists of a backbone of chitosan grafted with chlorogenic acid (CA-ECS), oxidized pullulan polysaccharides (OP), and zinc ions (Zn2+). The CA-ECS/OP/Zn2+ hydrogel displayed strong adhesion, good injectability, and high mechanical strength and was biodegradable and biocompatible. Furthermore, adding Zn2+ and CA enhanced the hydrogel's mechanical properties and antioxidant and antimicrobial activities. In a rat model of full-thickness skin wounds infected with S. aureus, the CA-ECS/OP/Zn2+ hydrogel demonstrated great anti-inflammatory, angiogenic, and folliculogenic properties, resulting in accelerated wound healing. The CA-ECS/OP/Zn2+ hydrogel has great potential for treating bacterial-infected wounds.

Asunto(s)

Quitosano , Polifenoles , Animales , Ratas , Hidrogeles , Staphylococcus aureus , Polisacáridos/farmacología , Metales , Antibacterianos/farmacología

RESUMEN

Chronic wounds of significant severity and acute injuries are highly vulnerable to fungal infections, drastically impeding the expected wound healing trajectory. The clinical use of antifungal therapeutic drug is hampered by poor solubility, high toxicity and adverse reactions, thereby necessitating the urgent development of novel antifungal therapy strategy. Herein, this study proposes a new strategy to enhance the bioactivity of small-molecule antifungal drugs based on multifunctional metal nanozyme engineering, using amphotericin B (AmB) as an example. AmB-decorated gold nanoparticles (AmB@AuNPs) are synthesized by a facile one-pot reaction strategy, and the AmB@AuNPs exhibit superior peroxidase (POD)-like enzyme activity, with maximal reaction rates (Vmax) 3.4 times higher than that of AuNPs for the catalytic reaction of H2O2. Importantly, the enzyme-like activity of AuNPs significantly enhanced the antifungal properties of AmB, and the minimum inhibitory concentrations of AmB@AuNPs against Candida albicans (C. albicans) and Saccharomyces cerevisiae (S. cerevisiae) W303 are reduced by 1.6-fold and 50-fold, respectively, as compared with AmB alone. Concurrent in vivo studies conducted on fungal-infected wounds in mice underscored the fundamentally superior antifungal ability and biosafety of AmB@AuNPs. The proposed strategy of engineering antifungal drugs with nanozymes has great potential for enhanced therapy of fungal infections and related diseases.

Asunto(s)

Anfotericina B , Antifúngicos , Candida albicans , Oro , Nanopartículas del Metal , Pruebas de Sensibilidad Microbiana , Oro/química , Antifúngicos/farmacología , Antifúngicos/química , Antifúngicos/uso terapéutico , Anfotericina B/farmacología , Anfotericina B/química , Anfotericina B/uso terapéutico , Nanopartículas del Metal/química , Nanopartículas del Metal/uso terapéutico , Candida albicans/efectos de los fármacos , Animales , Saccharomyces cerevisiae/efectos de los fármacos , Ratones

RESUMEN

Bacterial infections are major problems in wound care due to their impact on the retarded process of wound healing, leading to chronic wounds. Most of the presently utilized wound dressing products exhibit poor antimicrobial properties. Wound dressings formulated from chitosan have been reported to be effective for treating infected wounds, resulting from the antibacterial properties of chitosan. The antibacterial properties of chitosan-based wound dressings can be further enhanced by incorporating metallic nanoparticles into them, such as silver, zinc, titanium, etc. The incorporation of silver nanoparticles into chitosan-based wound dressings has been widely explored in the design of antimicrobial wound dressings. The incorporation of silver nanoparticles into chitosan-based wound dressings promotes accelerated wound-healing processes due to enhanced antimicrobial activity. The accelerated wound healing by these metal-based nanoparticles is via the regulation of re-epithelialization and inflammation without affecting the viability of normal cells. However, there have been few reports that evaluate these wound dressings in infectious animal models to prove their efficacy. The in vivo toxicity of silver nanoparticles still needs to be addressed, revealing the need for further preclinical and clinical trials. The fabrication of wound dressings incorporated with silver nanoparticles has not been fully explored, especially for wounds requiring immediate treatment. The possible interactions between silver nanoparticles and chitosan scaffolds that result in synergistic effects still need to be understood and studied. This review provides a comprehensive report on the preclinical outcomes of chitosan wound dressing materials loaded with silver nanoparticles for managing infected wounds.

RESUMEN

Bacterial wound infection has emerged as a pivotal threat to human health worldwide, and the situation has worsened owing to the gradual increase in antibiotic-resistant bacteria caused by the improper use of antibiotics. To reduce the use of antibiotics and avoid the increase in antibiotic-resistant bacteria, researchers are increasingly paying attention to  photodynamic therapy, which uses light to produce reactive oxygen species to kill bacteria. Treating bacteria-infected wounds by photodynamic therapy requires fixing the photosensitizer (PS) at the wound site and maintaining a certain level of wound humidity. Hydrogels are materials with a high water content and are well suited for fixing PSs at wound sites for antibacterial photodynamic therapy. Therefore, hydrogels are often loaded with PSs for treating bacteria-infected wounds via antibacterial photodynamic therapy. In this review, we systematically summarised the antibacterial mechanisms and applications of PS-loaded hydrogels for treating bacteria-infected wounds via photodynamic therapy. In addition, the recent  studies and the research status progresses of novel antibacterial hydrogels are discussed. Finally, the challenges and future prospects of PS-loaded hydrogels are reviewed.

Asunto(s)

Antibacterianos , Vendajes , Hidrogeles , Fármacos Fotosensibilizantes , Infección de Heridas , Humanos , Antibacterianos/farmacología , Antibacterianos/administración & dosificación , Infecciones Bacterianas/tratamiento farmacológico , Hidrogeles/farmacología , Fotoquimioterapia/métodos , Fármacos Fotosensibilizantes/farmacología , Cicatrización de Heridas/efectos de los fármacos , Infección de Heridas/tratamiento farmacológico , Infección de Heridas/microbiología

RESUMEN

Wounds infected with multidrug-resistant (MDR) bacteria are increasingly threatening public health and challenging clinical treatments because of intensive bacterial colonization, excessive inflammatory responses, and superabundant oxidative stress. To overcome this malignant burden and promote wound healing, a multifunctional cryogel (HA/TA2/KR2) composed of hyaluronic acid (HA), tannic acid (TA), and KR-12 peptides is designed. The cryogel exhibited excellent shape-memory properties, strong absorption performance, and hemostatic capacity. In vitro experiments demonstrated that KR-12 in the cryogel can be responsively released by stimulation with hyaluronidase produced by bacteria, reaching robust antibacterial activity against Escherichia coli (E. coli), MDR Pseudomonas aeruginosa (MDR-PA), and methicillin-resistant Staphylococcus aureus (MRSA) by disrupting bacterial cell membranes. Furthermore, the synergetic effect of KR-12 and TA can efficiently scavenge ROS and decrease expression of pro-inflammatory cytokines (tumor necrosis factor (TNF)-α & interleukin (IL)-6), as well as modulate the macrophage phenotype toward the M2 type. In vivo animal tests indicated that the cryogel can effectively destroy bacteria in the wound and promote healing process via accelerating angiogenesis and re-epithelialization. Proteomic analysis revealed the underlying mechanism by which the cryogel mainly reshaped the infected wound microenvironment by inhibiting the Nuclear factor kappa B (NF-κB) signaling pathway and activating the Janus kinase-Signal transducer and activator of transcription (JAK-STAT6) signaling pathway. Therefore, the HA/TA2/KR2 cryogel is a promising dressing candidate for MDR bacteria-infected wound healing.

Asunto(s)

Antibacterianos , Criogeles , Modelos Animales de Enfermedad , Hialuronoglucosaminidasa , Especies Reactivas de Oxígeno , Cicatrización de Heridas , Animales , Ratones , Antibacterianos/farmacología , Criogeles/farmacología , Criogeles/química , Escherichia coli/efectos de los fármacos , Ácido Hialurónico/farmacología , Hialuronoglucosaminidasa/metabolismo , Inflamación/tratamiento farmacológico , Staphylococcus aureus Resistente a Meticilina/efectos de los fármacos , Pseudomonas aeruginosa/efectos de los fármacos , Especies Reactivas de Oxígeno/metabolismo , Cicatrización de Heridas/efectos de los fármacos , Infección de Heridas/tratamiento farmacológico , Infección de Heridas/microbiología , Ratones Endogámicos BALB C

RESUMEN

For the treatment of MRSA-infected wounds, the spatiotemporally sequential delivery of antibacterial and anti-inflammatory drugs is a promising strategy. In this study, ROS-responsive HA-PBA/PVA (HPA) hydrogel was prepared by phenylborate ester bond cross-linking between hyaluronic acid-grafted 3-amino phenylboronic acid (HA-PBA) and polyvinyl alcohol (PVA) to achieve spatiotemporally controlled release of two kinds of drug to treat MRSA-infected wound. The hydrophilic antibiotic moxifloxacin (M) was directly loaded in the hydrogel. And hydrophobic curcumin (Cur) with anti-inflammatory function was first mixed with Pluronic F127 (PF) to form Cur-encapsulated PF micelles (Cur-PF), and then loaded into the HPA hydrogel. Due to the different hydrophilic and hydrophobic nature of moxifloxacin and Cur and their different existing forms in the HPA hydrogel, the final HPA/M&Cur-PF hydrogel can achieve different spatiotemporally sequential delivery of the two drugs. In addition, the swelling, degradation, self-healing, antibacterial, anti-inflammatory, antioxidant property, and biocompatibility of hydrogels were tested. Finally, in the MRSA-infected mouse skin wound, the hydrogel-treated group showed faster wound closure, less inflammation and more collagen deposition. Immunofluorescence experiments further confirmed that the hydrogel promoted better repair by reducing inflammation (TNF-α) and promoting vascular (VEGF) regeneration. In conclusion, this HPA/M&Cur-PF hydrogel that can spatiotemporally sequential deliver antibacterial and anti-inflammatory drugs showed great potential for the repair of MRSA-infected skin wounds.

RESUMEN

High-grade gliomas (HGGs) may be amenable to the neurosurgical technique known as laser interstitial thermal therapy (LITT), which delivers thermal energy to interstitial brain injuries and wounds with pinpoint accuracy. The purpose of this extensive meta-analysis was to evaluate the effects of LITT on wound complications among patients who have brain tumours. Diverse conclusions emerge from a systematic review of pertinent studies, necessitating a comprehensive examination. The meta-analysis, performed utilizing the meta library provided by the R package meta, reveals an initial significant overall effect (RR: -2.1262, 95% CI [-2.7466, -1.5059], p < 0.0001) accompanied by considerable heterogeneity among studies (I2 = 61.13%). Following analyses that specifically examined the incidence of wounds, a complex correlation was found (RR: 0.0471, 95% CI [0.0264, 0.0842], p < 0.0001), indicating that LITT has a discernible but insignificant effect on the occurrence of wounds. Although the meta-analysis emphasizes a notable decrease in wound complications subsequent to LITT treatment, additional research is warranted due to constraints in standardized reporting, data accessibility, and small sample sizes. The results of this study underscore the need for exhaustive protocols to analyse wound complications in patients with brain tumours undergoing LITT.

Asunto(s)

Neoplasias Encefálicas , Hipertermia Inducida , Terapia por Láser , Humanos , Neoplasias Encefálicas/etiología , Neoplasias Encefálicas/cirugía , Hipertermia Inducida/efectos adversos , Hipertermia Inducida/métodos , Terapia por Láser/efectos adversos , Terapia por Láser/métodos , Rayos Láser , Cicatrización de Heridas

Asunto(s)

Infección de Heridas , Humanos , Infección de Heridas/microbiología , Infección de Heridas/terapia , Bacterias