Chronic Wound Infections Research Articles

Facile Formulation of a Resveratrol-Mediated Multibond Network Hydrogel with Efficient Sustainable Antibacterial, Reactive Oxygen Species Scavenging, Pro-Angiogenesis, and Immunomodulation Activities for Accelerating Infected Wound Healing.

The management of chronic infected wounds remains a significant clinical challenge, largely due to the deficiency of optimal wound dressings with adequate mechanical strength, appropriate adhesiveness, and efficient sustainable antibacterial, reactive oxygen species (ROS) scavenging, pro-angiogenesis, and immunomodulation properties. To address such a dilemma, we employed a simple and facile strategy to utilize resveratrol (RSV) as a functional component to mediate hydrogel gelation in this study. The structure of this obtained hydrogel was supported by a multibond network, which not only endowed the resultant product with superior mechanical strength and moderate adhesiveness but also effectively prolonged the bioavailability of RSV. This strategy successfully integrated the entire system with sustainable antibacterial, ROS scavenging, pro-angiogenesis, and immunomodulation properties. Subsequent in vivo evidence has verified that this material was capable to accelerate the healing of chronic infected wounds. The underlying mechanism can be explained that this hydrogel is capable of propelling macrophage polarization from the M1 to M2 phenotype through modulating the PI3K/AKT signaling pathway to activate the nuclear factor erythroid 2-related factor 2 (Nrf2) signaling as well as maintaining the mitochondrial membrane potential level in the normal state under excessive inflammatory and oxidative stimulus. In summary, this multifunctional hydrogel wound dressing provides a feasible way to promote the bioavailability of RSV, which is conducive for preparing a promising candidate for chronic infected wound healing. What is more important, it is also beneficial to reveal the correlative mechanisms to establish advanced therapeutic platform for targeting other complex infection microenvironment.

Evaluation of the antibacterial properties of four bioactive biomaterials for chronic wound management.

Chronic wound infections present a prevalent medical issue and a multifaceted problem that significantly impacts healthcare systems worldwide. Biofilms formed by pathogenic bacteria are fundamental virulence factors implicated in the complexity and persistence of bacterial-associated wound infections, leading to prolonged recovery times and increased risk of infection. This study aims to investigate the antibacterial effectiveness of commonly employed bioactive wound healing compositions with a particular emphasis on their effectiveness against common bacterial pathogens encountered in chronic wounds - Staphylococcus epidermidis, Escherichia coli, and Pseudomonas aeruginosa to identify optimal wound product composition for managing chronic wound infections. This study tested the antibacterial and antibiofilm effectiveness of four bioactive wound healing materials by performing in vitro antibacterial assays and measuring ion release profiles. The anti-biofilm effectiveness differed extensively among the biomaterials tested and slightly among the bacterial species. Particularly, copper and zinc-doped borate bioactive glass wound healing compositions inhibited the three clinically relevant bacteria in both planktonic and biofilm forms, which were found to be ascribed to the copper and zinc gradual release. The findings suggest that copper and zinc-doped bioactive glasses hold great promise for improving chronic wound management by providing strong antibacterial action and promoting faster healing.

Synergistic antimicrobial efficacy of glabrol and colistin through micelle-based co-delivery against multidrug-resistant bacterial pathogens.

Widespread bacterial infection and the spread of multidrug resistance (MDR) exhibit increasing threats to the public and thus require new antibacterial strategies. Coupled with the current slow pace of antibiotic development, the use of antibiotic adjuvants to revitalize existing antibiotics offers great potential. We aim to explore the synergistic antimicrobial mechanism of glabrol (GLA) and colistin (COL) while developing an innovative multifunctional micelle-based drug delivery system to enhance therapeutic efficacy. The synergy between GLA and COL was assessed through a combination of high-throughput screening and checkerboard analysis techniques. Moreover, we performed fluorescence-based assays to investigate the underlying mechanisms of action of the GLA and COL combination. We also developed a multifunctional drug delivery platform that integrates GLA and COL into co-loaded composite micelles, aimed at improving antibacterial efficacy against peritoneal sepsis and chronic bacterial wound infections caused by diverse microbial pathogens. We have discovered that natural flavonoids found in plants act synergistically with colistin against MDR bacterial infections, effectively improving its efficacy through a co-delivery strategy. The combination therapy consisting of GLA and COL exhibits enhanced antibacterial efficacy and is capable of clearing 99% of MDR Gram-positive and Gram-negative bacteria in 4 h. Mechanistic studies showed that COL increases the outer membrane permeability, which promotes the adhesion of GLA to the inner membrane, disrupting bacterial metabolism, and ultimately leading to bacterial death. Furthermore, a novel pH-responsive hydrogel system was developed and dispersed with GLA and COL co-loaded composite micelles to mitigate the selective pressure of antibiotics with fewer side effects. Lastly, such a system showed high efficacy in two animal models. Our findings provide a potential therapeutic option using a co-delivery system functionalized with combination therapy, to address the prevalent infections caused by complex bacterial infections and even MDR bacterial infections.

Bacterial predatory potentials of indigenous Bdellovibrio species in southwest Nigeria: Targeting multidrug-resistant Klebsiella pneumoniae and Enterobacter species isolated from chronic wound infections

Background: Chronic wound infections could become life-threatening conditions when caused by multi-drug-resistant Gram-negative ESKAPE (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa and Enterobacter spp) pathogens. Alternative therapeutic approaches are vital for the therapy of infections caused by these pathogens and one of the biocontrol therapies is the application of Bdellovibrio spp, a Gram-negative bacterium with predatory potential against pathogenic Gram-negative bacteria.Methodology: This study isolated, and phenotypically and genotypically characterized Bdellovibrio spp from environmental sources including soil, pond waters, and faecal materials from cattle and poultry in Osogbo, southwest Nigeria using double-layered agar plating technique, with Klebsiella spp as prey. The prey range and predatory potentials of the isolated Bdellovibrio spp against 25 clinical bacterial isolates including 6 K. pneumoniae and 19 Enterobacter spp, recovered from chronic wound infections, was assessed using the same double-layered agar technique.Results: Five strains of Bdellovibrio isolated formed characteristic plaques on lawns of Klebsiella spp used as prey. At the molecular level, all the five strains, designated UAB, STU, PW2, PW5, and PW6, belonged to the genus Bdellovibrio, however, they exhibited different clustering patterns on the phylogenetic tree. Additionally, the prey range of the five Bdellovibrio strains on the bacterial isolates varied, with UAB, PW6, PW5, and PW2 preying upon 12 (48.0%), 12 (48.0%), 7 (28.0%), and 1 (4.0%) bacterial isolate respectively, while STU did not prey on any of the bacteria isolates.Conclusion: This research presents the first molecular characterization of Bdellovibrio spp in Nigeria, hence serving as a baseline study for future Bdellovibrio research in Nigeria. It also highlights the promising potential of Bdellovibrio spp in control of K. pneumoniae and Enterobacter spp associated with chronic wound infections.

Wound healing and the antimicrobial impact by using biosynthesized iron oxide nanoparticles

Chronic wound infections are a major cause of chronic wound development. This study aimed to investigate the role of Fe2O3 nanoparticles (Fe2O3 NPs) in the growth inhibition of multidrug resistant bacteria (MDR) and enhancement of human foreskin cell line migration and proliferation. For this aim, Fe2O3 NPs were synthesized from the bacterial extract and characterized it with UV-Vis, EDS, FTIR, AFM and FESEM assays. In addition, investigate the antibacterial effect using the well diffusion method. as well as study the cytotoxicity effect via MTT assay and the migration of cells through the scratch wound assay for human foreskin (HFF) cell line. The results confirmed the synthesis of Fe2O3 as the UV-Vis, which showed a peak at 288 nm; EDS showed peaks that corresponded to that of Fe2O3 NPs; FTIR showed absorption of functional groups belonging to bacterial extract, while FESEM revealed the irregular agglomerated shape, and AFM showed a mean diameter of 84.45 nm for Fe2O3 NPs. The green synthesized Fe2O3 revealed an antibacterial activity on MDR bacteria (Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus). Moreover, a significant increase in the viability of HFF cell line in dose dependent manner leading to the enhancement of these cells to migrate and proliferate to close the scratched line in 12h of incubation under the effect of these NPs. In conclusion, the findings of the current study exhibited a successful synthesized nanoparticles Fe2O3 from bacterial extract. These NPs presented a significant antibacterial impact against MDR bacteria. Most importantly, they showed a significant biocompatibility and promoted cell viability, migration and proliferation in HFF cells. These findings point up the capability of Fe2O3 as a promising treatment for wound healing applications.

Efficient Photolysis of Multidrug-Resistant Polymicrobial Biofilms.

Chronic wounds are prone to infections with multidrug-resistant bacteria, forming polymicrobial biofilms that limit treatment options and increase the risk of severe complications. Current cleansing options are insufficient to disrupt and remove tenacious biofilms; antibiotic treatments, on the other hand, often fall short against these biofilm-embedded bacteria. This study explores an non-antibiotic approach that extends beyond conventional porphyrin-based phototherapy by using blue light (BL) in conjunction with ferric ions (Fe(III)) to disrupt and eradicate biofilms. The dual not only degraded biofilm extracellular polymeric substances (EPS) in mono-species and polymicrobial biofilms by specifically targeting carboxyl-containing polysaccharides within the matrix but also exhibited broad-spectrum antimicrobial activity by affecting key components of the outer membrane and cell wall. Bacteria, such as K. pneumoniae, with compromised EPS after photolysis, demonstrated increased susceptibility to macrophage phagocytosis. Disruption of the polymicrobial biofilm structure also enhanced the bacterial susceptibility to bactericidal drugs. Treating wounds infected by mixed-species biofilm in diabetic mice demonstrated a substantial reduction in bacterial colonization and improved tissue repair. The BL-Fe(III) modality offers a safe, efficient alternative for managing chronic wound infections, making it ideal for repeated, non-invasive use at home, especially in resource-limited areas.

Topical Honey Application In Treating Large Ulcerated Wound As a Complication of Vascular Malformation In a 5-Month-Old Baby

Background: The ancient Egyptians and Greeks have used honey for wound care, and a broad spectrum of wounds are treated all over the world with natural unprocessed honeys from different sources. In lots of studies, honey as a conventional wound treatment may help improve wound healing, prevent invasive infections and eliminate colonization. With the increasing frequency of antibiotic-resistant bacteria, modern medicine give attention to natural products. The aim of this report is to gain insight into the practical use of topical honey in wound management. Methods: We report a case of five-month-old girl with sepsis and large ulcerated necrotizing wound at the external genitalia and perineum extending to gluteal area as complication of vein malformation after treated with intravenous injection of Bleomycin and Vincristine. Result: She was successfully treated with unprocessed local honey. Conclusion: Honey is shown to be a good option for treating infected chronic wound with dramatic result.

Smart copper-doped clays in biomimetic microparticles for wound healing and infection control

Chronic wounds are non-healing lesions characterized by a high degree of inflammation, posing significant challenges in clinical management due to the increased risk of severe infection. This study focuses on developing a powder for cutaneous application to enhance healing and prevent infections in chronic wounds. The smart nanocomposite-based biomimetic microparticles here developed combine the properties of chitosan and of clays and represent a significant innovation in the field of biomaterials for skin regeneration since they possess enhanced antimicrobial properties, are multi-functional scaffolds and promote cell proliferation, support tissue reconstruction by mimicking the natural extracellular matrix, and provide hemostatic properties to control bleeding during wound closure. The microparticles were made of chitosan and doped with clay minerals, specifically montmorillonite or layered double hydroxides containing copper ions. The synergistic combination of biomimetic polymers and clays aims to regulate cellular responses, angiogenesis, and extracellular matrix (ECM) deposition, leveraging the bioactive properties of both components to promote wound healing. Montmorillonite and layered double hydroxides were enriched with copper ions through intercalation or coprecipitation methods, respectively. The water-insoluble microparticles were prepared using a chitosan derivative, chitosan carbamate, synthesized to obtain chitosan-based microparticles via spray-drying without crosslinkers. Physico-chemical characterization confirmed the successful doping of Cu-clay interaction products in the microparticles. In addition to enhanced cell proliferation and haemostatic properties, the presence of Cu-clays boosted the microparticles’ antibacterial properties. Encouraging preclinical in vitro and in vivo results suggest that these smart nanocomposite biomimetic microparticles doped with Cu-enriched clay minerals could be promising candidates for simultaneously enhancing healing and controlling infections in chronic wounds.

Gene-engineered polypeptide hydrogels with on-demand oxygenation and ECM-cell interaction mimicry for diabetic wound healing

The treatment of infected diabetic wounds remains a significant clinical challenge due to pathogen infection, excessive inflammation, and impaired angiogenesis with troubled extracellular matrix (ECM) - cell and cell - cell interaction. Herein, we prepared a Janus polypeptide-engineered hydrogel with programmable function driven by self-assembly of the same A domain. The hydrogel was composed of a V8-degradable AC10A layer loaded with hybrid phages for precise bacterial inhibition (ABC) and a PC10ARGD layer loaded with Mn-based mineralized erythrocyte for continuous supply oxygen on demand (PEM). The results of laser speckle contrast imaging, photoacoustic imaging, and hyperspectral imaging demonstrated that the AC10A@BP-Ce6/PC10AR@EM hydrogel (ABC/PEM) accelerated the reconstruction of normal skin structure by breaking the oxygen diffusion barrier and supplying oxygen on demand to promote angiogenesis and functionalization. In addition, in vitro and in vivo experiment results showed that the ABC/PEM hydrogel can mimic positive ECM - cell interaction to inhibit the polarization of macrophage towards M1-type to slow down the inflammatory process by down-regulated yes-associated protein (YAP), and relieve the mechanical tension of fibroblasts to reduce scar formation. Finally, the ABC/PEM hydrogel promotes a healing rate of 98.83% on day 21 and results in the number of dermal appendages being eight times that of the negative group. This work presents an effective strategy for diabetes-related chronic infected wound management.

Clinical management of chronic wound infections: The battle against biofilm.

Bacteria constitute the most abundant life form on earth, of which the majority exist in a protective biofilm state. Since the 1980s, we have learned much about the role of biofilm in human chronic infections, with associated global healthcare costs recently estimated at ~$386 billion. Chronic wound infection is a prominent biofilm-induced condition that is characterised by persistent inflammation and associated host tissue destruction, and clinical signs that are distinct from signs of acute wound infection. Biofilm also enables greater tolerance to antimicrobial agents in chronic wound infections compared with acute wound infections. Given the difficulty in eliminating wound biofilm, a multi-targeted strategy (namely biofilm-based wound care) involving debridement and antimicrobial therapies were introduced and have been practiced since the early 2000s. More recently, acknowledgement of the speed at which biofilm can develop and hence quickly interfere with wound healing has highlighted the need for an early anti-biofilm strategy to combat biofilm before it takes control and prevents wound healing. This strategy, referred to as wound hygiene, involves multiple tools in combination (debridement, cleansing, and antimicrobial dressings) to maximise success in biofilm removal and encourage wound healing. This review is intended to highlight the issues and challenges associated with biofilm-induced chronic infections, and specifically address the challenges in chronic wound management, and tools required to combat biofilm and encourage wound healing.

Low Voltage-Enhanced Mechano-Bactericidal Biopatch.

Mechano-bactericidal strategies represent a safe and sustainable method for preventing microbial contamination in the postantibiotic era. However, their effectiveness against Gram-positive bacteria (≤55%) is still limited due to the thick peptidoglycan layer in their cell walls. Herein, an intelligent biomimetic nanopillared biopatch is developed. It is assisted by low-voltage (8 V) electrical stimulation from TENG and significantly enhances antibacterial efficacy (>99%) against three types of stubborn Gram-positive bacteria. These collaborative antibacterial behaviors are solely based on purely physical actions, thus avoiding the risk of triggering bacterial resistance. Moreover, the slight mechanical energy generated by human physiological activities is converted into a power source, exhibiting energy-efficient, eco-friendly, and sustainable features. The conductive hydrogel in the biopatch can also act as an intelligent temperature sensor, monitoring, and real-time assessment of wound conditions. This intelligent biopatch holds immense potential for efficient healing and safe management of both acute and chronic wound infections.

Inflammatory Microenvironment‐Responsive Nanomotors with NIR Photothermal Effect for Deep Inflammation Elimination and Infection Inhibition

AbstractThe infected chronic wound area has a unique microenvironment featuring hypoxia, excessive reactive oxygen species (ROS), and inflammatory conditions. Bacteria‐formed biofilms limit the anti‐inflammation efficiency of most therapeutics by hindering their penetration into deep infected wound tissues and increasing drug resistance. The unitary modulation of pro‐inflammatory M1 macrophage polarization cannot relieve inflammation immediately. Here, the “all in one” folic acid‐modified small organic molecule‐based nanoparticles (2TT‐mC6B@CeO2@FA, PCFs) are developed, which possess dual‐targeting to bacteria and M1 macrophages, double modulation to M1 macrophages, photothermal therapy (PTT), and enzymatic‐like activities. Based on the considerable catalase‐ and superoxide dismutase‐like activities, PCFs can efficiently scavenge ROS and produce oxygen (O2). The generated O2 can automatically drive PCFs movement as nanomotors to further promote deep penetration and rescue hypoxia. The scavenging of ROS promotes M1 macrophages polarized into anti‐inflammatory M2 macrophages. The study also identifies that FA‐modified PCFs can target bacteria and M1 macrophages to selectively eliminate M1 macrophages and bacteria through PTT, which relieves inflammation and chronic wound healing. Transcriptome analysis confirms that PCFs inhibit the expression of inflammatory‐related genes while increasing the expression of anti‐inflammatory cytokines. In vivo experiments identify that PCFs benefit neovascularization in neonatal tissues and tissue generation at wound sites.

A novel polyurethane-based silver foam dressing with superior antimicrobial action for management of infected chronic wounds

Wound healing is a complex and dynamic process supported by several cellular events. Around 13 million individuals globally suffer from chronic wounds yearly, for which dressings with excellent antimicrobial activity and cell viability (>70%, as per ISO 10993) are needed. Excessive use of silver can cause cytotoxicity and has been linked to increasing antimicrobial resistance. In this study, HDI Ag foam was synthesized using a safer hexamethylene diisocyanate-based prepolymer (HDI prepolymer) instead of commonly used diisocyanates like TDI and MDI and substantially lower Ag content than that incorporated in other Ag foams. In vitro characteristics of the HDI Ag foam were evaluated in comparison with leading clinically used foam-based dressings. All dressings underwent a detailed characterization in accordance with industrially accepted BS EN 13726 standards. The HDI Ag foam exhibited highest antimicrobial efficiency againstS. aureusandP. aeruginosa(static condition), with the lowest amount of Ag (0.2 wt%) on the wound contact surface. The extracts from HDI Ag foam showed superior cell viability (>70%), when tested on the L929 mouse fibroblast cell line. Measurements of moisture vapor transmission, fluid handling, physico-chemical and mechanical properties ensured that the HDI foam was clinically acceptable for chronic wound patients.

Novel papain and bacterial cellulose/alginate biocomposites for bioactive wound dressing

The potential of bacterial cellulose membranes in the biomedical field as a wound dressing agent including contributing to chronic wound infections. The occurrence of antibiotic resistance mechanisms that protect bacteria, this is a problem that needs to be considered in the wound healing process. To accelerate the wound healing process and avoid infection, it is necessary to choose the right wound dressing material. In this study, alginate biopolymers and papain enzymes immobilized on BC pellicle to protect wounds from infection by several bacteria were investigated. The purpose of this study was to obtain a BC composite that has the potential as antibacterial wound dressing. Antibacterial activity, biodegradability, and hemocompatibility were assessed. The 8% papain concentration showed the strongest antibacterial effect against S. aureus (5.9 ± 5.05 mm) and E. coli (6.4 ± 6.27 mm). All composites exhibited high biodegradability (94–97% weight loss). The 6% and 8% papain concentrations were hemocompatible, with low hemolysis rates (<2%). These results suggest that BC/AG/Papain composites have the potential as effective antibacterial wound dressings.

Impact of mixed Staphylococcus aureus-Pseudomonas aeruginosa biofilm on susceptibility to antimicrobial treatments in a 3D in vitro model

Staphylococcus aureus and Pseudomonas aeruginosa are the most common bacteria co-isolated from chronic infected wounds. Their interactions remain unclear but this coexistence is beneficial for both bacteria and may lead to resistance to antimicrobial treatments. Besides, developing an in vitro model where this coexistence is recreated remains challenging, making difficult their study. The aim of this work was to develop a reliable polymicrobial in vitro model of both species to further understand their interrelationships and the effects of different antimicrobials in coculture. In this work, bioluminescent and fluorescent bacteria were used to evaluate the activity of two antiseptics (chlorhexidine and thymol) against these bacteria planktonically grown, or when forming single and mixed biofilms. At the doses tested (0.4-1,000 mg/L), thymol showed selective antimicrobial action against S. aureus in planktonic and biofilm states, in contrast with chlorhexidine which exerted antimicrobial effects against both bacteria. Furthermore, the initial conditions for both bacteria in the co-culture determined the antimicrobial outcome, showing that P. aeruginosa impaired the proliferation and metabolism of S. aureus. Moreover, S. aureus showed an increased tolerance against antiseptic treatments when co-cultured, attributed to the formation of a thicker mixed biofilm compared to those obtained when monocultured, and also, by the reduction of S. aureus metabolic activity induced by diffusible molecules produced by P. aeruginosa. This work underlines the relevance of polymicrobial populations and their crosstalk and microenvironment in the search of disruptive and effective treatments for polymicrobial biofilms.

Local Treatment of Wound Infections: A Review of Clinical Trials from 2013 to 2024.

Significance: Management of infection is a critical aspect of wound care. It involves the application of various interventions to treat the wound and prevent the infection from spreading to other parts of the body, which may lead to serious complications, including sepsis. Local treatment of skin wound infections is the favored route of administration, reducing the risk of adverse systemic effects while providing very high therapeutic concentrations at the target site. The purpose of this article was to review clinical trials from 2013 and onward, focusing on local treatment of acute wounds and burns as well as chronic wounds as their primary outcome measurement. Recent Advances: Based on our literature search, 49 clinical trials were focusing on treating infected chronic wounds, and 6 trials studied infection as their primary outcome in acute wounds during the last 10 years. Critical Issues: Currently commercially available local treatments do not prevent the onset of invasive infection. Therefore, there is a need for more effective local therapies. Future Directions: Despite multiple preclinical studies introducing novel and promising strategies in terms of novel antimicrobial agents and delivery methods to prevent and treat skin wound infections locally, many have yet to be tested in a clinical setting. These preclinically tested approaches could still be valuable additions to today's care of infected skin wounds.

Broad-Spectrum Bactericidal Multifunctional Tiny Silicon-Based Nanoparticles Modified with Tannic Acid for Healing Infected Diabetic Wounds.

Infected chronic wounds, in particular, diabetic wounds, are hard to heal, posing a global health concern with high morbidity and mortality rates. Diabetic full-thickness wounds infected with E. coli belong to the most difficult to heal chronic infected wounds. Here, we introduced tannic acid-modified silicon-based nanoparticles (TA-SiNPs) with broad-spectrum bactericidal activity that bacteria develop minimal resistance to, and they can effectively treat full-thickness wounds in diabetic mice infected with E. coli. Our findings indicate that these TA-SiNPs could achieve 100% antibacterial efficiency against S. aureus and 99.83% against E. coli, underlied by a positive surface charge and tannic acid groups facilitating bacterial membrane chemical composition depletion and depolarization of the membrane. In addition, we showed that spraying TA-SiNPs onto the skin wound of diabetic mice infected with E. coli resulted in wound healing with 98% closure after 12 days, in stark contrast to 49% of the control (PBS) and 68% of the one treated with Ofloxacin. Along with infection inhibition and ROS scavenging, we identified cell proliferation stimulation, inflammatory cytokine downregulation, and healing cytokine upregulation in the lesion, favoring the healing process. This study not only demonstrates the feasibility of employing silicon-based nanoparticles in diabetic wound healing for the first time, but also reports the first broad-spectrum bactericidal silicon nanodots. Furthermore, this provides novel insights into the mechanism of tannin-based nanoparticles disrupting bacterial membranes by depleting their chemical constituents. Our results highlighted that the developed TA-SiNPs are an effective nanomaterial for treating the infected chronic wounds.

Evidence-based practices on nanotechnology in wound treatment

Nanotechnology has revolutionized wound treatment by offering innovative solutions that accelerate healing, reduce infections, and promote tissue regeneration. This article reviews evidence-based practices regarding the use of nanotechnology in wound care, with a focus on antimicrobial nanoparticles, smart dressings, and regenerative scaffolds. Studies reviewed between 2010 and 2024 indicate that silver, zinc oxide, and gold nanoparticles are effective in combating antibiotic-resistant bacteria, such as methicillin-resistant Staphylococcus aureus (MRSA), thereby preventing infections in chronic and acute wounds. Additionally, smart dressings equipped with embedded sensors have demonstrated the ability to monitor the wound environment, detecting signs of infection or inflammation and delivering drugs in a controlled manner. Another aspect addressed is the use of nanomaterial-based scaffolds, which mimic the extracellular matrix and promote cell proliferation, facilitating tissue regeneration in hard-to-heal wounds, such as diabetic ulcers and severe burns. Although the results are promising, the article highlights the need for more large-scale clinical trials and long-term studies to assess the safety and efficacy of these technologies across diverse populations. Moreover, the high cost of some nanotechnological products remains a challenge for widespread implementation, particularly in resource-limited healthcare systems. The conclusion is that nanotechnology holds great potential to transform wound care, but its broad adoption will depend on further studies, improved accessibility, and greater awareness among healthcare professionals and patients.

Polymicrobial interactions between Staphylococcus aureus and Pseudomonas aeruginosa promote biofilm formation and persistence in chronic wound infections.

Chronic, non-healing wounds are a leading cause of prolonged patient morbidity and mortality due to biofilm- associated, polymicrobial infections. Staphylococcus aureus and Pseudomonas aeruginosa are the most frequently co-isolated pathogens from chronic wound infections. Competitive interactions between these pathogens contribute to enhanced virulence, persistence, and antimicrobial tolerance. P. aeruginosa utilizes the extracellular proteases LasB, LasA, and AprA to degrade S. aureus surface structures, disrupt cellular physiology, and induce cell lysis, gaining a competitive advantage during co-infection. S. aureus evades P. aeruginosa by employing aggregation mechanisms to form biofilms. The cell wall protein SasG is implicated in S. aureus biofilm formation by facilitating intercellular aggregation upon cleavage by an extracellular protease. We have previously shown that proteolysis by a host protease can induce aggregation. In this study, we report that P. aeruginosa proteases LasA, LasB, and AprA cleave SasG to induce S. aureus aggregation. We demonstrate that SasG contributes to S. aureus biofilm formation in response to interactions with P. aeruginosa proteases by quantifying aggregation, SasG degradation, and proteolytic kinetics. Additionally, we assess the role of SasG in influencing S. aureus biofilm architecture during co-infection in vivo, chronic wound co-infections. This work provides further knowledge of some of the principal interactions that contribute to S. aureus persistence within chronic wounds co-infected with P. aeruginosa, and their impact on healing and infection outcomes.

Effectiveness of negative-pressure wound therapy with instillation compared to standard negative-pressure wound therapy and traditional gauze layer dressing for the treatment of acute traumatic wounds: A randomized controlled trial

Acute traumatic wounds often require prolonged healing time and hospitalization. Negative-pressure wound therapy with instillation and dwell time (NPWTi-d) has demonstrated effectiveness in accelerating patient healing over traditional NPWT, and its benefits are well established in the treatment of chronic infected wounds. However, randomized studies examining the use of NPWTi-d in acute traumatic wounds are scarce. This study aimed to examine the effectiveness of NPWTi-d compared to traditional gauze layer dressing and standard NPWT. This single-center, randomized, pragmatic, controlled clinical trial included 120 adult patients with acute traumatic wounds from traffic accidents randomized to NPWTi-d (n=39), NPWT (n=41), and gauze dressing (n=40). Following surgical debridement of the wound bed, all patients underwent definitive wound closure with delayed primary closure, skin grafting, or surgical flaps. The primary outcomes were wound closure time, number of surgical procedures, and hospital length of stay. The secondary outcomes were primary closure type, amputations, complications, and death. Wound closure time was significantly lower in patients with NPWTi-d compared to patients with NPWT and gauze dressing (6.1 vs. 10 vs. 11.7 days, respectively; p<0.001). Patients with NPWTi-d had fewer surgical procedures than patients with NPWT and gauze dressing (3.0 vs. 3.5 vs. 6.2, respectively; p<0.001). No significant differences in length of stay were observed among the groups. In this study, patients with acute traumatic wounds who received NPWTi-d experienced shorter wound closure time and fewer surgical procedures than patients who received NPWT or gauze dressing. The current study is registered on the Brazilian Clinical Trials Registry (ReBec) platform under the name Comparison between Traditional Dressing, V.A.C. Dressing and V.A.C. Dressing with Instillation in Complex Wounds, ID nº RBR-658g535 at https://ensaiosclinicos.gov.br/rg/RBR-658g535.