Manejo cirúrgico de ferimento auto-infligido por arma de fogo em região maxilofacial / Surgical management of self-inflicted injury by gun in the maxillofacial region

INTRODUÇÃO: O manejo dos pacientes vítimas de PAF possui vertentes divergentes a respeito do tratamento cirúrgico, que pode ser realizado de forma imedata ou tardia. Em lesões auto-infligidas, a distância entre a arma e a região acometida é menor, causando consequências estéticas e funcionais mais devastadoras. Aliado ao fato desse tipo de trauma criar uma ferida suja devido à comunicação com a cavidade oral e seios paranasais, o manejo das lesões representam um desafio mesmo à cirurgiões experientes. OBJETIVO: Estre trabalho relata o manejo cirúrgico de uma ferida auto-infligida por arma de fogo que resultou em avulsão dos tecidos moles na região maxilofacial. DESCRIÇÃO DO CASO: Paciente do sexo masculino, 35 anos, vítima de projétil de arma de fogo auto-infligido em região maxilofacial, cursando com extenso ferimento em região de língua e mento. Clinicamente, o paciente não apresentava sinais de fratura em ossos da face. Ambos os ferimentos apresentavam secreção purulenta e o paciente manifestava disfonia devido a grande destruição tecidual. CONSIDERAÇÕES FINAIS: O tratamento de ferimentos por arma de fogo não só é um grande desafio para o cirurgião, como para toda a equipe multidisciplinar requerida para tais casos, visto que não há protocolos bem definidos para o tratamento dessas lesões(AU)

INTRODUCTION: The management of patients who are victims of FAP has divergent aspects regarding surgical treatment, which can be performed immediately or late. In self-inflicted injuries, the distance between the weapon and the affected region is smaller, causing more devastating aesthetic and functional consequences. Allied to the fact that this type of trauma creates a dirty wound due to the communication with the oral cavity and paranasal sinuses, the management of injuries represents a challenge even for experienced surgeons. OBJECTIVE: This paper reports the surgical management of a self-inflicted gunshot wound that resulted in soft tissue avulsion in the maxillofacial region. CASE DESCRIPTION: Male patient, 35 years old, victim of a self-inflicted firearm projectile in the maxillofacial region, coursing with extensive injury in the region of the tongue and chin. Clinically, the patient did not show signs of facial bone fractures. Both wounds had purulent secretion and the patient had dysphonia due to extensive tissue destruction. FINAL CONSIDERATIONS: The treatment of gunshot wounds is not only a great challenge for the surgeon, but also for the entire multidisciplinary team required for such cases, since there are no well-defined protocols for the treatment of these injuries(AU)

Analysis of therapeutic effect of silver-based dressings on chronic wound healing.

Chronic wounds are susceptible to bacterial infections and at high risk of developing antibiotic-resistant bacterial infections. Silver is an antimicrobial by targeting almost all types of bacteria in chronic wounds to reduce the bacterial load in the infected area and further facilitate the healing process. This study focused on exploring whether silver-based dressings were superior to non-silver dressings in the treatment of chronic wounds. PubMed, Web of Science and Embase were comprehensively searched from inception to March 2024 for randomized clinical trials and observational studies. The endpoints in terms of wound healing rate, complete healing time, reduction on wound surface area and wound infection rate were analysed using Review Manager 5.4 software. A total of 15 studies involving 5046 patients were eventually included. The results showed that compared with patients provided with non-silver dressings, patients provided with silver-based dressings had higher wound healing rate (OR: 1.43, 95% CI: 1.10-1.85, p = 0.008), shorter complete healing time (MD: -0.96, 95% CI: -1.08 ~ -0.85, p < 0.00001) and lower wound infection rate (OR: 0.56, 95% CI: 0.40-0.79, p = 0.001); no significant difference in the reduction on wound surface area (MD: 12.41, 95% CI: -19.59-44.40, p = 0.45) was found. These findings suggested that the silver-based dressings were able to enhance chronic wound healing rate, shorten the complete healing time and reduce wound infection rate, but had no significant improvement in the reduction on wound surface area. Large-scale and rigorous studies are required to confirm the beneficial effects of silver-based dressings on chronic wound healing.

Selenium Bandages and Cotton Cloth That Kill Microorganisms in Wounds.

INTRODUCTION: The material of a bandage plays an important role in wound management. Microorganisms can colonize the dressing and release toxins, which create dead cells in the wound. This allows the microorganisms to bind the dead cells and infect the wound. Thus, a dressing is needed that kills bacteria in the bandage. To combat health care-associated infections, antimicrobial treatment of medical textiles, such as gauze, uniforms, curtains, bed sheets, gowns, and masks, is required. Besides, antimicrobial resistance is another major problem of this century. Antibacterial overuse has contributed to drug-resistant bacteria. To combat these two problems, we synthesized new organo-selenium compounds that can be attached to the cotton of the dressing. We then used an in vivo wound model, which allowed us to measure the effectiveness of selenium attached to a cotton dressing, to prevent bacteria from infecting a wound. MATERIALS AND METHODS: Organo-selenium was attached to cotton fabric, resulting in a fabric with 0.1% selenium covalently attached to it. Staphylococcus aureus (as well as methicillin-resistant S. aureus [MRSA]), Stenotrophomonas maltophilia, Enterococcus faecalis, Staphylococcus epidermidis, and Pseudomonas aeruginosa were chosen for the wound infection study. All the bacteria were enumerated in the wound dressing and in the wound tissue under the dressing. Wounds were made on the backs of mice. The material was used as a bandage over the wound. Bacteria were injected into the wound under the bandage. The amount of bacteria in the wound after 5 days was determined. A similar study was performed using dressing material that was soaked in phosphate buffered saline at 37 °C for 3 months before use. RESULTS: Cotton dressing with selenium attached showed complete inhibition (7 logs, as compared with control dressing) of different bacterial strains, in both the dressing and "the tissue" of the wound. Similar results were obtained using selenium cotton dressing that was soaked for 3 months before use. Control cotton with no selenium showed complete infiltration of bacteria into the wound and the dressing. In addition, a study was performed under Food and Drug Administration standard methods to show the ability of the selenium to kill bacteria in the fabric, using material that was washed 5 times in detergent. This also showed complete killing of bacteria in the fabric. CONCLUSIONS: The results show that the selenium remains in the dressing after washing and is able to completely protect the wound from bacterial infection. In the selenium bandage, no bacteria were found in the bandage or the wound after 5 days.

Promoting the healing of infected diabetic wound by nanozyme-containing hydrogel with anti-bacterial inflammation suppressing, ROS-scavenging and oxygen-generating properties.

Bacterial infections already pose a significant threat to skin wounds, especially in diabetic patients who have difficulty healing wounds. However, wound or bacterial infections are known to produce excess reactive oxygen species (ROS), and hypoxia may further hinder wound healing and the development of chronic wounds. In this study, a multifunctional hydrogel for ROS scavenging and bacterial inhibition was developed by cross-linking polyvinyl alcohol (PVA) and sodium alginate (SA) with graphene oxide (GO) loaded with silver-platinum hybrid nanoparticles (GO@Ag-Pt). The PVA/SA hydrogel loaded with GO@Ag-Pt exhibited the ability to scavenge different types of ROS, generate O2, and kill a broad spectrum of bacteria in vitro. The silver-platinum hybrid nanoparticles significantly increased the antibacterial ability against Escherichia coli and Staphylococcus aureus compared with silver nanoparticles (AgNps). GO@Ag-Pt loaded hydrogel was effective in treating infections caused by S.aureus, thereby significantly promoting wound healing during the inflammatory phase. Hydrogel therapy significantly reduced the level of ROS and alleviated inflammation levels. Notably, our ROS-scavenging, antibacterial hydrogels can be used to effectively treat various types of wounds, including difficult-to-heal diabetic wounds with bacterial infections. Thus, this study proposes an effective strategy for various chronic wound healing based on ROS clearance and bacteriostatic hydrogels.

Pediatric wound infections following 2023 Kahramanmaras earthquakes: case series.

BACKGROUND: The Kahramanmaras earthquakes in Turkey on February 6, 2023, resulted in more than 100 000 injuries and 50 500 deaths. The main causes of morbidity and mortality in earthquake-affected patients include crush syndrome, trauma-related extremity injuries, and wound infections. OBJECTIVE: To investigate infective complications, causative microorganisms, treatments, and treatment responses in pediatric patients. METHODS: The case series involved 12 earthquake victims admitted to a tertiary treatment center between February 9 and 24, 2023. Wound sample cultures were obtained from patients with infected wounds via wound secretions and tissue samples collected during surgery. RESULTS: Nine patients were male (75%), and the mean age of patients was 12.6 ± 3.7 years. Seven patients (58.3%) experienced crush syndrome. Seven patients (58.3%) underwent fasciotomy operations. The main infectious complications were wound infections (58.3%) and urinary tract infections (25%). Nine different organisms were found to cause wound infection, with Enterococcus faecium (41.6%), Acinetobacter baumanii (33.3%), and Pseudomonas aeruginosa (16.6%) being the major bacterial isolates. All Acinetobacter strains were multidrug-resistant (MDR). CONCLUSION: Major disasters such as earthquakes are rare, and infections are the major complications that increase morbidity and mortality. Initial appropriate treatment contributes to improved outcomes, as MDR strains are common pathogens in these patients.

Immunomodulatory Antibacterial Hydrogel for Wound Infection Management.

Background: Wound healing has always been a focal point in clinical work. Bacterial infections and immune microenvironment disorders can both hinder normal wound healing. Current wound dressings only serve a covering function. Developing wound dressings with antibacterial and immunomodulatory functions is crucial for aiding wound healing. To address this issue, we have developed a hydrogel with antibacterial and immunomodulatory functions for managing infected wounds. Methods: The present study describes a photo-crosslinked antibacterial hydrogel composed of curcumin, silver nanoparticles-loaded reduced graphene oxide, and silk fibroin methacryloyl for the treatment of infected wounds. The study assessed its antibacterial properties and its capacity to induce macrophage M2 polarization through in vitro and in vivo experiments. Results: The hydrogel demonstrates robust antibacterial properties and enhances macrophage M2 polarization in both in vitro and in vivo settings. Moreover, it accelerates the healing of infected wounds in vivo by stimulating collagen deposition and angiogenesis. Conclusion: Overall, this hydrogel shows great potential in managing wound infections.

Peptide clustering enhances large-scale analyses and reveals proteolytic signatures in mass spectrometry data.

Recent advances in mass spectrometry-based peptidomics have catalyzed the identification and quantification of thousands of endogenous peptides across diverse biological systems. However, the vast peptidomic landscape generated by proteolytic processing poses several challenges for downstream analyses and limits the comparability of clinical samples. Here, we present an algorithm that aggregates peptides into peptide clusters, reducing the dimensionality of peptidomics data, improving the definition of protease cut sites, enhancing inter-sample comparability, and enabling the implementation of large-scale data analysis methods akin to those employed in other omics fields. We showcase the algorithm by performing large-scale quantitative analysis of wound fluid peptidomes of highly defined porcine wound infections and human clinical non-healing wounds. This revealed signature phenotype-specific peptide regions and proteolytic activity at the earliest stages of bacterial colonization. We validated the method on the urinary peptidome of type 1 diabetics which revealed potential subgroups and improved classification accuracy.

PDIA iminosugar influence on subcutaneous Staphylococcus aureus and Pseudomonas aeruginosa infections in mice.

Introduction: Biofilm-associated infections persist as a therapeutic challenge in contemporary medicine. The efficacy of antibiotic therapies is ineffective in numerous instances, necessitating a heightened focus on exploring novel anti-biofilm medical strategies. Among these, iminosugars emerge as a distinctive class of compounds displaying promising biofilm inhibition properties. Methods: This study employs an in vivo wound infection mouse model to evaluate the effectiveness of PDIA in treating biofilm-associated skin wound infections caused by Staphylococcus aureus and Pseudomonas aeruginosa. Dermic wounds in mice were infected with biofilm-forming strains, specifically S. aureus 48 and P. aeruginosa 5, which were isolated from patients with diabetic foot, and are well-known for their strong biofilm formation. The subsequent analysis included clinical, microbiological, and histopathological parameters. Furthermore, an exploration into the susceptibility of the infectious strains to hydrogen peroxide was conducted, acknowledging its potential presence during induced inflammation in mouse dermal wounds within an in vivo model. Results: The findings revealed the efficacy of PDIA iminosugar against the S. aureus strain, evidenced by a reduction in bacterial numbers within the wound and the inflammatory focus. Discussion: This study suggests that PDIA iminosugar emerges as an active and potentially effective antibiofilm agent, positioning it as a viable treatment option for staphylococcal infections.

Treatment of bacterially contaminated lower extremity ulcers with a fatty acid-containing wound matrix: a case series.

OBJECTIVE: The aim was to evaluate the effectiveness of a marine omega fatty acid-containing multimodal wound matrix (MWM) in reducing bacterial contamination and supporting wound area reduction (WAR) in patients with hard-to-heal wounds of varying aetiologies. METHOD: A prospective, single-site, pilot case series of patients with hard-to-heal wounds. All wounds were considered non-healing prior to inclusion as they had failed to achieve at least 50% WAR after at least four weeks of standard of care (SoC) treatments. Patients were seen once weekly for wound assessments, matrix application and dressing changes. Baseline and weekly fluorescence images, standard wound images and wound measurements were obtained. RESULTS: A total of three patients, two with venous leg ulcers (VLUs) and one with a diabetic foot ulcer (DFU) were enrolled in this pilot study. The mean baseline wound age prior to study enrolment was 24 weeks, with a mean baseline wound size of 8.61cm2. The two VLUs went on to complete closure. The DFU displayed a total WAR of 53% by six weeks, when the patient was lost to follow-up due to a geographical relocation. The mean percentage area reduction of all wounds combined was 82% upon study completion. CONCLUSION: The use of MWM proved to be effective and safe in this patient cohort. The wounds included in this case series failed to enter a healing trajectory with SoC wound therapies. The MWM supported wound closure and reduced bacterial loads in this patient cohort.

Infectious Aspects of Chronic Wounds.

The treatment, maintenance, and suppression of infection in chronic wounds remain a challenge to all practitioners. From an infectious disease standpoint, knowing when a chronic wound has progressed from colonized to infected, when to use systemic antimicrobial therapy and when and how to culture such wounds can be daunting. With few standardized clinical guidelines for infections in chronic wounds, caring for them is an art form. However, there have been notable advances in the diagnosis, treatment, and management of infected wounds. This article will discuss the pathophysiology of infection in older adults, including specific infections such as cutaneous candidiasis, necrotizing soft tissue infection, osteomyelitis, and infections involving hardware.

Stimuli-Responsive Release-Active Dressing: A Promising Solution for Eradicating Biofilm-Mediated Wound Infections.

Biofilm-mediated wound infections pose a significant challenge due to the limitations of conventional antibiotics, which often exhibit narrow-spectrum activity, fail to eliminate recurrent bacterial contamination, and are unable to penetrate the biofilm matrix. While the search for alternatives has explored the use of metal nanoparticles and synthetic biocides, these solutions often suffer from unintended toxicity to surrounding tissues and lack controlled administration and release. In this study, we engineered a pH-responsive release-active dressing film based on carboxymethyl cellulose, incorporating a synthetic antibacterial molecule (SAM-17). The dressing film exhibited optimal mechanical stability for easy application and demonstrated excellent fluid absorption properties, allowing for prolonged moisturization at the site of injury. The film exhibited pH-dependent release of cargo, with 78% release within 24 h at acidic pH, enabling targeted antibacterial drug delivery within the wound microenvironment. Furthermore, the release-active film effectively eliminated repeated challenges of bacterial contamination. Remarkably, the film demonstrated a minimal toxicity profile in both in vitro and in vivo models. The film eliminated preformed bacterial biofilms, achieving a reduction of 2.5 log against methicillin-resistant Staphylococcus aureus (MRSA) and 4.1 log against vancomycin-resistant S. aureus (VRSA). In a biofilm-mediated MRSA wound infection model, this release-active film eradicated the biofilm-embedded bacteria by over 99%, resulting in accelerated wound healing. These findings highlight the potential of this film as an effective candidate for tackling biofilm-associated wound infections.

Analysis of wound infections among pediatric patients following the 2023 Türkiye-Syria earthquakes.

PURPOSE: On February 6, 2023, two earthquakes of magnitude 7.7 and 7.6 occurred consecutively in Turkey and Syria. This study aimed to investigate the predisposing factors for wound infection (WI) and the microbiological characteristics of wounds after earthquake-related injuries. METHODS: This descriptive study evaluated pediatric patients' frequency of WI, and the clinical and laboratory parameters associated with the development of WI were investigated. RESULTS: The study included 180 patients (91 female). The mean age of the patients was 123.9 ± 64.9 months and 81.7% (n = 147) of them had been trapped under rubble. Antibiotic treatment to prevent WI had been administered to 58.8% (n = 106) of all patients. WI was observed in 12.2% (n = 22) of the cases. In patients who developed WI, the incidence of exposure to a collapse, crush syndrome, compartment syndrome, multiple extremity injury, fasciotomy, amputation, peripheral nerve injury, thoracic compression, blood product use, intubation, and the use of central venous catheters, urinary catheters, and thoracic tubes were more frequent (p < 0.05). The need for blood product transfusion was associated with the development of WI (OR = 9.878 [95% CI: 2.504-38.960], p = 0.001). The negative predictive values of not developing WI at values of white blood cell count of < 11,630/mm3, creatine kinase < 810 U/L, potassium < 4.1 mEq/L, ALT < 29 U/L, AST < 32 U/L, and CRP < 45.8 mg/L were 93.7%, 96.8%, 90.8%, 93.3%, 100%, and 93.5%, respectively. Gram-negative pathogens (81%) were detected most frequently in cases of WI. Seventy-five percent of patients were multidrug- and extensively drug-resistant. CONCLUSION: This study leans empirical approach of our disaster circumstances. In cases with risk factors predisposing to the development of WI, it may be rational to start broad-spectrum antibiotics while considering the causative microorganisms and resistance profile to prevent morbidity.

Fast fabrication of "all-in-one" injectable hydrogels as antibiotic alternatives for enhanced bacterial inhibition and accelerating wound healing.

Skin wound infection has become a notable medical threat. Herein, the polysaccharide-based injectable hydrogels with multifunctionality were developed by a simple and fast gelation process not only to inactivate bacteria but also to accelerate bacteria-infected wound healing. Sodium nitroprusside (SNP) loaded PCN-224 nanoparticles were introduced into the polymer matrix formed by the dynamic and reversible coordinate bonds between Ag+ with carboxyl and amino or hydroxyl groups on carboxymethyl chitosan (CMCS), hydrogen bonds and electrostatic interactions in the polymer to fabricate SNP@PCN@Gel hydrogels. SNP@PCN@Gel displayed interconnected porous structure, excellent self-healing capacity, low cytotoxicity, good blood compatibility, and robust antibacterial activity. SNP@PCN@Gel could produce reactive oxygen species (ROS) and NO along with Fe2+, and showed long-term sustained release of Ag+, thereby effectively killing bacteria by synergistic photothermal (hyperthermia), photodynamic (ROS), chemodynamic (Fenton reaction), gas (NO) and ion (Ag+ and -NH3+ in CMCS) therapy. Remarkably, the hydrogels significantly promoted granulation tissue formation, reepithelization, collagen deposition and angiogenesis as well as wound contraction in bacteria-infected wound healing. Taken together, the strategy represented a general method to engineer the unprecedented photoactivatable "all-in-one" hydrogels with enhanced antibacterial activity and paved a new way for development of antibiotic alternatives and wound dressing.

Analysis of risk factors related to chronic non-healing wound infection and the construction of a clinical prediction model.

This study is aimed to analyse the risk factors associated with chronic non-healing wound infections, establish a clinical prediction model, and validate its performance. Clinical data were retrospectively collected from 260 patients with chronic non-healing wounds treated in the plastic surgery ward of Shanxi Provincial People's Hospital between January 2022 and December 2023 who met the inclusion criteria. Risk factors were analysed, and a clinical prediction model was constructed using both single and multifactor logistic regression analyses to determine the factors associated with chronic non-healing wound infections. The model's discrimination and calibration were assessed via the concordance index (C-index), receiver operating characteristic (ROC) curve and calibration curve. Multivariate logistic regression analysis identified several independent risk factors for chronic non-healing wound infection: long-term smoking (odds ratio [OR]: 4.122, 95% CI: 3.412-5.312, p < 0.05), history of diabetes (OR: 3.213, 95% CI: 2.867-4.521, p < 0.05), elevated C-reactive protein (OR: 2.981, 95% CI: 2.312-3.579, p < 0.05), elevated procalcitonin (OR: 2.253, 95% CI: 1.893-3.412, p < 0.05) and reduced albumin (OR: 1.892, 95% CI: 1.322-3.112, p < 0.05). The clinical prediction model's C-index was 0.762, with the corrected C-index from internal validation using the bootstrap method being 0.747. The ROC curve indicated an area under the curve (AUC) of 0.762 (95% CI: 0.702-0.822). Both the AUC and C-indexes ranged between 0.7 and 0.9, suggesting moderate-to-good predictive accuracy. The calibration chart demonstrated a good fit between the model's calibration curve and the ideal curve. Long-term smoking, diabetes, elevated C-reactive protein, elevated procalcitonin and reduced albumin are confirmed as independent risk factors for bacterial infection in patients with chronic non-healing wounds. The clinical prediction model based on these factors shows robust performance and substantial predictive value.

Maggot therapy for resistant infections: the disconnect between scientific evidence, clinical acceptance and practice.

OBJECTIVE: Practitioners and scientists are re-examining marginalised wound care therapies to find strategies that combat the growing problem of antimicrobial resistance (AMR) without compromising patient outcomes. Maggot therapy (MT) makes up just an estimated 0.02% of UK's National Health Service spending on wound care. This study aims to uncover why MT is not used more often, despite its affordability and high level of efficacy for both debridement and disinfection, particularly in the context of AMR infections, and to determine what can be done to ensure MT is more effectively used in the future to improve patient outcomes and manage the growing problem of AMR. METHOD: For this investigation, a qualitative review of case studies using MT against AMR infections and a quantitative analysis of randomised control trials (RCTs) were performed using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses framework. RESULTS: Analysis showed that MT is highly effective against a range of infections and wound types, and compares well against conventional therapies. The low use of MT may be due in part to the documented 'yuck factor', often associated with maggots as well as misconceptions around the cost, efficacy and accessibility of MT. To overcome these factors, more RCTs on the spectrum and efficacy of MT across various clinical manifestations are needed, as well as professional and public engagement campaigns. CONCLUSION: MT is an underused therapy, particularly regarding AMR infections, and expanding its use in these circumstances appears warranted. MT could play a vital role in conserving the efficacy of the existing pool of antimicrobials available and should be considered in the development of antimicrobial stewardship programmes. DECLARATION OF INTEREST: This work was supported by the Swansea Employability Academy, Swansea University (internal funding). The authors have no conflicts of interest to declare.

Unlocking Wearable Microbial Fuel Cells for Advanced Wound Infection Treatment.

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.

Development of magnesium hydroxide-doped nanofibrous spheres for repairing infected skin wounds.

The healing of skin wounds is a continuous and coordinated process, typically accompanied by microbial colonization and growth. This may result in wound infection and subsequent delay in wound healing. Therefore, it is of particular importance to inhibit the growth of microorganisms in the wound environment. In this study, magnesium hydroxide-doped polycaprolactone (PCL/MH) nanofibrous spheres were fabricated by electrospinning and electrospray techniques to investigate their effects on infected wound healing. The prepared PCL/MH nanofibrous spheres had good porous structure and biocompatibility, providing a favorable environment for the delivery and proliferation of adipose stem cells. The incorporation of MH significantly enhanced the antimicrobial properties of the spheres, in particular, the inhibition of the growth of S. aureus and E. coli. We showed that such PCL/MH nanofibrous spheres had good antimicrobial properties and effectively promoted the regeneration of infected wound tissues, which provided a new idea for the clinical treatment of infected wounds.

Plerixafor for pathogen-agnostic treatment in murine thigh infection and zebrafish sepsis.

Plerixafor is a CXCR4 antagonist approved in 2008 by the FDA for hematopoietic stem cell collection. Subsequently, plerixafor has shown promise as a potential pathogen-agnostic immunomodulator in a variety of preclinical animal models. Additionally, investigator-led studies demonstrated plerixafor prevents viral and bacterial infections in patients with WHIM syndrome, a rare immunodeficiency with aberrant CXCR4 signaling. Here, we investigated whether plerixafor could be repurposed to treat sepsis or severe wound infections, either alone or as an adjunct therapy. In a Pseudomonas aeruginosa lipopolysaccharide (LPS)-induced zebrafish sepsis model, plerixafor reduced sepsis mortality and morbidity assessed by tail edema. There was a U-shaped response curve with the greatest effect seen at 0.1 µM concentration. We used Acinetobacter baumannii infection in a neutropenic murine thigh infection model. Plerixafor did not show reduced bacterial growth at 24 h in the mouse thigh model, nor did it amplify the effects of a rifampin antibiotic therapy, in varying regimens. While plerixafor did not mitigate or treat bacterial wound infections in mice, it did reduce sepsis mortality in zebra fish. The observed mortality reduction in our LPS model of zebrafish was consistent with prior research demonstrating a mortality benefit in a murine model of sepsis. However, based on our results, plerixafor is unlikely to be successful as an adjunct therapy for wound infections. Further research is needed to better define the scope of plerixafor as a pathogen-agnostic therapy. Future directions may include the use of longer acting CXCR4 antagonists, biased CXCR4 signaling, and optimization of animal models.