Search Results (3,180)

The global threat of multidrug-resistant infections requires new approaches for its management. A blend of polymethyl methacrylate (PMMA) and poly(ε-caprolactone) (PCL) electrospun nanofibrous membrane was utilised as a scaffold to sustain the release of three broad-spectrum antiseptics to combat multidrug-resistant (MDR) microorganisms. The scaffold was characterised by Fourier transform infrared spectroscopy, contact angle, and scanning electron microscopy. The latter revealed a random and smooth structure. The contact angle value of 81.8 ± 1.8 confirmed the hydrophilic nature of the scaffold, which is important for wound healing. The high surface-to-volume ratio of the scaffolds was utilised for loading benzoic acid (BA), methylparaben (MPB), and propylparaben (PPB) which were released during 72 h concentrations ranging between 0.20 and 0.8 mg mL⁻¹. The initial release of antiseptics was high and was then sustained for over 72 h. After 8 h, the burst release was 61.64 ± 4.11% for BA, 41.11 ± 2.98% for MPB and 34.32 ± 3.13% for PPB. The release profile of BA was superior to that of the MPB and PPB. The loaded scaffolds inhibited MDR-resistant methicillin-resistant Staphylococcus aureus, Escherichia coli and Candida albicans and were not cytotoxic to a fibroblast cell line. They inhibited their colonisation by the tested microorganisms to non-detectable counts or at least reduced microbial counts by at least 6–7 logs (p ≤ 0.001) for 72 h. Crystal violet techniques and electron microscopy confirmed colonisation inhibition. Because of their non-cytotoxicity and broad-spectrum antimicrobial activity, the antiseptic-loaded PMMA/PCL nanofibrous scaffolds could be utilised as wound dressings, particularly in non-healing wounds. Full article

Objective: This multicenter, prospective, single-arm study evaluated the safety and preliminary clinical performance of a flowable porcine urinary bladder matrix (UBM) particulate for managing tunneling and undermining features in complex wounds. These features are associated with delayed healing, chronic inflammation, and infection risk. Flowable UBM enables targeted delivery into wound tunnels and cavities. Method: Twenty-five subjects from 3 United States (U.S.) sites were enrolled, with 21 meeting protocol criteria for analysis (15 with undermining and 6 with tunneling wounds). Participants received flowable UBM applied directly to tunneling or undermining areas, along with additional UBM particulate or sheet forms applied to the wound surface. The primary endpoint was the percentage reduction in tunneling volume or undermining depth at 12 weeks, with secondary assessment of reduction in overall wound volume. Safety was evaluated through evaluation of device-related adverse events. Results: At 12 weeks, 90.5% of wounds demonstrated positive response, with mean ± standard deviation and median reduction in tunneling or undermining dimensions of 84.6 ± 29.3% and 100.0%, respectively. Complete resolution of these features occurred in 52.4% of wounds (53.3% in undermining and 50.0% in tunneling wounds) with higher closure rates in non-pressure wounds compared to pressure injuries. No device-related adverse events were reported. Conclusions: Overall, flowable UBM was well tolerated and associated with favorable clinical trajectories demonstrated by reduction in tunneling and undermining dimensions; however, comparative effectiveness cannot be inferred from this limited single-arm pilot study. Further controlled studies are needed to confirm comparative effectiveness and optimize clinical use. Full article

Chronic wounds are complex environments marked by persistent inflammation, oxidative stress, hypoxia, and conditions that favor antimicrobial resistance (AMR). Conventional antibiotics often fail due to bacterial persistence and the physicochemical barriers of the wound milieu. Biofilm-associated extracellular polymeric substances (EPS), efflux pump activity, quorum sensing (QS), and horizontal gene transfer (HGT) collectively drive antimicrobial tolerance and resistance dissemination, turning chronic wounds into reservoirs of multidrug-resistant pathogens. Consequently, emerging wound therapies demand multifunctional strategies that modulate the wound microenvironment while interfering with resistance-associated phenotypes. Hydrogel–metal–organic framework (MOF) composites have been explored as multifunctional interfaces that combine extracellular matrix-mimetic properties, tunable porosity, stimuli-responsiveness, and controlled therapeutic delivery with the bioactive functions of MOFs. Depending on their composition and architecture, these systems may exert antimicrobial and antibiofilm effects through ionic, electrostatic, osmotic, catalytic, and oxidative mechanisms, while also influencing ROS levels, inflammation, angiogenesis, and local drug transport. However, antimicrobial activity alone does not equate to resistance modulation. Evidence for direct effects on efflux systems, resistance phenotypes, or HGT remains inconsistent across reported platforms. This review critically examines representative hydrogel–MOF systems for chronic wound applications, comparing their composition, physicochemical properties, biological functions, proposed resistance-related mechanisms, advantages, limitations, and current level of evidence. We emphasize distinguishing experimentally demonstrated resistance-modulating effects from mechanistically proposed functions, and identifying design trade-offs and evidence gaps that must be addressed to develop wound interfaces capable of both supporting tissue regeneration and improving infection control. Full article

Multidrug-resistant Acinetobacter baumannii isolates pose a threat to healthcare systems worldwide. The antibacterial activity of essential oil components (EOCs)—linalool, geraniol, eugenol, citronellol, 1,8-cineole, carvacrol, and trans-anethole—was evaluated both alone and in combinations against multidrug-resistant A. baumannii clinical strains from wound infections, and against two reference strains. The minimum inhibitory concentrations (MICs) and minimum bactericidal concentrations (MBCs) of EOCs were determined using the broth microdilution method. The interactions between EOCs were investigated using the checkerboard microdilution method. Carvacrol and eugenol showed the strongest inhibitory effects against the tested strains. The MICs and MBCs of carvacrol were 1.70–3.39 mg/mL. The MICs of eugenol were 4.10–16.41 mg/mL, while the MBCs were 4.10–32.81 mg/mL. MIC/MBC analysis showed that all tested EOCs had bactericidal activity against A. baumannii in vitro; however, some required higher concentrations. Most EOC mixtures showed synergistic interactions. The combination of eugenol and carvacrol induced the strongest synergistic effect, leading to the greatest reduction in the MICs of both compounds (MIC of carvacrol decreased by 8–30-fold, while the MIC of eugenol decreased by 16–64-fold). Our results indicate that some EOCs, especially when combined, exhibit significant antibacterial activity against A. baumannii. Full article

Background and Objectives: Severe traumatic limb injuries, particularly those involving extensive soft tissue damage, present significant challenges in clinical management. Thus, we aimed to critically assess the effectiveness of hyperbaric oxygen therapy (HBOT) as an adjunctive treatment for severe traumatic limb injuries. Materials and Methods: For this systematic review and meta-analysis, we conducted a systematic search of MEDLINE/PubMed, Embase, and the Cochrane Library for studies published up to 7 March 2026. We included studies evaluating the effectiveness of adjunctive HBOT in patients with severe limb injuries. The prespecified primary outcome was complete wound healing, while secondary outcomes included time to wound healing, wound necrosis, length of hospital stay (LOS), and wound infection. Risk of bias was assessed using the ROBINS-I tool for observational studies and the Cochrane RoB 2.0 for randomized controlled trials (RCTs). Results: Seven studies (three RCTs and four observational) were included. A high risk of bias was identified in two RCTs, and a serious risk of bias was noted across all four observational studies. Complete wound healing was reported in one randomized trial and favored HBOT, but the certainty of evidence was very low. The time to wound healing did not differ between the HBOT and control groups (MD, −1.44; 95% CI, −6.70 to 3.82, I² = 0%). The LOS did not differ between the HBOT and control groups (MD, −3.39; 95% CI, −14.74 to 7.79, I² = 94%). However, wound infection rates were lower in the HBOT group compared to the control group (OR, 0.31; 95% CI, 0.22–0.45, I² = 20%). Similarly, wound necrosis rates were reduced in the HBOT group (OR, 0.23; 95% CI, 0.12–0.45, I² = 41%). Conclusions: Evidence is insufficient to determine whether HBOT improves complete wound healing. Although HBOT may reduce wound infection and necrosis, the certainty of evidence was low to very low. Full article

Implant-associated infections (IAIs) persist as a critical complication in biomaterial transplantation, driven by rapid microbial colonization, biofilm encapsulation, and escalating antibiotic resistance. Conventional antibiotic-based treatments and passive antimicrobial coatings often fail to achieve long-term infection control due to limited biofilm penetration, localized cytotoxicity, and active agent depletion. To overcome these limitations, piezoelectric nanocomposite coatings utilize a dynamic, stimulus-responsive framework that converts physiological mechanical forces or external ultrasound into localized electrical signals. These surface-bound electric fields systematically mitigate bacterial adhesion, eradicate mature biofilms via targeted reactive oxygen species (ROS) generation, disrupt microbial metabolic pathways, and favorably modulate the peri-implant immune microenvironment while supporting host tissue repair. This review evaluates the material design principles and classifications of inorganic, organic, and hybrid piezoelectric nanocoatings. We detail their multifaceted antibacterial mechanisms and trace their therapeutic potential in orthopedic and dental implants, as well as wound management. Lastly, we analyze current engineering bottlenecks to chart a clear trajectory for their clinical translation. Full article

Background: Chronic lower limb wounds, such as diabetic and vascular ulcers, affect up to 2% of the global population, imposing high healthcare costs and a significant risk of amputation. Although nursing care and traditional treatments are fundamental, single-use portable Negative Pressure Wound Therapy PICO 7 system, has emerged as a cost-effective alternative. The objective of this study was to evaluate the effectiveness of PICO 7, compared to the usual treatment in chronic lower limb wounds or their dehiscence in amputations. Methodology: A randomized, controlled, open-label clinical trial was conducted at the Hospital Universitario de Toledo (2024–2026). The final analyzed sample consisted of 31 patients (Intervention Group, IG: 14; Control Group, CG: 17). Both groups followed the dynamic TIME strategy to standardize wound bed preparation. Primary variables included healing rate, healing time, wound area reduction, clinical safety (infections and adverse effects), pain levels, health-related quality of life, and physical activity. Statistical analysis was performed using SPSS v.28. Results: The IG showed a higher mean percentage reduction in wound size, although the between-group difference did not reach statistical significance. No infections were recorded in the IG. Regarding quality of life and physical activity, the CG showed a significant post-intervention decline, whereas the IG remained stable. A significant negative correlation was found between final wound size and hours of sleep, suggesting that wound reduction facilitates better rest. Conclusions: The PICO 7 system appears to be a safe and feasible alternative to conventional wound care. Favorable trends in wound area reduction should be interpreted cautiously given the lack of statistically significant between-group differences. Full article

Plant-mediated green synthesis of silver nanoparticles (AgNPs) predominantly relies on single botanical sources, constraining reduction efficiency and forfeiting the therapeutic potential of residual biomass. This study employed aloe vera and birch bark extracts as reducing agents. A combination of single-factor analysis and response surface methodology was employed to prepare monodisperse 30 nm AgNPs (with a Zeta potential of −35.3 mV and confirmed by XPS as metallic Ag⁰). It was loaded into carboxymethyl chitosan-vanillin-polyvinyl alcohol (CVP) gel microneedles using the vacuum casting method. The mechanical strength of these microneedles reaches 0.302 N/needle, exceeding the skin penetration threshold. Throughout the entire preparation process, both its Ag⁰ chemical state and crystal structure were maintained (by FT-IR and XRD). The MIC values of AgNPs@CVP against four pathogens ranged from 0.977 to 7.813 μg/mL, with a biofilm disruption rate exceeding 70%, and demonstrated excellent biocompatibility (hemolytic rate < 1.6%, cell survival rate > 80%). In a rat wound infection model, high-dose microneedle therapy reduced the residual wound area to 10.9% by day 9. This strategy inhibited the secretion of TNF-α and IL-6 while promoting epithelial regeneration, angiogenesis, and collagen deposition. This bifunctional Aloe-Birch strategy converges green nanomaterial synthesis with therapeutic delivery within a single bio-based platform, advancing sustainable nanomedicine paradigms and providing a resource-efficient blueprint for clinical infectious wound management. Full article

Wound management continues to represent a major global healthcare challenge, with the wound care market growing each year and a rising incidence of chronic wounds worldwide. Effective wound healing requires dressings that protect injured tissue, prevent infection, and actively modulate the wound microenvironment to promote tissue regeneration. In recent years, smart polymeric wound dressings have emerged as a functional, more advanced class of wound dressings, engineered from materials capable of responding to stimuli. Physically responsive systems include moisture-adaptive dressings that prevent wound dryness or maceration, pressure-sensitive dressings incorporating flexible capacitive sensors for high mechanical stress mapping, thermoresponsive dressings exploiting sol–gel transitions for temperature-controlled drug release, light-responsive dressings enabling photothermal and photodynamic therapy, and electro-responsive dressings integrating conductive polymers for self-powered electrical stimulation or closed-loop wound monitoring. Chemically responsive systems exploit endogenous biochemical signals, including pH shifts for wound monitoring, reactive oxygen species-cleavable bonds for on-demand drug release, and glucose-responsive platforms for autonomous glycemic regulation in diabetic wounds. Biologically responsive dressings use enzymatic triggers, such as matrix metalloproteinases, hyaluronidase, and bacterial proteases, to achieve autonomous drug delivery. Film-forming sprays further expand the versatility of smart polymeric dressings by enabling contactless application adaptable to irregular wound shapes. In this review, we summarize recent advances in the design, stimuli-responsive mechanisms, characterization methods, and therapeutic outcomes of smart polymeric dressings for wound treatment. Despite promising preclinical results, challenges related to clinical translation, regulatory standardization, and scalable production remain and must be addressed to facilitate widespread clinical adoption. Future directions include multi-stimuli responsive platforms, artificial intelligence-guided wound monitoring, bioprinting of specific dressings, and environmentally sustainable biomaterial design. Full article

Background: Loss of epithelial integrity leaves the wound bed open to opportunistic bacterial colonization, and the risk of secondary infection persists for as long as the defect remains unclosed. Wound dressings must therefore provide an immediate external barrier while accelerating restoration of the skin’s own barrier. This study aims to develop and evaluate a bioactive nanotechnological platform comprising dexpanthenol (Dxp)-engineered extracellular vesicles (EVs) embedded within cross-linked hyaluronic acid hydrogels (HA@Dxp-engineered EVs) for targeted wound treatment and protection against external contaminants. Methods: EVs were engineered via exogenous (extrusion; Exo EV) and endogenous (co-incubation; Endo EV) strategies to encapsulate Dxp. The physicochemical properties of the HA@Dxp-engineered EV systems were characterized, and their therapeutic efficacy was validated through in vitro assays, including fibroblast migration and endothelial tube formation, and in vivo using a full-thickness excisional wound model in mice. Results: Both engineering strategies successfully encapsulated Dxp while preserving the structural integrity of the EVs. The HA hydrogel enabled sustained EV release and provided a physical barrier. In vitro, HA@Endo EVs significantly promoted fibroblast proliferation, migration, and the formation of mature capillary-like networks in HUVECs compared to controls. In vivo, the HA@Endo EV group demonstrated accelerated wound closure, achieving 99.88% healing by day 10, and promoted tissue remodeling with upregulated expression of COL1A1, VEGF, and HIF-1α. Conclusions: The HA@Endo EV system provides a dual-action strategy against secondary infection risk. It supplies an immediate physical barrier over the wound bed and simultaneously accelerates re-epithelialization, thereby shortening the interval during which the tissue remains exposed. Full article

Background/Objectives: Verbena officinalis has long been used in traditional medicine for treating skin disorders, yet its potential in advanced wound-dressing systems remains insufficiently explored. This study aimed to characterize V. officinalis extracts obtained using different solvents, evaluate their antimicrobial, antibiofilm, cytotoxic, and wound-healing activities, and develop electrospun polycaprolactone–polyethylene glycol (PCL–PEG) nanofibers as a delivery platform for the most active extract. Methods: Extracts were chemically characterized by LC–MS and evaluated against clinical bacterial, yeast, and dermatophyte isolates associated with skin infections. Antibiofilm activity was assessed against Staphylococcus lugdunensis. The most active hydroalcoholic extract (EW7.5) was incorporated into PCL–PEG nanofibers (1–10%, w/w). Metabolite release was monitored by semi-quantitative LC–MS analysis. Cytotoxicity and wound-healing activity were evaluated using HaCaT keratinocytes, while in vivo efficacy was assessed in a full-thickness excisional wound model in Dark Agouti rats (five animals per group in two independent experiments). Results: EW7.5 exhibited the strongest antimicrobial activity, with MIC values of 0.06 mg/mL against all tested bacterial and Candida strains and 0.06–0.5 mg/mL against dermatophytes. It inhibited S. lugdunensis biofilm formation by 79.43% at MIC/4 and reduced pre-formed biofilm biomass by 64.98% at 2 × MBC. EW7.5 and EW7.5-loaded nanofibers showed no cytotoxicity up to 400 μg/mL. In the scratch assay, the free extract achieved 42.34 ± 1.58% wound closure, while nanofibers containing 10% EW7.5 achieved 25.87 ± 2.52%, compared to 7.73 ± 0.07% for the control. In vivo, EW7.5-loaded membranes significantly accelerated wound closure and the 10% formulation significantly improved extracellular matrix deposition and vascular remodeling compared to the control membrane. Conclusions: EW7.5-loaded PCL–PEG nanofibers combine antimicrobial, antibiofilm, biocompatible, and wound-healing properties, supporting their potential as multifunctional wound dressings. Nevertheless, further studies with mechanistic investigations are required to fully establish their therapeutic applicability. Full article

Background/Objectives: Postoperative infection is the leading cause of limb loss after microsurgical reconstruction of diabetic foot ulcers (DFUs), and povidone-iodine alone neither disrupts wound-bed biofilm nor penetrates hyperkeratotic debris. We assessed the feasibility of whole-field preoperative antisepsis with a pH-optimized sodium hypochlorite (NaOCl) cleanser applied before povidone-iodine draping. Methods: Consecutive patients undergoing microsurgical DFU reconstruction (January 2023–May 2024) were grouped by date of protocol introduction into pre-protocol (n = 9) and post-protocol (n = 6) cohorts. Primary outcome: technical feasibility, assessed by protocol completion, operative time, flap survival, limb salvage, and flap revision. Secondary, descriptive: postoperative infection, early (≤30 days) or late (>30 days). Results: The protocol was delivered as specified in all six post-protocol patients, without procedural modification or attributable adverse event. Operative time did not differ (388 vs. 430 min; p = 0.596); flap survival and limb salvage were 100% in both groups, with one flap revision per group. Baseline characteristics were comparable. Early infection was similar (16.7% vs. 11.1%; p = 1.000); late infection was absent post-protocol versus 33.3% pre-protocol (OR 0.14, 95% CI 0.01–3.4); and total infection was 16.7% versus 44.4% (OR 0.33, 95% CI 0.04–3.0). Follow-up was asymmetric (4.5 vs. 24.5 months); a 6-month landmark analysis showed 0 of 3 versus 3 of 6 (p = 0.464). Conclusions: Whole-field preoperative NaOCl antisepsis was technically feasible, with no adverse effect on flap survival or limb salvage. No statistically significant differences in the parameters were detected, though the sample is too small to establish comparability. An adequately powered trial is required. Full article

Acute and chronic wounds remain a major clinical burden, motivating the design of multilayer biomedical composite systems capable of combining structural support, antimicrobial protection, and controlled release of therapeutic agents within a single device. These architectures integrate natural and synthetic biomaterials, hydrogels, electrospun membranes, bioactive nanoparticles, and 3D-printed scaffolds to reproduce the multifunctionality of the native extracellular matrix. This review examines how layer-by-layer design and biomaterial selection govern mechanical strength, as well as bioactivity, and how these parameters can be tuned to the distinct phases of wound repair. Particular emphasis is placed on strategies for incorporating growth factors, antimicrobial agents, metal/metal-oxide nanoparticles to enhance re-epithelialization, angiogenesis, and infection control; emerging gene-based delivery strategies are also discussed. The main technologies and biomaterial combinations reported to date are compared, alongside a critical overview of their in vitro and in vivo performance. Reproducibility, scalability, and regulatory standardization remain the main barriers to clinical translation. We conclude by outlining priority research directions to advance multilayer composites from bench-scale prototypes toward approved wound-care products. Full article

In this study, bacitracin—a small-molecule antibacterial agent—was incorporated into the network structure of a type I collagen/bacterial cellulose (Col/BC) composite via in situ recombination and impregnation adsorption, leveraging the well-established drug-loading capacity and sustained-release characteristics of type I collagen. The obtained BA@Col/BC (BA@CBC) functional dressing features a well-defined nanoporous architecture, high porosity (83.9 ± 1.8%), rapid water absorption kinetics, substantial water absorption capacity (48.7 ± 2.4 g/g), and satisfactory moisture permeability (2984 ± 56 g·m²·day). Critically, the introduction of type I collagen not only effectively delays the release of bacitracin, but also significantly improves the cytocompatibility of the bacterial cellulose-based dressing. BA@CBC exhibits powerful antibacterial activities against S. aureus and MRSA, and can promote the proliferation of NIH3T3 and HUVEC, demonstrating excellent cytocompatibility. In vivo studies in a murine infected-wound model revealed that BA@CBC significantly accelerates wound closure compared to controls; histological evaluation further showed the most organized re-epithelialization, robust granulation tissue formation, and de novo hair follicle regeneration in the BA@CBC group. Fluorescence immunohistochemical analysis confirmed markedly reduced expression of pro-inflammatory cytokines IL-1β and TNF-α in BA@CBC-treated wounds, indicating effective suppression of excessive inflammation and consequent improvement of the wound microenvironment. Collectively, BA@CBC integrates favorable physicochemical properties, sustained antibacterial functionality, and superior cytocompatibility—positioning it as a promising candidate for clinical management of infected wounds. Full article

Background: Bacteria of the genus Providencia are emerging pathogens associated with a wide range of infections, particularly in healthcare settings. In veterinary medicine, infections caused by these organisms are uncommon, and, to date, there have been no reports of carbapenem-resistant Providencia spp. causing infection in companion animals. Methods and Results: This study describes a comprehensive investigation of bacterial endocarditis caused by carbapenem-resistant Providencia rettgeri in a cat, including clinical, imaging, pathological, microbiological, and genomic findings. A 1.5-year-old mixed-breed female cat was admitted to a referral veterinary hospital with an extensive pelvic limb wound and a recent history of laparotomy. During hospitalization, a heart murmur was detected, and echocardiographic examination revealed vegetation-like lesion on the mitral valve. Despite intensive treatment, the patient’s clinical condition progressively deteriorated over a 15-day period, ultimately leading to euthanasia. Necropsy confirmed bacterial endocarditis with evidence of systemic septic embolization. P. rettgeri was isolated from blood collected from both heart ventricles and from an endocardial swab and its identity was confirmed by MALDI-ToF mass spectrometry. Antimicrobial susceptibility testing demonstrated resistance to meropenem. Whole-genome sequencing confirmed the species identification and revealed a Col3M plasmid carrying multiple antimicrobial resistance genes, including the carbapenemase gene bla_NDM-1. Discussion: To the best of our knowledge, this is the first report of carbapenem-resistant Providencia spp. causing infection in a companion animal. This case highlights the emergence of Providencia spp. as potential veterinary pathogens capable of causing severe, invasive and fatal infections. Full article