Chronic Wound Infections Research Articles

Exploring grape pomace extracts for the formulation of new bioactive multifunctional chitosan/alginate-based hydrogels for wound healing applications

Chronic wounds incidence is increasing and affects millions of people around the world, causing great psychological and socio-economic impacts. However, treatments that can effectively promote wound healing are still lacking. In this study, grape pomace (GP), the main residue from winemaking production was explored as a source of high added-value raw material directed for the topical treatment of Staphylococcus aureus chronic wound infections. Crude GP extracts (composed of stalks or a skin and seeds mixture–from red and white grape varieties) obtained using a modified solid-liquid extraction (water, ethanol, and acetone solvents) were evaluated for their antioxidant capacity (ABTS and DPPH assays), as well as the richness of phenolic compounds (total phenolic content-TPC, total flavonoid content-TFC, and HPLC-DAD assays). The GP extracts with the most favorable results were incorporated in a chitosan-alginate hydrogel (cross-linked with glutaraldehyde and calcium chloride), characterized (swelling, degradation, and release properties), and tested for its bioactivity (antioxidant and antimicrobial potential). TPC and TFC were higher in red GP extracts, as confirmed by the HPLC analysis, indicating a greater diversity of compounds in these extracts. Ethanolic white GP extracts (from skin-seeds mixture) showed the highest extraction yield and antioxidant activity. Their incorporation into the chitosan-alginate hydrogel improved its swelling and antimicrobial properties (total cytoplasmic membranes disruption and culturability reduction). A biomaterial with high swelling capacity and antibacterial activity against S. aureus was obtained, which can potentially promote wound healing by exudate absorption and infection clearance while promoting valorization of by-products and stimulating a circular economy.

Antibacterial Electrospun Membrane with Hierarchical Bead-on-String Structured Fibres for Wound Infections.

Chronic wounds often result in multiple infections with various kinds of bacteria and uncontrolled wound exudate, resulting in several healthcare issues. Advanced medicated nanofibres prepared by electrospinning have gained much attention for their topical application on infected chronic wounds. The objective of this work is to enhance the critical variables of ciprofloxacin-loaded polycaprolactone-silk sericin (PCL/SS-PVA-CIP) nanofibre production via the process of electrospinning. To examine the antibacterial effectiveness of PCL/SS-PVA-CIP nanocomposites, the material was tested against P. aeruginosa and S. aureus. The combination of PCL/SS-PVA-CIP exhibited potent inhibitory properties, with the most effective concentrations of ciprofloxacin (CIP) being 3 μg/g and 7.0 μg/g for each bacterium, respectively. The biocompatibility was evaluated by conducting cell reduction and proliferation studies using the human epidermal keratinocyte (HaCaT) cells and human gingival fibroblasts (HGFs) in vitro cell lines. The PCL/SS-PVA-CIP showed good cell compatibility with HaCaT and HGF cells, with effective proliferation even at antibiotic doses of up to 7.0 μg/g. The drug release effectiveness of the nanocomposites was assessed at various concentrations of CIP, resulting in a maximum cumulative release of 76.5% and 74.4% after 72 h for CIP concentrations of 3 μg/g and 7 μg/g, respectively. In summary, our study emphasizes the possibility of combining silk sericin (SS) and polycaprolactone (PCL) loading with CIP nanocomposite for wound management.

Chitosan-carrageenan microbeads containing nano-encapsulated curcumin: Nano-in-micro hydrogels as alternative-therapeutics for resistant pathogens associated with chronic wounds

Antimicrobial resistance is an issue of global relevance for the treatment of chronic wound infections. In this study, nano-in-micro hydrogels (microbeads) of chitosan and κ-carrageenan (CCMBs) containing curcumin-loaded rhamnosomes (Cur-R) were developed. The potential of Cur-R-CCMBs for improving the antibacterial activity and sustained release of curcumin was evaluated. Curcumin-loaded rhamnosomes (rhamnolipids functionalized liposomes) had a mean particle size of 116 ± 7 nm and a surface-charge of −24.5 ± 9.4 mV. The encapsulation efficiency of curcumin increased from 42.83 % ± 0.69 % in Cur-R to 95.24 % ± 3.61 % respectively after their embedding in CCMBs. SEM revealed smooth surface morphology of Cur-R-CCMBs. FTIR spectroscopy confirmed the presence of weak electrostatic and hydrophobic interactions among curcumin, rhamnosomes, and microbeads. Cur-R-CCMBs had demonstrated significant antibacterial activity against multi-drug resistant chronic wound pathogens including Staphylococcus aureus and Pseudomonas aeruginosa. Cur-R-CCMBs also exhibited significantly higher anti-oxidant (76.85 % ± 2.12 %) and anti-inflammatory activity (91.94 % ± 0.41 %) as well as hemocompatibility (4.024 % ± 0.59 %) as compared to pristine microbeads. In vivo infection model of mice revealed significant reduction in the viable bacterial count of S. aureus (∼2.5 log CFU/mL) and P. aeruginosa (∼2 log CFU/mL) for Cur-R-CCMBs after 5 days. Therefore, nano-in-micro hydrogels can improve the overall efficacy of hydrophobic antimicrobials to develop effective alternative-therapeutics against resistant-pathogens associated with chronic wound infections.

PLGA Nanoparticles Formulations Loaded With Antibiotics Induce Sustained and Controlled Antibiotics Release for Prolonged Antibacterial Action Against MRSA, and Pseudomonas aeruginosa FRD1.

The purpose of the present study was to create resorbable nanoparticles (NPs) using poly(lactic-co-glycolic acid) (PLGA) to develop novel antibacterial therapeutics for the treatment of chronic wound infections that are susceptible to recurrent infections. By first performing a release study, it was possible to predict the behavior of the different PLGA NP formulations and assess the efficacy of the nanocomposite drug delivery system. These PLGA NP formulations consisted of varying ratios of PLGA without polyvinyl alcohol (PVA) and PLGA with PVA (PLGA-PVA) (i.e., 25:75[PLGA25], 50:50[PLGA50], and 75:25[PLGA75]). Then, different antibiotics (i.e., ciprofloxacin and gentamicin) were incorporated into the PLGA NP formulations to test the antibacterial efficacy of these antimicrobial NPs against different pathogens (i.e., methicillin-resistant Staphylococcus aureus USA300 [MRSA], Pseudomonas aeruginosa FRD1, and Acinetobacter baumannii BAA1605). Of particular interest was testing against the MRSA strain USA300 and the P. aeruginosa strain FRD1. This was possible by measuring the zone of inhibition. A 3-day period was used to monitor the antibacterial efficacy of the different PLGA NP formulations (i.e., PLGA25, PLGA50, and a 1:1 combination of PLGA25:PLGA50) against A. baumannii BAA1605, MRSA, and P aeruginosa FRD1. Throughout the study, A. baumannii was a negative control and was resistant to all the PLGA NP formulations loaded with ciprofloxacin and gentamicin. At the end of the 3-day period, the PLGA and PLGA50 ciprofloxacin-loaded formulations produced zones of inhibition of 27 mm and 23 mm, respectively, against P. aeruginosa FRD1. This indicated that P. aeruginosa FRD1 was susceptible to both formulations. The mixed formulations with equal parts PLGA25:PLGA50 loaded with ciprofloxacin produced a zone of inhibition (i.e., 25 mm). This again indicated that P. aeruginosa FRD1 was susceptible to ciprofloxacin. The formulations tested against MRSA showed that only gentamicin-loaded formulations produced intermediate results, and that ciprofloxacin-loaded formulations were ineffective. The PLGA25 and the PLGA50 NP formulations loaded with gentamicin both produced zones of inhibition of 13 mm. This indicated that MRSA was intermediate to both the formulations. The PLGA25:PLGA50 loaded with gentamicin produced a zone of inhibition of 14 mm, which again showed that MRSA was intermediate to this formulation. Overall, these PLGA NP formulations showed the sustained antibacterial potential of a burst release, followed by a sustained release of antibiotics from antibiotics loaded PLGA NPs in a controlled manner. In the future, this can help prevent the emergence of recurrent infections in the treatment of chronic wounds and reduce the number of medical dressing changes.

Anaerobic bacteria in chronic wounds: Roles in disease, infection and treatment failure.

Infection is among the most common factors that impede wound healing, yet standard treatments routinely fail to resolve chronic wound infections. The chronic wound environment is largely hypoxic/anoxic, and wounds are predominantly colonised by facultative and obligate anaerobic bacteria. Oxygen (O2) limitation is an underappreciated driver of microbiota composition and behaviour in chronic wounds. In this perspective article, we examine how anaerobic bacteria and their distinct physiologies support persistent, antibiotic-recalcitrant infections. We describe the anaerobic energy metabolisms bacteria rely on for long-term survival in the wound environment, and why many antibiotics become less effective under hypoxic conditions. We also discuss obligate anaerobes, which are among the most prevalent taxa to colonise chronic wounds, yet their potential roles in influencing the microbial community and wound healing have been overlooked. All of the most common obligate anaerobes found in chronic wounds are opportunistic pathogens. We consider how these organisms persist in the wound environment and interface with host physiology to hinder wound healing processes or promote chronic inflammation. Finally, we apply our understanding of anaerobic physiologies to evaluate current treatment practices and to propose new strategies for treating chronic wound infections.

Accelerated healing of intractable biofilm-infected diabetic wounds by trypsin-loaded quaternized chitosan hydrogels that disrupt extracellular polymeric substances and eradicate bacteria

Complex and stubborn bacterial biofilm infections significantly hinder diabetic wound healing and threaten public health. Therefore, a dressing material that effectively clears biofilms and promotes wound healing is urgently required. Herein, we introduce a novel strategy for simultaneously dispersing extracellular polymeric substances and eradicating drug-resistant bacteria. We prepared an ultrabroad-spectrum and injectable quaternized chitosan (QCS) hydrogel loaded with trypsin, which degrades biofilm extracellular proteins. Increased temperature initiated QCS gelation to form the hydrogel, enabling the sustained release of trypsin and effective adherence of the hydrogel to irregularly shaped wounds. To reproduce clinical scenarios, biofilms formed by a mixture of Staphylococcus aureus (S. aureus), Methicillin-resistant S. aureus, and Pseudomonas aeruginosa were administered to the wounds of rats with streptozotocin-induced diabetes. Under these severe infection conditions, the hydrogel efficiently suppressed inflammation, promoted angiogenesis, and enhanced collagen deposition, resulting in accelerated healing of diabetic wounds. Notably, the hydrogel demonstrates excellent biocompatibility without cytotoxicity. In summary, we present a trypsin-loaded QCS hydrogel with tremendous clinical applications potential for the treatment of chronic infected wounds.

Long-Term Stability and Efficacy of NCT Solutions.

To realize the potential for the use of N-chlorotaurine (NCT) in healthcare, a better understanding of the long-term stability of the compound in water is needed. An array of analytical procedures is required that can measure changes in NCT concentration over time and allow for the detection and identification of contaminants and likely degradation end products. We used UV-Vis and NMR spectroscopy, HPLC, and LCMS to establish the stability of NCT in solutions subjected to prolonged ambient and elevated temperatures. Stability proved to be dependent on concentration with half-lives of ~120 days and ~236 days for 1% and 0.5% solutions of NCT at ~20 °C. Regardless of initial pH, all solutions shifted toward and maintained a pH of ~8.3 at 20 °C and 40 °C. NCT at 500 µg/mL and 250 µg /mL inhibited biofilm formation by Pseudomonas aeruginosa and Staphylococcus aureus but did not disperse established biofilms. NCT exposure to the biofilms had profound effects on the viability of both bacteria, reducing live organisms by >90%. Exposure of Interleukin-6 (IL-6) to 11 µM NCT reduced the binding of IL-6 to an immobilized specific antibody by ~48%, which is 5× the amount required for HOCl to bring about the same effect in this test system. Our data demonstrate the potency of the compound as an antimicrobial agent with potential benefits in the management of infected chronic wounds and suggest that NCT may contribute to anti-inflammatory processes in vivo by direct modification of cytokine mediators.

Nanomedicine: An Emerging Tool in Healing Chronic Wounds and its Opportunities

Chronic wounds generally take a lot of time to recover, which becomes a cause of worry for the patient and also makes it difficult to manage them. Chronic wound affects the minds of millions of people worldwide, which results in a high mortality rate. Nanomedicine has emerged as a promising tool in addressing this issue of chronic wounds. Nanomedicine in chronic wound healing holds the potential to revolutionize wound care by offering various personalized treatments and improving patient outcomes. Advanced wound dressings and nanofibresscaffolds promote tissue regeneration, which also accelerates wound closure. Nanomedicine is also able to provoke the various cellular and molecular mechanisms that are involved in the wound microenvironment, showing the anti-inflammatory, antibacterial, and angiogenetic effects. The gene therapy and various inflammation modulations using this emerging tool of nanotechnology show promising results in managing the various chronic wounds. Nanomedicine offers innovative approaches to address these challenges. Nanomedicine also plays a crucial role in tissue engineering, which can also be used for chronic wound treatment. Nanotechnology has enabled the various development of advanced wound dressings and has improved various properties. Nanomedicine also uses antimicrobial nanomaterials, such as silver nanoparticles, to combat the various infections in chronic wounds. The main aim of the review is to provide a concise overview of nanomedicine as a recent tool in healing chronic wounds and also its various opportunities for curing chronic wounds.

Pseudomonas aeruginosa surface motility and invasion into competing communities enhance interspecies antagonism.

The polymicrobial nature of many chronic infections makes their eradication challenging. Particularly, coisolation of Pseudomonas aeruginosa and Staphylococcus aureus from airways of people with cystic fibrosis and chronic wound infections is common and associated with severe clinical outcomes. The complex interplay between these pathogens is not fully understood, highlighting the need for continued research to improve management of chronic infections. Our study unveils that P. aeruginosa is attracted to S. aureus, invades into neighboring colonies, and secretes anti-staphylococcal factors into the interior of the colony. Upon inhibition of P. aeruginosa motility and thus invasion, S. aureus colony architecture changes dramatically, whereby S. aureus is protected from P. aeruginosa antagonism and responds through physiological alterations that may further hamper treatment. These studies reinforce accumulating evidence that spatial structuring can dictate community resilience and reveal that motility and chemotaxis are critical drivers of interspecies competition.

5-aminolevulinic acid photodynamic therapy for chronic wound infection in rats with diabetes

Recent research indicated that ulcers and peripheral vascular disease resulting from drug-resistant bacterial infections are the main causes of delayed healing in chronic diabetic wounds. 5-Aminolevulinic acid (ALA) is a second-generation endogenous photosensitizer. The therapeutic effect and mechanism of ALA-mediated photodynamic therapy (ALA-PDT) on methicillin-resistant Staphylococcus aureus (MRSA)-infected wounds in diabetic rats were investigated in this study. The results revealed the promising antibacterial effects of ALA-PDT MRSA in vitro, with a minimum inhibitory concentration and minimum bactericidal concentration of 250 and 500 μM, respectively. ALA-PDT also changed the permeability and structural integrity of bacterial cell membranes by producing reactive oxygen species. Meanwhile, ALA-PDT accelerated wound healing in MRSA-infected diabetic rats, with 5 % ALA-PDT achieving complete sterilization in 14 days and wound closure in 21 days. Treatment with 5 % ALA-PDT additionally improved the histopathological appearance of skin tissue, as well as fibrosis, inflammatory cytokine release, and angiogenesis-related protein expression. These findings indicated that ALA-PDT significantly promoted the healing of MRSA-infected wounds in diabetic rats by eliminating bacteria, inhibiting inflammation, generating granulation tissues, promoting neovascularization, and restoring damaged nerves. In addition, the healing mechanism was related to the activation of inflammatory and angiogenesis pathways through the regulation of tumor necrosis factor-alpha and interleukin-6 expression and upregulation of CD206, CD31, and VEGF. These findings underscored the potential role of ALA-PDT in promoting the healing of chronic diabetic wounds.

Reirradiation after osteocutaneous free flap reconstruction for locally recurrent head and neck cancer

PurposeRecurrent head and neck cancer poses difficult management. Even after salvage surgery, many patients are considered high-risk for further recurrence and benefit from reirradiation, despite the sequelae such as chronic wounds, tissue necrosis, osteoradionecrosis and vascular damage associated with re-irradiation. Free flaps not only enable the reconstruction following salvage surgery, but there has been limited studies suggesting that free flap reconstruction may reduce the amount of reirradiation complications. However, there are no studies to date specifically examining the effects of osteocutaneous free flap reconstruction upon reirradiation outcomes. Materials and methodsIn this retrospective study, patients with recurrent head and neck cancer that had a history of prior head and neck radiation who underwent salvage surgery with osteocutaneous free flaps followed by reirradiation were identified. Descriptive statistics were performed to assess outcomes. ResultsFive patients met criteria. Complications included chronic wound infection in one patient, fistula in one patient, plate exposure in two patients and plate removal in one patient. No patients had osteoradionecrosis or carotid rupture after reirradiation. There was an association between complications and further local disease recurrence. All patients were tube feed dependent at their most recent follow-up and two patients were tracheostomy dependent 12 months post-irradiation. Two patients had disease recurrence. Median overall survival was 16 months after reirradiation. ConclusionsOsteocutaneous free flap surgery with reirradiation may result in high rates of complications and low functional status with an equivocal improvement in survival. Larger studies are needed to substantiate these findings and assess the risk-benefit analysis.

Determination of the Course of Cyan Fluorescence of Pseudomonas aeruginosa with a Handheld Bacterial Imaging Device.

Chronic wound infections are of clinical concern as they often lead to high rates of mortality and morbidity. A point-of-care handheld bacterial fluorescence imaging has been designed to detect the auto-fluorescent characteristics of most clinically relevant species of bacteria. This device causes most species of bacteria to exhibit red fluorescence due to the production of exoproduct porphyrins. One of the most significant contributors to the pathogenicity of chronic wounds is the pathogen Pseudomonas aeruginosa, and interestingly, this organism exhibits an additional unique cyan fluorescence signature. There is an over 90% positive predictive value that, when a chronic wound exhibits cyan fluorescence with the bacterial fluorescence imaging device, the wound will harbor P. aeruginosa. This project seeks to understand what genetic factor(s) contribute to the cyan phenotype observed.

Photodynamic activation of phytochemical-antibiotic combinations for combatting Staphylococcus aureus from acute wound infections

Staphylococcus aureus is characterized by its high resistance to conventional antibiotics, particularly methicillin-resistant (MRSA) strains, making it a predominant pathogen in acute and chronic wound infections. The persistence of acute S. aureus wound infections poses a threat by increasing the incidence of their chronicity. This study investigated the potential of photodynamic activation using phytochemical-antibiotic combinations to eliminate S. aureus under conditions representative of acute wound infections, aiming to mitigate the risk of chronicity. The strategy applied takes advantage of the promising antibacterial and photosensitising properties of phytochemicals, and their ability to act as antibiotic adjuvants. The antibacterial activity of selected phytochemicals (berberine, curcumin, farnesol, gallic acid, and quercetin; 6.25–1000 μg/mL) and antibiotics (ciprofloxacin, tetracycline, fusidic acid, oxacillin, gentamicin, mupirocin, methicillin, and tobramycin; 0.0625–1024 μg/mL) was screened individually and in combination against two S. aureus clinical strains (methicillin-resistant and -susceptible–MRSA and MSSA). The photodynamic activity of the phytochemicals was assessed using a light-emitting diode (LED) system with blue (420 nm) or UV-A (365 nm) variants, at 30 mW/cm2 (light doses of 9, 18, 27 J/cm2) and 5.5 mW/cm2 (light doses of 1.5, 3.3 and 5.0 J/cm2), respectively. Notably, all phytochemicals restored antibiotic activity, with 9 and 13 combinations exhibiting potentiating effects on MSSA and MRSA, respectively. Photodynamic activation with blue light (420 nm) resulted in an 8- to 80-fold reduction in the bactericidal concentration of berberine against MSSA and MRSA, while curcumin caused 80-fold reduction for both strains at the light dose of 18 J/cm2. Berberine and curcumin-antibiotic combinations when subjected to photodynamic activation (420 nm light, 10 min, 18 J/cm2) reduced S. aureus culturability by ≈9 log CFU/mL. These combinations lowered the bactericidal concentration of antibiotics, achieving a 2048-fold reduction for gentamicin and 512-fold reduction for tobramycin. Overall, the dual approach involving antimicrobial photodynamic inactivation and selected phytochemical-antibiotic combinations demonstrated a synergistic effect, drastically reducing the culturability of S. aureus and restoring the activity of gentamicin and tobramycin.

Prevalence of Chronic Wounds Microbial Contaminations and their Susceptibility Pattern to Current Antibiotics in Mbingo and Nkwen Baptist Hospitals

Abstract BACKGROUND: Antimicrobial resistance among pathogens causing chronic wound infections is a growing concern, particularly in low-income countries. Understanding the microbial profile and antibiotic susceptibility patterns in chronic wounds is crucial for guiding effective treatment strategies. This study aimed to investigate the prevalence of microbial contamination and antibiotic susceptibility patterns in chronic wounds among patients treated at Mbingo Baptist Hospital and Nkwen Baptist Hospital in Northwest Cameroon. METHODS: A cross-sectional, hospital-based study was conducted from March to June 2022. Wound samples were collected from patients with chronic wounds, and microbiological analyses were performed to identify the isolates and assess their antimicrobial susceptibility. RESULTS: A total of 54 chronic wounds were examined, with venous ulcers being the most common type (42.6%). Bacterial and fungal growth was detected in 89% of the wound swabs. Gram-negative bacteria, including Salmonella spp. (14.8%) and Pseudomonas aeruginosa (7.4%), were frequently isolated, along with Gram-positive organisms such as Staphylococcus aureus (18.5%) and Staphylococcus spp. (11.1%). Polymicrobial infections were observed in 11.2% of the cases. The isolates exhibited high-resistance rates to commonly used antibiotics, such as sulfamethoxazole/trimethoprim (83%), amoxicillin (80.9%), ceftriaxone (74.5%), azithromycin (66%), and doxycycline (61.7%). Diphtheria spp. and S. aureus showed resistance to nearly all the tested antibiotics. CONCLUSION: This study highlights the significant burden of antimicrobial-resistant bacteria in chronic wound infections in the studied health-care facilities in Cameroon. These findings underscore the urgent need for improved antimicrobial stewardship and the development of novel treatment strategies to address the growing challenge of drug-resistant pathogens in chronic wound management.

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.

Macrochannel-aligned cryogels with oxygen release and antibacterial properties for MRSA-infected diabetic wound healing

Wounds in diabetic patients suffer from bacterial infection, reduced angiogenesis, and inadequate oxygen supply, which prolong healing time and form chronic wounds. Long-term hypoxia is one of the main causes of delayed wound healing. Therefore, it is particularly urgent to develop new dressings with oxygen release and antibacterial properties for the infected diabetic wound. In this paper, we developed oxygen-releasing and macrochannel-aligned cryogels based on acylhydrazone bond cross-linking between the adipic dihydrazide grafted hyaluronic acid (AHA) and oxidized dextran (OD). The aligned macroporous structure of cryogels formed by the unidirectional freezing technique is favorable for the release of oxygen. The incorporated calcium peroxide (CPO) can react with water to produce oxygen and hydrogen peroxide (H2O2), which can provide good antibacterial properties, while excess H2O2 can be decomposed into oxygen by catalase (CAT), achieving oxygen release for up to 10 days. The macrochannel-aligned cryogels have suitable mechanical properties, oxygen release property, good biological property, and antibacterial property resulting from H2O2 release. In the MRSA-infected diabetic full-thickness defect wound model, compared to the commercial dressing, the cryogel showed excellent bactericidal property and better wound healing by providing oxygen, regulating inflammation, accelerating collagen deposition, and promoting granulation tissue formation and vascularization. In brief, this study developed an efficient oxygen-releasing and antibacterial cryogel with an aligned macroporous structure, which may provide a new strategy for the management of chronic hypoxic infected diabetic wounds.

Clinical nursing application of nano-silver dressing on radiation injury chronic infected wound

ObjectiveTo explore the clinical nursing application of nano-silver dressing in the nursing of radiation injury chronic infected wound. MethodsIn this study, 52 patients who met the standard of chronic infected wounds were randomly divided into two groups for nursing intervention, namely the experimental group using nano silver dressing and the control group using medical gauze, with 26 patients in each group. Age, body mass index, blood glucose and wound area were recorded in both groups before nursing intervention. The blood C-reactive protein value, white blood cell count and pain score were recorded on the intervention day, the intervention 7 d and the intervention 14 d. The therapeutic effect, dressing change times and wound healing time of each group after intervention were analyzed. ResultsOn the 7 d and 14 d after using nano silver dressing, the C-reactive protein value, white blood cell count and pain score of patients, as well as the therapeutic effect, dressing times and wound healing time were better than those without using nano silver dressing. ConclusionNano-silver dressing can accelerate the healing of radiation injury chronic infected wound, and can achieve significant therapeutic effect in clinical treatment.

H2Se-evolving bio-heterojunctions promote cutaneous regeneration in infected wounds by inhibiting excessive cellular senescence

Pathogenic infection leads to excessive senescent cell accumulation and stagnation of wound healing. To address these issues, we devise and develop a hydrogen selenide (H2Se)-evolving bio-heterojunction (bio-HJ) composed of graphene oxide (GO) and FeSe2 to deracinate bacterial infection, suppress cellular senescence and remedy recalcitrant infected wounds. Excited by near-infrared (NIR) laser, the bio-HJ exerts desired photothermal and photodynamic effects, resulting in rapid disinfection. The crafted bio-HJ could also evolve gaseous H2Se to inhibit cellular senescence and dampen inflammation. Mechanism studies reveal the anti-senescence effects of H2Se-evolving bio-HJ are mediated by selenium pathway and glutathione peroxidase 1 (GPX1). More critically, in vivo experiments authenticate that the H2Se-evolving bio-HJ could inhibit cellular senescence and potentiate wound regeneration in rats. As envisioned, our work not only furnishes the novel gasotransmitter-delivering bio-HJ for chronic infected wounds, but also gets insight into the development of anti-senescence biomaterials.

A First-in-Human Randomized Clinical Study Investigating the Safety and Tolerability of Stabilized Hypochlorous Acid in Patients with Chronic Leg Ulcers.

Objective: Biofilm infections in chronic wounds are common and pose a significant clinical challenge. This challenge was addressed by developing the SoftOx Biofilm Eradicator (SBE) composed of hypochlorous acid (HOCl) and acetic acid with strong broad-spectrum antimicrobial activity. Approach: First-in-human study investigating the safety and tolerability as primary endpoints and wound size effect and antimicrobial efficacy as secondary endpoints of SBE treatment in chronic leg wound patients. The study was divided into two as follows: a randomized, double-blinded, Single Ascending Dose (SAD) phase (n = 16 SBE; n = 4 placebo), where patients were treated with SBE or saline (placebo) only once, followed by an open-label, Multiple Ascending Dose (MAD) phase (n = 8), where patients were treated with SBE once daily or twice daily over five days. Reporting is according to CONSORT guidelines. Results: SBE was safe and well-tolerated in chronic leg wound patients. There were no significant differences in pain during and after treatment with SBE or the placebo. The SBE treatment reduced bioburden in wounds compared to baseline, with 98% and 49% median reduction after SBE or placebo treatment, respectively. A dose-dependent trend in absolute wound size reduction was observed in the MAD groups with a median (min, max) change of -2.99 (-14.25, -1.5) cm2 in the once-daily and -10.48 (-17.95, -0.38) cm2 in the twice-daily group, respectively. Innovation and Conclusion: This study demonstrated the safe use of HOCl-based SBE in chronic leg wounds with promising trends of immediate antimicrobial action and beneficial effect on wound healing.

Evaluation of treatment of methicillin-resistant Staphylococcus aureus biofilms with intermittent electrochemically generated H2O2 or HOCl.

Chronic wound infections can be difficult to treat and may lead to impaired healing and worsened patient outcomes. Novel treatment strategies are needed. This study evaluated the effects of intermittently produced hydrogen peroxide (H2O2) and hypochlorous acid (HOCl), generated via an electrochemical bandage (e-bandage), against methicillin-resistant Staphylococcus aureus biofilms in an agar membrane biofilm model. By changing the working electrode potential, the e-bandage generated either HOCl (1.5 VAg/AgCl) or H2O2 (-0.6 VAg/AgCl). The degree of biocidal activity of intermittent treatment with HOCl and H2O2 correlated with HOCl treatment time; HOCl treatment durations of 0, 1.5, 3, 4.5, and 6 hours (with the rest of the 6-hour total treatment time devoted to H2O2 generation) resulted in mean biofilm reductions of 1.36 ± 0.2, 2.22 ± 0.16, 3.46 ± 0.38, 4.63 ± 0.74, and 7.66 ± 0.5 log CFU/cm2, respectively, vs. non-polarized controls, respectively. However, application of H2O2 immediately after HOCl treatment was detrimental to biofilm removal. For example, 3 hours HOCl treatment followed by 3 hours H2O2 resulted in a 1.90 ± 0.84 log CFU/cm2 lower mean biofilm reduction than 3 hours HOCl treatment followed by 3 hours non-polarization. HOCl generated over 3 hours exhibited biocidal activity for at least 7.5 hours after e-bandage operation ceased; 3 hours of HOCl generation followed by 7.5 hours of non-polarization resulted in a biofilm cell reduction of 7.92 ± 0.12 log CFU/cm2 vs. non-polarized controls. Finally, intermittent treatment with HOCl (i.e., interspersed with periods of e-bandage non-polarization) for various intervals showed similar effects (approximately 6 log CFU/cm2 reduction vs. non-polarized control) to continuous treatment with HOCl for 3 hours, followed by 3 hours of non-polarization. These findings suggest that timing and sequencing of HOCl and H2O2 treatments are crucial for maximizing biofilm control when using an e-bandage strategy.