Biofilm-infected Wounds Research Articles

Comparison of antibiofilm activity of low-concentrated hypochlorites vs polyhexanide-containing antiseptic.

Chronic wound infection is highly associated with morbidity and endangers the patient's life. Therefore, wound care products must have a potent antimicrobial and biofilm-eradicating effect. In this work, the antimicrobial/antibiofilm activity of two low-concentrated chlorine-based and releasing solutions was investigated on a total of 78 strains of methicillin-resistant Staphylococcus aureus, Pseudomonas aeruginosa, and Candida albicans, using the cohesive spectrum of in vitro settings, including microtiter plate models, biofilm-oriented antiseptic test, cellulose-based biofilm model, biofilm bioreactors and Bioflux model. The antiseptic containing polyhexamethylene biguanide was used in the character of usability control of performed tests. The results obtained by static biofilm models indicate that low-concentrated chlorine-based and releasing solutions display none to moderate antibiofilm activity, while data obtained by means of the Bioflux model, providing flow conditions, indicate the moderate antibiofilm activity of substances compared with the polyhexanide antiseptic. Considering in vitro data presented in this manuscript, the earlier reported favorable clinical results of low-concentrated hypochlorites should be considered rather an effect of their rinsing activity combined with low cytotoxicity but not the antimicrobial effect per se. For the treatment of heavily biofilm-infected wounds, polyhexanide should be considered the agent of choice because of its higher efficacy against pathogenic biofilms.

Anti-biofilm effects and healing promotion by silver oxynitrate-based dressings

Microbial growth within a wound often manifests as biofilms, which can prevent healing and is difficult to eradicate. Novel silver dressings claim to combat wound infection, but anti-biofilm efficacy and effects on healing independent of infection are often unclear. Using in vitro and in vivo S. aureus and P. aeruginosa biofilm models, we report the efficacy of a dressing which produces Ag1+ ions; an Ag1+ dressing containing ethylenediaminetetraacetic acid and benzethonium chloride (Ag1+/EDTA/BC), and a dressing containing silver oxynitrate (Ag Oxysalts) which produces Ag1+, Ag2+ and Ag3+ ions, against wound biofilms, and their effects on healing. Ag1+ dressings had minimal effect on in vitro and murine (C57BL/6j) wound biofilms. In contrast, Ag Oxysalts and Ag1+/EDTA/BC dressings significantly reduced viable bacteria within in vitro biofilms and demonstrated a visible reduction in bacteria and EPS components within murine wound biofilms. The dressings had different effects on the healing of biofilm-infected and uninfected wounds, with Ag Oxysalts dressings having a greater beneficial effect on re-epithelialisation, wound size and inflammation than the control treatment and the other silver dressings. The different physicochemical properties of the silver dressings result in varied effects on wound biofilms and healing which should be considered when selecting dressings to treat biofilm-infected wounds.

Self-supply of H2O2 and O2 by a composite nanogenerator for chemodynamic therapy/hypoxia improvement and rapid therapy of biofilm-infected wounds

Bacterial wound infection is a major challenge to human health worldwide. In this study, a composite nanogenerator, CaO2@ZIF-67-PLL, was fabricated via a bottom-up approach with chemodynamic therapy (CDT)/hypoxia improvement for rapid therapy of biofilm-infected wounds. Under a pathologically acidic microenvironment, the out layer ZIF-67 can be decomposed to rapidly release Co2+ and CaO2; Subsequently, the unprotected CaO2 reacts with H2O to produce O2 and H2O2. The self-supply of O2 relieves hypoxia and inflammatory response induced by infections, while the generated H2O2 and poly-l-lysine (PLL) exhibited synergistic strong anti-biofilm capability against Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) as assessed by reactive oxygen species (ROS) generation, membrane permeability change, ATP reduction, o-nitrophenyl-β-d-galactopyranoside (ONPG) hydrolysis and intracellular component leakage. Meanwhile, CaO2@ZIF-67-PLL exhibited good cytocompatibility and promoted the adhesion, proliferation, and migration of NIH-3T3 cells by enhancing the expression of wound healing-related genes (TGF-β1, VEGF, α-SMA, Col I, Col III, and Wnt-5a). Notably, CaO2@ZIF-67-PLL could significantly improve the healing process of S. aureus-infected wounds via suppressed inflammatory responses, enhanced collagen disposition and angiogenesis, and stimulated HIF-1α, CD31, and Wnt-5a/β-Catenin signaling pathways. These results indicated the potential of CaO2@ZIF-67-PLL nanogenerator for clinical application in infected wound treatment.

Alternative Copper-Based Single-Atom Nanozyme with Superior Multienzyme Activities and NIR-II Responsiveness to Fight against Deep Tissue Infections.

Nanozymes are considered to represent a new era of antibacterial agents, while their antibacterial efficiency is limited by the increasing tissue depth of infection. To address this issue, here, we report a copper and silk fibroin (Cu-SF) complex strategy to synthesize alternative copper single-atom nanozymes (SAzymes) with atomically dispersed copper sites anchored on ultrathin 2D porous N-doped carbon nanosheets (CuN x -CNS) and tunable N coordination numbers in the CuN x sites (x = 2 or 4). The CuN x -CNS SAzymes inherently possess triple peroxidase (POD)-, catalase (CAT)-, and oxidase (OXD)-like activities, facilitating the conversion of H2O2 and O2 into reactive oxygen species (ROS) through parallel POD- and OXD-like or cascaded CAT- and OXD-like reactions. Compared to CuN2-CNS, tailoring the N coordination number from 2 to 4 endows the SAzyme (CuN4-CNS) with higher multienzyme activities due to its superior electron structure and lower energy barrier. Meanwhile, CuN x -CNS display strong absorption in the second near-infrared (NIR-II) biowindow with deeper tissue penetration, offering NIR-II-responsive enhanced ROS generation and photothermal treatment in deep tissues. The in vitro and in vivo results demonstrate that the optimal CuN4-CNS can effectively inhibit multidrug-resistant bacteria and eliminate stubborn biofilms, thus exhibiting high therapeutic efficacy in both superficial skin wound and deep implant-related biofilm infections.

Antimicrobial polymer-siRNA polyplexes as a dual-mode platform for the treatment of wound biofilm infections.

Treatment of wound biofilm infections faces challenges from both pathogens and uncontrolled host immune response. Treating both issues through a single vector would provide enhanced wound healing. Here, we report the use of a potent cationic antimicrobial polymer to generate siRNA polyplexes for dual-mode treatment of wound biofilms in vivo. These polyplexes act both as an antibiofilm agent and a delivery vehicle for siRNA for the knockdown of biofilm-associated pro-inflammatory MMP9 in host macrophages. The resulting polyplexes were effective in vitro, eradicating MRSA biofilms and efficiently delivering siRNA to macrophages in vitro with concomitant knockdown of MMP9. These polyplexes were likewise effective in an in vivo murine wound biofilm model, significantly reducing bacterial load in the wound (∼99% bacterial clearance) and reducing MMP9 expression by 80% (qRT-PCR). This combination therapeutic strategy dramatically reduced wound purulence and significantly expedited wound healing. Taken together, these polyplexes provide an effective and translatable strategy for managing biofilm-infected wounds.

Hyperbaric oxygen therapy augments ciprofloxacin effect against Pseudomonas aeruginosa biofilm infected chronic wounds in a mouse model

IntroductionChronic wounds have a compromised microcirculation which leads to restricted gas exchange. The majority of these hypoxic wounds is infested with microorganisms congregating in biofilms which further hinders the antibiotic function. We speculate whether this process can be counteracted by hyperbaric oxygen therapy (HBOT). MethodologyTwenty-eight BALB/c mice with third-degree burns were included in the analyses. Pseudomonas aeruginosa embedded in seaweed alginate beads was injected under the eschar to mimic a biofilm infected wound. Challenged mice were randomized to receive either 4 days with 1 x ciprofloxacin combined with 2 × 90 min HBOT at 2.8 standard atmosphere daily, 1 x ciprofloxacin as monotherapy or saline as placebo. The mice were clinically scored, and wound sizes were estimated by planimetry daily. Euthanasia was performed on day 8. Wounds were surgically removed in toto, homogenized and plated for quantitative bacteriology. Homogenate supernatants were used for cytokine analysis. ResultsP. aeruginosa was present in all wounds at euthanasia. A significant lower bacterial load was seen in the HBOT group compared to either the monotherapy ciprofloxacin group (p = 0.0008), or the placebo group (p < 0.0001). IL-1β level was significantly lower in the HBOT group compared to the placebo group (p = 0.0007). Both treatment groups had higher osteopontin levels than the placebo group (p = 0.002 and p = 0.004). The same pattern was seen in the S100A9 analysis (p = 0.01 and p = 0.008), whereas no differences were detected between the S100A8, the VEGF or the MMP8 levels in the three groups. ConclusionThese findings show that HBOT improves the bactericidal activity of ciprofloxacin against P. aeruginosa wound biofilm in vivo. HBOT in addition to ciprofloxacin also modulates the host response to a less inflammatory phenotype.

Levofloxacin loaded clove oil nanoscale emulgel promotes wound healing in Pseudomonas aeruginosa biofilm infected burn wound in mice

Owing to their tolerance to antibiotics, bacterial biofilms continue to pose a threat to mankind and are leading cause for non-healing of burn wounds. Within the biofilm matrix, antibiotics become functionally inactive due to restricted penetration and enzymatic degradation leading to rise of antimicrobial resistance. The objective of present investigation was to develop and characterize levofloxacin (LFX) loaded clove oil nanoscale emulgel (LFX-NE gel) and evaluate its in vivo therapeutic efficacy in Pseudomonas aeruginosa biofilm infected burn wound in mice. The optimized emulgel was found to possess good texture profile and showed shear thinning behavior. In vitro release study demonstrated complete drug release in 8 h and emulgel was found to be stable for 3 months at 25 °C and 40 °C. In vivo study revealed biofilm dispersal, complete wound closure, re-epithelialization and collagen deposition by LFX-NE gel in comparison to various control groups. LFX-NE gel was able to clear the infection within 7 days of treatment and promote wound healing as well. Therefore, administration of LFX-incorporated NE gel could be a beneficial treatment strategy for P. aeruginosa biofilm-infected burn wounds.

A Highly Efficacious Electrical Biofilm Treatment System for Combating Chronic Wound Bacterial Infections.

Biofilm infection has a high prevalence in chronic wounds and can delay wound healing. Current treatment using debridement and antibiotic administration imposes a significant burden on patients and healthcare systems. To address their limitations, a highly efficacious electrical antibiofilm treatment system is described in this paper. This system uses high-intensity current (75mA cm-2 ) to completely debride biofilm above the wound surface and enhance antibiotic delivery into biofilm-infected wounds simultaneously. Combining these two effects, this system uses short treatments (≤2h) to reduce bacterial count of methicillin-resistant S.aureus (MRSA) biofilm-infected ex vivo skin wounds from 1010 to 105.2 colony-formingunits(CFU) g-1 . Taking advantage of the hydrogel ionic circuit design, this system enhances the in vivo safety of high-intensity current application compared to conventional devices. The in vivo antibiofilm efficacy of the system is tested using a diabetic mouse-based wound infection model. MRSA biofilm bacterial count decreases from 109.0 to 104.6 CFU g-1 at 1 day post-treatment and to 103.3 CFU g-1 at 7 days post-treatment, both of which are below the clinical threshold for infection. Overall, this novel technology provides a quick, safe, yet highly efficacious treatment to chronic wound biofilm infections.

Ultrasound-Responsive Microneedles Eradicate Deep-Layered Wound Biofilm Based on TiO2 Crystal Phase Engineering.

Wound biofilm infection has an inherent resistance to antibiotics, requiring physical debridement combined with chemical reagents or antibiotics in clinical treatment, but it is invasive and may exist as incomplete debridement. So, a new type of noninvasive and efficient treatment is needed to address this problem. Here, the crystal phase engineering of TiO2 is presented to explore the sonocatalytic properties of TiO2 nanoparticles with different phases, and find that the anatase-brookiteTiO2 (AB) has the best antibacterial efficiency of 99.94% against S. aureus under 15min of ultrasound (US) irradiation. The type II homojunction of AB not only enhances the adsorption and decreases the activation energy of O2 , respectively, but also has a great interfacial charge transfer efficiency under US, which can produce more reactive oxygen species than other types of TiO2 . The microneedles (MN) penetrate the biofilm in wound tissue and quickly disperse the loaded AB into the biofilm because the ultrasonic cavitation accelerates the dissolution of microneedles, which non-invasively and efficiently eradicates the deep-layered biofilm under US. This work explores the relationship between the phase composition of TiO2 and sonocatalytic property for the first time, and provides a new treatment strategy for wound biofilm infection through US-assisted microneedles therapy.

Anti-Biofilm Activity of a Tunable Hypochlorous Acid-Generating Electrochemical Bandage Controlled By a Wearable Potentiostat.

Chronic wound biofilm infections represent a major clinical challenge which results in a substantial burden to patients and healthcare systems. Treatment with topical antibiotics is oftentimes ineffective as a result of antibiotic-resistant microorganisms and biofilm-specific antibiotic tolerance. Use of biocides such as hypochlorous acid (HOCl) has gained increasing attention due to the lack of known resistance mechanisms. We designed an HOCl-generating electrochemical bandage (e-bandage) that delivers HOCl continuously at low concentrations targeting infected wound beds in a similar manner to adhesive antimicrobial wound dressings. We developed a battery-operated wearable potentiostat that controls the e-bandage electrodes at potentials suitable for HOCl generation. We demonstrated that e-bandage treatment was tunable by changing the applied potential. HOCl generation on electrode surfaces was verified using microelectrodes. The developed e-bandage showed time-dependent responses against in vitro Acinetobacter baumannii and Staphylococcus aureus biofilms, reducing viable cells to non-detectable levels within 6 and 12 hours of treatment, respectively. The developed e-bandage should be further evaluated as an alternative to topical antibiotics to treat wound biofilm infections.

Efficacy of Paracrine Factors from Mesenchymal Stem Cells for Treating Biofilm-Infected Wounds in a Murine Model

Background: Chronic wounds are a serious medical condition affecting over 6 million people in the United States. Biofilms, which alter the host immune response and establish a microenvironment that prevents wound healing, are intimately associated with the development of chronic wounds. Current treatment options do not specifically target the underlying molecular mechanisms of biofilm pathology. Paracrine factors secreted by mesenchymal stem cells (MSCs) have been demonstrated to play an important role in wound healing. The objective of this study was to examine the effects of the paracrine factors secreted from MSCs on reducing infection and accelerating wound closure in biofilm-infected wounds.Methods: MSCs were cultured by seeding on an extracellular matrix (ECM). The supernatant from MSCs containing paracrine factors were applied to mature &lt;i&gt;Pseudomonas aeruginosa&lt;/i&gt; biofilms &lt;i&gt;in vitro&lt;/i&gt; and the number of viable bacteria were quantitated. BALB/cJ mice were wounded and infected with &lt;i&gt;P. aeruginosa&lt;/i&gt; biofilms and the paracrine factors from reprogrammed MSCs were applied topically. The wound surface area and colony forming units counts of the treatment group were compared to control (culture media) and biofilm (untreated) groups. Results: The paracrine factors from MSCs grown on ECM were found to reduce &lt;i&gt;P. aeruginosa&lt;/i&gt; biofilm growth significantly (P&lt;0.01). Wounds in the treatment group had lower bacterial counts and an increased rate of wound closure compared to non-treated mice wounds. Conclusion: The results indicate that paracrine factors from reprogrammed MSCs accelerated wound healing and reduced the bacterial burden in biofilm-infected wounds. Future studies are needed to further characterize this phenomenon.

TARGETING MICROBIAL BIOFILMS ALTERING CHRONIC WOUND HEALING: NEW BREAKTHROUGH IN DRUG DEVELOPMENT USING SILVER

Biofilm development is a potent inducer for many microorganisms that inflict chronic infections. Conventional antimicrobials face significant hurdles in dealing with biofilms and drug resistance because of the multi-factor nature of these processes. Despite this, bacterial biofilms remain a mystery, and their management methods are still lacking. Biofilms may lead to persistent illness and need surgical excision of affected regions if standard antimicrobial treatments fail to eliminate them. One of the most significant concerns in antibacterial medication research is discovering effective treatments for biofilm infections. Recent wound biofilm infection therapy research focuses on nanotechnology-based medication delivery systems and combination therapies. Biofilm-targeting medications are still in the early stages of research, although several promising techniques are already being tested. Current understanding of biofilm physiology and pathology is reviewed and discussed here, as is how a thorough understanding of biofilm physical and biological properties might influence treatment techniques and molecular targets for the creation of anti-biofilm medications. Specifically, we are interested in treatment approaches targeting the extracellular matrix, dormant cells, additional crucial microbial biofilm structure, functional features, and drug tolerance mechanisms. In many clinical investigations, silver has been found to improve the healing of chronic, non-healing wounds, including silver nanoparticles. The purpose of this review is to provide an overview of recent developments in silver nanoparticle-based biofilm therapeutics and to understand the current development path.&#x0D;

Activity of a hypochlorous acid-producing electrochemical bandage as assessed with a porcine explant biofilm model.

The activity of a hypochlorous acid-producing electrochemical bandage (e-bandage) in preventing methicillin-resistant Staphylococcus aureus infection (MRSA) infection and removing biofilms formed by MRSA was assessed using a porcine explant biofilm model. e-Bandages inhibited S. aureus infection (p = 0.029) after 12 h (h) of exposure and reduced 3-day biofilm viable cell counts after 6, 12, and 24 h exposures (p = 0.029). Needle-type microelectrodes were used to assess HOCl concentrations in explant tissue as a result of e-bandage treatment; toxicity associated with e-bandage treatment was evaluated. HOCl concentrations in infected and uninfected explant tissue varied between 30 and 80 µM, decreasing with increasing distance from the e-bandage. Eukaryotic cell viability was reduced by an average of 71% and 65% in fresh and day 3-old explants, respectively, when compared to explants exposed to nonpolarized e-bandages. HOCl e-bandages are a promising technology that can be further developed as an antibiotic-free treatment for wound biofilm infections.

Layer-by-layer assembly of peptides-decorated coaxial nanofibrous membranes with antibiofilm and visual pH sensing capability

The countermeasure of biofilm infections leaving a challenge due to a dense antibiotic-resistant barrier formed by extracellular polymeric substances (EPS). Although antibiotic alternative methods have been developed to combat biofilms, develop effective remedies coupling with timely feedback about the therapeutic effect are still in urgent demand. To this end, we construct an intelligent coaxial electrospun nanofibrous membranes (ENMs) that integrated therapy of infections and in situ visualized diagnosis. Specifically, pH-sensitive alizarin was incorporated into polyamide 6 to subtly consist core layer and curcumin (Cur) was formulated with degradable polyglycolic acid (PGA) to composed of the shell layer. The shell layer can gradually release curcumin along with the degradation of PGA. Moreover, epsilon-poly-L-lysine (ε-PL) was deposited on coaxial ENMs via layer-by-layer self-assembly technique to disturb EPS integrity. As a result of the treatment, two different Gram-positive and Gram-negative bacteria displayed increased susceptibility to the drug hybrids. The degradation of PGA would trigger a sustained release of Cur and ε-PL, and once the core layer exposing, the acidic microenvironment of Staphylococcus aureus and Pseudomonas aeruginosa biofilm could be detected in situ by emerging visualized color change to timely feedback. Besides, the ENMs showed good biocompatibility. It paves a feasible and effective avenue for constructing a facile treatment and diagnosis platform for wound biofilm infections.

Potentiating hypoxic microenvironment for antibiotic activation by photodynamic therapy to combat bacterial biofilm infections

Traditional antibiotic treatment has limited efficacy for the drug-tolerant bacteria present in biofilms because of their unique metabolic conditions in the biofilm infection microenvironment. Modulating the biofilm infection microenvironment may influence the metabolic state of the bacteria and provide alternative therapeutic routes. In this study, photodynamic therapy is used not only to eradicate methicillin-resistant Staphylococcus aureus biofilms in the normoxic condition, but also to potentiate the hypoxic microenvironment, which induces the anaerobic metabolism of methicillin-resistant Staphylococcus aureus and activates the antibacterial activity of metronidazole. Moreover, the photodynamic therapy-activated chemotherapy can polarize the macrophages to a M2-like phenotype and promote the repair of the biofilm infected wounds in mice. This biofilm infection microenvironment modulation strategy, whereby the hypoxic microenvironment is potentiated to synergize photodynamic therapy with chemotherapy, provides an alternative pathway for efficient treatment of biofilm-associated infections.

Dual antimicrobial-loaded biodegradable nanoemulsions for synergistic treatment of wound biofilms.

Wound biofilm infections caused by multidrug-resistant (MDR) bacteria constitute a major threat to public health; acquired resistance combined with resistance associated with the biofilm phenotype makes combatting these infections challenging. Biodegradable polymeric nanoemulsions that encapsulate two hydrophobic antimicrobial agents (eugenol and triclosan) (TE-BNEs) as a strategy to combat chronic wound infections are reported here. The cationic nanoemulsions efficiently penetrate and accumulate in biofilms, synergistically eradicating MDR bacterial biofilms, including persister cells. Notably, the nanoemulsion platform displays excellent biocompatibility and delays emergence of resistance to triclosan. The TE-BNEs are active in an in vivo murine model of mature MDR wound biofilm infections, with 99% bacterial elimination. The efficacy of this system coupled with prevention of emergence of bacterial resistance highlight the potential of this combination platform to treat MDR wound biofilm infections.

Zn2+ Cross-Linked Alginate Carrying Hollow Silica Nanoparticles Loaded with RL-QN15 Peptides Provides Promising Treatment for Chronic Skin Wounds.

Chronic and non-healing wounds pose a great challenge to clinical management and patients. Many studies have explored novel interventions against skin wounds, with bioactive peptides, nanoparticles, and hydrogels arousing considerable attention regarding their therapeutic potential. In this study, the prohealing peptide RL-QN15 was loaded into hollow silica nanoparticles (HSNs), with these HSN@RL-QN15 nanocomposites then combined with zinc alginate (ZA) gels to obtain HSN@RL-QN15/ZA hydrogel. The characteristics, biological properties, and safety profiles of the hydrogel composites were then evaluated. Results showed that the hydrogel had good porosity, hemocompatibility, biocompatibility, and broad-spectrum antimicrobial activity, with the slow release of loaded RL-QN15. Further analysis indicated that the hydrogel promoted skin cell proliferation and keratinocyte scratch repair, regulated angiogenesis, reduced inflammation, and accelerated re-epithelialization and granulation tissue formation, resulting in the rapid healing of both full-thickness skin wounds and methicillin-resistant Staphylococcus aureus biofilm-infected chronic wounds in mice. This peptide-based hydrogel provides a novel intervention for the treatment of chronic skin wounds and shows promise as a wound dressing in the field of tissue regeneration.

51 Wireless Electroceutical Dressing for the Treatment of Biofilm Infected Burn Wounds

IntroductionBurn injuries are common to all military conflicts. In combat, eradication and prevention of burn wound infection is complicated by high rates of soft tissue contamination and prolonged delays to definitive stateside care. Furthermore, in the battlefield setting the salvage rate for infected burned extremities is low. Therefore, a simple, easy, non-invasive and rapid method to protect the wound, while also inhibiting infection, would represent a significant advance in the treatment of combat burn wounds. The purpose of this clinical trial was to investigate the efficacy of an FDA approved disposable and easily portable, wireless electroceutical dressing (WED) in the treatment of burn wounds. The hypothesis was that a low electric field generated by the moisture-activated WED will reduce infection load, improve graft survival and take, enhance wound healing and restore skin barrier function of biofilm infected wounds.MethodsA phase I, prospective, randomized, controlled clinical trial was performed to evaluate the efficacy of the WED dressing as compared to the standard of care (SoC) dressing to prevent and disrupt biofilms. Subjects were screened from inpatient admissions for traumatic burns >300cm2 in size. In total 38 subjects were enrolled to the study. Subject burn wounds were divided into two parts and randomized to receive either the SoC dressing or the WED dressing. Dressings were changed on day 4, removed on day 7 and the burns were followed for 30 days. Small biopsies were collected on days 4 and 7 for histology, SEM examination of biofilm and for quantitative bacteriological analysis. In addition, non-invasive wound imaging techniques were utilized to study wound healing. Furthermore, Vancouver scar scale and patient observer scar assessment were used to evaluate quality of healing.ResultsThe results showed that at the time of dressing removal, non-grafted burns that were treated with the WED dressing presented statistically significantly less biofilm in comparison to the SoC treated burns (p < 0.05). The results also demonstrated that the WED dressing was more efficient at eradicating biofilm than the SoC dressing. At the time of the dressing removal, biofilm score [0-3] had decreased in 48% of the WED dressing treated burns in comparison to 28% in the SoC treated burns. In terms of wound healing and quality of healing no significant differences were observed between the WED and the SoC dressings.ConclusionsThis trial demonstrated that the WED dressing was more efficient against biofilm infection than the SoC dressing. In addition, the study concluded that the WED dressing performed equally well as the SoC in terms of burn wound healing.

Synergy of light-controlled Pd nanozymes with NO therapy for biofilm elimination and diabetic wound treatment acceleration

The presence of bacteria, existing as highly organized biofilm communities, in chronic non-healing wounds has been identified as a significant impediment for wound healing. Nanozymes, with unique antimicrobial mechanisms, as a new alternative for antibiotics, have the potential to synergize with nitric oxide (NO) with enhanced antibacterial and antibiofilm ability. However, the always-on state of nanozymes and the reactivity of NO limit their clinical applications. In this context, an intelligent and multifunctional Pd-MOF@PAzo@SNP nanoplatform was fabricated using UiO-66 as a palladium (Pd) nanozyme-loading vehicle, then a surface modification with photosensitive polyazobenzene (PAzo), and the adsorption of the NO donor sodium nitroprusside (SNP) via a host-guest interaction between β-cyclodextrin-modified hyaluronic acid (β-CD-HA) and azobenzene. The activity of Pd-nanozyme was easily controlled via ultraviolet (UV) light, and its photosensitivity was regulated by changing the side-chain unit length of PAzo. Furthermore, NO was released in response to the UV irradiation and played a synergistic role with the peroxidase activity of Pd nanozyme, exhibiting excellent antibacterial and antibiofilm activity in the presence of 0.01 mM hydrogen peroxide (H2O2). In vivo, Pd-MOF@PAzo@SNP accelerated the healing of a biofilm-infected diabetic wound by dispersing the biofilm, reducing bacterial burden, and promoting angiogenesis and collagen deposition. Overall, the nanoplatform provides a reliable and highly efficient strategy to develop an intelligent nanozyme synergy with NO therapy in chronic wound management.

Engineered Nanotechnology: An Effective Therapeutic Platform for the Chronic Cutaneous Wound.

The healing of chronic wound infections, especially cutaneous wounds, involves a complex cascade of events demanding mutual interaction between immunity and other natural host processes. Wound infections are caused by the consortia of microbial species that keep on proliferating and produce various types of virulence factors that cause the development of chronic infections. The mono- or polymicrobial nature of surface wound infections is best characterized by its ability to form biofilm that renders antimicrobial resistance to commonly administered drugs due to poor biofilm matrix permeability. With an increasing incidence of chronic wound biofilm infections, there is an urgent need for non-conventional antimicrobial approaches, such as developing nanomaterials that have intrinsic antimicrobial-antibiofilm properties modulating the biochemical or biophysical parameters in the wound microenvironment in order to cause disruption and removal of biofilms, such as designing nanomaterials as efficient drug-delivery vehicles carrying antibiotics, bioactive compounds, growth factor antioxidants or stem cells reaching the infection sites and having a distinct mechanism of action in comparison to antibiotics—functionalized nanoparticles (NPs) for better incursion through the biofilm matrix. NPs are thought to act by modulating the microbial colonization and biofilm formation in wounds due to their differential particle size, shape, surface charge and composition through alterations in bacterial cell membrane composition, as well as their conductivity, loss of respiratory activity, generation of reactive oxygen species (ROS), nitrosation of cysteines of proteins, lipid peroxidation, DNA unwinding and modulation of metabolic pathways. For the treatment of chronic wounds, extensive research is ongoing to explore a variety of nanoplatforms, including metallic and nonmetallic NPs, nanofibers and self-accumulating nanocarriers. As the use of the magnetic nanoparticle (MNP)-entrenched pre-designed hydrogel sheet (MPS) is found to enhance wound healing, the bio-nanocomposites consisting of bacterial cellulose and magnetic nanoparticles (magnetite) are now successfully used for the healing of chronic wounds. With the objective of precise targeting, some kinds of “intelligent” nanoparticles are constructed to react according to the required environment, which are later incorporated in the dressings, so that the wound can be treated with nano-impregnated dressing material in situ. For the effective healing of skin wounds, high-expressing, transiently modified stem cells, controlled by nano 3D architectures, have been developed to encourage angiogenesis and tissue regeneration. In order to overcome the challenge of time and dose constraints during drug administration, the approach of combinatorial nano therapy is adopted, whereby AI will help to exploit the full potential of nanomedicine to treat chronic wounds.