ABSTRACT
Bacterial infections are a serious threat to wound healing and skin regeneration. In recent years, photothermal therapy (PTT) has become one of the most promising tools in the treatment of infectious diseases. However, wound dressings with photo-responsive properties are currently still limited by the difficulties of biosafety and thermal stability brought by the introduction of photosensitizers or photothermal agents. Therefore, how to improve the therapeutic efficiency and biosafety from material design is still a major challenge at present. In this study, the carboxymethyl chitosan (CMCS) and protocatechuic aldehyde (PA) hydrogels based on horseradish peroxidase (HRP) and hydrogen peroxide (H2O2) enzymatic catalysis was developed. Therein, HRP and H2O2 catalyzed cross-linking while polymerizing PA, which not only endowed the hydrogels with photothermal responsiveness but also with good biosafety through this enzyme-catalyzed green approach. Meanwhile, the hydrogels possessed highly efficient bacteriostatic ability with the assistance of near infrared (NIR). Moreover, the ultra-rapid gelation, strong tissue adhesion, high swelling ability, good antioxidant property and hemostatic property of the CMCS-PA hydrogels based on HRP/H2O2 enzymatic catalysis were suitable for the treatment of skin wounds. Meanwhile, NIR-assistant CMCS-PA hydrogels based on HRP/H2O2 enzymatic catalysis reduced inflammation, decreased bacterial infection, and promoted collagen deposition and angiogenesis, which showed remarkable therapeutic effects in a skin wound infection model. All results indicate that this green approach to introduce photothermal property by HRP-catalyzed PA polymerization endows the hydrogels with efficient photothermal conversion efficiency, suggesting that they are promising to provide new options for replacing photothermal agents and photosensitizers. STATEMENT OF SIGNIFICANCE: In recent years, wound dressings with photo-responsive properties are currently still limited by the difficulties of biosafety and thermal stability brought by the introduction of agent photosensitizers or photothermal agents. In this study, the carboxymethyl chitosan and protocatechuic aldehyde hydrogels based on horseradish peroxidase and hydrogen peroxide enzymatic catalysis was developed. The photothermal properties of hydrogels were transformed from absent to present just by horseradish peroxidase-catalyzed protocatechuic aldehyde polymerization in a green approach. Meanwhile, the hydrogels possessed highly efficient bacteriostatic ability with the assistance of near infrared. The green approach of introducing photothermal properties from material design solves the biosafety challenge. Therefore, this study is expected to provide new options for alternative photothermal agents and photosensitizers.
Subject(s)
Anti-Bacterial Agents , Antioxidants , Chitosan , Hydrogels , Wound Healing , Hydrogels/chemistry , Hydrogels/pharmacology , Hydrogels/chemical synthesis , Wound Healing/drug effects , Animals , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/chemical synthesis , Antioxidants/pharmacology , Antioxidants/chemistry , Chitosan/chemistry , Chitosan/pharmacology , Chitosan/analogs & derivatives , Hydrogen Peroxide , Green Chemistry Technology , Skin/pathology , Skin/drug effects , Hemostasis/drug effects , Mice , Horseradish Peroxidase/chemistry , Wound Infection/drug therapy , Wound Infection/pathology , Wound Infection/microbiologyABSTRACT
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.
Subject(s)
Cellular Senescence , Graphite , Wound Healing , Animals , Cellular Senescence/drug effects , Wound Healing/drug effects , Rats , Graphite/chemistry , Graphite/pharmacology , Rats, Sprague-Dawley , Regeneration/drug effects , Humans , Male , Skin/pathology , Skin/drug effects , Wound Infection/drug therapy , Wound Infection/pathology , MiceABSTRACT
Wound infections are an escalating clinical challenge with continuous inflammatory response and the threat of drug-resistant bacteria. Herein, a series of self-healing conductive hydrogels were designed based on carboxymethyl chitosan/oxidized sodium alginate/polymerized gallic acid/Fe3+ (CMC/OSA/pGA/Fe3+, COGFe) for promoting infected wound healing. The Schiff base and catechol-Fe3+ chelation in the dynamical dual network structure of the hydrogels endowed dressings with good toughness, conductivity, adhesion, and self-healing properties, thus flexibly adapting to the deformation of skin wounds. In terms of ultraviolet (UV) resistance and scavenging of reactive oxygen species (ROS), the hydrogels significantly reduced oxidative stress at the wound site. Additionally, the hydrogels with photothermal therapy (PTT) achieved a 95% bactericidal rate in 5 min of near-infrared (NIR) light radiation by disrupting the bacterial cell membrane structure through elevated temperature. Meanwhile, the inherent antimicrobial properties of GA could reduce healthy tissue damage caused by excessive heat. The composite hydrogels could effectively promote the proliferation and migration of fibroblasts and possess good biocompatibility and hemostatic effect. In full-thickness infected wound repair experiments in rats, the COGFe5 hydrogel combined with NIR effectively killed bacteria, modulated macrophage polarization (M1 to M2 phenotype) to improve the immune microenvironment of the wound, and shortened the repair time by accelerating the expression of collagen deposition (TGF-ß) and vascular factors (CD31). This combined therapy might provide a prospective strategy for infectious wound treatment.
Subject(s)
Anti-Bacterial Agents , Chitosan , Hydrogels , Wound Healing , Hydrogels/chemistry , Hydrogels/pharmacology , Wound Healing/drug effects , Animals , Rats , Chitosan/chemistry , Chitosan/pharmacology , Chitosan/analogs & derivatives , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Mice , Photothermal Therapy , Staphylococcus aureus/drug effects , Alginates/chemistry , Alginates/pharmacology , Rats, Sprague-Dawley , Wound Infection/drug therapy , Wound Infection/microbiology , Wound Infection/pathology , Inflammation/drug therapy , Inflammation/pathology , MaleABSTRACT
BACKGROUND: Medical dressings are designed to promote wound healing and reduce infection. The aim of project is to investigate the effect of natural brown colored cotton dressings on the healing of infected wounds in E.coli animals. MATERIALS AND METHODS: In this study, degreased white cotton gauze was used as the control group, with degreased brown cotton gauze and degreased bleached brown cotton gauze as the experimental group 1 and experimental group 2, to investigate the effect on the repair of post-infectious wound damage in animals by establishing an infected wound model in rats with E.coli as the infecting organism. RESULTS: The ability to promote healing of infected wounds was investigated by analyzing the wound healing status, macroscopic wound healing rate, hematoxylin-eosin staining, Masson staining, secretion of inflammatory factors by Elisa assay. The result showed that at day 14 of wound healing, the macroscopic wound healing rate was greater than 98% for all three groups of dressings; the collagen content reached 49.85 ± 5.84% in the experimental group 1 and 53.48 ± 5.32% in the experimental group 2, which was higher than the control group; brown cotton gauze promotes skin wound healing by shortening the inflammatory period in both groups. The expression of three inflammatory factors THF-α, IL-2, and IL-8 and three cytokines MMP-3, MMP-8, and MMP-9 were lower than that of the control group. CONCLUSIONS: It was found that natural brown cotton gauze has better repairing and promoting healing effect on infected wounds. It opens up the application of natural brown cotton gauze in the treatment of infected wounds.
Subject(s)
Bandages , Cotton Fiber , Wound Healing , Wound Infection , Animals , Wound Healing/physiology , Rats , Wound Infection/therapy , Wound Infection/pathology , Male , Rats, Sprague-Dawley , Disease Models, Animal , Escherichia coli , Skin/injuries , Skin/pathology , Collagen/metabolismABSTRACT
The use of traditional Ag-based antibacterial agents is usually accompanied by uncontrollable silver release, which makes it difficult to find a balance between antibacterial performance and biosafety. Herein, we prepared a core-shell system of ZIF-8-derived amorphous carbon-coated Ag nanoparticles (Ag@C) as an ideal research model to reveal the synergistic effect and structure-activity relationship of the structural transformation of carbon shell and Ag core on the regulation of silver release behavior. It is found that Ag@C prepared at 600 °C (AC6) exhibits the best ion release kinetics due to the combination of relatively simple shell structure and lower crystallinity of the Ag core, thereby exerting stronger antibacterial properties (>99.999 %) at trace doses (20â µg mL-1) compared with most other Ag-based materials. Meanwhile, the carbon shell prevents the metal Ag from being directly exposed to the organism and thus endows AC6 with excellent biocompatibility. In animal experiments, AC6 can effectively promote wound healing by inactivating drug-resistant bacteria while regulating the expression of TNF-α and CD31. This work provides theoretical support for the scientific design and clinical application of controllable ion-releasing antibacterial agents.
Subject(s)
Anti-Bacterial Agents , Metal Nanoparticles , Microbial Sensitivity Tests , Silver , Silver/chemistry , Silver/pharmacology , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Animals , Metal Nanoparticles/chemistry , Mice , Wound Healing/drug effects , Drug Resistance, Bacterial/drug effects , Carbon/chemistry , Carbon/pharmacology , Wound Infection/drug therapy , Wound Infection/microbiology , Wound Infection/pathology , Drug Liberation , Humans , Staphylococcus aureus/drug effectsABSTRACT
Chemotherapy and surgery stand as primary cancer treatments, yet the unique traits of the tumor microenvironment hinder their effectiveness. The natural compound epigallocatechin gallate (EGCG) possesses potent anti-tumor and antibacterial traits. However, the tumor's adaptability to chemotherapy due to its acidic pH and elevated glutathione (GSH) levels, coupled with the challenges posed by drug-resistant bacterial infections post-surgery, impede treatment outcomes. To address these challenges, researchers strive to explore innovative treatment strategies, such as multimodal combination therapy. This study successfully synthesized Cu-EGCG, a metal-polyphenol network, and detailly characterized it by using synchrotron radiation and high-resolution mass spectrometry (HRMS). Through chemodynamic therapy (CDT), photothermal therapy (PTT), and photodynamic therapy (PDT), Cu-EGCG showed robust antitumor and antibacterial effects. Cu+ in Cu-EGCG actively participates in a Fenton-like reaction, generating hydroxyl radicals (·OH) upon exposure to hydrogen peroxide (H2O2) and converting to Cu2+. This Cu2+ interacts with GSH, weakening the oxidative stress response of bacteria and tumor cells. Density functional theory (DFT) calculations verified Cu-EGCG's efficient GSH consumption during its reaction with GSH. Additionally, Cu-EGCG exhibited outstanding photothermal conversion when exposed to 808 nm near-infrared (NIR) radiation and produced singlet oxygen (1O2) upon laser irradiation. In both mouse tumor and wound models, Cu-EGCG showcased remarkable antitumor and antibacterial properties.
Subject(s)
Anti-Bacterial Agents , Antineoplastic Agents , Catechin , Copper , Nanocomposites , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Copper/chemistry , Copper/pharmacology , Nanocomposites/chemistry , Antineoplastic Agents/pharmacology , Antineoplastic Agents/chemistry , Animals , Mice , Humans , Catechin/chemistry , Catechin/pharmacology , Catechin/analogs & derivatives , Microbial Sensitivity Tests , Drug Resistance, Bacterial/drug effects , Photochemotherapy , Wound Infection/drug therapy , Wound Infection/pathology , Wound Infection/microbiology , Drug Screening Assays, Antitumor , Staphylococcus aureus/drug effects , Photothermal Therapy , Particle Size , Escherichia coli/drug effects , Cell Survival/drug effects , Cell Line, Tumor , Surface Properties , Cell Proliferation/drug effectsABSTRACT
Most antimicrobials treat wound infections by an oxidation effect, which is induced by the generation of reactive oxygen species (ROS). However, the potential harm of the prolonged high level of ROS should not be ignored. In this study, we presented a novel cascade-reaction nanoparticle, Ir@Cu/Zn-MOF, to effectively regulate the ROS level throughout the healing progress of the infected wound. The nanoparticles consisted of a copper/zinc-modified metal-organic framework (Cu/Zn-MOF) serving as the external structure and an inner core composed of Ir-PVP NPs, which were achieved through a process known as "bionic mineralization". The released Cu2+ and Zn2+ from the shell structure contributed to the production of ROS, which acted as antimicrobial agents during the initial stage. With the disintegration of the shell, the Ir-PVP NP core was gradually released, exhibiting the property of multiple antioxidant enzyme activities, thereby playing an important role in clearing excessive ROS and alleviating oxidative stress. In a full-layer infected rat wound model, Ir@Cu/Zn-MOF nanoparticles presented exciting performance in promoting wound healing by clearing the bacteria and accelerating neovascularization as well as collagen deposition. This study provided a promising alternative for the repair of infected wounds.
Subject(s)
Copper , Metal-Organic Frameworks , Nanoparticles , Reactive Oxygen Species , Wound Healing , Zinc , Reactive Oxygen Species/metabolism , Wound Healing/drug effects , Animals , Metal-Organic Frameworks/chemistry , Metal-Organic Frameworks/pharmacology , Copper/chemistry , Copper/pharmacology , Zinc/chemistry , Nanoparticles/chemistry , Nanoparticles/therapeutic use , Rats , Wound Infection/drug therapy , Wound Infection/microbiology , Wound Infection/pathology , Wound Infection/metabolism , Rats, Sprague-Dawley , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/therapeutic use , Male , Staphylococcus aureus/drug effects , Oxidative Stress/drug effects , Antioxidants/pharmacology , Antioxidants/chemistryABSTRACT
Bacterial infection and immune imbalance are the primary culprits behind chronic wounds in individuals with diabetes, impeding the progression of damaged tissues towards normal healing. To achieve a harmonious balance between pro- and anti-inflammation within these infected areas, herein, we propose a one-two punch strategy for on-demand therapy of diabetes-infected wounds, utilizing an azithromycin (AZM)-hybrid nanocomposite termed GOx@FexSy/AZM. During the infective stage, the nanocomposite facilitates the production of ROS, coupled with the burst release of AZM and H2S gas, effectively dismantling biofilms and achieving rapid sterilization. Subsequently, the hyperinflammatory response induced by antibiosis is significantly mitigated through the synergistic action of tissue H2S and the prolonged half-life of AZM. These components inhibit the activity of pro-inflammatory transcription factors (AP-1 and NF-κB) within macrophages, thereby promoting the polarization of macrophages towards a reparative M2 phenotype and facilitating tissue remodeling. By catering to the diverse requirements of wound healing at different stages, this nanocomposite accelerates a sensible transition from inflammation to the reparative phase. In summary, this one-two punch strategy gives an instructive instance for procedural treatment of diabetes wound infection. STATEMENT OF SIGNIFICANCE: The treatment of diabetic wound infection presents two major challenges: the diminished antibacterial efficacy arising from biofilm formation and bacterial resistance, as well as the inadequate transition of the wound microenvironment from pro-inflammatory to anti-inflammatory states after bacterial clearance. In this work, a biomineralized iron sulfide nanocomposite was prepared to mediate cascade catalytic (ROS storm) / antibiotic (AZM) / gas (H2S) triple-synergetic antibacterial therapy during the initial stage of bacterial infection, achieving the goal of rapid bactericidal effect; Subsequently, the residual H2S and long half-life AZM would inhibit the key pro-inflammatory transcription factors and promote the macrophages polarization to reparative M2, which effectively mediated tissue repair after hyperinflammatory reactions, leading to orderly treatment of hyperglycemic infected wounds.
Subject(s)
Anti-Bacterial Agents , Wound Healing , Anti-Bacterial Agents/pharmacology , Animals , Wound Healing/drug effects , Mice , RAW 264.7 Cells , Wound Infection/drug therapy , Wound Infection/pathology , Macrophages/metabolism , Macrophages/drug effects , Ferrous Compounds/pharmacology , Ferrous Compounds/chemistry , Male , Nanoparticles/chemistry , Biofilms/drug effects , Diabetes Mellitus, Experimental/pathology , HumansABSTRACT
Methicillin-resistant Staphylococcus aureus (MRSA) is the primary pathogenic agent responsible for epidermal wound infection and suppuration, seriously threatening the life and health of human beings. To address this fundamental challenge, we propose a heterojunction nanocomposite (Ca-CN/MnS) comprised of Ca-doped g-C3N4 and MnS for the therapy of MRSA-accompanied wounds. The Ca doping leads to a reduction in both the bandgap and the singlet state S1-triplet state T2 energy gap (ΔEST). The Ca doping also facilitates the two-photon excitation, thus remarkably promoting the separation and transfer of 808 nm near-infrared (NIR) light-triggered electron-hole pairs together with the built-in electric field. Thereby, the production of reactive oxygen species and heat are substantially augmented nearby the nanocomposite under 808 nm NIR light irradiation. Consequently, an impressive photocatalytic MRSA bactericidal efficiency of 99.98 ± 0.02â¯% is achieved following exposure to NIR light for 20 min. The introduction of biologically functional elements (Ca and Mn) can up-regulate proteins such as pyruvate kinase (PKM), L-lactate dehydrogenase (LDHA), and calcium/calmodulin-dependent protein kinase (CAMKII), trigger the glycolysis and calcium signaling pathway, promote cell proliferation, cellular metabolism, and angiogenesis, thereby expediting the wound-healing process. This heterojunction nanocomposite, with its precise charge-transfer pathway, represents a highly effective bactericidal and bioactive system for treating multidrug-resistant bacterial infections and accelerating tissue repair. STATEMENT OF SIGNIFICANCE: Due to the bacterial resistance, developing an antibiotic-free and highly effective bactericidal strategy to treat bacteria-infected wounds is critical. We have designed a heterojunction consisting of calcium doped g-C3N4 and MnS (Ca-CN/MnS) that can rapidly kill methicillin-resistant Staphylococcus aureus (MRSA) without damaging normal tissue through a synergistic effect of two-photon stimulated photothermal and photodynamic therapy. In addition, the release of trace amounts of biofunctional elements Mn and Ca triggers glycolysis and calcium signaling pathways that promote cellular metabolism and cell proliferation, contributing to tissue repair and wound healing.
Subject(s)
Calcium , Glycolysis , Methicillin-Resistant Staphylococcus aureus , Methicillin-Resistant Staphylococcus aureus/drug effects , Glycolysis/drug effects , Animals , Calcium/metabolism , Staphylococcal Infections/drug therapy , Phototherapy , Wound Infection/microbiology , Wound Infection/pathology , Wound Infection/drug therapy , Humans , Nanocomposites/chemistry , Wound Healing/drug effects , Mice , Infrared RaysABSTRACT
Wound biofilms pose a great clinical challenge. Herein, this work reports a dissolvable microneedle patch for dual delivery of monoclonal antibodies anti-PBP2a and engineers antimicrobial peptides W379. In vitro antibacterial efficacy testing with microneedle patches containing a combination of 250 ng mL-1 W379 and 250 ng mL-1 anti-BPB2a decreases the bacterial count from ≈3.31 × 107 CFU mL-1 to 1.28 × 102 CFU mL-1 within 2 h without eliciting evident cytotoxicity. Ex vivo testing indicates W379 and anti-PBP2a co-loaded microneedle patch displayed a remarkable reduction of bacterial load by ≈7.18 log CFU after administered only once within 48 h. The bacterial count is significantly diminished compared to the treatment by either W379 or anti-PBP2a-loaded alone microneedle patches. When administered twice within 48 h, no bacteria are identified. Further in vivo study also reveals that after two treatments of W379 and anti-PBP2a co-loaded PVP microneedle patches within 48 h, the bacterial colonies are undetectable in a type II diabetic mouse wound biofilm model. Taken together, W379 and anti-PBP2a co-loaded PVP microneedle patches hold great promise in treating wound biofilms.
Subject(s)
Antibodies, Monoclonal , Antimicrobial Peptides , Biofilms , Needles , Biofilms/drug effects , Animals , Mice , Antibodies, Monoclonal/pharmacology , Antibodies, Monoclonal/administration & dosage , Antimicrobial Peptides/pharmacology , Antimicrobial Peptides/chemistry , Humans , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/administration & dosage , Drug Delivery Systems , Wound Healing/drug effects , Wound Infection/drug therapy , Wound Infection/microbiology , Wound Infection/pathologyABSTRACT
Importance: Limited literature exists on surgical outcomes after selective deep lobe parotidectomy (SDLP) with preservation of superficial lobe for patients with benign deep lobe tumors. Objective: To compare the following factors for SDLP vs total parotidectomy for patients with benign tumors in the deep lobe: postoperative complications, including facial nerve paresis or paralysis, Frey syndrome, first bite syndrome, cosmetic defect, sialocele formation, and wound infection; and tumor control and recurrence. Design, Setting, and Participants: This case series included 273 adults who underwent SDLP (n = 177) or total parotidectomy (n = 96) at a single tertiary care institution for benign parotid tumors located in the deep lobe or deep lobe and parapharynx from January 1, 2000, to December 31, 2020. Exposure: Selective deep lobe parotidectomy vs total parotidectomy. Main Outcomes and Measures: Incidence of postoperative complications and tumor recurrence. Results: Among 273 patients (SDLP, 177 [65%]; 122 women [69%]; median age at surgery, 58 years [IQR, 46-67 years]; total parotidectomy, 96 [35%]; 57 women [59%]; median age at surgery, 59 years [IQR, 40-68 years]), the most common tumor was pleomorphic adenoma (SDLP, 128 of 177 [72%]; total parotidectomy, 62 of 96 [65%]). An abdominal dermal fat graft was less commonly performed for patients who underwent SDLP than those who underwent total parotidectomy (2 of 177 [1%] vs 20 of 96 [21%]; difference, -20% [95% CI, -28% to -11%]). The rate of great auricular nerve preservation was higher in the SDLP group than in the total parotidectomy group (84 of 102 [82%] vs 20 of 34 [59%]; difference, 24% [95% CI, 5%-42%]). No meaningful difference in length of hospital stay was found. The percentage of patients with House-Brackmann grade I immediately after surgery was 48% (85 of 177) in the SDLP group and 21% (20 of 96) in the total parotidectomy group (difference, 28% [95% CI, 16%-40%]). There were no clinically meaningful differences in rates of hematoma, sialocele, seroma, ear numbness, wound infection, or unplanned return to emergency department or operating room. The SDLP group reported a lower rate of Frey syndrome than the total parotidectomy group (1 of 137 [1%] vs 12 of 78 [15%]; difference, -15% [95% CI, -23% to -7%]), as well as a lower rate of facial contour defect (28 of 162 [17%] vs 25 of 84 [30%]; difference, -13% [95% CI, -24% to -1%]) and a higher rate of first bite syndrome (34 of 148 [23%] vs 7 of 78 [9%]; difference, 14% [95% CI, 5%-23%]). The percentage of patients with House-Brackmann grade I at their first follow-up visit was 67% (118 of 177) in the SDLP group compared with 49% (47 of 96) in the total parotidectomy group (difference, 17% [95% CI, 4%-30%]). There was no clinically meaningful difference in House-Brackmann grade after 1 year. Conclusions and Relevance: Findings of this case series study suggest that SDLP can be considered an effective and even superior technique for management of benign tumors in the deep parotid lobe. Advantages associated with SDLP include reduction in need for reconstruction for facial contour defect and reduction in complications, such as immediate facial nerve weakness and Frey syndrome. The incidence of first bite syndrome was higher in the SDLP group. Tumor control was not compromised by SLDP.
Subject(s)
Cysts , Parotid Neoplasms , Sweating, Gustatory , Wound Infection , Adult , Humans , Female , Middle Aged , Aged , Parotid Neoplasms/pathology , Sweating, Gustatory/complications , Sweating, Gustatory/pathology , Retrospective Studies , Neoplasm Recurrence, Local/pathology , Parotid Gland/surgery , Parotid Gland/pathology , Postoperative Complications/epidemiology , Cysts/pathology , Wound Infection/complications , Wound Infection/pathologyABSTRACT
Currently, clinical tumor resection is faced with two options: open and minimally invasive surgery. Open surgery is easy to completely remove the lesion but is prone to infection, while minimally invasive surgery recovers faster but may cause tumor recurrence. To fill the shortcomings of the two surgical modes and make the choice for tumor resection more effortlessly, we developed a postoperative black phosphorus-Ag nanocomposites-loaded dopamine-modified hyaluronic acid-Pluronic® F127 (BP-Ag@HA-DA-Plu) hydrogel implantation system that can prevent tumor recurrence and wound infection simultaneously. Experiments have shown that the hydrogel system combined with 808 nm near-infrared (NIR) irradiation has excellent anti-tumor, antibacterial, and wound healing abilities. Additionally, unlike existing surgical hydrogel products that require inconvenient in-situ cross-linking, the BP-Ag@HA-DA-Plu hydrogel system offers "plug-and-play" functionality during surgery due to its thermo-responsiveness, injectability, and adhesion, thereby greatly improving the efficiency of surgery.
Subject(s)
Hydrogels , Wound Infection , Humans , Hydrogels/pharmacology , Neoplasm Recurrence, Local , Hyaluronic Acid/pharmacology , Wound Infection/pathology , Anti-Bacterial Agents/pharmacologyABSTRACT
Pathogenic bacterial infection is the most frequent wound complication, which has become a major clinical and healthcare challenge in wound management worldwide, leading to impaired healing processes, the risk of amputation, and even death. Here, collagen-based nanocomposite dressings (APZC) with broad-spectrum antibacterial activity are developed to promote the infected full-thickness wound healing. Short rod-like shaped ZnO NPs are synthesized and then coated with polydopamine (PDA) to obtain PDA coated ZnO NPs (PDA@ZnO NPs). Afterward, PDA@ZnO NPs are conjugated on the backbone of a collagen chain, and the obtained collagen-PDA@ZnO NPs conjugate is crosslinked by dialdehyde sodium alginate to fabricate APZC dressings. PDA@ZnO NPs show well dispersibility and are uniformly incorporated into the collagen matrix. APZC dressings have interconnected microporous structure and great physicochemical properties, besides good blood coagulation performance and well cytocompatibility. APZC dressings demonstrate long-lasting and excellently broad-spectrum antimicrobial activity, which can relieve the inflammatory reaction by killing pathogenic bacteria and induce the generation of blood vessels and the orderly deposition of collagen in the wound site, thus promoting infected full-thickness wound healing without obvious scar formation. Overall, the functionalized collagen-based nanocomposite dressings have great potential in the clinical treatment against bacteria-associated wound infection.
Subject(s)
Nanocomposites , Wound Infection , Zinc Oxide , Humans , Zinc Oxide/chemistry , Wound Healing , Collagen/pharmacology , Bacteria , Nanocomposites/therapeutic use , Bandages , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Wound Infection/pathologyABSTRACT
Nanozymes with peroxidase-like activity have great application potential in combating pathogenic bacterial infections and are expected to become an alternative to antibiotics. However, the near-neutral pH and high glutathione (GSH) levels in the bacterial infection microenvironment severely limit their applications in antibacterial therapy. In this work, a metal-organic framework (MOF)-based cascade catalytic glutathione-depleting system named MnFe2O4@MIL/Au&GOx (MMAG) was constructed. The MMAG cascade-catalyzed glucose to provide H+ and produces a large amount of toxic reactive oxygen species. In addition, MMAG consumed GSH, which can result in bacterial death more easily. Systematic antibacterial experiments illustrated that MMAG has superior antibacterial effects on both Gram-positive bacteria and Gram-negative bacteria.
Subject(s)
Anti-Bacterial Agents/pharmacology , Glutathione/metabolism , Nanoparticles/chemistry , Nanoparticles/metabolism , Animals , Bacterial Infections/drug therapy , Bacterial Infections/pathology , Catalysis , Glucose/metabolism , Gram-Negative Bacteria/drug effects , Gram-Positive Bacteria/drug effects , Metal-Organic Frameworks , Mice, Inbred BALB C , Protons , Reactive Oxygen Species/metabolism , Wound Infection/drug therapy , Wound Infection/pathologyABSTRACT
Bacterial infections are a common problem associated with wound treatment that imposes a significant burden on healthcare systems and patients. As a result, healthcare providers urgently need new treatment strategies to protect people. Hydrogel biomaterials with inherent antimicrobial properties offer an attractive and viable solution to this issue. Here, for the first time, we have developed a new efficient synthetic strategy to prepare cationic hydrogels (PHCI) with intrinsically efficient antimicrobial properties by chemically cross-linking trans-1,4-cyclohexanediamine with 1,3-dibromo-2-propanol using a condensation reaction without the use of toxic cross-linking agents. As expected, the prepared PHCI hydrogel possessed an inherent antibacterial ability that can adsorb and kill Staphylococcus aureus and Escherichia coli electrostatically. Notably, in vivo experiments on normal and diabetic rat models confirmed that the PHCI hydrogel can quickly stop bleeding, efficiently kill bacteria, promote the conversion of macrophages from the proinflammatory M1 phenotype to the repaired M2 phenotype, and accelerate collagen deposition and blood vessel formation, thereby achieving rapid wound healing. Overall, this work presents an effective antibacterial dressing that might provide a facile but effective approach for clinical wound management.
Subject(s)
Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/pharmacology , Bacterial Infections/drug therapy , Hydrogels/chemistry , Hydrogels/pharmacology , Wound Healing/drug effects , Wound Infection/drug therapy , Animals , Anti-Bacterial Agents/therapeutic use , Cell Line , Cell Survival/drug effects , Diabetes Mellitus, Experimental/complications , Escherichia coli/drug effects , Hemolysis/drug effects , Hemostatics/chemistry , Hemostatics/pharmacology , Hemostatics/therapeutic use , Hydrogels/therapeutic use , Male , Mice , Rats, Sprague-Dawley , Staphylococcus aureus/drug effects , Wound Infection/complications , Wound Infection/metabolism , Wound Infection/pathologyABSTRACT
BACKGROUND: Residual Legg-Calvé-Perthes (LCP) deformities represent one of the most challenging disorders in hip reconstructive surgery. In complex cases, both instability (acetabular dysplasia) and multifocal femoroacetabular impingement (FAI) (proximal femoral deformities) require correction. We assessed intermediate-term patient-reported outcome measures, radiographic correction, complications, and survivorship for combined surgical dislocation (SD) and periacetabular osteotomy (PAO) for the treatment of complex LCP deformities. METHODS: A retrospective cohort study was performed on 31 hips with complex LCP deformities undergoing combined SD and PAO for concurrent instability and FAI. Treatment included femoral head reshaping, trochanteric advancement and relative femoral neck lengthening, management of intra-articular lesions, and PAO. Twenty-seven hips (87%) had a minimum follow-up of 5 years. The mean age was 19.8 years, 56% of patients were female, and 44% of patients had undergone a previous surgical procedure. RESULTS: At a mean of 8.4 years, 85% of hips (23 of 27) remained preserved (no conversion to total hip arthroplasty). The survivorship estimates were 93% at 5 years and 85% at 10 years. The median (and interquartile range) increased from 64 points (55, 67 points) to 92 points (70, 97 points) (p < 0.001) for the modified Harris hip score (mHHS) and from 60 points (45, 75 points) to 86 points (75, 100 points) (p = 0.001) for the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain score. Symptoms (mHHS < 70 points) were reported for an additional 19% of hips (n = 5) at the final follow-up. The University of California Los Angeles (UCLA) activity score increased from a median of 8 points (6, 10 points) to 9 points (7, 10 points) (p = 0.207). Structural correction included mean improvement (and standard deviation) of 15.3° ± 7.6° for acetabular inclination, 20.7° ± 10.8° for the lateral center-edge angle, 23.4° ± 16.3° for the anterior center-edge angle, and 18 ± 10 mm for trochanteric height (p < 0.001 for all). Complications occurred in 2 hips (7%), including 1 deep wound infection and 1 superficial wound infection. There was 1 reoperation due to complication, but there were no nerve palsies, thromboembolic events, fractures, or nonunions. CONCLUSIONS: At an intermediate follow-up of combined SD and PAO for complex LCP deformities, 85% of hips were preserved. This procedure provides reliable deformity correction, major pain relief, improved function, and acceptable complication and failure rates. LEVEL OF EVIDENCE: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.
Subject(s)
Femoracetabular Impingement , Wound Infection , Acetabulum/pathology , Adult , Female , Hip Joint/surgery , Humans , Male , Osteotomy/methods , Pain , Retrospective Studies , Treatment Outcome , Wound Infection/pathology , Young AdultABSTRACT
Abstract Despite decades of research, wound healing remains a significant public health problem. This study aimed to develop and evaluate a topical sodium alginate gel containing vancomycin (Van) loaded MMT NPs for wound healing applications. Van was loaded in MMT at different conditions (pHs of 6, 7 and temperatures of 40, 50 °C) (Van/MMT NPs). The optimum formulation (with the smallest particle size and a high value of zeta potential; 270.8 ± 77.35 nm and -35.96 ± 2.73, respectively) showed a high drug-loading capacity (entrapment efficacy of 96%) and a sustained release pattern of Van (95%) over 480 min. The optimum Van/MMT NPs were embedded into the sodium alginate (SA) gel (Van/MMT NPs/SA gel). The Van/ MMT NPs/SA gel showed a sustained and slow release pattern of Van (95%) over 50 h. FTIR tests revealed the electrostatic interaction between MMT and Van. The broth macrodilution tube method was used to determine the minimum inhibitory concentration (MIC) of Van, Van/ MMT NPs, and Van/MMT NPs/SA gel against Staphylococcus aureus. The results showed the promising antibacterial activity of Van/MMT NPs/SA gel, thus, this gel can be a promising formulation for the management of infected wounds
Subject(s)
Wound Healing/drug effects , Wound Infection/pathology , Bentonite/antagonists & inhibitors , In Vitro Techniques/methods , Vancomycin/agonists , Alginates/analysis , Wounds and Injuries/drug therapy , Pharmaceutical Preparations/administration & dosage , Spectroscopy, Fourier Transform Infrared/methods , Anti-Bacterial Agents/classificationABSTRACT
OBJECTIVE: To compare bacteriologic culture results for superficial swab and tissue biopsy specimens obtained from dogs with open skin wounds. ANIMALS: 52 client-owned dogs. PROCEDURES: For each dog, 1 wound underwent routine preparation prior to collection of 2 specimens, 1 by superficial swab (Levine) technique and 1 by tissue biopsy. Specimens were processed for bacteriologic culture. Two observers determined whether any detected difference in culture results for the 2 types of specimen would have resulted in differing treatment plans. RESULTS: Culture results of swab and tissue biopsy specimens were identical in 11/52 (21.2%) cases. Tissue biopsy specimen and swab cultures yielded positive results for 44 (84.6%) and 40 (76.9%) wounds, respectively. With regard to mean recovery rates of bacteria from wounds with positive culture results, both the biopsy specimens and swabs yielded 3.4 bacterial species/wound. All wounds for which swab cultures yielded no growth also had negative culture results for biopsy specimens. Biopsy specimen and swab culture results were in agreement with regard to the most common bacteria cultured. In 7/52 (13%) wounds, the observers would have treated the patient differently on the basis of the results of the 2 cultures. CONCLUSIONS AND CLINICAL RELEVANCE: Results indicated that culture of a swab collected by the Levine technique is an appropriate noninvasive alternative to culture of a tissue biopsy specimen. A negative result obtained from culture of a swab is likely to be reliable. Disagreement between the results of swab and tissue biopsy specimen cultures is likely of low clinical importance.
Subject(s)
Dog Diseases , Wound Infection , Animals , Biopsy/veterinary , Dog Diseases/diagnosis , Dogs , Specimen Handling/veterinary , Wound Infection/drug therapy , Wound Infection/microbiology , Wound Infection/pathology , Wound Infection/veterinaryABSTRACT
Antibacterial photodynamic therapy (PDT) has attracted extremely attention due to not inducing bacteria to generate resistance. However, the poor utilization and low reactive oxygen species (ROS) field of photosensitizers hinder their further application for antibacterial. Here, we designed ultra-thin hollow silica nanoparticles (UHSN), followed by pore-engineering including covalent anchoring of chitosan (UHSN@CS) for enhanced loading and photodynamic property of photosensitizer. The UHSN@CS exhibit high loading efficiency (80.6%, pH = 6.0) and controllable pH-responsive release for Ce6. Additionally, UHSN@CS can enhance the ROS yield of photosensitizers and effectively adhere to S. aureus, thus enormously enhancing antibacterial performance toward bacteria. Moreover, UHSN@CS-Ce6 can obliterate mature S. aureus biofilm and cause an 81% decrease in the biomass, showing a better therapeutic effect than Ce6 (59.2%) under laser irradiation. In vivo results confirm that UHSN@CS-Ce6 is effective to promote infectious wound regeneration. As photodynamic-based nanoplatforms, UHSN@CS-Ce6 are potential antibacterial agents for skin infection therapy.
Subject(s)
Anti-Bacterial Agents/pharmacology , Chitosan/chemistry , Chlorophyllides/pharmacology , Drug Carriers , Nanoparticles , Photochemotherapy , Photosensitizing Agents/pharmacology , Staphylococcal Skin Infections/drug therapy , Staphylococcus aureus/drug effects , Wound Infection/drug therapy , Animals , Anti-Bacterial Agents/chemistry , Biofilms/drug effects , Biofilms/growth & development , Chlorophyllides/chemistry , Cricetinae , Delayed-Action Preparations , Drug Compounding , Hydrogen-Ion Concentration , Models, Animal , Nanotechnology , Photosensitizing Agents/chemistry , Reactive Oxygen Species/metabolism , Staphylococcal Skin Infections/microbiology , Staphylococcal Skin Infections/pathology , Staphylococcus aureus/growth & development , Staphylococcus aureus/metabolism , Wound Healing/drug effects , Wound Infection/microbiology , Wound Infection/pathologyABSTRACT
Bacterial cellulose (BC) holds several unique properties such as high water retention capability, flexibility, biocompatibility, and high absorption capacity. All these features make it a potential material for wound healing applications. However, it lacks antibacterial properties, which hampers its applications for infectious wound healings. This study reported BC-based dressings containing ε-polylysine (ε-PL), cross-linked by a biocompatible and mussel-inspired polydopamine (PDA) for promoting infectious wound healing. BC membranes were coated with PDA by a simple self-polymerization process, followed by treating with different contents of ε-PL. The resulted membranes showed strong antibacterial properties against tested bacteria by both in vitro and in vivo evaluations. The membranes also exhibited hemocompatibility and cytocompatibility by in vitro investigations. Moreover, the functionalized membranes promoted infected wound healing using Sprague-Dawley rats as a model animal. A complete wound healing was observed in the group treated with functionalized membranes, while wounds were still open for control and pure BC groups in the same duration. Histological investigations indicated that the thickness of newborn skin was greater and smoother in the groups treated with modified membranes in comparison to neat BC or control groups. These results revealed that the functionalized membranes have great potential as a dressing material for infected wounds in future clinical applications.