RESUMEN
In colorectal cancer patients, a high density of cytotoxic CD8+ T cells in tumors is associated with better prognosis. Using a Stat3 loss-of-function approach in two wnt/ß-catenin-dependent autochthonous models of sporadic intestinal tumorigenesis, we unravel a complex intracellular process in intestinal epithelial cells (IECs) that controls the induction of a CD8+ T cell based adaptive immune response. Elevated mitophagy in IECs causes iron(II)-accumulation in epithelial lysosomes, in turn, triggering lysosomal membrane permeabilization. Subsequent release of proteases into the cytoplasm augments MHC class I presentation and activation of CD8+ T cells via cross-dressing of dendritic cells. Thus, our findings highlight a so-far-unrecognized link between mitochondrial function, lysosomal integrity, and MHC class I presentation in IECs and suggest that therapies triggering mitophagy or inducing LMP in IECs may prove successful in shifting the balance toward anti-tumor immunity in colorectal cancer.
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Inmunidad Adaptativa , Mitofagia , Inmunidad Adaptativa/efectos de los fármacos , Animales , Azoximetano/toxicidad , Linfocitos T CD8-positivos/citología , Linfocitos T CD8-positivos/efectos de los fármacos , Linfocitos T CD8-positivos/metabolismo , Permeabilidad de la Membrana Celular , Neoplasias Colorrectales/mortalidad , Neoplasias Colorrectales/patología , Citocinas/metabolismo , Células Dendríticas/citología , Células Dendríticas/inmunología , Células Dendríticas/metabolismo , Femenino , Compuestos Ferrosos/metabolismo , Humanos , Interferón gamma/metabolismo , Interferón gamma/farmacología , Mucosa Intestinal/citología , Mucosa Intestinal/efectos de los fármacos , Mucosa Intestinal/metabolismo , Lisosomas/metabolismo , Masculino , Ratones , Ratones Noqueados , Mitofagia/efectos de los fármacos , Factor de Transcripción STAT3/genética , Factor de Transcripción STAT3/metabolismo , Tasa de SupervivenciaRESUMEN
Antigen cross-presentation, wherein dendritic cells (DCs) present exogenous antigen on major histocompatibility class I (MHC-I) molecules, is considered the primary mechanism by which DCs initiate tumor-specific CD8+ T cell responses. Here, we demonstrate that MHC-I cross-dressing, an antigen presentation pathway in which DCs acquire and display intact tumor-derived peptide:MHC-I molecules, is also important in orchestrating anti-tumor immunity. Cancer cell MHC-I expression was required for optimal CD8+ T cell activation in two subcutaneous tumor models. In vivo acquisition of tumor-derived peptide:MHC-I molecules by DCs was sufficient to induce antigen-specific CD8+ T cell priming. Transfer of tumor-derived human leukocyte antigen (HLA) molecules to myeloid cells was detected in vitro and in human tumor xenografts. In conclusion, MHC-I cross-dressing is crucial for anti-tumor CD8+ T cell priming by DCs. In addition to quantitatively enhancing tumor antigen presentation, MHC cross-dressing might also enable DCs to more faithfully and efficiently mirror the cancer cell peptidome.
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Células Dendríticas , Neoplasias , Presentación de Antígeno , Antígenos de Neoplasias , Vendajes , Linfocitos T CD8-positivos , Reactividad Cruzada , Antígenos de Histocompatibilidad Clase I , Humanos , Complejo Mayor de Histocompatibilidad , Neoplasias/metabolismo , PéptidosRESUMEN
Tumor-infiltrating dendritic cells (DCs) assume varied functional states that impact anti-tumor immunity. To delineate the DC states associated with productive anti-tumor T cell immunity, we compared spontaneously regressing and progressing tumors. Tumor-reactive CD8+ T cell responses in Batf3-/- mice lacking type 1 DCs (DC1s) were lost in progressor tumors but preserved in regressor tumors. Transcriptional profiling of intra-tumoral DCs within regressor tumors revealed an activation state of CD11b+ conventional DCs (DC2s) characterized by expression of interferon (IFN)-stimulated genes (ISGs) (ISG+ DCs). ISG+ DC-activated CD8+ T cells ex vivo comparably to DC1. Unlike cross-presenting DC1, ISG+ DCs acquired and presented intact tumor-derived peptide-major histocompatibility complex class I (MHC class I) complexes. Constitutive type I IFN production by regressor tumors drove the ISG+ DC state, and activation of MHC class I-dressed ISG+ DCs by exogenous IFN-ß rescued anti-tumor immunity against progressor tumors in Batf3-/- mice. The ISG+ DC gene signature is detectable in human tumors. Engaging this functional DC state may present an approach for the treatment of human disease.
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Linfocitos T CD8-positivos/inmunología , Células Dendríticas/inmunología , Antígenos de Histocompatibilidad Clase I/inmunología , Interferón Tipo I/inmunología , Linfocitos Infiltrantes de Tumor/inmunología , Animales , Antígenos de Neoplasias/inmunología , Antígeno CD11b/inmunología , Reactividad Cruzada , Células Dendríticas/efectos de los fármacos , Interferón beta/administración & dosificación , Interferón beta/farmacología , Ratones , Neoplasias/inmunología , Receptores de Interferón/inmunología , Transducción de Señal/inmunología , Microambiente Tumoral/inmunologíaRESUMEN
Dendritic cells are crucial for anti-tumor immune responses due to their ability to activate cytotoxic effector CD8+ T cells. Canonically, in anti-tumor immunity, dendritic cells activate CD8+ T cells in a process termed cross-presentation. Recent studies have demonstrated that another type of antigen presentation, MHC-dressing, also serves to activate CD8+ T cells against tumor cell-derived antigens. Understanding MHC-dressing's specific contributions to anti-tumor immunity can open up novel therapeutic avenues. In this review, we summarize the early studies that identified MHC-dressing as a relevant antigen presentation pathway before diving into a deeper discussion of the biology of MHC-dressing, focusing in particular on which dendritic cell subsets are most capable of performing MHC-dressing and how MHC-dressing compares to other forms of antigen presentation. We conclude by discussing the implications MHC-dressing has for anti-tumor immunity.
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Presentación de Antígeno , Antígenos de Neoplasias , Células Dendríticas , Neoplasias , Humanos , Antígenos de Neoplasias/metabolismo , Linfocitos T CD8-positivos , Células Dendríticas/inmunología , Células Dendríticas/metabolismo , Antígenos de Histocompatibilidad Clase I , Neoplasias/inmunologíaRESUMEN
Adhesives typically fall into two categories: those that have high but irreversible adhesion strength due to the formation of covalent bonds at the interface and are slow to deploy, and others that are fast to deploy and the adhesion is reversible but weak in strength due to formation of noncovalent bonds. Synergizing the advantages from both categories remains challenging but pivotal for the development of the next generation of wound dressing adhesives. Here, we report a fast and reversible adhesive consisting of dynamic boronic ester covalent bonds, formed between poly(vinyl alcohol) (PVA) and boric acid (BA) for potential use as a wound dressing adhesive. Mechanical testing shows that the adhesive film has strength in shear of 61 N/cm2 and transcutaneous adhesive strength of 511 N/cm2, generated within 2 min of application. Yet the film can be effortlessly debonded when exposed to excess water. The mechanical properties of PVA/BA adhesives are tunable by varying the cross-linking density. Within seconds of activation by water, the surface boronic ester bonds in the PVA/BA film undergo fast debonding and instant softening, leading to conformal contact with the adherends and reformation of the boronic ester bonds at the interface. Meanwhile, the bulk film remains dehydrated to offer efficient load transmission, which is important to achieve strong adhesion without delamination at the interface. Whether the substrate surface is smooth (e.g., glass) or rough (e.g., hairy mouse skin), PVA/BA adhesives demonstrate superior adhesion compared to the most widely used topical skin adhesive in clinical medicine, Dermabond.
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Adhesivos , Vendas Hidrocoloidales , Cicatrización de Heridas , Adhesivos/química , Animales , Ésteres , Hidrogeles/química , Ratones , Alcohol Polivinílico/química , Agua/químicaRESUMEN
Systematic management of infected wounds requires simultaneous antiinfection and wound healing, which has become the current treatment dilemma. Recently, a multifunctional silver nanoclusters (AgNCs)-based hydrogel dressing to meet these demands is developed. Here a diblock DNA with a cytosine-rich fragment (as AgNCs template) and a guanine-rich fragment (to form G-quadruplex/hemin DNAzyme, termed G4/hemin) is designed, for G4/hemin functionalization of AgNCs. Inside bacteria, G4/hemin can not only accelerate the oxidative release of Ag+ from AgNCs but also generate reactive oxygen species (ROS) via catalase- and peroxidase-mimic activities, which enhance the antibacterial effect. On the other hand, the AgNCs exhibit robust anti-inflammatory and antioxidative activities to switch M1 macrophages into M2 phenotype, which promotes wound healing. Moreover, the hemin is released to upregulate the heme oxygenase-1, an intracellular enzyme that can relieve oxidative stress, which significantly alleviates the cytotoxicity of silver. As a result, such silver-based dressing achieves potent therapeutic efficacy on infected wounds with excellent biosafety.
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ADN Catalítico , Nanopartículas del Metal , Plata , Hemina , ADN , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , HidrogelesRESUMEN
Healing of complex wounds requires dressings that must, at least, not hinder and should ideally promote the activity of key healing cells, in particular fibroblasts. This in vitro study assessed the effects of three wound-dressings (a pure Ca2+ alginate: Algostéril®, a Ca2+ alginate + carboxymethylcellulose: Biatain alginate® and a polyacrylate impregnated with lipido-colloid matrix: UrgoClean®) on dermal fibroblast activity. The results showed the pure calcium alginate to be non-cytotoxic, whereas the other wound-dressings showed moderate to strong cytotoxicity. The two alginates stimulated fibroblast migration and proliferation, whereas the polyacrylate altered migration and had no effect on proliferation. The pure Ca2+ alginate significantly increased the TGF-ß-induced fibroblast activation, which is essential to healing. This activation was confirmed by a significant increase in Vascular endothelial growth factor (VEGF) secretion and a higher collagen production. The other dressings reduced these fibroblast activities. The pure Ca2+ alginate was also able to counteract the inhibitory effect of NK cell supernatants on fibroblast migration. These in vitro results demonstrate that tested wound-dressings are not equivalent for fibroblast activation. Only Algostéril was found to promote all the fibroblast activities tested, which could contribute to its healing efficacy demonstrated in the clinic.
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Alginatos , Movimiento Celular , Proliferación Celular , Fibroblastos , Factor A de Crecimiento Endotelial Vascular , Cicatrización de Heridas , Fibroblastos/efectos de los fármacos , Cicatrización de Heridas/efectos de los fármacos , Humanos , Alginatos/farmacología , Movimiento Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Factor A de Crecimiento Endotelial Vascular/metabolismo , Colágeno/metabolismo , Vendajes , Factor de Crecimiento Transformador beta/metabolismo , Carboximetilcelulosa de Sodio , Células Cultivadas , Células Asesinas Naturales/efectos de los fármacos , Resinas Acrílicas , Ácidos Hexurónicos , Ácido Glucurónico , PielRESUMEN
In this study, a new biomaterial with polyvinyl alcohol (PVA)/sodium caseinate (SodCa)/reduced graphene oxide (rGO) structure was developed. Antibacterial effective nanofibers were successfully produced by electrospinning method from 1%, 3%, 5%, and 7% rGO added PVA/SodCa (60:40, w:w) solution mixtures prepared for use as modern wound dressings. To create a usage area, especially in exuding wounds, hydrophilic PVA/SodCa/rGO electrospun mats were cross-linked by dipping them in a glutaraldehyde (GLA) bath. The surface micrographs of all nanofibers were homogeneous and smooth. rGO-doped biomaterials were obtained as thin nanofibers in the range of 301-348 nm. Nanofibers, which were completely soluble in water, after cross-linking preserved their existence in the range of 87%-81% at the end of the 24th hour in distilled water. It was reported that these biomaterials that persist in an aqueous environment show swelling behavior in the range of 275%-608%. The porosity of uncross-linked pure PVA/SodCa nanofibers increased by 46.75% after cross-linking. Moreover, the tensile strength of cross-linked PVA/SodCa electrospun mats increased in the presence of rGO. Provided that wound dressing is done every 24 h with 3% rGO-doped PVA/SodCa nanofiber and provided that wound dressing is done every 48 h with 5% rGO-doped PVA/SodCa nanofiber showed antibacterial activity against S. aureus as 99.38% and 99.55%, respectively.
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Antibacterianos , Vendajes , Caseínas , Grafito , Nanofibras , Alcohol Polivinílico , Alcohol Polivinílico/química , Grafito/química , Antibacterianos/farmacología , Antibacterianos/química , Nanofibras/química , Caseínas/química , Resistencia a la Tracción , Staphylococcus aureus/efectos de los fármacos , Reactivos de Enlaces Cruzados/química , Materiales Biocompatibles/química , Materiales Biocompatibles/farmacologíaRESUMEN
An ideal antibacterial wound dressing with strong antibacterial behavior versus highly drug-resistant bacteria and great wound-healing capacity is still being developed. There is a clinical requirement to progress the current clinical cares that fail to fully restore the skin structure due to post-wound infections. Here, we aim to introduce a novel two-layer wound dressing using decellularized bovine skin (DBS) tissue and antibacterial nanofibers to design a bioactive scaffold with bio-mimicking the native extracellular matrix of both dermis and epidermis. For this purpose, polyvinyl alcohol (PVA)/chitosan (CS) solution was loaded with antibiotics (colistin and meropenem) and electrospun on the surface of the DBS scaffold to fabricate a two-layer antibacterial wound dressing (DBS-PVA/CS/Abs). In detail, the characterization of the fabricated scaffold was conducted using biomechanical, biological, and antibacterial assays. Based on the results, the fabricated scaffold revealed a homogenous three-dimensional microstructure with a connected pore network, a high porosity and swelling ratio, and favorable mechanical properties. In addition, according to the cell culture result, our fabricated two-layer scaffold surface had a good interaction with fibroblast cells and provided an excellent substrate for cell proliferation and attachment. The antibacterial assay revealed a strong antibacterial activity of DBS-PVA/CS/Abs against both standard strain and multidrug-resistant clinical isolates of Acinetobacter baumannii, Pseudomonas aeruginosa, and Escherichia coli. Our bilayer antibacterial wound dressing is strongly suggested as an admirable wound dressing for the management of infectious skin injuries and now promises to advance with preclinical and clinical research.
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Quitosano , Nanofibras , Infección de Heridas , Animales , Bovinos , Antibacterianos/farmacología , Antibacterianos/química , Piel , Cicatrización de Heridas , Quitosano/química , Alcohol Polivinílico/química , Infección de Heridas/tratamiento farmacológico , Nanofibras/químicaRESUMEN
BACKGROUND: Radial access is the default approach in interventional cardiology. The Axiostat® surgical hemostatic dressing, using chitosan as its active component, has demonstrated potential in accelerating blood clotting. This study aims to assess the efficacy and the safety of the Axiostat® dressing in achieving hemostasis in patients undergoing transradial coronary angioplasty (TRCA). METHODS: This prospective, single-center observational study, conducted in 2022, enrolled consecutive patients undergoing TRCA, with a target of 150 participants. The primary outcome was the success rate of radial artery hemostasis at 120 min, without bleeding necessitating immediate re-compression. The secondary outcome included Axiostat® performance at 24 h and 30 days Postprocedure. RESULTS: The study was terminated prematurely for ethical and patient safety reasons, after inclusion of 41 consecutive TRCA patients due to an unexpectedly high radial artery thrombosis rate (19.5%, n = 8/41) observed 24 h Postprocedure. The success rate of radial hemostasis with the Axiostat® dressing was 78.0%. Procedural details and patient characteristics were comparable between successful Axiostat® removal and device failure cases. CONCLUSION: The use of the Axiostat® dressing to achieve hemostasis after TRCA is effective but is associated with an unexpectedly high incidence of radial thrombosis. Our results should encourage caution in the future evaluation and use of this device for radial artery compression following TRCA.
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Cateterismo Periférico , Diseño de Equipo , Hemorragia , Técnicas Hemostáticas , Punciones , Arteria Radial , Humanos , Estudios Prospectivos , Masculino , Femenino , Anciano , Técnicas Hemostáticas/instrumentación , Técnicas Hemostáticas/efectos adversos , Persona de Mediana Edad , Resultado del Tratamiento , Cateterismo Periférico/efectos adversos , Factores de Tiempo , Hemorragia/prevención & control , Hemorragia/etiología , Quitosano , Hemostáticos/administración & dosificación , Hemostáticos/efectos adversos , Factores de Riesgo , Intervención Coronaria Percutánea/efectos adversos , Intervención Coronaria Percutánea/instrumentación , Vendajes , Trombosis/etiología , Trombosis/prevención & controlRESUMEN
AIM: To investigate the differences in utility between conventional dressings and hydrogel dressings for the treatment of diabetic foot ulcer (DFU). METHODS: The PubMed, Embase, Cochrane Library, CNKI, VIP and Wanfang databases were systematically searched up to 21 January 2023. Fixed/random-effect models were used to calculate the odds ratios (ORs) and mean differences (MDs) with 95% confidence intervals (CIs) for the effect size analysis, with heterogeneity determined by I2 statistics. Subgroup analyses of different classes of hydrogel were also conducted. RESULTS: A total of 15 randomized controlled trials with 872 patients were eligible for the present analysis. Compared with conventional dressings, hydrogel dressings significantly improved the healing rate (OR 4.09, 95% CI 2.83 to 5.91), shortened the healing time (MD -11.38, 95% CI -13.11 to -9.66), enhanced granulation formation (MD -3.60, 95% CI -4.21 to -3.00) and epithelial formation (MD -2.82, 95% CI -3.19 to -2.46), and reduced the incidence of bacterial infection (OR 0.10, 95% CI 0.05 to 0.18). CONCLUSION: The meta-analysis showed that hydrogel dressings are more effective in treating DFU compared with conventional dressings.
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Vendajes , Pie Diabético , Hidrogeles , Cicatrización de Heridas , Pie Diabético/terapia , Humanos , Hidrogeles/uso terapéutico , Ensayos Clínicos Controlados Aleatorios como Asunto , Resultado del Tratamiento , Femenino , Masculino , Vendas Hidrocoloidales , Persona de Mediana EdadRESUMEN
Burn injuries are a significant global health concern, with more than 11 million people requiring medical intervention each year and approximately 180,000 deaths annually. Despite progress in health and social care, burn injuries continue to result in socioeconomic burdens for victims and their families. The management of severe burn injuries involves preventing and treating burn shock and promoting skin repair through a two-step procedure of covering and closing the wound. Currently, split-thickness/full-thickness skin autografts are the gold standard for permanent skin substitution. However, deep burns treated with split-thickness skin autografts may contract, leading to functional and appearance issues. Conversely, defects treated with full-thickness skin autografts often result in more satisfactory function and appearance. The development of tissue-engineered dermal templates has further expanded the scope of wound repair, providing scar reductive and regenerative properties that have extended their use to reconstructive surgical interventions. Although their interactions with the wound microenvironment are not fully understood, these templates have shown potential in local infection control. This narrative review discusses the current state of wound repair in burn injuries, focusing on the progress made from wound cover to wound closure and local infection control. Advancements in technology and therapies hold promise for improving the outcomes for burn injury patients. Understanding the underlying mechanisms of wound repair and tissue regeneration may provide new insights for developing more effective treatments in the future.
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Quemaduras , Humanos , Quemaduras/cirugía , Quemaduras/patología , Piel/patología , Cicatrización de Heridas , Trasplante de Piel/métodos , Cicatriz/etiología , Cicatriz/prevención & control , Cicatriz/cirugíaRESUMEN
Wound dressing changes are essential procedures for wound management. However, ~50% of patients experience severe pain during these procedures despite the availability of analgesic medications, indicating a need for novel therapeutics that address underlying causes of pain. Along with other clinical factors, wound pathogens and inflammatory immune responses have previously been implicated in wound pain. To test whether these factors could contribute to severe pain during wound dressing changes, we conducted an exploratory, cross-sectional analysis of patient-reported pain, inflammatory immune responses, and wound microbiome composition in 445 wounds at the time of a study dressing change. We profiled the bacterial composition of 406 wounds using 16S ribosomal RNA amplicon sequencing and quantified gene expression of 13 inflammatory markers in wound fluid using quantitative real-time polymerase chain reaction (qPCR). Neither inflammatory gene expression nor clinically observed inflammation were associated with severe pain, but Corynebacterium and Streptococcus were of lower relative abundance in wounds of patients reporting severe pain than those reporting little or no pain. Wound microbiome composition differed by wound location, and correlated with six of the inflammatory markers, including complement receptor C5AR1, pro-inflammatory cytokine interleukin (IL)1ß, chemokine IL-8, matrix metalloproteinase MMP2, and the antimicrobial peptide encoding cathelicidin antimicrobial peptide. Interestingly, we found a relationship between the wound microbiome and vacuum-assisted wound closure (VAC). These findings identify preliminary, associative relationships between wound microbiota and host factors which motivate future investigation into the directional relationships between wound care pain, wound closure technologies, and the wound microbiome.
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StopBac is an innovative silver-impregnated antimicrobial dressing specifically designed to reduce surgical site infections and enhance healing. The primary objective of this study was to compare infection healing rate at 30 days after surgery between primarily closed surgical wounds covered with StopBac and those covered with Cosmorpor, a standard surgical dressing. Between 1.3.2023 and 30.4.2023, we conducted a prospective screening of all patients undergoing surgical operations within a single surgical department. Patients were randomised into either the Cosmopor group or the StopBac group. Outcome measures were superficial and deep surgical site infections and healed wounds. Data concerning patient and surgical factors were prospectively collected and analysed. The analysis comprised 275 patients, divided into two groups: 140 patients in the StopBac group and 135 in the Cosmopor group. The StopBac dressing was associated with a reduced rate of infection, with an odds ratio of 0.288 (p < 0.001), and an increased likelihood of wound healing at 30 days after surgery. The odds ratio for healing at 30 days was 4.661 (p < 0.001). StopBac was associated with a lower incidence of surgical wound infections and a higher probability of healing at 30 days after surgery, when compared with standard dressing.
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Quemaduras , Infección de la Herida Quirúrgica , Humanos , Infección de la Herida Quirúrgica/prevención & control , Plata/farmacología , Cicatrización de Heridas , Estudios Prospectivos , VendajesRESUMEN
Wounds pose significant challenges to public health, primarily due to the loss of the mechanical integrity and barrier function of the skin and impaired angiogenesis, causing physical morbidities and psychological trauma to affect patients. Reconstructing the vasculature of the wound bed is crucial for promoting wound healing, reducing scar formation and enhancing the quality of life for patients. The development of pro-angiogenic skin substitutes has emerged as a promising strategy to facilitate vascularization and expedite the healing process of burn wounds. This review provides an overview of the various types of skin substitutes employed in wound healing, explicitly emphasising those designed to enhance angiogenesis. Synthetic scaffolds, biological matrices and tissue-engineered constructs incorporating stem cells and primary cells, cell-derived extracellular vesicles (EVs), pro-angiogenic growth factors and peptides, as well as gene therapy-based skin substitutes are thoroughly examined. The review summarises the existing challenges, future directions and potential innovations in pro-angiogenic dressing for skin substitutes. It highlights the need for continued research to develop new technologies and combine multiple strategies and factors, and to overcome obstacles and advance the field, ultimately leading to improved outcomes for wound patients.
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Neovascularización Fisiológica , Piel Artificial , Ingeniería de Tejidos , Cicatrización de Heridas , Humanos , Cicatrización de Heridas/fisiología , Ingeniería de Tejidos/métodos , Quemaduras/terapia , Andamios del TejidoRESUMEN
BACKGROUND: Patients are often advised to keep the initial postoperative dressings dry and undisturbed for 24 to 72 hours. However, these requirements may result in significant disruption of patients' activities of daily living, such as bathing, leisure, and exercise. OBJECTIVE: Compare standard management of keeping wounds dry and covered (48 hours) with early (6 hours) postoperative water exposure. METHODS: Investigator-blinded, randomized (1:1), controlled trial evaluating rate of infection and additional outcomes of interest. RESULTS: Overall, 437 patients were randomized to either the early (6-hour) water exposure (n = 218) intervention group or the standard cohort (n = 219). The incidence of culture-proven infection in the intervention group (1.8%) was similar to the standard group (1.4%) (P > .99). There was also no difference in rates of bleeding or bruising. Scar assessment using the Patient and Observer Scar Assessment Scale revealed similar scar outcomes. LIMITATIONS: Single site, academic center. CONCLUSION: Surgical wounds can be allowed to get wet in the immediate postoperative period with no increased incidence of infection or other complications and with similar cosmesis.
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Polyionic liquid hydrogels attract increasing attention due to their unique properties and potential applications. However, research on amino acid-based polyionic liquid hydrogels is still in its infancy stage. Moreover, the effect of amino acid types on the properties of hydrogels is rarely studied to date. In this work, amino acid-based polyionic liquid hydrogels (D/L-PCAA hydrogels) are synthesized by copolymerizing vinyl choline-amino acid ionic liquids and acrylic acids using Al3+ as a crosslinking agent and bacterial cellulose (BC) as a reinforcing agent. The effects of amino acid types on mechanical and antimicrobial properties are systematically investigated. D-arginine-based hydrogel (D-PCArg) shows the highest tensile strength (220.7 KPa), D-phenylalanine-based hydrogel (D-PCPhe) exhibits the highest elongation at break (1346%), and L-aspartic acid-based hydrogel (L-PCAsp) has the highest elastic modulus (206.9 KPa) and toughness (1.74 MJ m-3). D/L-PCAsp hydrogels demonstrate stronger antibacterial capacity against Escherichia coli and Staphylococcus aureus, and D/L-PCPhe hydrogels possess higher antifungal activity against Cryptococcus neoformans. Moreover, the resultant hydrogels exhibit prominent hemocompatibility and low toxicity, as well as excellent self-healing capabilities (86%) and conductivity (2.8 S m-1). These results indicate that D/L-PCAA hydrogel provides a promise for applications in wound dressings.
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Aminoácidos , Antibacterianos , Escherichia coli , Hidrogeles , Líquidos Iónicos , Staphylococcus aureus , Hidrogeles/química , Hidrogeles/farmacología , Hidrogeles/síntesis química , Escherichia coli/efectos de los fármacos , Aminoácidos/química , Aminoácidos/farmacología , Staphylococcus aureus/efectos de los fármacos , Antibacterianos/química , Antibacterianos/farmacología , Antibacterianos/síntesis química , Líquidos Iónicos/química , Líquidos Iónicos/farmacología , Pruebas de Sensibilidad Microbiana , Antifúngicos/farmacología , Antifúngicos/química , Antifúngicos/síntesis química , Antiinfecciosos/química , Antiinfecciosos/farmacología , Antiinfecciosos/síntesis químicaRESUMEN
Chronic wound infections are generally of polymicrobial nature with aerobic and anaerobic bacteria, as well as fungi frequently observed in them. Wound treatment involves a series of steps, including debridement of the wound, flushing, and often the use of multiple wound dressings many of which are antimicrobial. Yet, many wound dressings are tested versus single species of planktonic microbes, which fails to mirror the real-life presence of biofilms. AIMS: Simple biofilm models are the first step to testing of any antimicrobial and wound dressing; therefore, the aim of this study was to develop and validate a simple polymicrobial colony biofilm wound model comprised of Pseudomonas aeruginosa, Staphylococcus aureus, and Candida albicans on RPMI-1640 agar. The model was then used to evaluate the topical disinfectant chlorohexidine and four commercially available wound dressings using the polymicrobial model. The model used was as a starting point to mimic debridement in clinical care of wounds and the effectiveness of wound dressings evaluated afterwards. METHODS AND RESULTS: Planktonic assessment using AATCC100-2004 demonstrated that all antimicrobial wound dressings reduced the planktonic microbial burden below the limit of detection; however, when challenged with polymicrobial colony biofilms, silver wound dressings showed limited effectiveness (1-2 log CFU reductions). In contrast, a single iodine releasing wound dressing showed potent antibiofilm activity reducing all species CFUs below the limit of detection (>6-10 log) depending on the species. A disrupted biofilm model challenge was performed to represent the debridement of a wound and wound silver-based wound dressings were found to be marginally more effective than in whole colony biofilm challenges while the iodine containing wound dressing reduced microbial recovery below the limit of detection. CONCLUSIONS: In this model, silver dressings were ineffective versus the whole colony biofilms but showed some recovery of activity versus the disrupted colony biofilm. The iodine wound dressing reduced the viability of all species below the level of detection. This suggests that mode of action of wound dressing should be considered for the type of biofilm challenge as should the clinical use, e.g. debridement.
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Antiinfecciosos , Yodo , Infección de Heridas , Humanos , Plata , Antiinfecciosos/farmacología , Vendajes , Yodo/farmacología , Yodo/uso terapéutico , Biopelículas , Infección de Heridas/prevención & control , Infección de Heridas/tratamiento farmacológico , Pseudomonas aeruginosaRESUMEN
The colonization of pathogenic microbes poses a significant clinical barrier that hinders the physiological wound-healing process. Addressing this challenge, we developed a novel wound dressing using a modified cotton gauze dressing coated with fucoidan and functionalized with silver nanoparticles (LB-Ag NPs-FN-OCG) for the rapid treatment of infected wounds. Firstly, phytochemical-capped LB-Ag NPs were synthesized and characterized using high performance liquid chromatography (HPLC), transmission electron microscopy (TEM), and zeta potential analysis. Secondly, different concentrations of LB-Ag NPs (0.1%-1%) were functionalized into FN-OCG to identify appropriate concentrations that were non-toxic with superior antibacterial activities. Screening assays, including antibacterial, hemolysis, chick chorioallantoic membrane (CAM) assay, and cytotoxicity assay, revealed that LB-Ag NPs (0.5%)-FN-OCG were non-toxic and demonstrated greater efficiency in inhibiting bacterial pathogens (Escherichia coli, Salmonella enterica, Staphylococcus aureus, and Listeria monocytogenes) and promoting fibroblast cell (NIH3T3) migration. In vivo assays revealed that LB-Ag NPs (0.5%)-FN-OCG treatment exhibited excellent wound healing activity (99.73 ± 0.01%) compared to other treatments by inhibiting bacterial colonization, maintaining the blood parameters, developing granulation tissue, new blood vessels, and collagen deposition. Overall, this study highlights that LB-Ag NPs (0.5%)-FN-OCG serve as a antibacterial wound dressing for infected wound healing applications.
Asunto(s)
Nanopartículas del Metal , Polisacáridos , Plata , Ratones , Animales , Plata/química , Nanopartículas del Metal/química , Células 3T3 NIH , Cicatrización de Heridas , Antibacterianos/farmacología , VendajesRESUMEN
BACKGROUND: Anal fistula and perianal abscess are commonly acquired anorectal pathologies in children. Surgical treatment options commonly adopted are fistulotomy, fistulectomy, cutting seton placement, and more recently video-assisted anal fistula treatment (VAAFT). Optimal postoperative wound dressing remains debated. This study aimed to report our series of pediatric patients, who received VAAFT and postoperative wound dressing using ozonide oil. METHODS: All patients who underwent VAAFT between August 2018 and May 2023 were included in the study. Demographics, clinical features, pre-operative imaging, surgical details, outcome, and mid-term outcome data were retrospectively reviewed for each patient. All VAAFT procedures were performed under general anesthesia and using a 10-Ch fistuloscope. RESULTS: Thirty-three VAAFT procedures were performed in 30 patients over the study period. The median patient age was 5.7 years (range 1.75-14). Anal fistula was idiopathic in 26/30 (86.6%), iatrogenic in 2/30 (6.7%), and secondary to Crohn's disease in 2/30 (6.7%). The median duration of surgery was 23 min (range 18-40). All patients received ozonide oil dressing twice a day for 5 weeks postoperatively. The median hospital stay was 24 h (range 9-36). The median healing time was 28 days (range 17-39). With a median follow-up of 2 years (range 0.5-5), disease recurrence occurred in 3/30 (10%) patients with idiopathic fistula, who were re-operated using the same technique, with no further recurrence. No fecal incontinence or soiling was observed. CONCLUSION: Our series confirmed that VAAFT is a safe and effective technique to treat children with perianal fistula. The technique is versatile, allowing to treat fistulae of different etiologies. Postoperative course was painless and fast. Future comparative prospective studies are needed to better establish these conclusions.