RESUMO
Extracellular vesicles (EVs), especially those derived from stem cells, have emerged as a novel treatment for promoting wound healing in regenerative medicine. However, the clinical application of mammalian cells-derived EVs is hindered by their high cost and low yields. Inspired by the ability of EVs to mediate interkingdom communication, we explored the therapeutic potential of EVs released by the probiotic strain Lactobacillus rhamnosus GG (LGG) in skin wound healing and elucidated the underlying mechanism involved. Using full-thickness skin wound-healing mouse models, we found that LGG-EVs accelerated wound healing procedures, including increased re-epithelialization and promoted angiogenesis. Using in vitro experiments, we further demonstrated that LGG-EVs boosted the proliferation and migration capacities of both epithelial and endothelial cells, as well as promoted endothelial tube formation. miRNA profiling analysis revealed that miR-21-5p was highly enriched in LGG-EVs and LGG-EV treatment significantly increased miR-21-5p level in recipient cells. Mechanically, LGG-EVs induced regulatory effects via miR-21-5p mediated metabolic signaling rewiring. Our results suggest that EVs derived from LGG could serve as a promising candidate for accelerating wound healing and possibly for treating chronic and impaired healing conditions.
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Vesículas Extracelulares , Lacticaseibacillus rhamnosus , MicroRNAs , Neovascularização Fisiológica , Cicatrização , MicroRNAs/metabolismo , MicroRNAs/genética , Vesículas Extracelulares/metabolismo , Vesículas Extracelulares/química , Animais , Camundongos , Humanos , Movimento Celular , Reepitelização , Proliferação de Células , Probióticos/farmacologia , Camundongos Endogâmicos C57BL , Pele/metabolismo , Pele/lesões , Masculino , Células Endoteliais/metabolismo , AngiogêneseRESUMO
PURPOSE: This study aimed to evaluate the effects of ozone therapy applied topically and/or by bagging on the healing of clean wounds induced in rat's skin. METHODS: One hundred and twenty male rats of about 16 weeks old was divided into five groups: G1) saline solution (0.9%); G2) sunflower oil; G3) ozonated sunflower oil; G4) ozone bagging; G5) association of ozonated sunflower oil and ozone bagging. The wounds were evaluated through macroscopic, morphometric, histopathologic, and tensile strength analyses. RESULTS: Analysis among groups showed a lower percentage of wound contraction in G1 compared to G4 only in M7D. The tensile strength of the wounds showed differences among groups in the seventh (M7D) and the 14th (M14D) postoperative day, and among time points in G1 (M14D > M7D). The elongation of the wounds showed differences in G3 (M7D > M14D). Histological evaluation of the wounds showed significant change in bleeding, mixed to mononuclear infiltrate, congestion, and tissue disorganization for tissue organization between groups and time points. CONCLUSIONS: Ozone therapy applied topically and/or by bagging was not deleterious to the healing of clean wounds induced in rat's skin, but ozone bagging showed the best contribution to the healing process.
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Ozônio , Ratos Wistar , Pele , Resistência à Tração , Cicatrização , Animais , Ozônio/administração & dosagem , Ozônio/uso terapêutico , Ozônio/farmacologia , Cicatrização/efeitos dos fármacos , Masculino , Pele/lesões , Pele/efeitos dos fármacos , Pele/patologia , Ratos , Resistência à Tração/efeitos dos fármacos , Óleo de Girassol , Administração Tópica , Fatores de Tempo , Resultado do Tratamento , Modelos Animais de Doenças , Reprodutibilidade dos TestesRESUMO
The management of acute full-thickness skin injuries presents a considerable challenge in clinical practice. The complexity of wound healing, involving diverse cell populations and the intricate wound microenvironment, complicates the assessment of treatment effects and their interactions using traditional experimental approaches. Single-cell transcriptome sequencing technology has revolutionized the understanding of cellular functions and mechanisms during wound healing. However, the variability in methodologies for creating mouse wound models introduces confounding factors that can impact experimental results. Furthermore, the process of dissociating mouse skin tissues presents significant technical hurdles, highlighting the critical need for high-quality single-cell suspensions for accurate transcriptome sequencing. Therefore, this study aims to optimize the construction of mouse wound models to accurately assess changes in wound closure while eliminating variables that could influence the subsequent sequencing result. Additionally, the preparation of single-cell suspensions was performed using both enzyme preparation protocols and test kit protocols to optimize cost and effectiveness.
Assuntos
Análise de Célula Única , Animais , Camundongos , Análise de Célula Única/métodos , Modelos Animais de Doenças , Cicatrização , Pele/lesões , Pele/citologiaRESUMO
The integumentary system in animals serves as an important line of defence against physiological and mechanical external forces. Over time, integuments have evolved layered structures (scales, cuticle and skin) with high toughness and strength to resist damage and prevent wound expansion. While previous studies have examined their defensive performance under low-rate conditions, the failure response and damage resistance of these thin layers under dynamic biological puncture remain underexplored. Here, we utilize a novel experimental framework to investigate the mechanics of dynamic puncture in both bilayer structures of synthetic tissue-mimicking composite materials and natural skin tissues. Our findings reveal the remarkable efficiency of a thin outer skin layer in reducing the overall extent of dynamic puncture damage. This enhanced damage resistance is governed by interlayer properties through puncture energetics and diminishes in strength at higher puncture rates due to rate-dependent effects in silicone tissue simulants. In addition, natural skin tissues exhibit unique material properties and failure behaviours, leading to superior damage reduction capability compared with synthetic counterparts. These findings contribute to a deeper understanding of the inherent biomechanical complexity of biological puncture systems with layered composite material structures. They lay the groundwork for future comparative studies and bio-inspired applications.
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Pele , Animais , Pele/lesões , Modelos BiológicosRESUMO
OBJECTIVE: To study the effect of physical plasma jet in treating open wounds in diabetic and non-diabetic dogs. METHODS: The experimental study was conducted at the College of Veterinary Medicine, University of Baghdad, Iraq, from 20 January, 2020 to 1st May 2020, according to (no. 1364/ P.G), and comprised adult male diabetic and nondiabetic dogs. They were divided into non-diabetic group N and diabetic group D. Each group was further divided into treatment subgroup T and control subgroup C. Each dog was subjected to 4 wounds 3×3cm in size. Homemade helium non-equilibrium atmospheric pressure plasma jet therapy was used for healing purposes. Clinical parameters were evaluated by observation, while histological images were scored based on the semi-quantitative evaluation of histological sections on days 3-, 7- and 21-days post-wound. Data was analysed using SPSS Version 26 with One-way ANOVA for statistical analysis between groups and sub-groups. RESULTS: Of the 24 dogs, 12(50%) were in each of the two groups, which were further divided into subgroups having 6(50%) dogs each. The therapy accelerated the process of wound healing in the NT and DT subgroups compared to NC and DC. Clinical observations revealed early and complete closure of plasma-treated wounds in NT and DT subgroups started at day 30 post-wounding, while in the NC subgroup it started at day 35, and in the DC subgroup, wounds failed to close even after 35 days post-wounding. Histological analysis suggested that a plasma jet supported epithelisation, angiogenesis, formation of new hair follicles and collagen fibres, while it also controlled inflammation. In addition, in NT and DT subgroups, it increased the proliferation of fibroblasts and deposition of collagen, and there is a very, highly significant difference between groups (P<0.001), and a significant difference between days (P<0.05). CONCLUSIONS: Home-made helium non-equilibrium atmospheric pressure plasma jet therapy improved the quality and pace of wound healing.
Assuntos
Gases em Plasma , Pele , Cicatrização , Animais , Cães , Cicatrização/fisiologia , Gases em Plasma/uso terapêutico , Masculino , Pele/lesões , Pele/patologiaRESUMO
OBJECTIVE: Currently there is limited real-world research on the adhesion qualities, pain and clinical performance of specific silicone adhesives products, and their role in maintaining skin integrity and preventing medical adhesive-related skin injuries (MARSI). This paper presents a clinical evaluation of performance and safety parameters of two silicone adhesive dressings on lacerations or surgical wounds and the surrounding skin in daily practice on fragile skin. METHOD: An observational, prospective, multicentre, uncontrolled post-market clinical observational study with Leukomed T skin sensitive and Leukomed T plus skin sensitive (both BSN medical GmbH, Essity Group) was undertaken at three sites across Germany between June 2021 to November 2022. Inclusion parameters were acute wounds (surgical or laceration) in patients with at least one fragile skin condition. Endpoints included: the percentage of adhered dressing area seven days after application of the dressings; and evaluation of any signs of skin damage and erythema following dressing removal. Furthermore, self-reported patient pain, comfort during dressing wear, and the health professionals' ease of dressing handling with gloves were assessed. RESULTS: A total of 42 patients with fragile skin and surgical wounds (35 patients) or lacerations (7 patients) were recruited. Mean age was 78 years. There were no signs of erythema following dressing removal and no MARSI (skin stripping, blister, skin tears, maceration, irritant contact dermatitis or allergic dermatitis) occurred at removal after seven days of wear time. Data demonstrated a reliable wound coverage with sufficient adhesion without negatively affecting the periwound skin and wound improvement was observed in 94% of patients. The vast majority of patients reported minimal pain at removal, reduced wound pain and high satisfaction with wearing comfort. Health professionals found the dressings easy to apply and remove, even with gloved hands. CONCLUSION: The results of this real-world evidence showed effective and well-tolerated use of transparent dressings with silicone adhesive in patients with fragile skin. The dressings may reduce the risk of skin damage including MARSI, while providing patients a high wearing comfort and allowing an almost pain-free dressing change.
Assuntos
Silicones , Humanos , Masculino , Feminino , Idoso , Estudos Prospectivos , Pessoa de Meia-Idade , Idoso de 80 Anos ou mais , Adesivos/efeitos adversos , Alemanha , Ferida Cirúrgica/terapia , Cicatrização , Lacerações , Bandagens , Adesivos Teciduais/uso terapêutico , Cuidados Pós-Operatórios/métodos , Curativos Oclusivos , Pele/lesõesRESUMO
Skin injuries are a major healthcare problem that are not well understood or prevented in the critically ill, suggesting that underappreciated variables are contributing. This pilot study tested the hypothesis that perfusion-related factors contribute to skin injuries diagnosed as hospital-acquired pressure injuries (HAPIs). A total of 533 adult patients were followed over 2574 critical care days (mean age 62.4, standard deviation (SD) 14.3 years, mean body mass index 30.4 (SD 7.4) kg/m2, 36.4% female). This was a secondary analysis of prospective, non-randomised clinical data from an intensive care unit at a large urban teaching hospital. Factors related to perfusion, specifically two or more infusions of vasopressors/inotropes, temporary mechanical circulatory support (MCS), extracorporeal membrane oxygenation, and durable MCS, were analysed to determine whether they were more strongly associated with HAPIs than immobility due to prolonged mechanical ventilation (>72 h) or operating room time (>6 h). Patients diagnosed with a HAPI had a statistically significant higher risk of being exposed to variables related to perfusion and immobility (P < 0.05 for each variable). Perfusion-related variables, except durable MCS, had a larger effect on skin breakdown (number needed to harm (NNH) 4-10) than immobility-associated variables (NNH 12-17). The finding that perfusion-related variables predicted HAPIs may warrant consideration of alternative diagnoses, such as skin failure due to impaired perfusion as a pathophysiological process that occurs concurrently with multisystem organ failure. Differentiation of skin injuries primarily from circulatory malfunction, rather than external pressure, may guide the development of more effective treatment and prevention protocols. This pilot study suggests that the contribution of perfusion to skin injuries should be explored further.
Assuntos
Úlcera por Pressão , Pele , Humanos , Feminino , Masculino , Pessoa de Meia-Idade , Idoso , Projetos Piloto , Estudos Prospectivos , Pele/lesões , Pele/irrigação sanguínea , Úlcera por Pressão/etiologia , Adulto , Oxigenação por Membrana Extracorpórea , Respiração ArtificialRESUMO
PURPOSE: To describe the effects of melatonin associated with bacterial cellulose-based hydrogel on healing of skin wounds in diabetic rats. METHODS: Streptozotocin was used to induce diabetes in Wistar rats. After wound induction, animals were randomly divided into groups GC, GDCC, GDCB, and GDMCB. Animals were evaluated in days 3, 7, and 14 for the following variables: glycemic levels, histopathological and histochemical analyses, healing rate, morphometry and C-reactive protein. RESULTS: There was no change in glycemic levels in the diabetic animals as a result of the treatments; histopathological analyses showed better healing in GDCB and GDMCB groups, as well as histochemistry; at day 14, the highest healing rate was observed in animals from the GDMCB group, reaching almost 100%; morphometry revealed a significant increase of fibroblasts and reduction of macrophages and blood vessels in lesions treated with bacterial cellulose associated or not with melatonin when compared to the other experimental groups. There was also an increase in C-reactive protein in GDCC group at day 14. CONCLUSION: Bacterial cellulose-based dressings associated with systemic melatonin showed beneficial results in experimentally induced wounds in diabetic rats, favoring the healing process.
Assuntos
Celulose , Diabetes Mellitus Experimental , Melatonina , Ratos Wistar , Pele , Cicatrização , Animais , Melatonina/uso terapêutico , Melatonina/farmacologia , Cicatrização/efeitos dos fármacos , Diabetes Mellitus Experimental/complicações , Celulose/uso terapêutico , Celulose/farmacologia , Masculino , Pele/efeitos dos fármacos , Pele/lesões , Pele/patologia , Hidrogéis/uso terapêutico , Distribuição Aleatória , Ratos , Proteína C-Reativa/análise , Fatores de Tempo , Reprodutibilidade dos Testes , Glicemia/análise , Glicemia/efeitos dos fármacos , Antioxidantes/uso terapêutico , Antioxidantes/farmacologiaRESUMO
The development of new wound dressings made from biomaterials, which offer a better cost-benefit ratio and accelerate the healing process, is increasing nowadays. Various biopolymers can be electrospun to form functional membranes for wound healing. Therefore, in this study, chitosan and nanochitosan membranes with or without hyaluronic acid were prepared using the electrospinning technique, characterized and evaluated in the healing of skin wounds in rats. Chitosan and nanochitosan solutions, with or without hyaluronic acid, were prepared at concentrations of 1%-4% using PEO (polyethylene oxide) and subjected to the electrospinning process to obtain membranes characterized by scanning electron microscopy (SEM), mechanical tests, and antimicrobial activity. The healing effect of the membranes was evaluated by monitoring the area of the lesions, contraction of the wounds, histologic analysis, and induction of pro-inflammatory cytokine (IL-1 α and TNF-α) production in rats. The nanochitosan and nanochitosan membranes with hyaluronic acid achieved greater fiber diameter and uniformity, resistance, elasticity, and thermal stability, in addition to good adhesion to the wound bed and permeation capacity. Despite not presenting antimicrobial activity in vitro, they contributed to the production of pro-inflammatory interleukins in the animals tested, provided physical protection, reduced the wound area more markedly until the seventh day of the evaluation, with an acceleration of the healing process and especially when functionalized with hyaluronic acid. These results indicate that the membranes may be promising for accelerating the healing process of chronic wounds in humans.
Assuntos
Quitosana , Ácido Hialurônico , Membranas Artificiais , Pele , Cicatrização , Quitosana/química , Quitosana/farmacologia , Animais , Ácido Hialurônico/química , Ácido Hialurônico/farmacologia , Cicatrização/efeitos dos fármacos , Ratos , Pele/lesões , Pele/metabolismo , Masculino , Ratos Wistar , BandagensRESUMO
In clinical practice, a large variety of medical devices adhere to skin to perform their function. The repeated application and removal of these devices can lead to skin damage or medical adhesive-related skin injury. Awareness of this problem has increased in the past decade, and this adverse event can be prevented with appropriate selection of adhesive products and the appropriate techniques for application and removal. A wide variety of adhesives and backing systems have been developed to create medical devices with an array of attributes, so they can accomplish many different indications in the clinical setting and meet various needs, including doing the clinical job without damaging the skin and causing further patient complications. The selection of an adhesive product should take into consideration a patient's skin assessment and history of medical adhesive-related skin injury, and using only the minimal adhesive strength needed to perform the function while protecting the skin from damage.
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Adesivos , Humanos , Adesivos/efeitos adversos , Adesivos Teciduais/efeitos adversos , Adesivos Teciduais/uso terapêutico , Pele/lesõesRESUMO
A burn is a type of injury to the skin or other tissues caused by heat, chemicals, electricity, sunlight, or radiation. Burn injuries have been proven to have the potential for long-term detrimental effects on the human body. The conventional therapeutic approaches are not able to effectively and easily heal these burn wounds completely. The main potential drawbacks of these treatments include hypertrophic scarring, contracture, infection, necrosis, allergic reactions, prolonged healing times, and unsatisfactory cosmetic results. The existence of these drawbacks and limitations in current treatment approaches necessitates the need to search for and develop better, more efficient therapies. The regenerative potential of microRNAs (miRNAs) and the exosomal miRNAs derived from various cell types, especially stem cells, offer advantages that outweigh traditional burn wound healing treatment procedures. The use of multiple types of stem cells is gaining interest due to their improved healing efficiency for various applications. Stem cells have several key distinguishing characteristics, including the ability to promote more effective and rapid healing of burn wounds, reduced inflammation levels at the wound site, and less scar tissue formation and fibrosis. In this review, we have discussed the stages of wound healing, the role of exosomes and miRNAs in improving thermal-induced wounds, and the impact of miRNAs in preventing the formation of hypertrophic scars. Research studies, pre-clinical and clinical, on the use of different cell-derived exosomal miRNAs and miRNAs for the treatment of thermal burns have been documented from the year 2000 up to the current time. Studies show that the use of different cell-derived exosomal miRNAs and miRNAs can improve the healing of burn wounds. The migration of exosomal miRNAs to the site of a wound leads to inhibition of apoptosis, induction of autophagy, re-epithelialization, granulation, regeneration of skin appendages, and angiogenesis. In conclusion, this study underscores the importance of integrating miRNA and exosome research into treatment strategies for burn injuries, paving the way for novel therapeutic approaches that could significantly improve patient outcomes and recovery times.
Assuntos
Queimaduras , Exossomos , MicroRNAs , Pele , Cicatrização , Exossomos/genética , Exossomos/metabolismo , MicroRNAs/genética , Cicatrização/genética , Humanos , Queimaduras/genética , Queimaduras/patologia , Queimaduras/terapia , Animais , Pele/patologia , Pele/lesões , Pele/metabolismo , Cicatriz/genética , Cicatriz/patologia , Células-Tronco/metabolismoRESUMO
Awareness of medical adhesive-related skin injury (MARSI) has increased in the decade since a foundational consensus report was published in 2013. Additional research has provided greater knowledge of the epidemiology of MARSI, along with its assessment, prevention, and management. To summarize knowledge generated in the past decade and review our current understanding of MARSI, a panel of nine clinical experts from four countries (United States of America, United Kingdom, Canada, and Brazil) convened to discuss the literature published since the initial 2013 document and develop updated recommendations for clinical practice. The group formulated 20 updated consensus statements covering the assessment, prevention, and management of skin injuries related to adhesive medical devices and proposed next steps to address remaining gaps in research and knowledge of this complex and clinically relevant condition.
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Adesivos , Consenso , Pele , Humanos , Adesivos/efeitos adversos , Brasil/epidemiologia , Canadá/epidemiologia , Pele/lesões , Reino Unido/epidemiologia , Estados Unidos/epidemiologiaRESUMO
INTRODUCTION: A common treatment for large deep-to-full-thickness burns is excision and grafting with a widely meshed split-thickness skin graft (mSTSG). Due to the differential healing of the interstices and adhered split-thickness skin graft, wound patterning and delayed wound healing are common outcomes of this treatment. Delayed healing may increase infection rates and wound care requirements, while wound patterning may be psychologically and aesthetically consequential for patients. Autologous skin cell suspension (ASCS) can be used to "over spray" a meshed autograft. It was hypothesized that the use of ASCS combined with mSTSG would increase the rate of wound healing and decrease patterning in healed burn wounds. METHODS: Full-thickness burns or excisional wounds (n = 8 each) were created in red Duroc pigs and received 4:1 mSTSGs after wound bed preparation. Half of the wounds received ASCS and half did not at the time of grafting. Percent re-epithelialization, patterning, rete ridge ratio, cellularity, dermal and epidermal thickness, immunofluorescent S100ß staining, and melanin index were assessed for each scar. RESULTS: Wounds that received ASCS exhibited increased rates of re-epithelialization (burn +ACSC versus burn-ASCS; day 3 (53.9 ± 3.1 versus 34.3 ± 3.3, P = 0.009): day 5 (68.1 ± 1.6 versus 40.8 ± 3.2, P < 0.001)). Excision +ASCS versus excision-ASCS; day 7 (98.1 ± 1.2 versus 86.4 ± 2.0, day 7 P = 0.022) compared to wounds not treated with ASCS. There was no difference in rete ridge ratio, cellularity, dermal thickness, epidermal thickness, S100ß staining, melanin index, or patterning was measured between wounds that received ASCS and those that did not. CONCLUSIONS: The addition of ASCS to 4:1 mSTSGs leads to increased rate of wound healing but does not impact the degree of patterning in this model, suggesting that ASCS application likely robustly transfers keratinocytes but not functioning melanocytes at acute timepoints.
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Queimaduras , Cicatriz , Transplante de Pele , Pele , Transplante Autólogo , Cicatrização , Animais , Transplante de Pele/métodos , Queimaduras/terapia , Queimaduras/cirurgia , Queimaduras/patologia , Cicatriz/etiologia , Cicatriz/patologia , Pele/lesões , Pele/citologia , Pele/patologia , Suínos , Reepitelização , FemininoRESUMO
Skin healing is a complex and dynamic physiological process that follows mechanical alteration of the skin barrier. Under normal conditions, this complex process can be divided into at least three continuous and overlapping phases: an inflammatory reaction, a proliferative phase that leads to tissue reconstruction and a phase of tissue remodeling. Macrophages critically contribute to the physiological cascade for tissue repair. In fact, as the inflammatory phase progresses, macrophage gene expression gradually shifts from pro-inflammatory M1-like to pro-resolutive M2-like characteristics, which is critical for entry into the repair phase. A dysregulation in this macrophage' shift phenotype leads to the persistence of the inflammatory phase. Mesenchymal stromal cells and specifically the MSC-derived from adipose tissue (ADSCs) are more and more use to treat inflammatory diseases and several studies have demonstrated that ADSCs promote the wound healing thanks to their neoangiogenic, immunomodulant and regenerative properties. In several studies, ADSCs and macrophages have been injected directly into the wound bed, but the delivery of exogenous cells directly to the wound raise the problem of cell engraftment and preservation of pro-resolutive phenotype and viability of the cells. Complementary approaches have therefore been explored, such as the use of biomaterials enriched with therapeutic cell to improve cell survival and function. This review will present a background of the current scaffold models, using adipose derived stromal-cells and macrophage as therapeutic cells for wound healing, through a discussion on the potential impact for future applications in skin regeneration. According to the PRISMA statement, we resumed data from investigations reporting the use ADSCs and bioscaffolds and data from macrophages behavior with functional biomaterials in wound healing models. In the era of tissue engineering, functional biomaterials, that can maintain cell delivery and cellular viability, have had a profound impact on the development of dressings for the treatment of chronic wounds. Promising results have been showed in pre-clinical reports using ADSCs- and macrophages-based scaffolds to accelerate and to improve the quality of the cutaneous healing.
Assuntos
Tecido Adiposo , Macrófagos , Alicerces Teciduais , Cicatrização , Macrófagos/fisiologia , Humanos , Tecido Adiposo/citologia , Pele/lesões , Células-Tronco Mesenquimais/fisiologia , Células-Tronco Mesenquimais/citologia , Animais , Células EstromaisRESUMO
INTRODUCTION: Skin tear (ST) will prolong the hospitalisation time of an older person, increase the cost of medical expenses and the difficulty in care for nursing staff, and seriously affect the quality of life of the older person. Early identification and intervention of the elderly at risk of ST are key factors in preventing the occurrence of ST in older persons. At present, risk factors for ST in older persons have not been systematically evaluated, let alone summarised to analyse risk factors for ST in older persons. Therefore, this systematic review and meta-analysis aims to synthesise existing research on risk factors for ST in older populations. METHODS AND ANALYSIS: The protocol is being reported by the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols statement. On 17 September 2023, we will start literature search in PubMed, Embase, Web of Science, Cochrane Library, Cumulative Index to Nursing and Allied Health Literature, Medline, Chinese Scientific Journal Database, Wan Fang Data Knowledge Service Platform, China National Knowledge Infrastructure, and Chinese Biomedical Literature Database. The language of the included literature is Chinese or English. Using RevMan V.5.4 software, we will perform a systematic review and meta-analysis of the final set of included studies to synthesise the data and draw meaningful conclusions. The Newcastle-Ottawa Quality Assessment Scale and the Agency for Healthcare Research and Quality will be used to assess the quality of the literature. The I2 test will be used to test heterogeneity. ETHICS AND DISSEMINATION: Ethical approval is not needed for this systematic review, as the study will not directly use information from human participants, and the data we use will be extracted from original studies. This systematic review and meta-analysis has been registered at the International Prospective Register of Systematic Reviews (PROSPERO). Once the systematic review and meta-analysis have been completed, we will publish our study in an academic journal. PROSPERO REGISTRATION NUMBER: CRD42023460810.
Assuntos
Lacerações , Pele , Idoso , Humanos , Lacerações/epidemiologia , Metanálise como Assunto , Qualidade de Vida , Projetos de Pesquisa , Fatores de Risco , Pele/lesões , Revisões Sistemáticas como AssuntoRESUMO
Chronic non-healing wounds are characterized by persistent inflammation, excessive matrix-degrading proteolytic activity and compromised extracellular matrix (ECM) synthesis. Previous studies showed that S100A8/A9 are strongly dysregulated in delayed wound healing and impair the proper function of immune cells. Here, we demonstrate an unrecognized pathological function of S100A9 overexpression in wounds with impaired healing that directly affects ECM functions in fibroblasts. S100A9 was analyzed in two different mouse models mimicking the features of the two most prominent types of non-healing wounds in humans. Db/db mice were used as a model for diabetes-associated impaired wound healing. Iron-overloaded mice were used to mimic the conditions of impaired wound healing in chronic venous leg ulcers. The skin wounds of both mouse models are characterized by delayed wound closure, high and sustained expression of pro-inflammatory mediators and a substantially decreased ECM deposition, all together the hallmarks of non-healing wounds in humans. The wounds of both mouse models also present a solid and prolonged expression of S100A8 and S100A9 that coincides with a compromised ECM deposition and that was confirmed in chronic wounds in humans. Mechanistically, we reveal that S100A9 directly affects ECM deposition by shifting the balance of expression of ECM proteins and ECM degrading enzymes in fibroblasts via toll-like-receptor 4-dependent signaling. Consequently, blocking S100A9 during delayed wound healing in db/db mice restores fibroblast ECM functions eliciting increased matrix deposition. Our data indicate that the dysregulation of S100A9 directly contributes to a compromised ECM deposition in chronic wounds and further suggests S100A9 as a promising therapeutic target to improve tissue repair in chronic wounds.
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Calgranulina B , Matriz Extracelular , Fibroblastos , Cicatrização , Animais , Humanos , Camundongos , Calgranulina A/metabolismo , Calgranulina A/genética , Calgranulina B/metabolismo , Calgranulina B/genética , Doença Crônica , Modelos Animais de Doenças , Matriz Extracelular/metabolismo , Fibroblastos/metabolismo , Camundongos Endogâmicos C57BL , Pele/metabolismo , Pele/patologia , Pele/lesões , Receptor 4 Toll-Like/metabolismoRESUMO
The majority of natural fungal ß-glucans exhibit diverse biological functionalities, such as immunomodulation and anti-inflammatory effects, attributed to their distinctive helix or highly branched conformation This study utilized ß-glucan with helix conformation and high-viscosity extracted from Hericium erinaceus, employing freeze-thaw and solvent exchange strategies to induce multiple hydrogen bonding between molecules, thereby initiating the self-assembly process of ß-glucan from random coil to stable helix conformation without chemical modifications. Subsequently, the natural bioactive compound tannic acid was introduced through physical entanglement, imparting exceptional antioxidant properties to the hydrogel. The HEBG/TA hydrogel exhibited injectable properties, appropriate mechanical characteristics, degradability, temperature-responsive tannic acid release, antioxidant activity, and hemostatic potential. In vivo experiments using skin full-thickness defect and deep second-degree burn wound models demonstrated significant therapeutic efficacy, including neovascularization, and tissue regeneration. Moreover, the HEBG/TA hydrogel demonstrated its ability to regulate cytokines by effectively inhibiting the production of inflammatory mediators (TNF-α, IL-6), while simultaneously enhancing the expression of cell proliferation factor KI-67 and markers associated with angiogenesis such as CD31 and α-SMA. This study highlights the potential of combining natural ß-glucan with bioactive molecules for skin repair.
Assuntos
Hericium , Hidrogéis , Ligação de Hidrogênio , Taninos , Cicatrização , beta-Glucanas , Hidrogéis/química , Hidrogéis/farmacologia , Cicatrização/efeitos dos fármacos , beta-Glucanas/química , beta-Glucanas/farmacologia , Animais , Taninos/química , Taninos/farmacologia , Hericium/química , Camundongos , Antioxidantes/farmacologia , Antioxidantes/química , Pele/efeitos dos fármacos , Pele/metabolismo , Pele/lesões , Queimaduras/tratamento farmacológico , Masculino , Reagentes de Ligações Cruzadas/química , PolifenóisRESUMO
BACKGROUND: The epidermal barrier acts as a defense against external agents as well as helps to maintain body homeostasis. Polynucleotides (PN), exogenous DNA fragments, promote wound repair through their stimulatory and anti-inflammatory effects. Recent findings indicate a synergistic effect of PN and hyaluronic acid (HA) combinations in regulating inflammation and promoting cell proliferation. This study aims to elucidate the effects of PN and HA on repairing the epidermal barrier following its disruption by tape stripping (TS) in a mouse model. MATERIALS AND METHODS: After disrupting the epidermal barrier using TS, a formulation containing PN (14 mg/mL) and HA (6 mg/mL) was applied. Trans-epidermal water loss (TEWL) was measured at 0, 3, 6, 24, 48, and 72 h. Mice were euthanized after the final application at 72 h, and tissue samples were analyzed for epidermal/dermal thickness, neutrophil infiltration, and filaggrin expression. RESULTS: We observed a significant reduction in TEWL in the PN+HA group compared to that in the control group (20.8 ± 0.5 vs. 43.7 ± 0.5 g/m2h at 72 h, p < 0.05), indicating an improvement in barrier function. Histological evaluation showed decreased epidermal and dermal thickening in the PN+HA group compared to that in the control group (epidermal: 29.4 ± 2.2 vs. 57.9 ± 3.5 µm; dermal: 464.8 ± 25.9 vs. 825.9 ± 44.8 µm, both p < 0.05). Additionally, neutrophil infiltration in the dermis was significantly reduced, and filaggrin protein levels were significantly higher in the PN+HA group compared to those in the control group (4.8 ± 0.4 vs. 21.1 ± 3.3 for neutrophils; 0.84 ± 0.04 vs. 0.42 ± 0.03 for filaggrin, both p < 0.05). CONCLUSION: These results suggest that PN+HA may be an effective therapeutic strategy for repairing skin barrier damage.
Assuntos
Epiderme , Ácido Hialurônico , Polinucleotídeos , Cicatrização , Ácido Hialurônico/farmacologia , Animais , Camundongos , Polinucleotídeos/farmacologia , Cicatrização/efeitos dos fármacos , Epiderme/efeitos dos fármacos , Epiderme/patologia , Hidrogéis/farmacologia , Proteínas Filagrinas , Proteínas de Filamentos Intermediários/metabolismo , Perda Insensível de Água/efeitos dos fármacos , Masculino , Pele/efeitos dos fármacos , Pele/lesões , Pele/patologia , Modelos Animais de DoençasRESUMO
BACKGROUND: The poor prognosis and clinical presentation of malignant fungating wounds (MFWs) can lead to service users experiencing various dimensions of fear. AIM: This article encourages district nurses (DNs) to explore the psychological factors associated with MFWs in the community setting. METHOD: The reviewed literature discusses DN practice, with supplementary sources utilised to provide a wider perspective on the multifaceted nature of the subject. FINDINGS: Guidelines advocate that DNs should promptly initiate dialogue to address fears, establish trust and enable service users with MFWs to express concerns, thus facilitating a holistic provision of care. It is crucial to leverage the multidisciplinary team and engage with other agencies to provide support for service users. Effective leadership qualities play a vital role in initiating practice changes that ultimately benefit service users, while also considering clinical governance aspects.