Showing papers on "Chronic wound published in 2017"
TL;DR: Wound healing physiology is reviewed and current approaches for treating a wound are discussed, showing how the healing of a superficial wound requires many factors to work in concert, and wound dressings and treatments have evolved considerably.
Abstract: Wound healing is a complex, highly regulated process that is critical in maintaining the barrier function of skin. With numerous disease processes, the cascade of events involved in wound healing can be affected, resulting in chronic, non-healing wounds that subject the patient to significant discomfort and distress while draining the medical system of an enormous amount of resources. The healing of a superficial wound requires many factors to work in concert, and wound dressings and treatments have evolved considerably to address possible barriers to wound healing, ranging from infection to hypoxia. Even optimally, wound tissue never reaches its pre-injured strength and multiple aberrant healing states can result in chronic non-healing wounds. This article will review wound healing physiology and discuss current approaches for treating a wound.
1,112 citations
TL;DR: A review of macrophage phenotype on the repair process and how alterations in the phenotypes might alter wound closure and the final repair quality can be found in this article, where it is also shown that dysregulated inflammation and altered macophage phenotypes are responsible for hindering closure of chronic wounds.
Abstract: Macrophages and inflammation play a beneficial role during wound repair with macrophages regulating a wide range of processes, such as removal of dead cells, debris and pathogens, through to extracellular matrix deposition re-vascularisation and wound re-epithelialisation. To perform this range of functions, these cells develop distinct phenotypes over the course of wound healing. They can present with a pro-inflammatory M1 phenotype, more often found in the early stages of repair, through to anti-inflammatory M2 phenotypes that are pro-repair in the latter stages of wound healing. There is a continuum of phenotypes between these ranges with some cells sharing phenotypes of both M1 and M2 macrophages. One of the less pleasant consequences of quick closure, namely the replacement with scar tissue, is also regulated by macrophages, through their promotion of fibroblast proliferation, myofibroblast differentiation and collagen deposition. Alterations in macrophage number and phenotype disrupt this process and can dictate the level of scar formation. It is also clear that dysregulated inflammation and altered macrophage phenotypes are responsible for hindering closure of chronic wounds. The review will discuss our current knowledge of macrophage phenotype on the repair process and how alterations in the phenotypes might alter wound closure and the final repair quality.
454 citations
TL;DR: The results of the meta-analysis support the clinical assumptions that biofilms are ubiquitous in human chronic non-healing wounds.
Abstract: The presence of biofilms in chronic non-healing wounds, has been identified through in vitro model and in vivo animal data. However, human chronic wound studies are under-represented and generally report low sample sizes. For this reason we sought to ascertain the prevalence of biofilms in human chronic wounds by undertaking a systematic review and meta-analysis. Our initial search identified 554 studies from the literature databases (Cochrane Library, Embase, Medline). After removal of duplicates, and those not meeting the requirements of inclusion, nine studies involving 185 chronic wounds met the inclusion criteria. Prevalence of biofilms in chronic wounds was 78.2 % (confidence interval [CI 61.6-89, p<0.002]). The results of our meta-analysis support our clinical assumptions that biofilms are ubiquitous in human chronic non-healing wounds.
343 citations
TL;DR: The cellular and molecular mechanisms that regulate wound healing in mouse tail epidermis are shown and, following wounding, progenitors divide more rapidly, but conserve their homoeostatic mode of division, leading to their rapid depletion, whereas SCs become active, giving rise to new progenitor that expand and repair the wound.
Abstract: Wound healing is essential to repair the skin after injury. In the epidermis, distinct stem cells (SCs) populations contribute to wound healing. However, how SCs balance proliferation, differentiation and migration to repair a wound remains poorly understood. Here, we show the cellular and molecular mechanisms that regulate wound healing in mouse tail epidermis. Using a combination of proliferation kinetics experiments and molecular profiling, we identify the gene signatures associated with proliferation, differentiation and migration in different regions surrounding the wound. Functional experiments show that SC proliferation, migration and differentiation can be uncoupled during wound healing. Lineage tracing and quantitative clonal analysis reveal that, following wounding, progenitors divide more rapidly, but conserve their homoeostatic mode of division, leading to their rapid depletion, whereas SCs become active, giving rise to new progenitors that expand and repair the wound. These results have important implications for tissue regeneration, acute and chronic wound disorders.
251 citations
TL;DR: The roles of growth factors in wound healing, their clinical applications for the treatment of chronic wounds, and advances in growth factor-loaded DDSs for enhanced wound healing are described, focusing on micro- and nano-particulate systems, scaffolds, hydrogels, and other miscellaneous systems.
Abstract: Growth factors are endogenous signaling molecules that regulate cellular responses required for wound healing processes such as migration, proliferation, and differentiation. However, exogenous application of growth factors has limited effectiveness in clinical settings due to their low in vivo stability, restricted absorption through skin around wound lesions, elimination by exudation prior to reaching the wound area, and other unwanted side effects. Sophisticated systems to control the spatio-temporal delivery of growth factors are required for the effective and safe use of growth factors as regenerative treatments in clinical practice, such as biomaterial-based drug delivery systems (DDSs). The current review describes the roles of growth factors in wound healing, their clinical applications for the treatment of chronic wounds, and advances in growth factor-loaded DDSs for enhanced wound healing, focusing on micro- and nano-particulate systems, scaffolds, hydrogels, and other miscellaneous systems.
232 citations
TL;DR: Evidence is provided that the dynamic wound microbiome is indicative of clinical outcomes and may be a valuable guide for personalized management and treatment of chronic wounds.
177 citations
TL;DR: The in vitro viability assay demonstrated that the membranes containing rhEGF and AV improved fibroblast proliferation, revealing the beneficial effect of the combination and demonstrated the potential of PLGA nanofibers containing rh EGF andAV for the treatment of chronic wounds.
134 citations
TL;DR: Wound healing dressings remarkably accelerated through enhancing re-epithelialization and granulation formation and effectively improved the organization of regenerated tissues including epidermal-dermal junction, which could be ascribed to the pro-angiogenesis, immunomodulation, and enhanced collagen synthesis provided by the sustained release of NO.
104 citations
TL;DR: The functions and skewed regulation of different MMPs during infection and chronic tissue repair are discussed and the potential of M MPs and their inhibitors as therapeutic agents in treating chronic wounds during distinct phases of the wound healing is pointed out.
101 citations
TL;DR: Although it is clear that the ideal clinical application of transgenic epidermis would aim at preventing the development of devastating chronic lesions,manypatients suffer from therapyresistant chronic ulcerations that are highly predisposed to cancer development and need timely closure (Goldberg).
100 citations
TL;DR: An overview of the understanding and use of applied electrical current in various aspects of wound healing and the evolving understanding of biomolecular mechanisms underlying the effects of electrical simulation on wound healing is presented.
Abstract: New developments in accelerating wound healing can have immense beneficial socioeconomic impact. The wound healing process is a highly orchestrated series of mechanisms where a multitude of cells and biological cascades are involved. The skin battery and current of injury mechanisms have become topics of interest for their influence in chronic wounds. Electrostimulation therapy of wounds has shown to be a promising treatment option with no-device-related adverse effects. This review presents an overview of the understanding and use of applied electrical current in various aspects of wound healing. Rapid clinical translation of the evolving understanding of biomolecular mechanisms underlying the effects of electrical simulation on wound healing would positively impact upon enhancing patient's quality of life.
TL;DR: It is shown that the context-dependent nature of the TGFβ signaling pathways on wound healing is the biggest challenge in order to gain a therapeutically applicable comprehensive knowledge of their specific involvement in chronic wounds.
TL;DR: The biological processes involved in wound healing, the miR involved at each stage, and how expression levels are modulated in the chronic wound environment are examined.
Abstract: Wound healing is a highly complex biological process composed of three overlapping phases: inflammation, proliferation, and remodeling. Impairments at any one or more of these stages can lead to compromised healing. MicroRNAs (miRs) are non-coding RNAs that act as post-transcriptional regulators of multiple proteins and associated pathways. Thus, identification of the appropriate miR involved in the different phases of wound healing could reveal an effective third-generation genetic therapy in chronic wound care. Several miRs have been shown to be upregulated or downregulated during the wound healing process. This article examines the biological processes involved in wound healing, the miR involved at each stage, and how expression levels are modulated in the chronic wound environment. Key miRs are highlighted as possible therapeutic targets, either through underexpression or overexpression, and the healing benefits are interrogated. These are prime miR candidates that could be considered as a gene therapy option for patients suffering from chronic wounds. The success of miR as a gene therapy, however, is reliant on the development of an appropriate delivery system that must be designed to overcome both extracellular and intracellular barriers.
TL;DR: The authors focused on the aspect of malignant degeneration in chronic wounds (leg ulcers, pressure sores) as a very rare, aggressive form of Marjolin’s ulcer as well as the principles of its treatment.
Abstract: Marjolin's ulcer is a rare, aggressive skin cancer developing in scar tissue, chronic ulcers and areas affected by inflammations. Its incidence is estimated to range from 1% to 2% of all burn scars. It most frequently takes the form of squamous cell carcinoma which sometimes is diagnosed during examination of lesions developing in scars and hard-to-heal chronic wounds (pressure sores, leg ulcers). Therapeutic management of Marjolin's ulcer requires well-designed treatment plan to ensure optimal medical care and good quality of life for the patient. The high risk of metastases and damage to the structure of vitally important organs determines the need for early diagnosis and prompt surgical intervention with supplementary therapy. The purpose of the study was to examine etiopathogenesis of Marjolin's ulcer and principles of its treatment. The authors focused on the aspect of malignant degeneration in chronic wounds (leg ulcers, pressure sores) as a very rare, aggressive form of Marjolin's ulcer. A review of the available literature on the issue of Marjolin ulcers was conducted using the key words; Marjolin ulcers, pressure sore, chronic wound. Malignant degeneration in chronic wounds is a very rare aggressive form of Marjolin ulcer. Increased oncological alertness should be displayed by nursing and medical personnel taking care of patients with chronic wounds.
TL;DR: The in vivo chronic wound healing model evaluation in diabetic rats revealed that the CW/NPs/HBC-HG dressing promoted wound healing and accelerated reepithelialization, collagen deposition and angiogenesis, and demonstrated that CW/ NPs/ HBC- HG is a promising dressing for chronic wounds.
Abstract: Cutaneous chronic wounds are characterized by impaired wound healing which may lead to infection and even amputation. To surmount this problem, we developed a chitin whisker (CW)/carboxymethyl chitosan nanoparticles (CMCS NPs)/thermosensitive hydroxybutyl chitosan (HBC) composite hydrogel (CW/NPs/HBC-HG) as a wound dressing for treating chronic wounds. Upon introduction of CWs, the composite hydrogel exhibited a significant decrease in gelation temperature and enhanced mechanical properties. The storage modulus (G′) of the CW/NPs/HBC-HG was 3.6 times that of the NPs/HBC-HG at 37 °C and the ex vivo rat skin test also showed that the mechanical properties were significantly improved. Linezolid, a wide-spectrum antibiotic, was dissolved directly in the water phase of the composite hydrogel, and the antibacterial activity of the composite hydrogel against Escherichia coli and Staphylococcus aureus was up to 99% until 7 days. When recombinant human epidermal growth factor (rhEGF) was encapsulated into the NPs, the CW/NPs/HBC-HG offered prolonged cell proliferation activity up to 5 days. More importantly, the in vivo chronic wound healing model evaluation in diabetic rats revealed that the CW/NPs/HBC-HG dressing promoted wound healing and accelerated reepithelialization, collagen deposition and angiogenesis. These findings demonstrated that CW/NPs/HBC-HG is a promising dressing for chronic wounds.
TL;DR: The global burden of disease associated with wounds is an increasingly significant public health concern and the challenge of overcoming current barriers associated with wound care requires innovative management techniques.
Abstract: The global burden of disease associated with wounds is an increasingly significant public health concern. Current treatments are often expensive, time-consuming and limited in their efficacy in chronic wounds. The challenge of overcoming current barriers associated with wound care requires innovative management techniques. Regenerative medicine is an emerging field of research that focuses on the repair, replacement or regeneration of cells, tissues or organs to restore impaired function. This article provides an overview of the pathophysiology of wound healing and reviews the latest evidence on the application of the principal components of regenerative medicine (growth factors, stem cell transplantation, biomaterials and tissue engineering) as therapeutic targets. Improved knowledge and understanding of the pathophysiology of wound healing has pointed to new therapeutic targets. Regenerative medicine has the potential to underpin the design of specific target therapies in acute and chronic wound healing. This personalised approach could eventually reduce the burden of disease associated with wound healing. Further evidence is required in the form of large animal studies and clinical trials to assess long-term efficacy and safety of these new treatments.
TL;DR: A multidisciplinary approach with the involvement of rheumatologists allows investigation for underlying systemic disease and improves clinical outcomes for many of these challenging patients.
Abstract: Objective Chronic wounds are a major cause of morbidity and mortality. Approximately 20% to 23% of nonhealing wounds that are refractory to vascular intervention have other causes, including vasculitis, pyoderma gangrenosum, and other autoimmune diseases. The purpose of this article was to review the literature across medical and surgical specialties with regard to refractory chronic wounds associated with vasculitis and autoimmune diseases and to delineate clinical outcomes of these wounds in response to vascular and other interventions. Methods An electronic search encompassing MEDLINE, PubMed, Cochrane Library, and Scopus was completed using the following search terms: rheumatoid arthritis; systemic sclerosis; systemic lupus erythematosus; antineutrophil cytoplasmic antibody-associated vasculitis; mixed connective tissue disease; antiphospholipid syndrome; pyoderma gangrenosum; thromboangiitis obliterans; cryoglobulinemia; hydroxyurea; sickle cell; atrophie blanche; livedoid vasculitis; cholesterol emboli; calciphylaxis; antiphospholipid antibodies; prothrombotic; combined with the terms: chronic wound and leg ulcer. Full-text articles published in English up to March 1, 2016, that investigated the clinical outcomes of chronic wounds associated with autoimmune diseases were included. Review articles and evaluations of management of chronic wounds were also reviewed. Primary outcomes included in the review were amputation, ulcer healing, reduction in wound size, overall survival, and freedom from reintervention. Owing to the heterogeneity of data reporting among articles, qualitative analysis is also reported. Results Vasculitis and autoimmune diseases play a role in 20% to 23% of patients with chronic lower extremity ulcers. Furthermore, patients with autoimmune disease have a significantly high rate of split thickness skin graft failure (50% compared to 97% in patients without autoimmune disease; P = .0002). The management of leg ulcers associated with autoimmune diseases is discussed. Conclusions Autoimmune and vasculitic causes should be considered in patients with chronic wounds who do not respond to appropriate vascular intervention and standard local wound care. A multidisciplinary approach with the involvement of rheumatologists allows investigation for underlying systemic disease and improves clinical outcomes for many of these challenging patients.
TL;DR: A fluorescent sensing system is demonstrated to monitor the wound status and to distinguish between an autonomously healing and a chronic wound at an early stage and allows monitoring two of the most relevant fluctuating wound parameters during the healing process which are pH and glucose concentration.
TL;DR: The results showed that an insulin-functionalized SF dressing accelerated wound closure, collagen deposition and vascularization, thus, significantly promoting wound healing, and provides new treatment options for chronic wounds.
TL;DR: Pathogenesis of delayed wound healing and fibrosis following radiotherapy is a complex, interdependent process involving cellular depletion, extracellular matrix changes, microvascular damage, and altered pro-inflammatory mediators.
TL;DR: The data presented suggest that opioid exposure is associated with reduced likelihood of healing in patients with chronic wounds, and whether this is a causal relationship will require further study.
Abstract: Opioids are routinely used analgesics in patients with chronic wounds; however the impact of opioid exposure on wound healing is poorly understood. The purpose of this study was to investigate the association between opioid exposure and wound outcome in the WE-HEAL study. This longitudinal observational study was conducted on 450 subjects enrolled in the WE-HEAL biorepository. Data were collected prospectively including baseline characteristics, pain score, longitudinal opioid exposure, and total wound surface area (tWSA). Data were analyzed using static multivariate models, fixed-effects mixed models, and time to event analysis. Using fixed-effects models, opioid dose was significantly associated with tWSA after accounting for the effects of pain score and baseline co-variates (p 0 to <10mg had a similar hazard of not healing as those with no opioid exposure (HR 0.88 [0.65-1.19], p=0.40). In conclusion, opioid analgesics are commonly prescribed to patients with chronic wounds; however, the data presented suggest that opioid exposure is associated with reduced likelihood of healing in patients with chronic wounds. Whether this is a causal relationship will require further study. This article is protected by copyright. All rights reserved.
TL;DR: The out‐of‐pocket cost incurred by individuals who self‐fund has not been the focus of extensive investigation, but there has been renewed interest in evaluating quality of life, in line with the shift to patient enablement and self‐care in chronic disease management.
Abstract: Chronic wounds are associated with financial and personal costs. The system level expense associated with chronic wounds has been established, however, the out-of-pocket cost incurred by individuals who self-fund has not been the focus of extensive investigation. Recently, there has been renewed interest in evaluating quality of life, in line with the shift to patient enablement and self-care in chronic disease management. The objectives of this research were to describe the out-of-pocket wound treatment costs and the quality of life of people who have chronic wounds. A questionnaire incorporating the Cardiff Wound Impact Schedule and purpose-designed instruments was completed by a non-probability, convenience sample of 113 people in Australia and Wales. Data was analysed using descriptive statistics. The sample was on average 63·6 years of age and had wounds that were on an average 109 weeks duration. Participants had spent on average AU$2475 on wound dressing products since the wound started, and AU$121·82 in the most recent 28 days which represented 10% of their disposable income. Health-related quality of life was sub-optimal, 6/10 (ave) according to the Cardiff Wound Impact Schedule. Younger participants reported significantly poorer quality of life on all CWIS sub-scales when compared to older participants. This study found that chronic wounds present a significant financial cost to individuals who must self-fund their wound dressings and other wound treatment related expenses. Participants who had access to wound product subsidisation also experienced personal financial costs. People who have chronic wounds experience sub-optimal quality of life therefore this condition is also costly to the individual's well-being. The quality of life of younger people has not received adequate attention and requires further consideration given the many years that younger people may have to live with this debilitating and often recurrent condition. Continued action is required to reduce the financial and personal costs experienced by people who have chronic wounds. It is imperative that healthcare funding is directed to people who have chronic wounds, in particular to alleviate the out-of-pocket costs experienced by self-funders. Continued attention to the quality of life of people who have chronic wounds is required to minimise the negative effects of this condition and enhance well-being.
TL;DR: This review discusses the different types of currently available commercial skin substitutes for use in chronic wounds as well as the paucity of strong evidence supporting their use, and delves into the limitations of these skin substitutes.
Abstract: Chronic wounds, including diabetic ulcers, pressure ulcers, venous ulcers, and arterial insufficiency ulcers, are both difficult and expensive to treat. Conventional wound care may sometimes lead to suboptimal wound healing and significant morbidity and mortality for patients. The use of skin substitutes provides an alternative therapy showing superior efficacy and, in some cases, similar cost-effectiveness compared to traditional treatments. This review discusses the different types of currently available commercial skin substitutes for use in chronic wounds as well as the paucity of strong evidence supporting their use. It then delves into the limitations of these skin substitutes and examines the most recent research targeting these limitations.
Journal Article•
TL;DR: An overview of literature- and experience- based criteria to help guide chronic wound diagnosis, assessment, treatment, and follow-up is presented and emphasis is placed on criteria to assist accurate diagnosis and dressing/therapy selection.
Abstract: Management of chronic wounds remains challenging in terms of prevalence and complexity. Considerable progress has been made in understanding the science of wound healing during the past decade, sparking volumes of publications and the development of hundreds of dressing and therapy options. There is a need for a simpli ed overview of evidence-based criteria to assist in the accurate diagnosis and appropriate management of chronic wounds in all care settings. An expert panel of 11 wound healing specialists experienced in various care settings convened to discuss best practices and recommended guidelines for managing major chronic wound types. Prior to the meeting, panel members reviewed 8 preselected peer-reviewed articles and 1 white paper containing treatment algorithms for all major chronic wound types. During the meeting, each panelist presented current evidence-based guidelines regarding a specific chronic wound type and case studies to illustrate concepts in the guidelines. This publication is a result of the panel discussion and presents an overview of literature- and experience- based criteria to help guide chronic wound diagnosis, assessment, treatment, and follow-up. A cycle of steps is presented as a framework to guide holistic care for all patients with chronic wounds, including de- hisced surgical wounds, diabetic foot ulcers, venous leg ulcers, arterial insu ciency ulcers, and pressure ulcers/injuries. Emphasis is placed on criteria to assist accurate diagnosis and dressing/therapy selection, holistic elements of patient and wound bed preparation, interventions to achieve patient adherence to a care plan, and follow-up to help prevent wound recurrence.
TL;DR: Multi-unctional hydrogels for chronic wound application produced by enzymatic cross-linking of thiolated chitosan and gallic acid showed high biocompatibility with human skin fibroblasts and reduced the population of the most frequently encountered in nonhealing wounds bacterial strains.
TL;DR: A class of short non-coding RNAs, microRNAs, has been found to be indispensable for all the phases of skin wound healing and plays important role in regulating cellular physiology and pathology.
Abstract: Significance: Wound healing is a basic physiological process that is utilized to keep the integrity of the skin. Impaired wound repair, such as chronic wounds and pathological scars, presents a major health and economic burden worldwide. To date, efficient targeted treatment for these wound disorders is still lacking, which is largely due to our limited understanding of the biological mechanisms underlying these diseases. Research driven around discovering new therapies for these complications is, therefore, an urgent need. Recent Advances: The vast majority of the human genome is transcribed to RNAs that lack protein-coding capacity. Intensive research in the recent decade has revealed that these non-coding RNAs (ncRNAs) function as important regulators of cellular physiology and pathology, which makes them promising therapeutic and diagnostic entities. Critical Issues: A class of short ncRNAs, microRNAs, has been found to be indispensable for all the phases of skin wound healing and plays important role...
TL;DR: Together, this review suggests that the RWM offers a unique fully-synthetic alternative to existing biologic matrices that is effective, widely available, easy to store, simple to apply and low cost.
Abstract: Wound matrix materials are used to improve the regeneration of dermal and epidermal layers in both acute and chronic wounds. Contemporary wound matrices are primarily composed of biologic materials such as processed xenogeneic and allogeneic tissues. Unfortunately, existing biologic wound matrices possess multiple limitations including poor longevity, durability, strength, and enzymatic resistance required for persistent support for new tissue formation. A fully-synthetic, resorbable electrospun material (Restrata Wound Matrix, Acera, St.Louis, Missouri ) that exhibits structural similarities to the native extracellular matrix offers a new approach to the treatment of acute and chronic wounds. This novel matrix is the first product to combine the advantages of synthetic construction (e.g. resistance to enzymatic degradation, excellent biocompatibility, strength/durability and controlled degradation) with the positive attributes of biologic materials (e.g. biomimetic architecture similar to human extracellular matrix (ECM), fibrous architecture optimized to support cellular migration and proliferation, engineered porosity to encourage tissue ingrowth and vascularization). These features allow RWM to achieve rapid and complete healing of full-thickness wounds that, in preclinical studies, is comparable to Integra Bilayer Wound Matrix (Integra LifeSciences, Plainsboro, New Jersey), a gold standard biologic material with diverse clinical indications in the wound care. Together, this review suggests that the RWM offers a unique fully-synthetic alternative to existing biologic matrices that is effective, widely available, easy to store, simple to apply and low cost.
Journal Article•
TL;DR: A chronic wound is a wound that does not heal in an orderly set of stages and in a predictable amount of time or wounds that do not heal within three months are often considered chronic.
Abstract: A chronic wound is a wound that does not heal in an orderly set of stages and in a predictable amount of time or wounds that do not heal within three months are often considered chronic. Chronic wounds often remain in the inflammatory stage for too long and may never heal or may take years. Chronic wound patients often report pain as dominant in their lives. Persistent pain is the main problem for patients with chronic ulcers. Many wounds pose no challenge to the body's innate ability to heal; some wounds, however, may not heal easily either because of the severity of the wounds themselves or because of the poor state of health of the individual. Any wound that does not heal within a few weeks should be examined by a healthcare professional because it might be infected, might reflect an underlying disease.
TL;DR: The higher expression of NLRP3, caspase1, and secretion of IL-1β, signaling, and activation might contribute to the hyperinflammation in the human diabetic wound and in high glucose induced macrophages.
Abstract: Introduction. To investigate the contribution and mechanism of NLRP3 inflammasome expression in human wounds in diabetes mellitus and in high glucose induced macrophages. Methods. In the present study, we compared the expression of NLRP3 inflammasome in debridement wound tissue from diabetic and nondiabetic patients. We also examined whether high glucose induces NLRP3 inflammasome expression in cultures THP-1-derived macrophages and the influence on IL-1 expression. Results. The expressions of NLRP3, caspase1, and IL-1, at both the mRNA and protein level, were significantly higher in wounds of diabetic patients compared with nondiabetic wounds (). High glucose induced a significant increase in NLRP3 inflammasome and IL-1 expression in THP-1-derived macrophages. M1 macrophage surface marker with CCR7 was significantly upregulated after high glucose stimulation. SiRNA-mediated silencing of NLRP3 expression downregulates the expression of IL-1. Conclusion. The higher expression of NLRP3, caspase1, and secretion of IL-1, signaling, and activation might contribute to the hyperinflammation in the human diabetic wound and in high glucose induced macrophages. It may be a novel target to treat the DM patients with chronic wound.
TL;DR: Knockout of the angiotensin subtype 2 receptors abolished the beneficial effects of ang Elliotensin type 1 receptor blockers, suggesting a role for angiotENSin sub type 2 receptors in chronic wound healing.