Advances in wound care最新文献

{"title":"Topical Reconstituted High-Density Lipoproteins Elicit Anti-Inflammatory Effects in Diabetic Wounds.","authors":"Zahra Lotfollahi, Joanne T M Tan, Victoria A Nankivell, Lauren Sandeman, Sanuri Liyanage, Emma L Solly, Liam Stretton, Anna E Williamson, Joseph Dawson, Stephen J Nicholls, Peter J Psaltis, Robert Fitridge, Christina A Bursill","doi":"10.1089/wound.2023.0162","DOIUrl":"https://doi.org/10.1089/wound.2023.0162","url":null,"abstract":"<p><p><b>Objective:</b> Reconstituted high-density lipoproteins (rHDL) improve wound healing in diabetes. We aimed to determine if rHDL elicit anti-inflammatory effects in diabetic wounds, as a mechanism to explain their wound healing benefits. <b>Approach:</b> Diabetes was induced using streptozotocin in C57Bl6/J mice. Two full-thickness wounds were placed on the subflanks of diabetic and nondiabetic (ND) mice. Phosphate-buffered saline (PBS) or rHDL (50 µg/wound/day) were applied topically. Wound closure was assessed daily. Inflammatory gene transcripts were measured by qPCR and proteins by Western blotting and enzyme-linked immunosorbent assay in wounds collected at baseline, 24 h, and 3 days postwounding. Wound macrophages were assessed by flow cytometry 7 days postwounding. The fate of fluorescent 3,3-dioctadecyloxacarbocyanine, perchlorate (DiO)-labeled rHDL was tracked by flow cytometry, fluorescent imaging, and microscopy. <b>Results:</b> In diabetic mice, rHDL increased wound closure rates at days 6 (+288%, p < 0.01) and 7 (+639%, p < 0.0001) postwounding, compared with PBS controls. After 3 days, rHDL-treated diabetic wounds had lower <i>Rela</i> (-65%) and C-C motif chemokine ligand 2 (<i>Ccl2</i>) (-59%) mRNA levels and CCL2 protein (29%) than PBS controls, p < 0.05 for all. Wound macrophage content was higher in diabetic than ND wounds, but rHDL did not change macrophage content or polarity. DiO-rHDL were taken up by key wound cells including fibroblasts, macrophages, keratinocytes and endothelial cells, and retained in wounds for at least 48 h. <b>Innovation:</b> rHDL exerts anti-inflammatory effects in diabetic wounds early postwounding, which may contribute to its wound healing properties. <b>Conclusion:</b> The anti-inflammatory properties of rHDL in diabetic wounds present topical rHDL as a novel treatment option for improving healing in patients with diabetic foot ulcers.</p>","PeriodicalId":7413,"journal":{"name":"Advances in wound care","volume":" ","pages":""},"PeriodicalIF":5.8,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142589774","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prediction of Healing Trajectory of Chronic Wounds Using a Machine Learning Approach.","authors":"Anissa C Dallmann, Mary Sheridan, Soeren Mattke, William Ennis","doi":"10.1089/wound.2024.0095","DOIUrl":"10.1089/wound.2024.0095","url":null,"abstract":"<p><p><b>Objective:</b> New treatment options are emerging for chronic wounds, which represent a growing problem because of population ageing and increasing burden of chronic disease. While promising, the existing evidence for advanced modalities is commonly derived from small and/or poorly controlled studies and clear criteria for selecting patients, who are likely to benefit from these expensive options are lacking. In this study, we develop and validate a machine learning model to predict if a chronic wound, independent of etiology, is expected to heal within 12 weeks to identify cases in potential need of advanced treatment options. <b>Approach:</b> Retrospective analysis of electronic health record data from 2014 to 2018 covering 532 wound care clinics in the United States and 261,398 patients with 620,356 unique wounds. Prediction of 12-week healing trajectories with a machine learning model. <b>Results:</b> The best-performing model in a training dataset of a randomly drawn 75% subset of wounds contained variables for patient demographics, comorbidities, wound characteristics at initial presentation, and changes in wound dimensions over time, with the latter group being the most influential predictors. The final machine learning model had a high predictive accuracy with area under the receiver operating characteristic curves of 0.9 and 0.92 after 4 and 5 weeks of treatment, respectively. <b>Innovation:</b> A machine learning model can identify chronic wounds at risk of not healing by week 12 with high accuracy in the early weeks of treatment. <b>Conclusions</b>: If embedded in real-world care, the generated information could be able to guide effective and efficient treatment decisions.</p>","PeriodicalId":7413,"journal":{"name":"Advances in wound care","volume":" ","pages":""},"PeriodicalIF":5.8,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142589765","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nitrous Oxide to Reduce Wound Care-Related Pain in Adults: A Systematic Review and Meta-Analysis.","authors":"Ziyang Wang, Fei Wang, Xiaochen Jiang, Weifeng Wang, Yihui Xing, Xueling Qiu, Chenxi Sun, Lu Tang","doi":"10.1089/wound.2023.0211","DOIUrl":"10.1089/wound.2023.0211","url":null,"abstract":"<p><p><b>Significance:</b> As an essential procedure, wound care comes with acute pain, which is short but high in intensity, causing patients to fear and affecting subsequent treatment. Nitrous oxide (N₂O) is used to relieve pain related to wound care; however, evidence regarding its application is conflicting. Thus, this systematic review and meta-analysis was performed to evaluate the efficacy of N₂O in wound care-related pain. <b>Recent Advances:</b> Randomized controlled trials that investigated the effect of N₂O in adults undergoing wound care were systematically searched from PubMed, Embase, the Cochrane Library, Web of Science, Scopus, and ClinicalTrials.gov up to February 2023. The primary outcome was the pain score. Secondary outcomes included patients' satisfaction and side effects. <b>Critical Issues:</b> Through screening the 265 identified articles, seven and six studies were finally included in the systematic review and meta-analysis, respectively. Pooled analysis suggested that there was no significant difference in reducing wound care-related pain between the N₂O group and the control group (mean difference [MD], -0.02, 95% confidence interval [CI], -1.46, 1.42; <i>p</i> = 0.98, <i>I</i>² = 96%). Subgroup analyses indicated that there was a significant difference in favor of N₂O for burns, not for ulcers, and N₂O was superior to oxygen and similar to topical or intravenous anesthesia. There was no significant difference in patients' satisfaction or the incidence of side effects between groups. <b>Future Directions:</b> This review suggests that N₂O might be effective for pain management in patients undergoing wound care. Caution must be taken when interpreting these results due to the high risk of biased methods in the included studies.</p>","PeriodicalId":7413,"journal":{"name":"Advances in wound care","volume":" ","pages":"542-552"},"PeriodicalIF":5.8,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140179051","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Standardized Reporting of Research on Exosomes to Ensure Rigor and Reproducibility.","authors":"Anita Yadav, Yi Xuan, Chandan K Sen, Subhadip Ghatak","doi":"10.1089/wound.2024.0093","DOIUrl":"10.1089/wound.2024.0093","url":null,"abstract":"<p><p><b>Significance:</b> The study of extracellular vesicles (EVs), especially exosomes, has unlocked new avenues in understanding cellular communication and potential therapeutic applications. <b>Recent Advances:</b> Advancements in EV research have shown significant contributions from the International Society for Extracellular Vesicles (ISEV), in establishing methodological standards. The evolution of the Minimal Information for Studies of Extracellular Vesicles (MISEV) guidelines from 2014 to 2023 reflects enhanced research rigor and reproducibility. The launch of EV-TRACK platform promotes uniformity and reproducibility by providing a centralized repository for data sharing and standardization practices. Furthermore, databases like EVpedia and ExoCarta have facilitated data sharing and collaboration within the scientific community. Concurrently, exosome-based therapies have emerged as a forefront area within regenerative medicine and targeted drug delivery, showcasing the potential of exosomes in promoting tissue regeneration. <b>Critical Issues:</b> Despite advancements, the field grapples with challenges such as vesicular heterogeneity, EV isolation complexity, and standardization. These issues impact research reproducibility and clinical applications. The inconsistency in exosomal preparations in clinical trials poses significant challenges to therapeutic efficacy and safety. <b>Future Directions:</b> The review outlines critical areas for future research, including the need for technological innovation in EV isolation and characterization, the establishment of standardized protocols, and a deeper understanding of exosome biology. The review also highlights the need to reassess guidelines, develop new EV isolation and characterization technologies, and establish standardized protocols to overcome current limitations. Emphasis is placed on interdisciplinary research and collaboration to address the complexities of EV biology, improve clinical trial design, and ultimately realize exosome's therapeutic and diagnostic potential. Continued evaluation and rigorous scientific validation are essential for successful exosome integration.</p>","PeriodicalId":7413,"journal":{"name":"Advances in wound care","volume":" ","pages":"584-599"},"PeriodicalIF":5.6,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12344122/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141417210","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A First-in-Human Randomized Clinical Study Investigating the Safety and Tolerability of Stabilized Hypochlorous Acid in Patients with Chronic Leg Ulcers.","authors":"Magnus Mustafa Fazli, Klaus Kirketerp-Møller, David Peick Sonne, Torben Balchen, Glenn Gundersen, Elin Jørgensen, Thomas Bjarnsholt","doi":"10.1089/wound.2024.0040","DOIUrl":"10.1089/wound.2024.0040","url":null,"abstract":"<p><p><b>Objective:</b> Biofilm infections in chronic wounds are common and pose a significant clinical challenge. This challenge was addressed by developing the SoftOx Biofilm Eradicator (SBE) composed of hypochlorous acid (HOCl) and acetic acid with strong broad-spectrum antimicrobial activity. <b>Approach:</b> First-in-human study investigating the safety and tolerability as primary endpoints and wound size effect and antimicrobial efficacy as secondary endpoints of SBE treatment in chronic leg wound patients. The study was divided into two as follows: a randomized, double-blinded, Single Ascending Dose (SAD) phase (<i>n</i> = 16 SBE; <i>n</i> = 4 placebo), where patients were treated with SBE or saline (placebo) only once, followed by an open-label, Multiple Ascending Dose (MAD) phase (<i>n</i> = 8), where patients were treated with SBE once daily or twice daily over five days. Reporting is according to CONSORT guidelines. <b>Results:</b> SBE was safe and well-tolerated in chronic leg wound patients. There were no significant differences in pain during and after treatment with SBE or the placebo. The SBE treatment reduced bioburden in wounds compared to baseline, with 98% and 49% median reduction after SBE or placebo treatment, respectively. A dose-dependent trend in absolute wound size reduction was observed in the MAD groups with a median (min, max) change of -2.99 (-14.25, -1.5) cm² in the once-daily and -10.48 (-17.95, -0.38) cm² in the twice-daily group, respectively. <b>Innovation and Conclusion:</b> This study demonstrated the safe use of HOCl-based SBE in chronic leg wounds with promising trends of immediate antimicrobial action and beneficial effect on wound healing.</p>","PeriodicalId":7413,"journal":{"name":"Advances in wound care","volume":" ","pages":"529-541"},"PeriodicalIF":5.8,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141080307","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association of Tryptophan/Kynurenine Metabolites with Healing in Chronic Venous Leg Ulcers.","authors":"Junglyun Kim, Joyce Stechmiller, Michael T Weaver, Debra Lyon, Timothy J Garrett, Fan Yi, Jungmin C Park, Magali R De Carvalho, Debra Lynch Kelly","doi":"10.1089/wound.2023.0137","DOIUrl":"10.1089/wound.2023.0137","url":null,"abstract":"<p><p><b>Objective:</b> Chronic wound healing is a complex process that is still not well understood. The tryptophan (TRP)-l-kynurenine (KYN) pathway has recently been under increased scrutiny with regard to wound healing. The study applied metabolomics to elucidate the TRP-l-KYN pathway associated with wound healing in chronic venous leg ulcers (CVLUs). <b>Approach:</b> This study used a longitudinal comparative design of 60 serum samples collected from 30 older adult patients with CVLUs, receiving weekly sharp debridement at a wound clinic. The serum samples were collected at baseline and week 4 (healed wounds) or week 8 (nonhealed wounds). Liquid chromatography-mass spectrometry (LC-MS) metabolomics was used to analyze targeted metabolites. A Bayesian approach was used to examine robust correlations between changes in metabolite values and linear healing slope and to compare by group. <b>Results:</b> The mean age was 71.13 (±9.46 years). Half of the sample were female and the minority (17%) were Black. The mean values of evaluated metabolites for the nonhealed group were consistently lower than those for the healed group. The healed group (<i>n</i> = 12) had higher KYN values. Those on a healing trajectory (<i>n</i> = 23) had lower KYN levels and higher TRP levels at baseline and over time. There was moderate support (Bayes factor = 3.70) for a negative association between change in kynurenic acid and linear healing slope (<i>r</i> = -0.35, credibility intervals [CrI] = -0.62, -0.04; probability of direction [PD] = 98%). Results suggest that KYN and TRP may be markers for healing in individuals with CVLUs. <b>Innovation and Conclusion:</b> Gaining a better understanding of the associations between the TRP-l-KYN pathway and the healing of CVLUs may help to clarify the links of inflammation with the rate and success of wound healing. Biomarker development focused on the TRP-l-KYN pathway could be pursued, if the associations are further supported by focused research studies.</p>","PeriodicalId":7413,"journal":{"name":"Advances in wound care","volume":" ","pages":"494-507"},"PeriodicalIF":5.8,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140179049","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Standardized Wound Care: Patchwork Practices?","authors":"Chandan K Sen","doi":"10.1089/wound.2024.0130","DOIUrl":"10.1089/wound.2024.0130","url":null,"abstract":"<p><p>Standardized care is crucial in health care for ensuring consistent, safe, high-quality, efficient, and evidence-based practices. Care pathways that standardize procedures promote adherence to best practices, reduce variability in treatment, and encourage collaboration among health care teams. This approach ultimately improves patient outcomes, enhances safety, and boosts the overall effectiveness of health care services. However, despite these benefits being widespread across most of the U.S. health care system, wound care stands out as an area where standards can vary significantly. The inconsistency in wound care standards in the United States can be traced to several factors. These include limited structured clinical wound care education, the discretion of health care providers in different business environments, differences in wound care settings, varying access to advanced treatments and technology, patient demographics and socioeconomic status, as well as differences in state laws and regional or institutional practices. Addressing these disparities requires a comprehensive approach that considers the complex interplay of the abovementioned factors. Active measures are needed to improve access, equity, and the quality of wound care services for all patients, regardless of where they live, their socioeconomic status, their health care coverage, or the business interests of providers and their institutions as well as of vendors marketing wound care products inconsistent with evidence-based practice. By understanding and actively addressing these factors, we can work toward achieving more standardized, evidence-based, and patient-centered practices in wound care across the nation.</p>","PeriodicalId":7413,"journal":{"name":"Advances in wound care","volume":" ","pages":"485-493"},"PeriodicalIF":5.8,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141465474","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Associations Among Wound-Related Factors Including Biofilm, Wound-Related Symptoms and Systemic Inflammation in Older Adults with Chronic Venous Leg Ulcers.","authors":"Junglyun Kim, Joyce Stechmiller, Michael Weaver, Garth James, Philip S Stewart, Debra Lyon","doi":"10.1089/wound.2023.0028","DOIUrl":"10.1089/wound.2023.0028","url":null,"abstract":"<p><p><b>Objective:</b> The purposes of this observational prospective study were to (1) characterize the wound-related factors (wound area, the presence of biofilm, and total bacteria), wound-related symptoms (fatigue, pain, exudate, itching, and edema or swelling), and systemic inflammation (level of serum C-reactive protein [CRP]), and (2) explore associations between wound-related factors, wound-related symptoms, and systemic inflammation in older individuals with chronic venous leg ulcers (CVLUs) over 8 weeks of wound treatment. <b>Approach:</b> A total of 117 participants who received standardized care (weekly sharp debridement) for chronic venous ulcer were enrolled. We collected clinical data every 2 weeks during the 8 weeks of the study period or until the wound was healed (if healed before 8 weeks). Associations among variables were estimated using a Bayesian approach applied to general linear mixed models. <b>Results:</b> Based on Bayes factor (BF) value, there was extremely strong evidence for the association of biofilm with mean total bacteria (BF >1,000). There was moderate evidence of a direct association between biofilm presence and levels of CRP (BF 4.3) and moderate evidence of direct associations between biofilm and wound-related symptoms, pain and exudate (BF 5.12, 8.49, respectively). <b>Innovation:</b> Wound-related symptoms and the level of systemic CRP were associated with biofilm among patients who were receiving weekly sharp debridement. Symptom severity associated with CVLUs requires assessment and management of wound-related factors and levels of inflammation in addition to symptom assessment. <b>Conclusion:</b> This study is the first to examine associations among biofilm, as wound-related factors, systemic inflammation, wound-related symptoms, and wound healing in clinical settings. Symptom severity, level of systemic CRP, and wound-related factors should be considered as well as assessment of biofilm in CVLU in older individuals with CVLU.</p>","PeriodicalId":7413,"journal":{"name":"Advances in wound care","volume":" ","pages":"518-527"},"PeriodicalIF":5.8,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11535467/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139110655","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Wound pH-Modulating Strategies for Diabetic Wound Healing.","authors":"Léo-Paul Tricou, Marie-Lynn Al-Hawat, Katia Cherifi, Gabriela Manrique, Benjamin R Freedman, Simon Matoori","doi":"10.1089/wound.2023.0129","DOIUrl":"10.1089/wound.2023.0129","url":null,"abstract":"<p><p><b>Significance:</b> Chronic diabetic wounds on the lower extremities (diabetic foot ulcers, DFU) are one of the most prevalent and life-threatening complications of diabetes, responsible for significant loss of quality of life and cost to the health care system. Available pharmacologic treatments fail to achieve complete healing in many patients. Recent studies and investigational treatments have highlighted the potential of modulating wound pH in DFU. <b>Recent Advances:</b> Data from <i>in vitro</i>, preclinical, and clinical studies highlight the role of pH in the pathophysiology of DFU, and topical administration of pH-lowering agents have shown promise as a therapeutic strategy for diabetic wounds. In this critical review, we describe the role of pH in DFU pathophysiology and present selected low-molecular-weight and hydrogel-based pH-modulating systems for wound healing and infection control in diabetic wounds. <b>Critical Issues:</b> The molecular mechanisms leading to pH alterations in diabetic wounds are complex and may differ between <i>in vitro</i> models, animal models of diabetes, and the human pathophysiology. Wound pH-lowering bandages for DFU therapy must be tested in established animal models of diabetic wound healing and patients with diabetes to establish a comprehensive benefit-risk profile. <b>Future Directions:</b> As our understanding of the role of pH in the pathophysiology of diabetic wounds is deepening, new treatments for this therapeutic target are being developed and will be tested in preclinical and clinical studies. These therapeutic systems will establish a target product profile for pH-lowering treatments such as an optimal pH profile for each wound healing stage. Thus, controlling wound bed pH could become a powerful tool to accelerate chronic diabetic wound healing.</p>","PeriodicalId":7413,"journal":{"name":"Advances in wound care","volume":" ","pages":"446-462"},"PeriodicalIF":5.6,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11535470/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139039365","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Use of Therapeutic RNAs to Accelerate Wound Healing in Diabetic Rabbit Wounds.","authors":"Brandon J Sumpio, Anne Dallas, Adam G Berger, Zhuqing Li, Enya Wang, Ikram Mezghani, Mauricio Contreras, Georgios Theocharidis, Heini Ilves, Paula T Hammond, Brian H Johnston, Aristidis Veves","doi":"10.1089/wound.2023.0056","DOIUrl":"10.1089/wound.2023.0056","url":null,"abstract":"<p><p><b>Introduction:</b> Diabetes mellitus (DM) affects over 422 million people globally. Patients with DM are subject to a myriad of complications, of which diabetic foot ulcers (DFUs) are the most common with ∼25% chance of developing these wounds throughout their lifetime. <b>Innovation:</b> Currently there are no therapeutic RNAs approved for use in DFUs. Use of dressings containing novel layer-by-layer (LbL)-formulated therapeutic RNAs that inhibit PHD2 and miR-210 can significantly improve diabetic wound healing. These dressings provide sustained release of therapeutic RNAs to the wounds locally without systemic side effects. <b>Clinical Problem Addressed:</b> Diabetic foot wounds are difficult to heal and often result in significant patient morbidity and mortality. <b>Materials and Methods:</b> We used the diabetic neuroischemic rabbit model of impaired wound healing. Diabetes was induced in the rabbits with alloxan, and neuroischemia was induced by ligating the central neurovascular bundle of each ear. Four 6-mm full-thickness wounds were created on each ear. A LbL technique was used to conformally coat the wound dressings with chemically modified RNAs, including an antisense oligonucleotide (antimiR) targeting microRNA-210 (miR-210), an short synthetic hairpin RNA (sshRNA) targeting PHD2, or both. <b>Results:</b> Wound healing was improved by the antimiR-210 but not the PHD2-sshRNA. Specific knockdown of miR-210 in tissue as measured by RT-qPCR was ∼8 Ct greater than nonspecific controls, and this apparent level of knockdown (>99%) suggests that delivery to the tissue is highly efficient at the administered dose. <b>Discussion:</b> Healing of ischemic/neuropathic wounds in diabetic rabbits was accelerated upon inhibition of miR-210 by LbL delivery to the wound bed. miR-210 inhibition was achieved using a chemically modified antisense RNA.</p>","PeriodicalId":7413,"journal":{"name":"Advances in wound care","volume":" ","pages":"435-445"},"PeriodicalIF":5.6,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11535488/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139110665","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}