Pub Date : 2026-02-08DOI: 10.1177/21621918261421637
Felix J Klimitz, Samuel Knoedler, Tobias Niederegger, Alzbeta Novotna, Stav Brown, Dany Y Matar, Aliyar Zahedi Vafa, Anna Pomahac, Alexander S Piribauer, Leonard Knoedler, Dennis P Orgill, Gabriel Hundeshagen, Martin Kauke-Navarro, Bohdan Pomahac, Adriana C Panayi
Objective: To determine whether frailty, as quantified using the Five-Item Modified Frailty Index (mFI-5), independently predicts postoperative complications in patients undergoing surgery for diabetic foot ulcers (DFUs), and to assess its utility as a clinical risk stratification tool.
Approach: A retrospective cohort analysis was conducted using the American College of Surgeons National Surgical Quality Improvement Program database (2015-2021). Adults with type 2 diabetes and International Classification of Diseases, 10th Revision-coded DFUs (E11.621) undergoing elective surgery were identified and stratified into frail (mFI-5 >2) and prefrail (mFI-5 ≤2) groups. Preoperative variables, perioperative characteristics, and 30-day postoperative outcomes were compared using univariate tests, followed by multivariable logistic regression adjusting for clinically relevant confounders. The study design, reporting, and analysis followed the Strengthening the Reporting of Observational Studies in Epidemiology guidelines for observational cohort studies.
Results: Among 2,819 patients, 714 (25.3%) were classified as frail. Frail patients had significantly higher rates of overall complications (50.6% vs. 32.9%), mortality (4.1% vs. 1.6%), and medical complications, including reintubation and urinary tract infection. In adjusted models, frailty independently predicted any postoperative complication (odds ratio [OR] = 1.34, 95% confidence interval [CI] 1.05-1.70, p = 0.02) and medical complications (OR = 1.53, 95% CI: 1.12-2.07, p = 0.007).
Innovation: This is the first large-scale study applying the mFI-5 to DFU surgery, demonstrating that frailty provides prognostic information beyond traditional comorbidity-based assessments and offers a rapid, objective tool for perioperative risk evaluation.
Conclusion: Frailty, as measured by the mFI-5, independently predicts postoperative morbidity and mortality after DFU surgery. Incorporating preoperative frailty screening may improve surgical decision making, resource allocation, and enhance outcomes in this high-risk population.
目的:确定用五项修正虚弱指数(mFI-5)量化的虚弱是否能独立预测糖尿病足溃疡(DFUs)手术患者的术后并发症,并评估其作为临床风险分层工具的实用性。方法:采用美国外科医师学会国家手术质量改进计划数据库(2015-2021)进行回顾性队列分析。接受择期手术的成人2型糖尿病和国际疾病分类第10版编码DFUs (E11.621)患者被确定并分层为虚弱组(mFI-5≤2)和虚弱前组(mFI-5≤2)。采用单变量检验比较术前变量、围手术期特征和术后30天的结果,然后对临床相关混杂因素进行多变量logistic回归调整。本研究的设计、报告和分析遵循《加强观察性队列研究的流行病学观察性研究报告指南》。结果:2819例患者中,虚弱714例(25.3%)。体弱患者的总并发症(50.6%对32.9%)、死亡率(4.1%对1.6%)和医疗并发症(包括再插管和尿路感染)的发生率均显著高于对照组。在调整后的模型中,虚弱独立预测任何术后并发症(优势比[OR] = 1.34, 95%可信区间[CI] 1.05-1.70, p = 0.02)和医学并发症(OR = 1.53, 95% CI: 1.12-2.07, p = 0.007)。创新:这是首次将mFI-5应用于DFU手术的大规模研究,表明虚弱提供了传统的基于合并症的评估之外的预后信息,并为围手术期风险评估提供了快速、客观的工具。结论:由mFI-5测量的虚弱可以独立预测DFU术后的发病率和死亡率。结合术前虚弱筛查可以改善手术决策,资源分配,并提高这一高危人群的预后。
{"title":"Frailty Predicts Postoperative Complications in Patients Undergoing Surgery for Diabetic Foot Ulcers.","authors":"Felix J Klimitz, Samuel Knoedler, Tobias Niederegger, Alzbeta Novotna, Stav Brown, Dany Y Matar, Aliyar Zahedi Vafa, Anna Pomahac, Alexander S Piribauer, Leonard Knoedler, Dennis P Orgill, Gabriel Hundeshagen, Martin Kauke-Navarro, Bohdan Pomahac, Adriana C Panayi","doi":"10.1177/21621918261421637","DOIUrl":"https://doi.org/10.1177/21621918261421637","url":null,"abstract":"<p><strong>Objective: </strong>To determine whether frailty, as quantified using the Five-Item Modified Frailty Index (mFI-5), independently predicts postoperative complications in patients undergoing surgery for diabetic foot ulcers (DFUs), and to assess its utility as a clinical risk stratification tool.</p><p><strong>Approach: </strong>A retrospective cohort analysis was conducted using the American College of Surgeons National Surgical Quality Improvement Program database (2015-2021). Adults with type 2 diabetes and International Classification of Diseases, 10th Revision-coded DFUs (E11.621) undergoing elective surgery were identified and stratified into frail (mFI-5 >2) and prefrail (mFI-5 ≤2) groups. Preoperative variables, perioperative characteristics, and 30-day postoperative outcomes were compared using univariate tests, followed by multivariable logistic regression adjusting for clinically relevant confounders. The study design, reporting, and analysis followed the Strengthening the Reporting of Observational Studies in Epidemiology guidelines for observational cohort studies.</p><p><strong>Results: </strong>Among 2,819 patients, 714 (25.3%) were classified as frail. Frail patients had significantly higher rates of overall complications (50.6% vs. 32.9%), mortality (4.1% vs. 1.6%), and medical complications, including reintubation and urinary tract infection. In adjusted models, frailty independently predicted any postoperative complication (odds ratio [OR] = 1.34, 95% confidence interval [CI] 1.05-1.70, <i>p</i> = 0.02) and medical complications (OR = 1.53, 95% CI: 1.12-2.07, <i>p</i> = 0.007).</p><p><strong>Innovation: </strong>This is the first large-scale study applying the mFI-5 to DFU surgery, demonstrating that frailty provides prognostic information beyond traditional comorbidity-based assessments and offers a rapid, objective tool for perioperative risk evaluation.</p><p><strong>Conclusion: </strong>Frailty, as measured by the mFI-5, independently predicts postoperative morbidity and mortality after DFU surgery. Incorporating preoperative frailty screening may improve surgical decision making, resource allocation, and enhance outcomes in this high-risk population.</p>","PeriodicalId":7413,"journal":{"name":"Advances in wound care","volume":" ","pages":"21621918261421637"},"PeriodicalIF":5.6,"publicationDate":"2026-02-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146140656","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}
Pub Date : 2026-02-05DOI: 10.1177/21621918261422388
Hsiu-Jung Liao, Tzu-Chi Liao, Yu-Feng Wu
Significance: Diabetic foot ulcers (DFUs) represent one of the most devastating complications of diabetes, leading to high rates of amputation and mortality. Their multifactorial pathogenesis-including neuropathy, ischemia, infection, and immune dysfunction-creates a chronic inflammatory microenvironment that impairs tissue repair and regeneration.
Recent advances: Emerging regenerative strategies using stem cells and extracellular vesicles (EVs) have demonstrated potential to restore vascularization and modulate inflammation. In particular, miRNA-enriched EVs regulate key wound-healing pathways such as angiogenesis, extracellular matrix remodeling, and oxidative stress response. Meanwhile, small-molecule drugs targeting hypoxia and inflammatory cascades are being explored to enhance re-epithelialization and fibroblast migration. Parallel advances in artificial intelligence (AI) and optical sensing-using visible, infrared, or hyperspectral imaging-enable automated wound detection, tissue classification, and healing prediction with high accuracy.
Critical issues: Despite these developments, translation remains limited by unstable therapeutic efficacy, variable biomarker expression, and the absence of standardized evaluation systems. AI-based wound assessment requires robust datasets and clinical validation to ensure reliability across diverse populations.
Future directions: Integrating molecular-targeted therapies with AI-assisted diagnostic platforms could establish a next-generation DFU management framework-combining precise molecular intervention, automated wound monitoring, and personalized treatment planning-to achieve reliable, real-time, and patient-centered wound care.
{"title":"Integrating Regenerative Therapies and Artificial Intelligence for Precision Management of Diabetic Foot Ulcers.","authors":"Hsiu-Jung Liao, Tzu-Chi Liao, Yu-Feng Wu","doi":"10.1177/21621918261422388","DOIUrl":"https://doi.org/10.1177/21621918261422388","url":null,"abstract":"<p><strong>Significance: </strong>Diabetic foot ulcers (DFUs) represent one of the most devastating complications of diabetes, leading to high rates of amputation and mortality. Their multifactorial pathogenesis-including neuropathy, ischemia, infection, and immune dysfunction-creates a chronic inflammatory microenvironment that impairs tissue repair and regeneration.</p><p><strong>Recent advances: </strong>Emerging regenerative strategies using stem cells and extracellular vesicles (EVs) have demonstrated potential to restore vascularization and modulate inflammation. In particular, miRNA-enriched EVs regulate key wound-healing pathways such as angiogenesis, extracellular matrix remodeling, and oxidative stress response. Meanwhile, small-molecule drugs targeting hypoxia and inflammatory cascades are being explored to enhance re-epithelialization and fibroblast migration. Parallel advances in artificial intelligence (AI) and optical sensing-using visible, infrared, or hyperspectral imaging-enable automated wound detection, tissue classification, and healing prediction with high accuracy.</p><p><strong>Critical issues: </strong>Despite these developments, translation remains limited by unstable therapeutic efficacy, variable biomarker expression, and the absence of standardized evaluation systems. AI-based wound assessment requires robust datasets and clinical validation to ensure reliability across diverse populations.</p><p><strong>Future directions: </strong>Integrating molecular-targeted therapies with AI-assisted diagnostic platforms could establish a next-generation DFU management framework-combining precise molecular intervention, automated wound monitoring, and personalized treatment planning-to achieve reliable, real-time, and patient-centered wound care.</p>","PeriodicalId":7413,"journal":{"name":"Advances in wound care","volume":" ","pages":"21621918261422388"},"PeriodicalIF":5.6,"publicationDate":"2026-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146123526","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}
Pub Date : 2026-02-04DOI: 10.1177/21621918261421628
Marcos R Rodriguez, Alan E Woessner, Kyle P Quinn
Objective: The expected increase in age-related health care costs over the coming decades underscores the need to characterize the effects of biological aging in our cells and tissues. Our objective is to use in vivo multiphoton microscopy (MPM) to find endogenous biomarkers of skin aging.
Approach: MPM was performed on the skin of 2- and 21-month-old mice to measure the autofluorescence of metabolic cofactors, nicotinamide adenine dinucleotide (NADH) and flavin adenine dinucleotide (FAD), and second-harmonic generation signal from collagen. A suite of quantitative biomarkers with sensitivity to age-related changes in bioenergetic demands, mitochondrial organization, and collagen composition and organization was evaluated using these optical sources of contrast.
Results: An optical redox ratio of FAD/(NADH + FAD) autofluorescence, NADH fluorescence lifetime imaging, and mitochondrial fractal dimension measurements indicated that aged keratinocytes have more fragmented mitochondria that undergo less catabolism of carbon substrates. Analysis of the dermal regions indicated that aged collagen has more nonenzymatic cross-links and has a more fragmented organization.
Innovation: This study identifies a suite of biomarkers from label-free MPM sensitive to intrinsic aging and provides the first in vivo demonstration of sensitivity to age-dependent metabolic changes in skin through multiple independent optical parameters.
Conclusion: Our results demonstrate that surrogate markers of metabolic function, mitochondrial organization, collagen cross-linking, and fiber organization are sensitive to a loss of homeostasis with advanced age and may be used in future studies to longitudinally assess the progression of aging.
{"title":"<i>In Vivo</i>, Label-Free Multiphoton Microscopy Is Sensitive to Altered Metabolism and Structure in Aged Skin.","authors":"Marcos R Rodriguez, Alan E Woessner, Kyle P Quinn","doi":"10.1177/21621918261421628","DOIUrl":"https://doi.org/10.1177/21621918261421628","url":null,"abstract":"<p><strong>Objective: </strong>The expected increase in age-related health care costs over the coming decades underscores the need to characterize the effects of biological aging in our cells and tissues. Our objective is to use <i>in vivo</i> multiphoton microscopy (MPM) to find endogenous biomarkers of skin aging.</p><p><strong>Approach: </strong>MPM was performed on the skin of 2- and 21-month-old mice to measure the autofluorescence of metabolic cofactors, nicotinamide adenine dinucleotide (NADH) and flavin adenine dinucleotide (FAD), and second-harmonic generation signal from collagen. A suite of quantitative biomarkers with sensitivity to age-related changes in bioenergetic demands, mitochondrial organization, and collagen composition and organization was evaluated using these optical sources of contrast.</p><p><strong>Results: </strong>An optical redox ratio of FAD/(NADH + FAD) autofluorescence, NADH fluorescence lifetime imaging, and mitochondrial fractal dimension measurements indicated that aged keratinocytes have more fragmented mitochondria that undergo less catabolism of carbon substrates. Analysis of the dermal regions indicated that aged collagen has more nonenzymatic cross-links and has a more fragmented organization.</p><p><strong>Innovation: </strong>This study identifies a suite of biomarkers from label-free MPM sensitive to intrinsic aging and provides the first <i>in vivo</i> demonstration of sensitivity to age-dependent metabolic changes in skin through multiple independent optical parameters.</p><p><strong>Conclusion: </strong>Our results demonstrate that surrogate markers of metabolic function, mitochondrial organization, collagen cross-linking, and fiber organization are sensitive to a loss of homeostasis with advanced age and may be used in future studies to longitudinally assess the progression of aging.</p>","PeriodicalId":7413,"journal":{"name":"Advances in wound care","volume":" ","pages":"21621918261421628"},"PeriodicalIF":5.6,"publicationDate":"2026-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146117517","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}
Pub Date : 2026-01-22DOI: 10.1177/21621918251411808
Chengcheng Zheng, Weiwei Tang, Xingwu Ran
Objective: The meta-analysis was performed to evaluate the efficacy and safety associated with the application of human amniotic membrane (HAM) in individuals with chronic nonhealing wounds.
Approach: The research conducted a comprehensive search of nine electronic databases from their inception to August 1, 2024, aiming to identify randomized controlled trials (RCTs) that evaluated the efficacy of HAM compared with conventional management alone in individuals suffering from chronic wounds. The risk of bias of included studies and the certainty of the evidence in the meta-analysis were evaluated by two investigators and confirmed by a third. The meta-analysis was performed using RevMan 5.4 software.
Results: We identified 14 RCTs encompassing a total of 1,056 participants. The potential risk of bias was determined to be moderate. HAM therapy demonstrated significantly greater efficacy than conventional treatment alone in achieving complete wound healing among patients with chronic ulcers (relative risk [RR] = 1.82; 95% confidence interval [CI]: 1.48-2.24; moderate-quality evidence). In patients with diabetic foot ulcers, HAM reduced the mean time to complete healing by 22 days compared with standard care alone (mean difference = -22.09 days; 95% CI: -39.13 to -5.05; low-quality evidence) and increased the rate of complete healing at 6 weeks (RR = 3.02; 95% CI: 2.04-4.47; moderate-quality evidence) and at 12 weeks (RR = 1.74; 95% CI: 1.37-2.21; low-quality evidence). Similarly, in patients with venous leg ulcers, HAM was associated with more than twice the likelihood of complete healing (RR = 2.03; 95% CI: 1.45-2.86; moderate-quality evidence). No statistically significant differences were noted in the incidence of adverse events among patients with chronic ulcers (moderate-quality evidence).
Innovation: Our study suggests that HAM represents a promising and viable therapeutic strategy for the management of chronic wounds, including lower-extremity diabetic ulcers and venous ulcers.
Conclusion: The application of HAM provides a safer and more effective therapeutic approach compared with conventional management alone for patients suffering from chronic refractory ulcers.
{"title":"Efficacy and Safety of Human Amniotic Membrane for Chronic Wounds: A Systematic Review and Meta-Analysis of Clinical Trials.","authors":"Chengcheng Zheng, Weiwei Tang, Xingwu Ran","doi":"10.1177/21621918251411808","DOIUrl":"https://doi.org/10.1177/21621918251411808","url":null,"abstract":"<p><strong>Objective: </strong>The meta-analysis was performed to evaluate the efficacy and safety associated with the application of human amniotic membrane (HAM) in individuals with chronic nonhealing wounds.</p><p><strong>Approach: </strong>The research conducted a comprehensive search of nine electronic databases from their inception to August 1, 2024, aiming to identify randomized controlled trials (RCTs) that evaluated the efficacy of HAM compared with conventional management alone in individuals suffering from chronic wounds. The risk of bias of included studies and the certainty of the evidence in the meta-analysis were evaluated by two investigators and confirmed by a third. The meta-analysis was performed using RevMan 5.4 software.</p><p><strong>Results: </strong>We identified 14 RCTs encompassing a total of 1,056 participants. The potential risk of bias was determined to be moderate. HAM therapy demonstrated significantly greater efficacy than conventional treatment alone in achieving complete wound healing among patients with chronic ulcers (relative risk [RR] = 1.82; 95% confidence interval [CI]: 1.48-2.24; moderate-quality evidence). In patients with diabetic foot ulcers, HAM reduced the mean time to complete healing by 22 days compared with standard care alone (mean difference = -22.09 days; 95% CI: -39.13 to -5.05; low-quality evidence) and increased the rate of complete healing at 6 weeks (RR = 3.02; 95% CI: 2.04-4.47; moderate-quality evidence) and at 12 weeks (RR = 1.74; 95% CI: 1.37-2.21; low-quality evidence). Similarly, in patients with venous leg ulcers, HAM was associated with more than twice the likelihood of complete healing (RR = 2.03; 95% CI: 1.45-2.86; moderate-quality evidence). No statistically significant differences were noted in the incidence of adverse events among patients with chronic ulcers (moderate-quality evidence).</p><p><strong>Innovation: </strong>Our study suggests that HAM represents a promising and viable therapeutic strategy for the management of chronic wounds, including lower-extremity diabetic ulcers and venous ulcers.</p><p><strong>Conclusion: </strong>The application of HAM provides a safer and more effective therapeutic approach compared with conventional management alone for patients suffering from chronic refractory ulcers.</p>","PeriodicalId":7413,"journal":{"name":"Advances in wound care","volume":" ","pages":"21621918251411808"},"PeriodicalIF":5.6,"publicationDate":"2026-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146027810","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}
Pub Date : 2026-01-22DOI: 10.1177/21621918261417702
Qilei Chen, Shujun Wan, Yuanyuan Duan, Jing Yan, Min Zhang
Significance: Keloids represent a persistent clinical challenge, with recurrence rates approaching 100% after conventional surgical excision. Historically viewed as fibroblast-driven scars, emerging evidence positions immune dysregulation as a central driver of keloid pathogenesis, reshaping diagnostic and therapeutic paradigms.
Recent advances: Multi-omics and single-cell analyses reveal profound alterations in immune cell populations and cytokine networks within keloid tissue. M2 macrophages, mast cells, Th2 and Th17 subsets, and dendritic cells dominate the inflammatory microenvironment, sustaining fibroblast activation and excessive extracellular matrix deposition. Key signaling axes-including transforming growth factor-β (TGF-β)/Smad, IL-4/IL-13, IL-6/JAK-STAT-3, and PI3K/AKT/mTOR-intersect with mechanical stress pathways, creating a self-perpetuating fibrotic loop. Notably, soluble human leukocyte antigen-E emerges as a predictive biomarker for disease progression and recurrence, while tissue-resident memory T cells may underlie postoperative relapse.
Therapeutic implications: Beyond corticosteroids and silicone gel, immune-targeted strategies are gaining traction. Dupilumab (IL-4/IL-13 blockade) demonstrates clinical efficacy in reducing keloid burden and pruritus. Experimental approaches targeting TGF-β signaling (Fresolizumab, AVID200), NKG2A/CD94 checkpoints (Monalizumab), IL-6 (Tocilizumab), and TSLP (Tezepelumab) hold promise for precision immunotherapy. Localized delivery and combination regimens may optimize outcomes while minimizing systemic toxicity.
Critical issues and future directions: The absence of validated keloid models and large-scale trials limits translation. Future research must integrate immune profiling, biomarker validation, and mechanistic modeling to enable personalized interventions. Immune dysregulation is not merely an epiphenomenon-it is the Achilles' heel of keloids, offering unprecedented opportunities for targeted therapy and recurrence prevention.
{"title":"Immune Imbalance Drives Keloid Pathogenesis: Emerging Targets for Precision Immunotherapy.","authors":"Qilei Chen, Shujun Wan, Yuanyuan Duan, Jing Yan, Min Zhang","doi":"10.1177/21621918261417702","DOIUrl":"https://doi.org/10.1177/21621918261417702","url":null,"abstract":"<p><strong>Significance: </strong>Keloids represent a persistent clinical challenge, with recurrence rates approaching 100% after conventional surgical excision. Historically viewed as fibroblast-driven scars, emerging evidence positions immune dysregulation as a central driver of keloid pathogenesis, reshaping diagnostic and therapeutic paradigms.</p><p><strong>Recent advances: </strong>Multi-omics and single-cell analyses reveal profound alterations in immune cell populations and cytokine networks within keloid tissue. M2 macrophages, mast cells, Th2 and Th17 subsets, and dendritic cells dominate the inflammatory microenvironment, sustaining fibroblast activation and excessive extracellular matrix deposition. Key signaling axes-including transforming growth factor-β (TGF-β)/Smad, IL-4/IL-13, IL-6/JAK-STAT-3, and PI3K/AKT/mTOR-intersect with mechanical stress pathways, creating a self-perpetuating fibrotic loop. Notably, soluble human leukocyte antigen-E emerges as a predictive biomarker for disease progression and recurrence, while tissue-resident memory T cells may underlie postoperative relapse.</p><p><strong>Therapeutic implications: </strong>Beyond corticosteroids and silicone gel, immune-targeted strategies are gaining traction. Dupilumab (IL-4/IL-13 blockade) demonstrates clinical efficacy in reducing keloid burden and pruritus. Experimental approaches targeting TGF-β signaling (Fresolizumab, AVID200), NKG2A/CD94 checkpoints (Monalizumab), IL-6 (Tocilizumab), and TSLP (Tezepelumab) hold promise for precision immunotherapy. Localized delivery and combination regimens may optimize outcomes while minimizing systemic toxicity.</p><p><strong>Critical issues and future directions: </strong>The absence of validated keloid models and large-scale trials limits translation. Future research must integrate immune profiling, biomarker validation, and mechanistic modeling to enable personalized interventions. Immune dysregulation is not merely an epiphenomenon-it is the Achilles' heel of keloids, offering unprecedented opportunities for targeted therapy and recurrence prevention.</p>","PeriodicalId":7413,"journal":{"name":"Advances in wound care","volume":" ","pages":"21621918261417702"},"PeriodicalIF":5.6,"publicationDate":"2026-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146027814","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}
Objective: Burn injuries affect over 11 million people annually, and methicillin-resistant Staphylococcus aureus (MRSA) infection significantly delays healing by sustaining inflammation and promoting scarring. This study evaluated N-benzyl benzenamine 4k-a novel dual-action compound with antibacterial and anti-inflammatory properties-in a murine model of MRSA-infected burn wounds. Approach: Skin safety of 4k was assessed through acute toxicity, sensitization, and irritation tests in BALB/c mice. A full-thickness burn model infected with MRSA2858 (1 × 108 CFU/mL) was treated topically with 4k, vancomycin (VAN), or vaseline. Outcomes included wound closure, bacterial load, histology, collagen organization, macrophage polarization markers (CD86/inducible nitric oxide synthase [iNOS] for M1; CD206/vascular endothelial growth factor [VEGF] for M2), cytokine levels, and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) pathway proteins. Results: 4k demonstrated excellent dermal tolerability with no toxicity or irritation. Topical 4k reduced MRSA colonization and accelerated wound closure (residual wound area at day 15: 4k = 8.4 ± 2.2%, VAN = 17.8 ± 3.5%). Histology revealed organized collagen deposition and minimal scarring in the 4k group (scar score: 2.33 ± 0.58 vs. 13.33 ± 0.58 for vaseline). Mechanistically, 4k suppressed NF-κB activation, downregulated M1 markers (CD86, iNOS, tumor necrosis factor-alpha, and interleukin [IL]-6), and upregulated M2 markers (CD206, VEGF, transforming growth factor-beta 1, and IL-10), promoting a prohealing immune environment. Innovation: This study introduces a dual-action topical therapy that combines potent antibacterial activity with immunomodulation, offering a promising strategy to overcome antibiotic resistance and improve burn wound outcomes. Conclusions:N-benzyl benzenamine 4k effectively eradicates MRSA, accelerates wound healing, and minimizes scarring through NF-κB inhibition and macrophage polarization, supporting its potential as a next-generation burn care agent.
{"title":"Dual-Action Topical Therapy Accelerates Healing of MRSA-Infected Burn Wounds by Targeting Infection and Inflammation.","authors":"Miaoqing Xiang, Zongze Yao, Wei Shao, Mengru Chen, Wenjian Tang, Dandan Liu, Jing Zhang","doi":"10.1177/21621918251405876","DOIUrl":"https://doi.org/10.1177/21621918251405876","url":null,"abstract":"<p><p><b>Objective:</b> Burn injuries affect over 11 million people annually, and methicillin-resistant <i>Staphylococcus aureus</i> (MRSA) infection significantly delays healing by sustaining inflammation and promoting scarring. This study evaluated <i>N</i>-benzyl benzenamine 4k-a novel dual-action compound with antibacterial and anti-inflammatory properties-in a murine model of MRSA-infected burn wounds. <b>Approach:</b> Skin safety of 4k was assessed through acute toxicity, sensitization, and irritation tests in BALB/c mice. A full-thickness burn model infected with MRSA2858 (1 × 10<sup>8</sup> CFU/mL) was treated topically with 4k, vancomycin (VAN), or vaseline. Outcomes included wound closure, bacterial load, histology, collagen organization, macrophage polarization markers (CD86/inducible nitric oxide synthase [iNOS] for M1; CD206/vascular endothelial growth factor [VEGF] for M2), cytokine levels, and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) pathway proteins. <b>Results:</b> 4k demonstrated excellent dermal tolerability with no toxicity or irritation. Topical 4k reduced MRSA colonization and accelerated wound closure (residual wound area at day 15: 4k = 8.4 ± 2.2%, VAN = 17.8 ± 3.5%). Histology revealed organized collagen deposition and minimal scarring in the 4k group (scar score: 2.33 ± 0.58 vs. 13.33 ± 0.58 for vaseline). Mechanistically, 4k suppressed NF-κB activation, downregulated M1 markers (CD86, iNOS, tumor necrosis factor-alpha, and interleukin [IL]-6), and upregulated M2 markers (CD206, VEGF, transforming growth factor-beta 1, and IL-10), promoting a prohealing immune environment. <b>Innovation:</b> This study introduces a dual-action topical therapy that combines potent antibacterial activity with immunomodulation, offering a promising strategy to overcome antibiotic resistance and improve burn wound outcomes. <b>Conclusions:</b> <i>N</i>-benzyl benzenamine 4k effectively eradicates MRSA, accelerates wound healing, and minimizes scarring through NF-κB inhibition and macrophage polarization, supporting its potential as a next-generation burn care agent.</p>","PeriodicalId":7413,"journal":{"name":"Advances in wound care","volume":" ","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-12-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145832162","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}
Pub Date : 2025-12-16DOI: 10.1177/21621918251405806
Jenny Du-Soriano, Diana Friscia, Robert S Kirsner
Objective: To evaluate wound healing with a novel bandage with hydrocolloid pad designed for daily use/replacement in a new model of laser-induced burns/wounds. Approach: In this randomized, controlled, single-center, 16-day study, healthy adults aged 25-55 years of age with Fitzpatrick skin type I-III and who met all eligibility criteria (N = 34) had four laser-induced wounds generated on each arm and were randomized as follows: (1) uncovered wound (control); (2) standard of care bandage (SoC); (3) petrolatum-based antibiotic ointment + SoC (petrolatum + SoC); (4) bandage with hydrocolloid pad. Primary endpoint: composite healing score (sum of scores for general wound appearance, smoothness, and epithelial confluence, minus scores for erythema, edema, and crusting/scabbing) on Days 1-7. Results: Mean composite healing score was significantly better with the hydrocolloid pad (Days 1-7) and petrolatum + SoC (Days 2-7) than SoC, and with either treatment than untreated controls (Days 1-7), and significantly better with the hydrocolloid pad than petrolatum + SoC (Days 1 to 2 and 7). The hydrocolloid pad and petrolatum + SoC both significantly reduced crusting/scabbing while improving epithelial confluence, smoothness, and general wound appearance, compared with untreated controls and SoC. Innovation: A laser-induced burn model producing consistent wounds was used to evaluate healing with a novel bandage with hydrocolloid pad versus other typical treatments. Conclusion: Wound healing with the novel bandage with hydrocolloid pad used daily was superior to SoC (Days 1-7), untreated wound (Days 1-7), and petrolatum + SoC (Days 1 to 2 and 7). [Figure: see text].
{"title":"Efficacy of a Novel Daily-Use Hydrocolloid Pad on Wound Healing: Findings of a 16-Day, Single-Center, Randomized, Controlled Study.","authors":"Jenny Du-Soriano, Diana Friscia, Robert S Kirsner","doi":"10.1177/21621918251405806","DOIUrl":"https://doi.org/10.1177/21621918251405806","url":null,"abstract":"<p><p><b>Objective:</b> To evaluate wound healing with a novel bandage with hydrocolloid pad designed for daily use/replacement in a new model of laser-induced burns/wounds. <b>Approach:</b> In this randomized, controlled, single-center, 16-day study, healthy adults aged 25-55 years of age with Fitzpatrick skin type I-III and who met all eligibility criteria (<i>N</i> = 34) had four laser-induced wounds generated on each arm and were randomized as follows: (1) uncovered wound (control); (2) standard of care bandage (SoC); (3) petrolatum-based antibiotic ointment + SoC (petrolatum + SoC); (4) bandage with hydrocolloid pad. Primary endpoint: composite healing score (sum of scores for general wound appearance, smoothness, and epithelial confluence, minus scores for erythema, edema, and crusting/scabbing) on Days 1-7. <b>Results:</b> Mean composite healing score was significantly better with the hydrocolloid pad (Days 1-7) and petrolatum + SoC (Days 2-7) than SoC, and with either treatment than untreated controls (Days 1-7), and significantly better with the hydrocolloid pad than petrolatum + SoC (Days 1 to 2 and 7). The hydrocolloid pad and petrolatum + SoC both significantly reduced crusting/scabbing while improving epithelial confluence, smoothness, and general wound appearance, compared with untreated controls and SoC. <b>Innovation:</b> A laser-induced burn model producing consistent wounds was used to evaluate healing with a novel bandage with hydrocolloid pad versus other typical treatments. <b>Conclusion:</b> Wound healing with the novel bandage with hydrocolloid pad used daily was superior to SoC (Days 1-7), untreated wound (Days 1-7), and petrolatum + SoC (Days 1 to 2 and 7). [Figure: see text].</p>","PeriodicalId":7413,"journal":{"name":"Advances in wound care","volume":" ","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145848764","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}
Significance: The combination of hydrogel biomaterials with exosomes to facilitate wound healing and skin regeneration is a promising approach. Recent Advances: Recent preclinical animal studies have focused on investigating the efficacy of hydrogel-based delivery systems for exosomes in promoting wound healing and skin regeneration. Critical Issues: Despite encouraging results, critical issues remain unresolved, such as optimizing hydrogel properties to enhance the efficacy of combined therapy with exosomes for wound and bridging the translational gap between preclinical and clinical applications. Future Directions: Future research endeavors should concentrate on refining hydrogel design to enhance exosome delivery efficacy, conducting rigorous clinical trials to assess the safety and efficacy of exosome-loaded hydrogels in human wound healing and skin regeneration, and exploring innovative strategies to maximize therapeutic outcomes.
{"title":"The Role of Hydrogel Biomaterials in the Intervention of Wound Healing and Skin Regeneration via Exosomes: A Systematic Review and Meta-Analysis of Preclinical Animal Studies.","authors":"Yujia Yang, Jinlei Cui, Yajie Kong, Yu Hou, Haixia Zhang, Cuiqing Ma","doi":"10.1089/wound.2024.0058","DOIUrl":"10.1089/wound.2024.0058","url":null,"abstract":"<p><p><b>Significance:</b> The combination of hydrogel biomaterials with exosomes to facilitate wound healing and skin regeneration is a promising approach. <b>Recent Advances:</b> Recent preclinical animal studies have focused on investigating the efficacy of hydrogel-based delivery systems for exosomes in promoting wound healing and skin regeneration. <b>Critical Issues:</b> Despite encouraging results, critical issues remain unresolved, such as optimizing hydrogel properties to enhance the efficacy of combined therapy with exosomes for wound and bridging the translational gap between preclinical and clinical applications. <b>Future Directions:</b> Future research endeavors should concentrate on refining hydrogel design to enhance exosome delivery efficacy, conducting rigorous clinical trials to assess the safety and efficacy of exosome-loaded hydrogels in human wound healing and skin regeneration, and exploring innovative strategies to maximize therapeutic outcomes.</p>","PeriodicalId":7413,"journal":{"name":"Advances in wound care","volume":" ","pages":"669-684"},"PeriodicalIF":5.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141316460","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}
Objective: To compare the effectiveness of "semiocclusive dressing (SOD)" treatment using plastic wrap or low-adherent absorbent wound dressings with that of occlusive dressing (OD) treatment for National Pressure Injury Advisory Panel stage III/IV pressure injuries in the inflammatory phase. Approach: This 12-week, open-label, randomized controlled trial was conducted at one hospital and three care facilities. Seventy-seven participants were enrolled; 40 comprised the SOD group and 37 comprised the OD group. The primary outcome was the surface area reduction. Secondary outcomes included the Bates-Jensen Wound Assessment Tool (BWAT) score reductions, incidence of adverse events, and material cost. This trial met the recommendations of the CONSORT 2010 statement. Results: The surface area reduction of the SOD group was greater than that of the OD group throughout the study period. The significant interaction was revealed between treatment and time course (p < 0.0001). The 95% confidence interval of the difference at 12 weeks was 3.4 to 21.9. The median BWAT score reduction of the SOD group at 12 weeks was 23, and that of the OD group was 18.5 (p = 0.0077). The incidence of adverse events was comparable between groups. The OD treatment cost was 3.0 times higher than the SOD treatment cost (p = 0.0012). Innovation: Because the SOD does not completely occlude the wound, excess exudate drains from the wound. Therefore, SOD can treat the wound with abundant exudate effectively and safely. Conclusion: SOD treatment is more effective and less expensive than OD treatment for stage III/IV pressure injuries. Clinical Trial Registration: UMIN Clinical Trials Registry [UMIN000023412]. Registered on July 31, 2016.
{"title":"Comparison of \"Semiocclusive Dressing\" Treatment Using Plastic Wrap or Low-Adherent Absorbent Wound Dressings Versus Occlusive Dressing Treatment for Stage III/IV Pressure Injuries in the Inflammatory Phase: A Randomized Controlled Trial.","authors":"Jun Takahashi, Kayoko Nakae, Osamu Yokota, Rena Nakata, Hayato Hasegawa, Masaharu Miyagawa","doi":"10.1089/wound.2024.0041","DOIUrl":"10.1089/wound.2024.0041","url":null,"abstract":"<p><p><b>Objective:</b> To compare the effectiveness of \"semiocclusive dressing (SOD)\" treatment using plastic wrap or low-adherent absorbent wound dressings with that of occlusive dressing (OD) treatment for National Pressure Injury Advisory Panel stage III/IV pressure injuries in the inflammatory phase. <b>Approach:</b> This 12-week, open-label, randomized controlled trial was conducted at one hospital and three care facilities. Seventy-seven participants were enrolled; 40 comprised the SOD group and 37 comprised the OD group. The primary outcome was the surface area reduction. Secondary outcomes included the Bates-Jensen Wound Assessment Tool (BWAT) score reductions, incidence of adverse events, and material cost. This trial met the recommendations of the CONSORT 2010 statement. <b>Results:</b> The surface area reduction of the SOD group was greater than that of the OD group throughout the study period. The significant interaction was revealed between treatment and time course (<i>p</i> < 0.0001). The 95% confidence interval of the difference at 12 weeks was 3.4 to 21.9. The median BWAT score reduction of the SOD group at 12 weeks was 23, and that of the OD group was 18.5 (<i>p</i> = 0.0077). The incidence of adverse events was comparable between groups. The OD treatment cost was 3.0 times higher than the SOD treatment cost (<i>p</i> = 0.0012). <b>Innovation:</b> Because the SOD does not completely occlude the wound, excess exudate drains from the wound. Therefore, SOD can treat the wound with abundant exudate effectively and safely. <b>Conclusion:</b> SOD treatment is more effective and less expensive than OD treatment for stage III/IV pressure injuries. <b>Clinical Trial Registration:</b> UMIN Clinical Trials Registry [UMIN000023412]. Registered on July 31, 2016.</p>","PeriodicalId":7413,"journal":{"name":"Advances in wound care","volume":" ","pages":"635-644"},"PeriodicalIF":5.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141316459","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}
Pub Date : 2025-12-01Epub Date: 2024-11-07DOI: 10.1089/wound.2024.0102
Verónica Salgado-Pacheco, Ramon Oller, Marta Ferrer-Solà, Clara Masó-Albareda, Marta Casals-Zorita, Elisabet Sarri, Emma Puigoriol-Juvanteny, Joan Espaulella-Panicot, Marta Otero-Viñas
Objective: Autologous platelet-rich plasma (PRP) has shown promising outcomes in treating wounds, but the profile of patients benefiting most from this therapy is not known. This study aimed to identify influential variables in the success of this therapy, analyzing its personalized therapeutic potential for complex wounds. Approach: A prospective observational study was conducted in elderly patients with complex wounds receiving autologous PRP. Patient's data about sociodemographic parameters, comorbidities, frailty (FI-VIG score), complete blood count including albumin, wound depth, location, chronicity, and etiology were collected at the beginning of the study. The wound area was monitored weekly. The data were analyzed using descriptive and inferential statistics, longitudinal data analysis, and survival analysis. Results: Ninety-seven elderly patients were included. The FI-VIG, baseline wound area, depth, and etiology were significantly correlated with wound outcome. Strong differences in wound area variation from treatment initiation were observed in healed wounds (13% reduction/week) compared with stagnant and complicated wounds (1 and 2% reduction/week, respectively). The healing time analysis showed that nearly 80% of patients required at least 15 weeks for complete healing. In addition, patients with smaller wound sizes, younger age, or lower FI-VIG scores had shorter healing times. Innovation: This is the first study that identifies prognostic indicators for wound outcomes to guide clinician decision-making for using autologous PRP. It also highlights the relevance of patient health baseline and wound features and evolution for the success of this therapy. Conclusion: This study demonstrates that personalizing autologous PRP therapy to treat complex wounds in elderly patients is possible.
{"title":"A Prospective Observational Study to Evaluate the Effectiveness of Platelet-Rich Plasma Therapy for Complex Wounds: Influential Clinical Variables on Wound Healing Outcomes.","authors":"Verónica Salgado-Pacheco, Ramon Oller, Marta Ferrer-Solà, Clara Masó-Albareda, Marta Casals-Zorita, Elisabet Sarri, Emma Puigoriol-Juvanteny, Joan Espaulella-Panicot, Marta Otero-Viñas","doi":"10.1089/wound.2024.0102","DOIUrl":"10.1089/wound.2024.0102","url":null,"abstract":"<p><p><b>Objective:</b> Autologous platelet-rich plasma (PRP) has shown promising outcomes in treating wounds, but the profile of patients benefiting most from this therapy is not known. This study aimed to identify influential variables in the success of this therapy, analyzing its personalized therapeutic potential for complex wounds. <b>Approach:</b> A prospective observational study was conducted in elderly patients with complex wounds receiving autologous PRP. Patient's data about sociodemographic parameters, comorbidities, frailty (FI-VIG score), complete blood count including albumin, wound depth, location, chronicity, and etiology were collected at the beginning of the study. The wound area was monitored weekly. The data were analyzed using descriptive and inferential statistics, longitudinal data analysis, and survival analysis. <b>Results:</b> Ninety-seven elderly patients were included. The FI-VIG, baseline wound area, depth, and etiology were significantly correlated with wound outcome. Strong differences in wound area variation from treatment initiation were observed in healed wounds (13% reduction/week) compared with stagnant and complicated wounds (1 and 2% reduction/week, respectively). The healing time analysis showed that nearly 80% of patients required at least 15 weeks for complete healing. In addition, patients with smaller wound sizes, younger age, or lower FI-VIG scores had shorter healing times. <b>Innovation:</b> This is the first study that identifies prognostic indicators for wound outcomes to guide clinician decision-making for using autologous PRP. It also highlights the relevance of patient health baseline and wound features and evolution for the success of this therapy. <b>Conclusion:</b> This study demonstrates that personalizing autologous PRP therapy to treat complex wounds in elderly patients is possible.</p>","PeriodicalId":7413,"journal":{"name":"Advances in wound care","volume":" ","pages":"655-668"},"PeriodicalIF":5.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142589742","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}