Burns & Trauma最新文献

{"title":"Hydrogel Microneedles for Chronic Wound Microenvironment Remodeling: From Drug Delivery to Intelligent Responsiveness","authors":"Rong Nie, Liang Zhao, Tao He, Zi-Yuan Feng, Yue-Qi Zhang, Ming-Hui Fan, Li-Ping Mou, Hui-Qi Xie","doi":"10.1093/burnst/tkag051","DOIUrl":"https://doi.org/10.1093/burnst/tkag051","url":null,"abstract":"The considerable strain that chronic wounds, including diabetic foot ulcers and pressure sores, place on healthcare systems worldwide is largely attributable to the intricate pathological microenvironment characteristic of these conditions, and conventional therapeutic approaches frequently fall short of desired outcomes, primarily because they cannot effectively disrupt biofilm barriers or adequately adapt to the dynamically changing pathological states involved. Hydrogel microneedles (HMNs) have by contrast emerged as a minimally invasive platform whose distinctive structural features and material properties enable both precise transdermal drug administration and active modulation of the wound microenvironment, and this dual capability is why HMNs are currently transforming chronic wound care by shifting the paradigm from passive occlusive dressings toward more proactive and targeted regenerative interventions. This review summarizes recent progress in HMN-based strategies for chronic wound healing and offers perspectives on future developments, beginning with an examination of fundamental design principles such as material choices, structural arrangements, and the various approaches developed to optimize performance metrics, then tracing the evolution of HMNs from simple drug carriers to intelligent multifunctional systems with special attention to their roles in breaking the pathological cycle through antibacterial effects, reactive oxygen species (ROS) scavenging, immune response modulation, and promotion of angiogenesis. Advances in stimuli-responsive systems that utilize endogenous signals including pH, enzymes, ROS, and glucose or external inputs like light and magnetic fields for on-demand release are also covered, as are combination platforms that integrate different therapeutic strategies for additive benefits. Clinical translation faces a number of challenges despite the considerable promise HMNs exhibit in theranostic applications, regenerative medicine integration, and customized fabrication, with obstacles remaining regarding scalable production that ensures consistent quality across batches, long-term biosafety verification, and unclear regulatory pathways; overcoming these hurdles will depend on sustained interdisciplinary efforts that address both scientific understanding and engineering practicality, and without such collaborative work the meaningful incorporation of HMNs into routine clinical management of chronic wounds along with the consequent availability of more effective, accurate, and intelligent treatment options could be difficult to achieve.","PeriodicalId":9553,"journal":{"name":"Burns & Trauma","volume":"7 1","pages":""},"PeriodicalIF":5.3,"publicationDate":"2026-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148682510","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Deciphering the cellular landscape of pathological scars","authors":"Yixin Sun, Sijing Yan, Mengdi Zhang, Wangfei Mo, Catharina Tao, Jingyu Li, Jiuzuo Huang, Nanze Yu, Yi Sun, Xiao Long","doi":"10.1093/burnst/tkag050","DOIUrl":"https://doi.org/10.1093/burnst/tkag050","url":null,"abstract":"Pathological scars (PSs) are characterized by excess dermal collagen deposition and primarily manifest as hypertrophic scars and keloids. The microenvironment of PSs is shaped by a diverse array of cells, collectively forming a profibrotic and proangiogenic niche. Recent advances in high-throughput sequencing have enhanced our understanding of the cellular heterogeneity, transcriptional changes, and intercellular communication within the PS microenvironment. This review comprehensively describes the cellular landscape of pathological scars, including mesenchymal cells, endothelial cells, epithelial cells and immune cells. Additionally, we evaluate precision medicine strategies ranging from biomarker-driven diagnostics to targeted biological therapies and innovative drug delivery systems. We aim to provide a mechanistic framework that accelerates the translation of basic experimental research into effective and personalized treatments for pathological scarring.","PeriodicalId":9553,"journal":{"name":"Burns & Trauma","volume":"453 1","pages":""},"PeriodicalIF":5.3,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148675392","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cryogenic 3D-Printed PLGA/Nano-selenium Scaffold for Bone Regeneration: A Dual-Functional Strategy Synergistically Regulating Macrophage Polarization and Osteogenic Differentiation","authors":"Shengwen Cheng, Yuqiao Wang, Yu Zhai, Mingfei Dong, Xiaole Peng, Xiaohong Luo, Jiacheng Liu, Junyan Liu, Yi He, Xiaoxiong Li, Ke Huang, Senrui Liu, Fengyuan Liu, Yuwei Zhang, Zhong Alan Li, Wei Huang, Chen Zhao, Yiting Lei","doi":"10.1093/burnst/tkag049","DOIUrl":"https://doi.org/10.1093/burnst/tkag049","url":null,"abstract":"Background Autologous and allogeneic bone grafts are primarily used for bone tissue defects; however, they have limitations such as limited supply, donor site morbidity, and immune rejection risks. Therefore, substitute synthetic bone grafts are required. Methods Using low-temperature 3D printing combined with freeze-drying technology, a hierarchically porous PLGA/HA@SeNPs composite scaffold was fabricated by compositing poly(lactic-co-glycolic acid) (PLGA) with hyaluronic acid-modified selenium nanoparticles (HA@SeNPs), enabling sustained immunomodulation and osteogenic activity through its engineered microtopography and bioactive components. Results In vitro evaluations confirmed that the unique microstructure and sustained selenium release from HA@SeNPs synergistically promoted macrophage polarization toward the M2 phenotype, accompanied by enhanced osteogenic differentiation as shown by upregulation of Runx2 and OCN and accelerated matrix mineralization. Implantation into a rat femoral critical-sized defect model resulted in substantially improved bone repair and architectural restoration. Conclusions These findings indicate that the intrinsic physicochemical properties of the PLGA/HA@SeNPs scaffold orchestrate a favorable osteo-immune environment, positioning it as a promising platform for bone regeneration.","PeriodicalId":9553,"journal":{"name":"Burns & Trauma","volume":"34 1","pages":""},"PeriodicalIF":5.3,"publicationDate":"2026-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148589027","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reversing Diabetic Wound Stagnation: Macrophage Polarization Dysregulation as a Therapeutic Linchpin from Pathogenesis to Precision Interventions","authors":"Shuwen Liu, Chenghao Cai, Huan Liu, Ziyue Zhao, Chunmao Han, Xingang Wang, Yiran Wang","doi":"10.1093/burnst/tkag044","DOIUrl":"https://doi.org/10.1093/burnst/tkag044","url":null,"abstract":"The stagnation of diabetic wound healing is a formidable global health challenge that is fundamentally driven by the dysregulation of macrophage plasticity. In the diabetic microenvironment, macrophages remain in a persistent proinflammatory (M1) state and fail to transition to the reparative (M2) phenotype essential for tissue regeneration. This review systematically elucidates the molecular pathology of this ‘conversion failure’ from a superficial to an in-depth level and provides a detailed explanation of the mechanisms underlying aberrant macrophage polarization in diabetic wounds, ranging from microenvironmental abnormalities to dysregulated signalling pathways. These perturbations create a vicious cycle of chronic inflammation, impaired angiogenesis, and pathological fibrosis. To address these challenges, we comprehensively outline current therapeutic strategies, including approaches that range from the precision molecular reprogramming of intracellular signalling hubs and gene networks to the engineering of microenvironment-responsive biomaterials capable of neutralizing oxidative stress and responding to pathological cues. Furthermore, we highlight the integration of exogenous bioactivity through stem cell- and exosome-based therapies aimed at replenishing the regenerative niche. Additionally, we critically assess translational bottlenecks, suggesting a paradigm shift from the binary M1/M2 model towards targeting intermediate phenotypes identified by single-cell multiomics. By integrating mechanistic insights with advanced immunomodulatory engineering, this review provides a theoretical framework for developing next-generation precision therapies to reverse the chronic nature of diabetic wounds.","PeriodicalId":9553,"journal":{"name":"Burns & Trauma","volume":"42 1","pages":""},"PeriodicalIF":5.3,"publicationDate":"2026-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148429066","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multifunctional pH-responsive HA-c-FZ1 hydrogel presents a promising therapeutic strategy for diabetic skin wounds","authors":"Zhe Fu, Jingyu Jiang, Yutong Wu, Zhaoxun Xiao, Yunhan Su, Hao Zhu, Shaowei Chen, Xinhe Shen, Xinyue Yang, Yunjian Luo, Tuanqing Li, Shibo Wang, Ying Wang, Xinwang Yang, Ying Yang","doi":"10.1093/burnst/tkag046","DOIUrl":"https://doi.org/10.1093/burnst/tkag046","url":null,"abstract":"Background Diabetic foot ulcers (DFUs) remain a major clinical challenge, driven by the convergent effects of microbial infection, chronic inflammation, oxidative stress, and inadequate neovascularization that collectively disrupt tissue repair. Although the integrin αvβ3 agonist peptide FZ1 exhibits promising pro-healing activity, limited delivery control and insufficient functional versatility have restricted its clinical translation. To overcome these constraints, a pH-responsive hyaluronic acid (HA)-based hydrogel, HA-c-FZ1, was developed to enable intelligent acidity-triggered peptide release while integrating antimicrobial activity, reactive oxygen species (ROS) scavenging, and inflammation control within a single wound dressing platform for diabetic wound repair. Methods First, photo-crosslinkable oxidized methacrylated HA (O-HAMA) was synthesized and covalently linked to FZ1 through a pH-labile Schiff base bond, yielding HA-c-FZ1 hydrogels at three concentrations (2%, 3%, and 4%). Hydrogel morphology, swelling behavior, mechanical properties, peptide-loading efficiency, pH-responsive release, antioxidant activity, antibacterial activity, biocompatibility, and anti-inflammatory effects were systematically evaluated in vitro. Therapeutic efficacy was then assessed in a diabetic mouse model with infected full-thickness skin wounds through wound closure analysis, histological staining, immunofluorescence detection of macrophage polarization markers (iNOS and ARG) and angiogenic markers (α-SMA and VEGF), and laser speckle imaging of blood perfusion. Transcriptomic profiling, RT-qPCR, and western blotting were performed to define the molecular mechanisms underlying HA-c-FZ1-mediated wound repair. Results HA-c-FZ1 formed a homogeneous porous hydrogel network with predictable swelling behavior, tunable mechanical performance, high FZ1 loading efficiency, and accelerated peptide release under acidic conditions. In vitro, HA-c-FZ1 promoted keratinocyte proliferation and migration, reduced ROS accumulation, and inhibited Staphylococcus aureus and Escherichia coli survival. In infected diabetic wounds, HA-c-FZ1 suppressed bacterial burden and accelerated wound closure, accompanied by enhanced re-epithelialization, collagen deposition, angiogenesis, and local blood perfusion. Mechanistic analyses indicated that HA-c-FZ1 attenuated NF-κB-associated inflammatory signaling, promoted M2 macrophage polarization, and activated FAK-AKT-dependent angiogenic responses. Conclusion HA-c-FZ1 functions as a pH-responsive hydrogel dressing that combines peptide delivery and antimicrobial, redox-regulatory, immunomodulatory, and pro-angiogenic functions. These findings position it as a therapy for chronic diabetic wound repair by simultaneously addressing infection, inflammation, oxidative stress, and vascular regeneration.","PeriodicalId":9553,"journal":{"name":"Burns & Trauma","volume":"30 1","pages":""},"PeriodicalIF":5.3,"publicationDate":"2026-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148385141","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"STUB1 Stabilizes SIRT6 via K63-Linked Ubiquitination to Promote NRF2 Deacetylation for Enhanced Ferroptosis Resistance after Spinal Cord Injury","authors":"Zhuanghui Wang, Wu Ye, Jiaxing Wang, Xuhui Ge, Yufeng Zhu, Wei Liu, Qinghong Ma, Weihua Cai, Yuluo Rong","doi":"10.1093/burnst/tkag047","DOIUrl":"https://doi.org/10.1093/burnst/tkag047","url":null,"abstract":"Background Spinal cord injury (SCI) is a severe traumatic condition with limited treatments. Ferroptosis, an iron-dependent type of controlled cell death, participates in SCI pathology. Nonetheless, the molecular mechanisms governing ferroptosis after SCI remain incompletely understood. Methods Ferroptosis markers were assessed in SCI mouse models and primary neurons. SIRT6 expression was regulated via lentiviral vectors and adeno-correlated viruses. Protein interactions were identified by immunoprecipitation coupled with mass spectrometry and co-immunoprecipitation. Ubiquitination assays were conducted using ubiquitin mutants. NRF2 knockout (NRF2-KO) mice were used for in vivo validation. Functional recovery was evaluated by Basso Mouse Scale score, rotarod test, footprint analysis, and electromyography. Results SIRT6 expression was downregulated following SCI and during erastin-induced ferroptosis. SIRT6 overexpression inhibited ferroptosis and triggered functional recovery, while SIRT6 suppression exacerbated these effects. Mechanistically, SIRT6 interacted with and deacetylated NRF2, promoting its nuclear translocation and antioxidant gene activation. STUB1 was identified as an upstream regulator that physically interacted with SIRT6 via its U-box domain. STUB1 stabilized SIRT6 by promoting K63-linked ubiquitination, protecting it from proteasomal degradation. STUB1 overexpression inhibited ferroptosis and improved functional recovery, effects that were abolished by SIRT6 knockdown or NRF2-KO. Conclusions The STUB1/SIRT6/NRF2 axis represents a novel regulatory pathway that suppresses neuronal ferroptosis and promotes functional recovery post-SCI. Targeting this axis may offer a prospective therapeutic strategy for SCI.","PeriodicalId":9553,"journal":{"name":"Burns & Trauma","volume":"13 1","pages":""},"PeriodicalIF":5.3,"publicationDate":"2026-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148393988","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Harnessing Plant-derived Extracellular Vesicles in Advanced Biomaterials: From Structural Scaffolds to Responsive Systems for Next-Generation Wound Therapeutics","authors":"Min Tan, Fengqin Luo, Ya Xu, Yuhe Dai, Junqi Yang, Qianbo Zhang, Xiuying Guo, Lele Liu, Ming Tang, Felicity Han, Xuqiang Nie","doi":"10.1093/burnst/tkag045","DOIUrl":"https://doi.org/10.1093/burnst/tkag045","url":null,"abstract":"Chronic non-healing wounds, particularly diabetic foot ulcers, persist as a significant clinical challenge due to the limited availability of therapeutic options and the complexity of their pathological microenvironments. Plant-derived extracellular vesicles (PDEVs), which are nanoscale lipid carriers rich in bioactive molecules, have emerged as a promising therapeutic approach due to their low immunogenicity, antioxidant and anti-inflammatory properties, and their ability to promote angiogenesis. Structurally, the biomaterial protects the integrity of PDEVs and extends their residency through modulated release. Biologically, PDEVs enhance the regenerative potential of the material by profoundly reprogramming the local cellular and immune microenvironments. However, their clinical application is severely impeded by their inherent instability in the dynamic wound microenvironment, which includes susceptibility to enzymatic degradation, disruption due to pH fluctuations, and rapid clearance by wound exudate. These factors collectively lead to premature cargo loss and reduced therapeutic efficacy. This review synthesizes how engineered biomaterials, serving as tailored structural platforms for controlled delivery, can overcome these stability challenges specific to PDEVs. By examining loading strategies and design principles, we demonstrate how composite systems surpass single-component therapies in diabetic wound models. Lastly, we address translational challenges and propose a development framework that integrates AI-driven design with mechanism-guided material optimization. This work lays the groundwork for the rational development of next-generation vesicle-enabled wound therapeutics.","PeriodicalId":9553,"journal":{"name":"Burns & Trauma","volume":"4 1","pages":""},"PeriodicalIF":5.3,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148385143","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mitochondrial Transfer: A Novel Paradigm for Wound Healing","authors":"Yin He, Hong-Chao Huang, Lei Li, Si-Ya Wang, Guang-Yi Wang, Shi-Chu Xiao, Yong-Jun Zheng","doi":"10.1093/burnst/tkag043","DOIUrl":"https://doi.org/10.1093/burnst/tkag043","url":null,"abstract":"Mitochondria not only serve as cellular powerhouses and metabolic regulatory hubs but also play crucial roles in calcium homeostasis, apoptosis regulation, and signal transduction. During wound repair, mitochondria modulate inflammatory and immune responses; drive angiogenesis; and supply energy for the proliferation, differentiation, and migration of repair cells such as fibroblasts and epithelial cells. When mitochondrial dysfunction exceeds the self-regulatory capacity, cellular energy deficits, metabolic disturbances, dysregulated signaling, and oxidative stress damage occur. These abnormalities collectively impair cellular repair mechanisms, ultimately contributing to chronic nonhealing wounds. Historically, mitochondria were thought to be acquired via vertical inheritance through cell division or mitochondrial biogenesis. However, the discovery of intercellular mitochondrial transfer provides novel insights into mitochondrial acquisition and presents new avenues for rescuing mitochondrial dysfunction. This article comprehensively reviews the dialectical relationship between mitochondrial dysfunction and impaired wound healing by integrating mechanisms of mitochondrial transfer, including modes, triggers, and regulatory pathways. It further highlights the therapeutic potential of mitochondrial transfer in wound repair. Additionally, this article provides forward-looking perspectives on clinical applications and future developments in mitochondrial transfer for wound healing, aiming to establish a theoretical foundation for mitochondrial transplantation therapies.","PeriodicalId":9553,"journal":{"name":"Burns & Trauma","volume":"49 1","pages":""},"PeriodicalIF":5.3,"publicationDate":"2026-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148342400","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"SFL-3D-cultured adipose mesenchymal cell-derived extracellular vesicles promote diabetic wound healing by alleviating microvascular endothelial senescence <i>via</i> PI3K/AKT/mTOR/4EBP1-mediated cap-dependent translation.","authors":"Yunwei Wang, Zhihan Hu, Ao Shi, Peng Cao, Luyang Zhao, Xiaoyu Di, Yuchen Kang, Jiatong Wang, Li Gong, Wenjiao Chen, Gang Wang, Guangtong Cao, Liang Luo, Ruomei Zhao, Xi Zhang, Yi Liu","doi":"10.1093/burnst/tkag042","DOIUrl":"10.1093/burnst/tkag042","url":null,"abstract":"<p><strong>Background: </strong>Diabetic foot ulcers (DFUs) are severe complications of diabetes, and treatment options for DFUs are limited. Current research on impaired angiogenesis in DFUs predominantly relies on generic endothelial cells, which inadequately reflect the pathophysiological microenvironment of the diabetic microvasculature. In contrast, this study focused specifically on human dermal microvascular endothelial cell (HDMEC) senescence as a central mechanism in DFU progression. We used a self-feeder layer 3D (SFL-3D) culture system to reprogram adipose-derived mesenchymal stem cells (ADSCs) to prepare functionally enhanced three-dimensional adipose stem cells (tdASCs) and their extracellular vesicles (tdASC-EVs) to mitigate HDMEC senescence and improve diabetic healing.</p><p><strong>Methods: </strong>EVs were isolated from SFL-3D-induced tdASCs and characterized. <i>In vitro</i>, high-glucose-induced HDMECs were treated with tdASC-EVs, after which senescence, oxidative stress, mitochondrial function, and angiogenesis were assessed. Pathway-specific inhibitors and a phosphorylation-mimetic 4EBP1 plasmid were used to validate the mechanistic involvement of the phosphatidylinositol 3-kinase/Ak strain transforming/mechanistic target of rapamycin/4E-binding protein 1 (PI3K/AKT/mTOR/4EBP1) axis and cap-dependent translation <i>via</i> m⁷GTP pull-down. <i>In vivo</i>, a fat graft model was used to assess the stem cell function of tdASCs, whereas a diabetic wound model was used to evaluate the therapeutic efficacy of tdASC-EVs.</p><p><strong>Results: </strong>tdASC-EVs significantly attenuated high-glucose-induced HDMEC senescence, oxidative stress, and mitochondrial dysfunction while increasing tube formation. Mechanistically, tdASC-EVs activated PI3K/AKT/mTOR signaling, increased 4EBP1 phosphorylation, and promoted eIF4E-eIF4G assembly. In diabetic mice, tdASC-EVs accelerated wound closure and increased microvascular density, which correlated with reduced p16 expression and increased CD31 and p-4EBP1 expression. In the Bama miniature pig diabetic large animal model, tdASC-EVs exhibited markedly superior therapeutic effects compared with those induced by conventional ADSC-EVs, as evidenced by significantly faster wound closure, greater neovascularization density, narrower scar width, and more orderly collagen deposition.</p><p><strong>Conclusions: </strong>tdASC-EVs ameliorated diabetic wound healing by targeting HDMEC senescence through PI3K/AKT/mTOR/4EBP1-mediated cap-dependent translational activation. The preclinical large animal data further confirmed the superior efficacy of tdASC-EVs over ADSC-EVs, highlighting the therapeutic potential of SFL-3D-modified EVs for DFU treatment.</p>","PeriodicalId":9553,"journal":{"name":"Burns & Trauma","volume":"14 ","pages":"tkag042"},"PeriodicalIF":11.0,"publicationDate":"2026-06-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13571603/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148963149","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neutrophil Extracellular Traps in Diabetic Wound Healing: Mechanisms, Pathological Roles, and Therapeutic Implications","authors":"Zhihan Hu, Yunwei Wang, Jiatong Wang, Guangtong Cao, Xiaoyu Di, Zongjiang Yao, Gang Wang, Yucheng Kang, Ruomei Zhao, Yi Liu","doi":"10.1093/burnst/tkag041","DOIUrl":"https://doi.org/10.1093/burnst/tkag041","url":null,"abstract":"Diabetic wound healing is a common yet challenging problem in clinical practice that involves complex pathophysiological processes and frequently progresses to chronic nonhealing wounds, imposing substantial burdens on both healthcare systems and patients while markedly decreasing quality of life. Persistent inflammatory responses represent a fundamental pathological feature of this condition. Accumulating evidence highlights the key role of neutrophil extracellular traps (NETs) in the chronic inflammatory response characteristic of diabetic wounds. As components of the innate immune system, NETs play pivotal roles in both host defence and tissue repair. NETosis is currently classified as vital NETosis or lytic NETosis. In this review, we synthesise existing evidence on the mechanistic heterogeneity of NETosis and further refine lytic NETosis subtypes on the basis of distinct molecular mechanisms and temporal dynamics—namely, NOX2-dependent classical lytic NETosis and mitochondrial ROS-driven rapid lytic NETosis. We also highlight the functional outcomes of NETs in response to specific stimuli within the diabetic wound milieu. Therapeutic strategies targeting NET formation, degradation, or neutralisation have shown considerable promise in preclinical studies; however, their clinical translation will require standardised biomarkers for NET quantification, localised delivery approaches to minimise systemic immunosuppression, and biomarker-guided frameworks to balance the risk of infection against healing benefits.","PeriodicalId":9553,"journal":{"name":"Burns & Trauma","volume":"156 1","pages":""},"PeriodicalIF":5.3,"publicationDate":"2026-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148286867","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}