Yunwei Wang, Luyang Zhao, Hao Ma, Ao Shi, Peng Cao, Feiyu Cai, Ruomei Zhao, Gang Wang, Zhihan Hu, Jiatong Wang, Yuchen Kang, Xiaoyu Di, Qingyi Zhang, Hao Zhang, Shuguang Hou, Babo Zhang, Han Wang, Yi Liu, Hao Guan
Background Hypertrophic scarring remains a critical challenge in regenerative medicine because of the limited efficacy of current antifibrotic therapies. Although dermal papilla cells (DPCs) exhibit intrinsic scar-inhibitory potential, their therapeutic utility is constrained by rapid replicative senescence and poor scalability in traditional monolayer cultures, necessitating innovative strategies to enhanceincrease cellular functionality and manufacturing feasibility. Methods A self-feeder layer 3D (SFL-3D) platform was established to reprogram primary human DPCs into rejuvenated tdDPC spheroids via autocrine–paracrine signalling activation. tdDPC-derived extracellular vesicles (tdDPC-EVs) were isolated from culture supernatants by differential centrifugation. The antifibrotic effects of tdDPC-EVs were systematically evaluated using human scar fibroblasts (HSFs) through scratch wound healing assays, CCK-8 proliferation assays, and fibrotic marker analysis (Western blotting and immunofluorescence staining for α-SMA and collagen I). Bioinformatics was used to predict key pathways involved in hypertrophic scar (HS) pathogenesis, whereas gain/loss-of-function studies investigated the miR-26a-5p/CCNE2 regulatory axis. Therapeutic validation was performed in a rabbit ear hypertrophic scar model with histopathological and molecular profiling. Results Compared with conventional 3D cultures, the SFL-3D system demonstrated superior proliferative support, enabling stable tdDPC expansion beyond 10 passages while maintaining high viability and enhanced EV biogenesis. miR-26a-5p-enriched tdDPC-EVs attenuated fibrosis through two mechanisms: (1) silencing CCNE2 to block PI3K/AKT-driven collagen overproduction and (2) suppressing α-SMA+ myofibroblast differentiation. In the rabbit ear HS model, tdDPC-EV administration reduced the scar elevation index and restored the collagen I/III ratio to near-physiological levels. Conclusions This study positions tdDPC-EVs as a scalable acellular therapy that overcomes the replicative senescence and manufacturing limitations of cellular approaches. The antiscarring efficacy of these EVs, which is mediated by the miR-26a-5p/CCNE2/PI3K/AKT axis, highlights their clinical potential as precision-targeted strategies for hypertrophic scar management. The SFL-3D platform further provides a translatable framework for EV-based regenerative therapeutics.
{"title":"Self-Organizing 3D Dermal Papilla Cell Spheroids Yield Therapeutic Extracellular Vesicles that Target Hypertrophic Scar Regression via the miR-26a-5p/CCNE2 Axis","authors":"Yunwei Wang, Luyang Zhao, Hao Ma, Ao Shi, Peng Cao, Feiyu Cai, Ruomei Zhao, Gang Wang, Zhihan Hu, Jiatong Wang, Yuchen Kang, Xiaoyu Di, Qingyi Zhang, Hao Zhang, Shuguang Hou, Babo Zhang, Han Wang, Yi Liu, Hao Guan","doi":"10.1093/burnst/tkaf048","DOIUrl":"https://doi.org/10.1093/burnst/tkaf048","url":null,"abstract":"Background Hypertrophic scarring remains a critical challenge in regenerative medicine because of the limited efficacy of current antifibrotic therapies. Although dermal papilla cells (DPCs) exhibit intrinsic scar-inhibitory potential, their therapeutic utility is constrained by rapid replicative senescence and poor scalability in traditional monolayer cultures, necessitating innovative strategies to enhanceincrease cellular functionality and manufacturing feasibility. Methods A self-feeder layer 3D (SFL-3D) platform was established to reprogram primary human DPCs into rejuvenated tdDPC spheroids via autocrine–paracrine signalling activation. tdDPC-derived extracellular vesicles (tdDPC-EVs) were isolated from culture supernatants by differential centrifugation. The antifibrotic effects of tdDPC-EVs were systematically evaluated using human scar fibroblasts (HSFs) through scratch wound healing assays, CCK-8 proliferation assays, and fibrotic marker analysis (Western blotting and immunofluorescence staining for α-SMA and collagen I). Bioinformatics was used to predict key pathways involved in hypertrophic scar (HS) pathogenesis, whereas gain/loss-of-function studies investigated the miR-26a-5p/CCNE2 regulatory axis. Therapeutic validation was performed in a rabbit ear hypertrophic scar model with histopathological and molecular profiling. Results Compared with conventional 3D cultures, the SFL-3D system demonstrated superior proliferative support, enabling stable tdDPC expansion beyond 10 passages while maintaining high viability and enhanced EV biogenesis. miR-26a-5p-enriched tdDPC-EVs attenuated fibrosis through two mechanisms: (1) silencing CCNE2 to block PI3K/AKT-driven collagen overproduction and (2) suppressing α-SMA+ myofibroblast differentiation. In the rabbit ear HS model, tdDPC-EV administration reduced the scar elevation index and restored the collagen I/III ratio to near-physiological levels. Conclusions This study positions tdDPC-EVs as a scalable acellular therapy that overcomes the replicative senescence and manufacturing limitations of cellular approaches. The antiscarring efficacy of these EVs, which is mediated by the miR-26a-5p/CCNE2/PI3K/AKT axis, highlights their clinical potential as precision-targeted strategies for hypertrophic scar management. The SFL-3D platform further provides a translatable framework for EV-based regenerative therapeutics.","PeriodicalId":9553,"journal":{"name":"Burns & Trauma","volume":"16 1","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144684743","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}
Jiaqiang Wang, Jie Zhang, Shan Zhong, Xuelian Chen, Hsin-Ying Liu, Chenghao Lu, Hanting Zhu, Yunsheng Chen, Jizhuang Wang, Jiarong Yu, Xiong Zhang, Yan Liu, Min Gao
Background Sepsis-induced myocardial injury (SIMI) is recognized as a severe complication of sepsis which characterized by a high mortality rate. Notably, the pathophysiology of SIMI involves complex mechanisms, including dysregulation of autophagy. Exosomes contribute to crucial biological processes during sepsis， modulating autophagy processes and facilitating communication between cells.. PIWI-interacting RNAs (piRNAs) are highly expressed in myocardial tissue and exert cardiovascular regulation properties. Therefore, we investigated the role of macrophage-derived exosome piRNAs, specifically piR-50 971, in SIMI and their impact on autophagy through m6A modification of mTOR. Methods A cecal ligation and puncture (CLP) model was established to mimic the pathophysiological features of SIMI. Plasma exosomes were isolated and sequenced to characterize the expression of sepsis-related piRNAs. Bioinformatics analysis was employed to predict the potential regulatory mechanisms involving piR-50 971. To investigate the direct interaction between piR-50 971 and mTOR, a dual-luciferase reporter assay was conducted. Moreover, a methylated RNA immunoprecipitation (MeRIP) assay was conducted to verify the involvement of piR-50 971 in the m6A methylation modification of mTOR transcripts. Additionally, the m6A methylation level was assessed using dot blotting. Results piR-50 971 was identified as a key piRNA upregulated in plasma exosomes during SIMI, which was correlated with the inhibition of autophagy. Increased macrophage infiltration was observed in the myocardium of rats with SIMI. Additionally, cardiomyocytes treated with macrophage-derived exosomes exhibited impaired autophagy. RNA binding protein immunoprecipitation assay demonstrated an interaction between WTAP protein and mTOR mRNA. piR-50 971 interacted with mTOR, leading to increased m6A modification through the regulation of WTAP and subsequent suppression of autophagy. Notably, this regulation upregulated mTOR translation, thereby inhibiting autophagy and exacerbating myocardial injury under septic conditions. In vivo experiments demonstrated that piR-50 971 inhibition ameliorated myocardial injury and improved autophagy in rats with SIMI. Conclusions Our findings reveal a novel mechanism by which macrophage-derived exosome piR-50 971 contributes to SIMI by suppressing autophagy via m6A modification of mTOR. Overall, our results implicate piR-50 971 as a potential target for therapeutic intervention in sepsis-related myocardial dysfunction.
{"title":"Macrophage-derived Exosome piR-50 971 Exacerbates Sepsis-induced Myocardial Injury by Inhibiting Autophagy through the Upregulation of N6-Methyladenosine Modification of mTOR","authors":"Jiaqiang Wang, Jie Zhang, Shan Zhong, Xuelian Chen, Hsin-Ying Liu, Chenghao Lu, Hanting Zhu, Yunsheng Chen, Jizhuang Wang, Jiarong Yu, Xiong Zhang, Yan Liu, Min Gao","doi":"10.1093/burnst/tkaf045","DOIUrl":"https://doi.org/10.1093/burnst/tkaf045","url":null,"abstract":"Background Sepsis-induced myocardial injury (SIMI) is recognized as a severe complication of sepsis which characterized by a high mortality rate. Notably, the pathophysiology of SIMI involves complex mechanisms, including dysregulation of autophagy. Exosomes contribute to crucial biological processes during sepsis， modulating autophagy processes and facilitating communication between cells.. PIWI-interacting RNAs (piRNAs) are highly expressed in myocardial tissue and exert cardiovascular regulation properties. Therefore, we investigated the role of macrophage-derived exosome piRNAs, specifically piR-50 971, in SIMI and their impact on autophagy through m6A modification of mTOR. Methods A cecal ligation and puncture (CLP) model was established to mimic the pathophysiological features of SIMI. Plasma exosomes were isolated and sequenced to characterize the expression of sepsis-related piRNAs. Bioinformatics analysis was employed to predict the potential regulatory mechanisms involving piR-50 971. To investigate the direct interaction between piR-50 971 and mTOR, a dual-luciferase reporter assay was conducted. Moreover, a methylated RNA immunoprecipitation (MeRIP) assay was conducted to verify the involvement of piR-50 971 in the m6A methylation modification of mTOR transcripts. Additionally, the m6A methylation level was assessed using dot blotting. Results piR-50 971 was identified as a key piRNA upregulated in plasma exosomes during SIMI, which was correlated with the inhibition of autophagy. Increased macrophage infiltration was observed in the myocardium of rats with SIMI. Additionally, cardiomyocytes treated with macrophage-derived exosomes exhibited impaired autophagy. RNA binding protein immunoprecipitation assay demonstrated an interaction between WTAP protein and mTOR mRNA. piR-50 971 interacted with mTOR, leading to increased m6A modification through the regulation of WTAP and subsequent suppression of autophagy. Notably, this regulation upregulated mTOR translation, thereby inhibiting autophagy and exacerbating myocardial injury under septic conditions. In vivo experiments demonstrated that piR-50 971 inhibition ameliorated myocardial injury and improved autophagy in rats with SIMI. Conclusions Our findings reveal a novel mechanism by which macrophage-derived exosome piR-50 971 contributes to SIMI by suppressing autophagy via m6A modification of mTOR. Overall, our results implicate piR-50 971 as a potential target for therapeutic intervention in sepsis-related myocardial dysfunction.","PeriodicalId":9553,"journal":{"name":"Burns & Trauma","volume":"14 1","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144629887","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}
Sepsis, a life-threatening syndrome driven by dysregulated immune responses to infection, presents significant global health challenges with high mortality rates. Neutrophil extracellular traps (NETs), composed of DNA and antimicrobial proteins, play a dual role in sepsis pathogenesis. While NETs trap pathogens and enhance immune responses via antimicrobial activity and immune cell activation, their overproduction exacerbates tissue damage, coagulopathy, and organ dysfunction. This review explores the mechanisms of NET formation, including suicidal, vital, and noncanonical NETosis, and their regulation through pattern recognition receptors, complement systems, and chemokine signaling. The interplay between NETs and immune cells—such as macrophages, T cells, and platelets - is highlighted, emphasizing NETs' role in both pathogen clearance and inflammatory injury. Excessive NETs contribute to sepsis-associated coagulopathy by activating platelets and damaging endothelial cells, while histones and proteases within NETs mediate cytotoxicity. Emerging therapeutic strategies targeting NETs, such as DNase, PAD4 inhibitors, and anti-inflammatory agents, show promise in preclinical studies but face clinical challenges due to their dual roles and off-target effects. Balancing NETs' protective and pathological functions remains critical for sepsis management. This review aims to provide a comprehensive understanding of NETs in sepsis, offering insights for future research and clinical applications.
{"title":"Neutrophil extracellular traps in sepsis: Trade-off between pros and cons","authors":"Fengying Liao, Jiangbo Fan, Rui Wang, Zhe Xu, Qinyuan Li, Wanda Bi, Jin Deng, Jianxin Jiang, Zhen Wang, Ling Zeng","doi":"10.1093/burnst/tkaf046","DOIUrl":"https://doi.org/10.1093/burnst/tkaf046","url":null,"abstract":"Sepsis, a life-threatening syndrome driven by dysregulated immune responses to infection, presents significant global health challenges with high mortality rates. Neutrophil extracellular traps (NETs), composed of DNA and antimicrobial proteins, play a dual role in sepsis pathogenesis. While NETs trap pathogens and enhance immune responses via antimicrobial activity and immune cell activation, their overproduction exacerbates tissue damage, coagulopathy, and organ dysfunction. This review explores the mechanisms of NET formation, including suicidal, vital, and noncanonical NETosis, and their regulation through pattern recognition receptors, complement systems, and chemokine signaling. The interplay between NETs and immune cells—such as macrophages, T cells, and platelets - is highlighted, emphasizing NETs' role in both pathogen clearance and inflammatory injury. Excessive NETs contribute to sepsis-associated coagulopathy by activating platelets and damaging endothelial cells, while histones and proteases within NETs mediate cytotoxicity. Emerging therapeutic strategies targeting NETs, such as DNase, PAD4 inhibitors, and anti-inflammatory agents, show promise in preclinical studies but face clinical challenges due to their dual roles and off-target effects. Balancing NETs' protective and pathological functions remains critical for sepsis management. This review aims to provide a comprehensive understanding of NETs in sepsis, offering insights for future research and clinical applications.","PeriodicalId":9553,"journal":{"name":"Burns & Trauma","volume":"29 1","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144639977","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}
Sepsis poses a critical threat to global health, mainly due to the disruption of immune homeostasis, which critically influences both early death and long-term adverse outcomes. Current evidence shows that regulatory T (Treg) cells—key mediators of adaptive immunity—play an essential role in maintaining immunological balance during the development of sepsis. During the initial hyperinflammatory phase, Treg cells actively suppress excessive inflammation, reducing tissue damage. Paradoxically, in the subsequent immunosuppressive phase, expanded Treg populations may worsen immunosuppression by inhibiting effector cell function, ultimately leading to poorer clinical outcomes. Recent research has identified novel Treg-specific biomarkers in sepsis and explained how the septic environment affects Treg numbers and function through various signalling pathways. This review combines current understanding of the phenotypic features and roles of Treg cells in sepsis, examines the regulatory mechanisms controlling Treg dynamics within the inflammatory setting, and explores therapeutic strategies targeting Treg cells across different immune phases, emphasizing both existing challenges and future directions.
{"title":"The Homeostasis and Heterogeneity of Regulatory T Cells in Sepsis","authors":"Dan Wu, Zhang Hao, Changhong Miao","doi":"10.1093/burnst/tkaf047","DOIUrl":"https://doi.org/10.1093/burnst/tkaf047","url":null,"abstract":"Sepsis poses a critical threat to global health, mainly due to the disruption of immune homeostasis, which critically influences both early death and long-term adverse outcomes. Current evidence shows that regulatory T (Treg) cells—key mediators of adaptive immunity—play an essential role in maintaining immunological balance during the development of sepsis. During the initial hyperinflammatory phase, Treg cells actively suppress excessive inflammation, reducing tissue damage. Paradoxically, in the subsequent immunosuppressive phase, expanded Treg populations may worsen immunosuppression by inhibiting effector cell function, ultimately leading to poorer clinical outcomes. Recent research has identified novel Treg-specific biomarkers in sepsis and explained how the septic environment affects Treg numbers and function through various signalling pathways. This review combines current understanding of the phenotypic features and roles of Treg cells in sepsis, examines the regulatory mechanisms controlling Treg dynamics within the inflammatory setting, and explores therapeutic strategies targeting Treg cells across different immune phases, emphasizing both existing challenges and future directions.","PeriodicalId":9553,"journal":{"name":"Burns & Trauma","volume":"39 1","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144629888","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}
Bingxue Qi, Siyang Chai, Yang Chen, Guannan Zhou, Peihong Li, Xueqing Li, Xiaodan Lu, Li-Hao Huang
O-linked β-D-N-acetylglucosamine (O-GlcNAc) modification represents a common form of posttranslational glycosylation orchestrated by two pivotal enzymes, namely, O-GlcNAc transferase and O-GlcNAcase. In recent years, emerging research has revealed a significant association between O-GlcNAc modification and the pathogenesis of diabetic foot ulcers (DFUs). Elevated O-GlcNAc levels under high-glucose conditions contribute to the pathogenesis of DFUs by modifying specific proteins, which are implicated in peripheral neuropathy, peripheral vascular disease, and impaired chronic wound healing. This process includes prolonged inflammation, compromised granulation tissue formation, disordered re-epithelialization, and blocked tissue remodelling. This review focuses on the pathogenesis of DFUs and on the correlation between protein O-GlcNAc modification and DFUs, offering potential new insights for the diagnosis and treatment of this condition.
O-linked β- d - n -乙酰氨基葡萄糖（O-GlcNAc）修饰是翻译后糖基化的一种常见形式，由两种关键酶，即O-GlcNAc转移酶和O-GlcNAcase介导。近年来，新兴研究揭示了O-GlcNAc修饰与糖尿病足溃疡（DFUs）发病机制之间的显著关联。在高糖条件下，O-GlcNAc水平升高通过改变与周围神经病变、周围血管疾病和慢性伤口愈合受损有关的特定蛋白，促进了DFUs的发病机制。这一过程包括炎症延长、肉芽组织形成受损、再上皮化紊乱和组织重构受阻。本文就DFUs的发病机制以及O-GlcNAc蛋白修饰与DFUs的相关性进行综述，为DFUs的诊断和治疗提供新的思路。
{"title":"The role of O-linked β-N-acetylglucosamine (O-GlcNAc) modification in diabetic foot ulcer pathogenesis","authors":"Bingxue Qi, Siyang Chai, Yang Chen, Guannan Zhou, Peihong Li, Xueqing Li, Xiaodan Lu, Li-Hao Huang","doi":"10.1093/burnst/tkaf044","DOIUrl":"https://doi.org/10.1093/burnst/tkaf044","url":null,"abstract":"O-linked β-D-N-acetylglucosamine (O-GlcNAc) modification represents a common form of posttranslational glycosylation orchestrated by two pivotal enzymes, namely, O-GlcNAc transferase and O-GlcNAcase. In recent years, emerging research has revealed a significant association between O-GlcNAc modification and the pathogenesis of diabetic foot ulcers (DFUs). Elevated O-GlcNAc levels under high-glucose conditions contribute to the pathogenesis of DFUs by modifying specific proteins, which are implicated in peripheral neuropathy, peripheral vascular disease, and impaired chronic wound healing. This process includes prolonged inflammation, compromised granulation tissue formation, disordered re-epithelialization, and blocked tissue remodelling. This review focuses on the pathogenesis of DFUs and on the correlation between protein O-GlcNAc modification and DFUs, offering potential new insights for the diagnosis and treatment of this condition.","PeriodicalId":9553,"journal":{"name":"Burns & Trauma","volume":"87 1","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144629889","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}
Traumatic brain injury (TBI) is a serious condition that poses a significant threat to human health globally. It is typically caused by direct trauma to the brain due to external forces such as impact or compression. The progression of TBI occurs in two stages based on physiological and pathological changes: primary and secondary brain injury. During the secondary stage, a large number of damage-associated molecular patterns (DAMPs) are released from injured cells into the extracellular space. These DAMPs trigger or exacerbate pathological conditions, including neuroinflammation, brain edema, diffuse axonal injury (DAI), and programmed cell death. The three main types of neural cells—neurons, microglia, and astrocytes—facilitate intercellular communication and functional crosstalk through the release and transmission of DAMPs. This forms the cellular foundation of secondary brain injury pathology. In the later stages of TBI, DAMPs are transported to various organs throughout the body via extracellular vesicles (EVs), leading to systemic changes and secondary injuries. Recent research has increasingly recognized the correlation between TBI and specific DAMPs. However, there remains a lack of comprehensive reviews exploring this relationship from a broader perspective. This review summarizes the primary pathological changes that occur after TBI, the types of DAMPs and their related signaling pathways, the role of DAMPs in mediating intercellular communication and neuronal crosstalk, the relationship between DAMPs and systemic changes following TBI. This study also highlights that DAMPs represent promising targets for the clinical diagnosis and treatment, which emphasizes the critical role of DAMPs in TBI.
{"title":"Role of damage-associated molecular patterns (DAMPs) in the pathogenesis and therapeutics of traumatic brain injury","authors":"Bowen Sun, Jiarui Zhang, Zhiqiang Li, Jialu Wang, Chuansheng Zhao, Xiaoxue Xu","doi":"10.1093/burnst/tkaf043","DOIUrl":"https://doi.org/10.1093/burnst/tkaf043","url":null,"abstract":"Traumatic brain injury (TBI) is a serious condition that poses a significant threat to human health globally. It is typically caused by direct trauma to the brain due to external forces such as impact or compression. The progression of TBI occurs in two stages based on physiological and pathological changes: primary and secondary brain injury. During the secondary stage, a large number of damage-associated molecular patterns (DAMPs) are released from injured cells into the extracellular space. These DAMPs trigger or exacerbate pathological conditions, including neuroinflammation, brain edema, diffuse axonal injury (DAI), and programmed cell death. The three main types of neural cells—neurons, microglia, and astrocytes—facilitate intercellular communication and functional crosstalk through the release and transmission of DAMPs. This forms the cellular foundation of secondary brain injury pathology. In the later stages of TBI, DAMPs are transported to various organs throughout the body via extracellular vesicles (EVs), leading to systemic changes and secondary injuries. Recent research has increasingly recognized the correlation between TBI and specific DAMPs. However, there remains a lack of comprehensive reviews exploring this relationship from a broader perspective. This review summarizes the primary pathological changes that occur after TBI, the types of DAMPs and their related signaling pathways, the role of DAMPs in mediating intercellular communication and neuronal crosstalk, the relationship between DAMPs and systemic changes following TBI. This study also highlights that DAMPs represent promising targets for the clinical diagnosis and treatment, which emphasizes the critical role of DAMPs in TBI.","PeriodicalId":9553,"journal":{"name":"Burns & Trauma","volume":"26 1","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-07-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144622219","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}
Mingzhou Yuan, Xu He, Guangtao Huang, Meifang Yin, Ilaria Dal’ Pra, Jinqing He, Jie Xiao, Dehua He, Jun Li, Xiaofang Liu, Rong Zhong, Yuncan Ma, Jun Wu
Background From the perspective of aesthetic surgery and regenerative medicine, the precision of surgical instruments is critical for preventing aesthetic complications during procedures such as skin debridement and the removal of unwanted tissues, as well as for better regeneration. Femtosecond lasers (fs-lasers) can achieve micrometer-level tissue removal. However, an uneven skin texture can cause the laser to defocus, leading to iatrogenic injury and hindering clinical application. Overcoming the defocusing tendency of fs-lasers is therefore crucial for their clinical use. Methods Our self-developed fs-laser microfabrication platform was used to implement a focus-corrected method based on two-dimensional interpolation for uneven skin surfaces, using different laser powers and velocities for linear, planar, and three-dimensional scanning of porcine skin. Leveraging the identified dose–response relationship, the optimized device and parameters were used for precise tissue ablation in an in vivo rat experiment. The structural integrity and viability of the remaining skin were evaluated histologically. Results Our study revealed that focus-corrected fs-laser ablation enabled controllable micrometer-level removal of target skin tissues. The depth of tissue removal was correlated with the fs-laser single-pulse energy. Unlike other laser devices, the scanning velocity did not affect the ablation depth, as the focusing mechanism of the focus-corrected fs-laser restricts ablation beyond the focal point. Appropriate fs-laser parameters for parallel linear scanning enabled tissue removal in various three-dimensional shapes. Increased depth of field, increased single-pulse energy, and faster scanning velocity enabled precise, rapid, and safe ablation of skin tissue in the rat model. Histological and biochemical analyses demonstrated that focus-corrected fs-laser debridement did not damage the surrounding collagen structure or cell viability of the wound. Conclusions We demonstrated that focus-corrected fs-laser ablation enables micron-scale skin removal with minimal collateral damage. By selectively adjusting single-pulse energy for depth-specific ablation and operation at the maximum permissible scanning velocity, this technique enables precise skin removal in the desired shape, offering an innovative and ultrahigh-precision surgical approach for skin as well as other tissues or organ surgery.
{"title":"Precision Removal of Uneven Skin Tissue at the Micrometer Level via Focus-Corrected Femtosecond-Laser Ablation","authors":"Mingzhou Yuan, Xu He, Guangtao Huang, Meifang Yin, Ilaria Dal’ Pra, Jinqing He, Jie Xiao, Dehua He, Jun Li, Xiaofang Liu, Rong Zhong, Yuncan Ma, Jun Wu","doi":"10.1093/burnst/tkaf042","DOIUrl":"https://doi.org/10.1093/burnst/tkaf042","url":null,"abstract":"Background From the perspective of aesthetic surgery and regenerative medicine, the precision of surgical instruments is critical for preventing aesthetic complications during procedures such as skin debridement and the removal of unwanted tissues, as well as for better regeneration. Femtosecond lasers (fs-lasers) can achieve micrometer-level tissue removal. However, an uneven skin texture can cause the laser to defocus, leading to iatrogenic injury and hindering clinical application. Overcoming the defocusing tendency of fs-lasers is therefore crucial for their clinical use. Methods Our self-developed fs-laser microfabrication platform was used to implement a focus-corrected method based on two-dimensional interpolation for uneven skin surfaces, using different laser powers and velocities for linear, planar, and three-dimensional scanning of porcine skin. Leveraging the identified dose–response relationship, the optimized device and parameters were used for precise tissue ablation in an in vivo rat experiment. The structural integrity and viability of the remaining skin were evaluated histologically. Results Our study revealed that focus-corrected fs-laser ablation enabled controllable micrometer-level removal of target skin tissues. The depth of tissue removal was correlated with the fs-laser single-pulse energy. Unlike other laser devices, the scanning velocity did not affect the ablation depth, as the focusing mechanism of the focus-corrected fs-laser restricts ablation beyond the focal point. Appropriate fs-laser parameters for parallel linear scanning enabled tissue removal in various three-dimensional shapes. Increased depth of field, increased single-pulse energy, and faster scanning velocity enabled precise, rapid, and safe ablation of skin tissue in the rat model. Histological and biochemical analyses demonstrated that focus-corrected fs-laser debridement did not damage the surrounding collagen structure or cell viability of the wound. Conclusions We demonstrated that focus-corrected fs-laser ablation enables micron-scale skin removal with minimal collateral damage. By selectively adjusting single-pulse energy for depth-specific ablation and operation at the maximum permissible scanning velocity, this technique enables precise skin removal in the desired shape, offering an innovative and ultrahigh-precision surgical approach for skin as well as other tissues or organ surgery.","PeriodicalId":9553,"journal":{"name":"Burns & Trauma","volume":"61 1","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-06-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144513152","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}
Articular cartilage injury is a significant concern in osteoarthritis (OA), and while traditional pharmacological treatments and surgical interventions have provided some pain relief and promoted cartilage regeneration to a certain extent, long-term therapeutic outcomes remain suboptimal. The advancement of cartilage tissue engineering has introduced novel perspectives for cartilage regeneration. Hydrogel scaffolds, as crucial components in tissue functionality, have evolved from their initial role of physical coverage or single functionality to current combinations of diverse functionalities. This review thoroughly examines recent applications of functional hydrogels in cartilage regeneration. This article begins by discussing essential background information, including treatment strategies for cartilage defects and the fundamental characteristics of hydrogels. Next, within the framework of cartilage tissue engineering, we analyse five categories of functional hydrogels, emphasizing their distinctive physicochemical properties, drug delivery capabilities, and stimulus-responsive features for cartilage repair. The discussion extends to their mechanisms of action, classification, and limitations. Clinical products related to hydrogels in this field are also summarized. Finally, recommendations are offered to address current challenges and future directions in the development of functional hydrogels for cartilage regeneration.
{"title":"Evolving Functional Hydrogel Strategies for Cartilage Engineering: From Fundamentals to Functional Regeneration","authors":"Aikang Li, Jingtao Huang, Jiaqing Chen, Liangbin Wu, Hui Zeng, Zhenhan Deng, Peng Liu, Jianjing Lin","doi":"10.1093/burnst/tkaf041","DOIUrl":"https://doi.org/10.1093/burnst/tkaf041","url":null,"abstract":"Articular cartilage injury is a significant concern in osteoarthritis (OA), and while traditional pharmacological treatments and surgical interventions have provided some pain relief and promoted cartilage regeneration to a certain extent, long-term therapeutic outcomes remain suboptimal. The advancement of cartilage tissue engineering has introduced novel perspectives for cartilage regeneration. Hydrogel scaffolds, as crucial components in tissue functionality, have evolved from their initial role of physical coverage or single functionality to current combinations of diverse functionalities. This review thoroughly examines recent applications of functional hydrogels in cartilage regeneration. This article begins by discussing essential background information, including treatment strategies for cartilage defects and the fundamental characteristics of hydrogels. Next, within the framework of cartilage tissue engineering, we analyse five categories of functional hydrogels, emphasizing their distinctive physicochemical properties, drug delivery capabilities, and stimulus-responsive features for cartilage repair. The discussion extends to their mechanisms of action, classification, and limitations. Clinical products related to hydrogels in this field are also summarized. Finally, recommendations are offered to address current challenges and future directions in the development of functional hydrogels for cartilage regeneration.","PeriodicalId":9553,"journal":{"name":"Burns & Trauma","volume":"90 1","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144503568","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}
Pub Date : 2025-06-12eCollection Date: 2025-01-01DOI: 10.1093/burnst/tkaf031
Ling Zhou, Haisheng Li, Gaoxing Luo
Necrotizing fasciitis (NF) is a disease characterized by severe infection of the skin and its underlying soft tissues as the initial symptom. NF is known for its difficulty in early diagnosis and rapid progression. If not treated promptly, NF can quickly evolve into systemic infection, sepsis, and multiple organ failure, and it may even lead to patient death. Currently, many controversies and challenges remain in clinical practice for the diagnosis and treatment of NF. To promote the standardization of NF diagnosis and treatment, Chinese Burn Association, Editorial Board of the Chinese Journal of Burns and Wounds, and Burn Medicine Branch of China International Exchange and Promotion Association for Medical and Health Care, based on the latest relevant guidelines, literature, and clinical practice experience and in accordance with the principles of evidence-based medicine, have jointly developed the Consensus on the Diagnosis and Treatment of Adult Necrotizing Fasciitis (2025 Edition) through repeated discussion and voting. This consensus aims to provide scientific and standardized guidance for clinical diagnosis and treatment.
{"title":"Consensus on the Diagnosis and Treatment of Adult Necrotizing Fasciitis (2025 Edition).","authors":"Ling Zhou, Haisheng Li, Gaoxing Luo","doi":"10.1093/burnst/tkaf031","DOIUrl":"10.1093/burnst/tkaf031","url":null,"abstract":"<p><p>Necrotizing fasciitis (NF) is a disease characterized by severe infection of the skin and its underlying soft tissues as the initial symptom. NF is known for its difficulty in early diagnosis and rapid progression. If not treated promptly, NF can quickly evolve into systemic infection, sepsis, and multiple organ failure, and it may even lead to patient death. Currently, many controversies and challenges remain in clinical practice for the diagnosis and treatment of NF. To promote the standardization of NF diagnosis and treatment, Chinese Burn Association, <i>Editorial Board of the Chinese Journal of Burns and Wounds</i>, and Burn Medicine Branch of China International Exchange and Promotion Association for Medical and Health Care, based on the latest relevant guidelines, literature, and clinical practice experience and in accordance with the principles of evidence-based medicine, have jointly developed the Consensus on the Diagnosis and Treatment of Adult Necrotizing Fasciitis (2025 Edition) through repeated discussion and voting. This consensus aims to provide scientific and standardized guidance for clinical diagnosis and treatment.</p>","PeriodicalId":9553,"journal":{"name":"Burns & Trauma","volume":"13 ","pages":"tkaf031"},"PeriodicalIF":6.3,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12225674/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144559300","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}
Background Chronic nonhealing wounds are major complications in diabetic patients, with impaired angiogenesis playing a critical role in the delayed healing process. Current treatments for diabetic wounds are inadequate. The dysregulation of endothelial cell genes, particularly thrombospondin-1 (TSP-1), impairs neovascularization and delays wound repair. In recent years, hydrogel-based wound dressings have gained widespread application in biomedicine. The study introduced a new therapeutic approach, embedding miR-221-3p-loaded small extracellular vesicles (miR-221OE-sEVs) within gelatin methacryloyl (GelMA) hydrogels to reduce TSP-1 level and improve healing in diabetic wounds. Methods First, we observed upregulated TSP-1 expression in human umbilical vein endothelial cells (HUVECs) when cultured in a high glucose (HG) environment. We employed siRNA and miR-221-3p to suppress TSP-1 expression then evaluate the functional effects on HUVECs. Subsequently, miR-221-3p was encapsulated in sEVs via lentiviral transfection. The effects of miR-221OE-sEVs on HUVECs under HG conditions were evaluated. Finally, miR-221OE-sEVs were incorporated into a GelMA hydrogel (G-miR-221OE-sEVs) and applied to a diabetic murine wound model to evaluate their effects on wound closure and angiogenesis. Results Under HG conditions, the use of siTSP-1 to silence TSP-1 enhanced the proliferation, migration, and tube formation capabilities of HUVECs. Similarly, miR-221-3p treatment exerted proregenerative effects via the targeting of TSP-1. We successfully generated miR-221OE-sEVs that exhibited a 28-fold increase in miR-221-3p expression, which significantly enhanced HUVEC functionality under HG conditions. Encapsulation within the GelMA hydrogel enabled G-miR-221OE-sEVs to significantly accelerate diabetic wound healing via increased angiogenesis. Conclusion This study demonstrated the successful fabrication of a novel bioactive wound dressing (G-miR-221OE-sEVs), which promotes diabetic wound healing by promoting angiogenesis through the regulation of TSP-1. This approach offers a potential therapeutic option for enhancing the management of diabetic wounds.
{"title":"Engineered sEVs encapsulated in GelMA facilitated diabetic wound healing by promoting angiogenesis via targeting thrombospondin-1","authors":"Yan Cong, Sheng Meng, Xiaoye Xie, Yiqi Chen, Yucong Li, Yingqian Zhou, Wandi Li, Lipeng Zhang, Guoqing Yang, Qian Wei, Chuan'an Shen","doi":"10.1093/burnst/tkaf036","DOIUrl":"https://doi.org/10.1093/burnst/tkaf036","url":null,"abstract":"Background Chronic nonhealing wounds are major complications in diabetic patients, with impaired angiogenesis playing a critical role in the delayed healing process. Current treatments for diabetic wounds are inadequate. The dysregulation of endothelial cell genes, particularly thrombospondin-1 (TSP-1), impairs neovascularization and delays wound repair. In recent years, hydrogel-based wound dressings have gained widespread application in biomedicine. The study introduced a new therapeutic approach, embedding miR-221-3p-loaded small extracellular vesicles (miR-221OE-sEVs) within gelatin methacryloyl (GelMA) hydrogels to reduce TSP-1 level and improve healing in diabetic wounds. Methods First, we observed upregulated TSP-1 expression in human umbilical vein endothelial cells (HUVECs) when cultured in a high glucose (HG) environment. We employed siRNA and miR-221-3p to suppress TSP-1 expression then evaluate the functional effects on HUVECs. Subsequently, miR-221-3p was encapsulated in sEVs via lentiviral transfection. The effects of miR-221OE-sEVs on HUVECs under HG conditions were evaluated. Finally, miR-221OE-sEVs were incorporated into a GelMA hydrogel (G-miR-221OE-sEVs) and applied to a diabetic murine wound model to evaluate their effects on wound closure and angiogenesis. Results Under HG conditions, the use of siTSP-1 to silence TSP-1 enhanced the proliferation, migration, and tube formation capabilities of HUVECs. Similarly, miR-221-3p treatment exerted proregenerative effects via the targeting of TSP-1. We successfully generated miR-221OE-sEVs that exhibited a 28-fold increase in miR-221-3p expression, which significantly enhanced HUVEC functionality under HG conditions. Encapsulation within the GelMA hydrogel enabled G-miR-221OE-sEVs to significantly accelerate diabetic wound healing via increased angiogenesis. Conclusion This study demonstrated the successful fabrication of a novel bioactive wound dressing (G-miR-221OE-sEVs), which promotes diabetic wound healing by promoting angiogenesis through the regulation of TSP-1. This approach offers a potential therapeutic option for enhancing the management of diabetic wounds.","PeriodicalId":9553,"journal":{"name":"Burns & Trauma","volume":"102 1","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144278355","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}
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