Oxidative stress is an inherent pathophysiological feature in burn wound healing. Severe burns trigger rapid changes in patients' conditions, leading to ischemia–reperfusion injury from early fluid resuscitation, neuroendocrine stress and fluid imbalances, which exacerbate oxidative damage and organ dysfunction. This review highlights the critical role of oxidative stress in post-burn wound healing, its potential to cause cellular and tissue damage, and oxidative stress mechanisms. Antioxidant therapy is recommended as a cost-effective method of modulating inflammation and burn outcome. Preparative measures of successful antioxidant therapy should be developed in improving burn patients' wound healing.
{"title":"Role of oxidative stress in post-burn wound healing","authors":"Ruiqi Chen, Hongbiao Xu, Xueshi Li, Jie Dong, Shengli Wang, Jianlei Hao, Guangping Liang","doi":"10.1093/burnst/tkaf040","DOIUrl":"https://doi.org/10.1093/burnst/tkaf040","url":null,"abstract":"Oxidative stress is an inherent pathophysiological feature in burn wound healing. Severe burns trigger rapid changes in patients' conditions, leading to ischemia–reperfusion injury from early fluid resuscitation, neuroendocrine stress and fluid imbalances, which exacerbate oxidative damage and organ dysfunction. This review highlights the critical role of oxidative stress in post-burn wound healing, its potential to cause cellular and tissue damage, and oxidative stress mechanisms. Antioxidant therapy is recommended as a cost-effective method of modulating inflammation and burn outcome. Preparative measures of successful antioxidant therapy should be developed in improving burn patients' wound healing.","PeriodicalId":9553,"journal":{"name":"Burns & Trauma","volume":"587 1","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144268724","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}
Biomimetic nano dressings have superior biological activity, biocompatibility, and stimuli-responsive properties compared with traditional wound dressings due to their biomimetic design integration and show great potential in wound management. This review summarizes the materials and techniques used to prepare current biomimetic nano dressings, focusing on biomimetic design strategies. Moreover, we explore the application of biomimetic nano dressings in treating wounds associated with infections, burns, diabetes, and postoperative skin cancer. This review provides new perspectives on the design of biomimetic nano dressings and highlights future research directions to further advance innovative wound treatment strategies.
{"title":"Biomimetic Nano Dressing in Wound Healing: Design Strategies and Application","authors":"Menglei Wang, Haiqing Li, Yawen Luo, Jiawen Chen, Ziyi Tang, Yu Wei, Qianwen Yang, Wantong Xiao, Wanchun You, Meixin Feng, Jing Shen, Li Li","doi":"10.1093/burnst/tkaf038","DOIUrl":"https://doi.org/10.1093/burnst/tkaf038","url":null,"abstract":"Biomimetic nano dressings have superior biological activity, biocompatibility, and stimuli-responsive properties compared with traditional wound dressings due to their biomimetic design integration and show great potential in wound management. This review summarizes the materials and techniques used to prepare current biomimetic nano dressings, focusing on biomimetic design strategies. Moreover, we explore the application of biomimetic nano dressings in treating wounds associated with infections, burns, diabetes, and postoperative skin cancer. This review provides new perspectives on the design of biomimetic nano dressings and highlights future research directions to further advance innovative wound treatment strategies.","PeriodicalId":9553,"journal":{"name":"Burns & Trauma","volume":"47 1","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144252084","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}
Peripheral nerve injury (PNI) results in sensory and motor dysfunction, which is an enormous economic burden for patients and society. Complete recovery of peripheral nerve function after injury is complicated. Utilizing the electrophysiological properties of natural nerves for neuronal regulation and axon regeneration has attracted considerable interest. Electroactive biomaterials induce an active state of electrical stimulation (ES) at the site of peripheral nerve injury when incorporated into nerve guidance channels (NGCs). Numerous studies have demonstrated that combining ES with electroactive biomaterials can enhance peripheral nerve repair. This review summarizes the regulation of signal pathways by ES and the functions of various electroactive biomaterials, including metals, carbon-based materials, conductive polymers and piezoelectric materials. Recent advances and research of ES combined with electroactive biomaterials in peripheral nerve repair are reviewed, which may help to come up with more effective strategies to restore neural function after PNI.
{"title":"Review on electrical stimulation combined with electroactive biomaterials to promote peripheral nerve regeneration","authors":"Jiahui Song, Zhengchao Yuan, Xiao Yu, Yihong Shen, Jinglei Wu, Binbin Sun, Cheng Xue Qin, Mohamed EL-Newehy, Xiumei Mo, Hongbing Gu","doi":"10.1093/burnst/tkaf039","DOIUrl":"https://doi.org/10.1093/burnst/tkaf039","url":null,"abstract":"Peripheral nerve injury (PNI) results in sensory and motor dysfunction, which is an enormous economic burden for patients and society. Complete recovery of peripheral nerve function after injury is complicated. Utilizing the electrophysiological properties of natural nerves for neuronal regulation and axon regeneration has attracted considerable interest. Electroactive biomaterials induce an active state of electrical stimulation (ES) at the site of peripheral nerve injury when incorporated into nerve guidance channels (NGCs). Numerous studies have demonstrated that combining ES with electroactive biomaterials can enhance peripheral nerve repair. This review summarizes the regulation of signal pathways by ES and the functions of various electroactive biomaterials, including metals, carbon-based materials, conductive polymers and piezoelectric materials. Recent advances and research of ES combined with electroactive biomaterials in peripheral nerve repair are reviewed, which may help to come up with more effective strategies to restore neural function after PNI.","PeriodicalId":9553,"journal":{"name":"Burns & Trauma","volume":"3 1","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144188839","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}
Xiaoran Zu, Yudi Han, Yongqiang Zhou, Long Zhu, Youbai Chen, Xi Lu, Chenxuan Yang, Xiaomin Hu, Tengwen Zhang, Ming Zhang, Wei Zhou, Chaoji Huangfu, Yue Gao, Yan Han
Background Infected wounds caused by bacteria such as Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) pose significant challenges during the healing process. Hydrogels have emerged as promising materials for the treatment of such infections, as they have the potential to deliver therapeutic agents while supporting tissue repair. Methods In this study, we developed ε-PLL@SA/Gel (PSG) hydrogels by embedding different concentrations of ε-poly-L-lysine (ε-PLL) into sodium alginate (SA)/gelatin (Gel) hydrogels using calcium chloride as a crosslinking agent. The mechanical properties, biocompatibility, antibacterial activity, and wound healing efficacy of the hydrogels were evaluated in vitro and in vivo in mouse models of infected wounds. Results PSG hydrogels exhibited excellent mechanical strength, injectability, and self-adhesive properties. In vitro, hydrogel treatment resulted in high cell viability and promoted human skin fibroblast proliferation. PSG15 exhibited the highest antibacterial activity and inhibited E. coli and S. aureus by 89.53% and 92.21%, respectively. In vivo, PSG15 significantly accelerated wound healing, enhanced angiogenesis, and regulated macrophage polarization by increasing CD206 expression and decreasing CD80 expression. Additionally, PSG15 modulated the skin microbiota, reduced pathogenic bacterial abundance and maintained microbiota diversity. Conclusion The PSG15 hydrogel is a promising candidate for the treatment of infected wounds because it inhibits bacterial growth, promotes tissue repair, and modulates the wound microbiota.
{"title":"A multifunctional injectable ε-poly-L-lysine-loaded sodium-alginate/gelatin hydrogel promotes the healing of infected wounds by regulating macrophage polarization and the skin microbiota","authors":"Xiaoran Zu, Yudi Han, Yongqiang Zhou, Long Zhu, Youbai Chen, Xi Lu, Chenxuan Yang, Xiaomin Hu, Tengwen Zhang, Ming Zhang, Wei Zhou, Chaoji Huangfu, Yue Gao, Yan Han","doi":"10.1093/burnst/tkaf037","DOIUrl":"https://doi.org/10.1093/burnst/tkaf037","url":null,"abstract":"Background Infected wounds caused by bacteria such as Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) pose significant challenges during the healing process. Hydrogels have emerged as promising materials for the treatment of such infections, as they have the potential to deliver therapeutic agents while supporting tissue repair. Methods In this study, we developed ε-PLL@SA/Gel (PSG) hydrogels by embedding different concentrations of ε-poly-L-lysine (ε-PLL) into sodium alginate (SA)/gelatin (Gel) hydrogels using calcium chloride as a crosslinking agent. The mechanical properties, biocompatibility, antibacterial activity, and wound healing efficacy of the hydrogels were evaluated in vitro and in vivo in mouse models of infected wounds. Results PSG hydrogels exhibited excellent mechanical strength, injectability, and self-adhesive properties. In vitro, hydrogel treatment resulted in high cell viability and promoted human skin fibroblast proliferation. PSG15 exhibited the highest antibacterial activity and inhibited E. coli and S. aureus by 89.53% and 92.21%, respectively. In vivo, PSG15 significantly accelerated wound healing, enhanced angiogenesis, and regulated macrophage polarization by increasing CD206 expression and decreasing CD80 expression. Additionally, PSG15 modulated the skin microbiota, reduced pathogenic bacterial abundance and maintained microbiota diversity. Conclusion The PSG15 hydrogel is a promising candidate for the treatment of infected wounds because it inhibits bacterial growth, promotes tissue repair, and modulates the wound microbiota.","PeriodicalId":9553,"journal":{"name":"Burns & Trauma","volume":"12 1","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144188837","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}
Background Angiogenesis is vital for tissue repair but insufficient in chronic wounds due to paradoxical growth factor overexpression yet reduced neovascularization. Therapeutics physiologically promoting revascularization remain lacking. This study aims to investigate the molecular mechanisms underlying fibroblast-derived exosome-mediated angiogenesis during wound repair. Methods To assess the effects of fibroblasts derived exosomes on wound healing and angiogenesis, a full-thickness mouse skin injury model was established, followed by pharmacological inhibition of exosome secretion. The number and state of blood vessels in wounds were assessed by immunofluorescence, immunohistochemistry, hematoxylin–eosin staining, and laser Doppler imaging system. The high-throughput miRNA sequencing was carried out to detect the miRNA profiles of fibroblast-derived exosomes. The roles of candidate miRNAs, their target genes, and relevant pathways were predicted by bioinformatic online software. The knockdown and overexpression of candidate miRNAs, co-culture system, matrigel assay, pharmacological blockade, cell migration, EdU incorporation assay, and cell apoptosis were employed to investigate their contribution to angiogenesis mediated by fibroblast-derived exosomes. The expression of vascular endothelial growth factor A (VEGFA), vascular endothelial growth factor receptor 2 (VEGFR2), hypoxia-inducible factor 1α (HIF-1α), von Hippel–Lindau (VHL), and proline hydroxylases 2 was detected by western blot, co-immunoprecipitation, immunofluorescence, real-time quantitative polymerase chain reaction, flow cytometry, and immunohistochemistry. Furthermore, a full-thickness mouse skin injury model based on type I diabetes mellitus induced by streptozotocin was established for estimating the effect of fibroblast-derived exosomes on chronic wound healing. Results Pharmacological inhibition of exosome biogenesis markedly reduces neovascularization and delays murine cutaneous wound closure. Topical administration of fibroblast-secreted exosomes rescues these defects. Mechanistically, exosomal microRNA-24-3p suppresses VHL E3 ubiquitin ligase levels in endothelial cells to stabilize hypoxia-inducible factor-1α and heighten vascular endothelial growth factor signaling. MicroRNA-24-3p-deficient exosomes exhibit attenuated pro-angiogenic effects. Strikingly, topical application of exosomes derived from fibroblasts onto chronic wounds in diabetic mice improves neovascularization and healing dynamics. Conclusions Overall, we demonstrate central roles for exosomal miR-24-3p in stimulating endothelial HIF-VEGF signaling by inhibiting VHL-mediated degradation. The findings establish fibroblast-derived exosomes as promising acellular therapeutic candidates to treat vascular insufficiency underlying recalcitrant wounds.
{"title":"Exosomes derived from fibroblasts enhance skin wound angiogenesis by regulating HIF-1α/VEGF/VEGFR pathway","authors":"Yunxia Chen, Wenjing Yin, Zhihui Liu, Guang Lu, Xiaorong Zhang, Jiacai Yang, Yong Huang, Xiaohong Hu, Cheng Chen, Ruoyu Shang, Wengang Hu, Jue Wang, Han-Ming Shen, Jun Hu, Gaoxing Luo, Weifeng He","doi":"10.1093/burnst/tkae071","DOIUrl":"https://doi.org/10.1093/burnst/tkae071","url":null,"abstract":"Background Angiogenesis is vital for tissue repair but insufficient in chronic wounds due to paradoxical growth factor overexpression yet reduced neovascularization. Therapeutics physiologically promoting revascularization remain lacking. This study aims to investigate the molecular mechanisms underlying fibroblast-derived exosome-mediated angiogenesis during wound repair. Methods To assess the effects of fibroblasts derived exosomes on wound healing and angiogenesis, a full-thickness mouse skin injury model was established, followed by pharmacological inhibition of exosome secretion. The number and state of blood vessels in wounds were assessed by immunofluorescence, immunohistochemistry, hematoxylin–eosin staining, and laser Doppler imaging system. The high-throughput miRNA sequencing was carried out to detect the miRNA profiles of fibroblast-derived exosomes. The roles of candidate miRNAs, their target genes, and relevant pathways were predicted by bioinformatic online software. The knockdown and overexpression of candidate miRNAs, co-culture system, matrigel assay, pharmacological blockade, cell migration, EdU incorporation assay, and cell apoptosis were employed to investigate their contribution to angiogenesis mediated by fibroblast-derived exosomes. The expression of vascular endothelial growth factor A (VEGFA), vascular endothelial growth factor receptor 2 (VEGFR2), hypoxia-inducible factor 1α (HIF-1α), von Hippel–Lindau (VHL), and proline hydroxylases 2 was detected by western blot, co-immunoprecipitation, immunofluorescence, real-time quantitative polymerase chain reaction, flow cytometry, and immunohistochemistry. Furthermore, a full-thickness mouse skin injury model based on type I diabetes mellitus induced by streptozotocin was established for estimating the effect of fibroblast-derived exosomes on chronic wound healing. Results Pharmacological inhibition of exosome biogenesis markedly reduces neovascularization and delays murine cutaneous wound closure. Topical administration of fibroblast-secreted exosomes rescues these defects. Mechanistically, exosomal microRNA-24-3p suppresses VHL E3 ubiquitin ligase levels in endothelial cells to stabilize hypoxia-inducible factor-1α and heighten vascular endothelial growth factor signaling. MicroRNA-24-3p-deficient exosomes exhibit attenuated pro-angiogenic effects. Strikingly, topical application of exosomes derived from fibroblasts onto chronic wounds in diabetic mice improves neovascularization and healing dynamics. Conclusions Overall, we demonstrate central roles for exosomal miR-24-3p in stimulating endothelial HIF-VEGF signaling by inhibiting VHL-mediated degradation. The findings establish fibroblast-derived exosomes as promising acellular therapeutic candidates to treat vascular insufficiency underlying recalcitrant wounds.","PeriodicalId":9553,"journal":{"name":"Burns & Trauma","volume":"58 1","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144153363","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}
Shurong Zhang, Tian Xia, Xuesong Dai, Gregory S DiFelice, Lars Engebretsen, Alberto Gobbi, Christiaan H Heusdens, Gordon M MacKay, Bertrand Sonnery-cottet, Jelle P van der List, Shu-Hang P Yung, Jianquan Wang, Yinghui Hua
The application of primary repair for anterior cruciate ligament (ACL) injuries remains controversial, and evidence-based guidelines have not yet been established. Remarkable advancements in arthroscopic techniques and biological stimuli have been achieved in the past decades, which may change expectations regarding the potential of ACL healing and clinical outcomes for patients. In this study, a global expert consensus on the primary repair of proximal ACL injuries was established. A panel of 16 experts from the fields of sports medicine and arthroscopic surgery was invited to participate in the compilation of this consensus statement. This project followed the Delphi approach to the consensus process involving steering, rating, and peer review groups. Ultimately, 14 statements were retained: four achieved unanimous support, six achieved strong consensus, and four did not achieve consensus. The expert consensus statement established in this study focused on surgical indications, decision-making, surgical techniques, adjunctive methods, prognostic factors, and rehabilitation following ACL repair. The accepted recommendations in these areas will assist doctors and therapists in standardizing the management of related pathologies. The consensus statement clearly states that the tear site and tissue quality are important for ensuring successful ACL repair, while other factors should also be considered. ACL reconstruction remains the gold standard for ACL repair until long-term follow-up data demonstrates otherwise.
{"title":"Primary repair of proximal anterior cruciate ligament injury: a global expert consensus statement","authors":"Shurong Zhang, Tian Xia, Xuesong Dai, Gregory S DiFelice, Lars Engebretsen, Alberto Gobbi, Christiaan H Heusdens, Gordon M MacKay, Bertrand Sonnery-cottet, Jelle P van der List, Shu-Hang P Yung, Jianquan Wang, Yinghui Hua","doi":"10.1093/burnst/tkae079","DOIUrl":"https://doi.org/10.1093/burnst/tkae079","url":null,"abstract":"The application of primary repair for anterior cruciate ligament (ACL) injuries remains controversial, and evidence-based guidelines have not yet been established. Remarkable advancements in arthroscopic techniques and biological stimuli have been achieved in the past decades, which may change expectations regarding the potential of ACL healing and clinical outcomes for patients. In this study, a global expert consensus on the primary repair of proximal ACL injuries was established. A panel of 16 experts from the fields of sports medicine and arthroscopic surgery was invited to participate in the compilation of this consensus statement. This project followed the Delphi approach to the consensus process involving steering, rating, and peer review groups. Ultimately, 14 statements were retained: four achieved unanimous support, six achieved strong consensus, and four did not achieve consensus. The expert consensus statement established in this study focused on surgical indications, decision-making, surgical techniques, adjunctive methods, prognostic factors, and rehabilitation following ACL repair. The accepted recommendations in these areas will assist doctors and therapists in standardizing the management of related pathologies. The consensus statement clearly states that the tear site and tissue quality are important for ensuring successful ACL repair, while other factors should also be considered. ACL reconstruction remains the gold standard for ACL repair until long-term follow-up data demonstrates otherwise.","PeriodicalId":9553,"journal":{"name":"Burns & Trauma","volume":"47 1","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144130672","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}
Aiping Liu,Marien Ochoa,Matthew S Reed,Mary Junak,Joana Pashaj,Brian W Pogue,Angela L F Gibson
{"title":"Indocyanine green and protoporphyrin IX fluorescence imaging of inflammation, hypoxia, and necrosis of burns.","authors":"Aiping Liu,Marien Ochoa,Matthew S Reed,Mary Junak,Joana Pashaj,Brian W Pogue,Angela L F Gibson","doi":"10.1093/burnst/tkaf021","DOIUrl":"https://doi.org/10.1093/burnst/tkaf021","url":null,"abstract":"","PeriodicalId":9553,"journal":{"name":"Burns & Trauma","volume":"31 1","pages":"tkaf021"},"PeriodicalIF":5.3,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144114266","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}
Shuai Wei, Jin Dong, Qian Hu, Jinyu Bai, Xiang Gao, Huajian Shan, Lei Sheng, Jun Dai, Fengxian Jiang, Lide Tao, Bing Yan, Xiaozhong Zhou
Peripheral nerve injury constitutes a complex neurotraumatic pathology characterized by mechanical disruption of neural integrity, manifesting as multimodal sensorimotor deficits and impaired neuromuscular coordination. The primary clinical interventions include surgical tension-free suturing of the severed nerve ends and autologous nerve transplantation. Despite these interventions, patients often experience complications, and the outcomes are not entirely satisfactory for either patients or clinicians. Mesenchymal stem cells (MSCs) have gradually become a novel therapeutic option, with burgeoning preclinical evidence elucidating their multimodal therapeutic potential in peripheral nerve reconstruction. This research has produced promising outcomes, contributing to both fundamental research and translational medicine. However, a comprehensive synthesis of the roles of MSCs and their derivatives in nerve regeneration is still lacking. This article presents a review of the current research advancements in this area, aiming to encourage further investigations and therapeutic applications of MSCs and their derivatives in peripheral nerve injury and regenerative medicine.
{"title":"Advances in mesenchymal stem cells and their derivatives for promoting peripheral nerve regeneration","authors":"Shuai Wei, Jin Dong, Qian Hu, Jinyu Bai, Xiang Gao, Huajian Shan, Lei Sheng, Jun Dai, Fengxian Jiang, Lide Tao, Bing Yan, Xiaozhong Zhou","doi":"10.1093/burnst/tkaf027","DOIUrl":"https://doi.org/10.1093/burnst/tkaf027","url":null,"abstract":"Peripheral nerve injury constitutes a complex neurotraumatic pathology characterized by mechanical disruption of neural integrity, manifesting as multimodal sensorimotor deficits and impaired neuromuscular coordination. The primary clinical interventions include surgical tension-free suturing of the severed nerve ends and autologous nerve transplantation. Despite these interventions, patients often experience complications, and the outcomes are not entirely satisfactory for either patients or clinicians. Mesenchymal stem cells (MSCs) have gradually become a novel therapeutic option, with burgeoning preclinical evidence elucidating their multimodal therapeutic potential in peripheral nerve reconstruction. This research has produced promising outcomes, contributing to both fundamental research and translational medicine. However, a comprehensive synthesis of the roles of MSCs and their derivatives in nerve regeneration is still lacking. This article presents a review of the current research advancements in this area, aiming to encourage further investigations and therapeutic applications of MSCs and their derivatives in peripheral nerve injury and regenerative medicine.","PeriodicalId":9553,"journal":{"name":"Burns & Trauma","volume":"25 1","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144097243","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}
Li-yu Zheng, Peng-yi He, Peng-yue Zhao, Yu Duan, Meng-yao Wu, Shu-ting Wei, Yao Wu, Ning Dong, Lei Zheng, Ren-qi Yao, Yong-ming Yao
Background Dendritic cells are crucial in the development of sepsis, yet the effect of ribophagy on dendritic cell activation remains unclear. This study aimed to investigate the potential role of nuclear fragile X mental retardation-interacting protein 1 (NUFIP1), a selective autophagy receptor, on sequestering ribosomes in autophagosomes to maintain dendritic cell function during early stages of sepsis. Methods Splenic dendritic cells were isolated using CD11c+microbeads and treated with lipopolysaccharide. Sepsis models were generated using cecal ligation and puncture. Expression of dendritic cell surface molecules was detected using flow cytometry. Cytokine level was quantified using enzyme-linked immunosorbent assay kits. Laser scanning confocal microscopy was employed to observe ribophagy and endoplasmic reticulum (ER) morphology. Transmission electron microscopy was used to examine autophagosomes containing ribosomes. Western blotting was performed to determine the levels of ribophagy- and ER stress-associated proteins. Results The results showed that NUFIP1-mediated ribophagy was significantly activated under septic challenge and facilitated the functional activation of dendritic cells by mitigating excessive ER stress. Deletion of Nufip1resulted in reduced expression of surface molecules on dendritic cells, inhibited T-cell proliferation, exacerbated peripheral immunosuppression and severe multiple organ damage, and increased mortality. Salubrinal, a specific inhibitor of EIF2A dephosphorylation, rescued dendritic cell dysfunction in septic mice with Nufip1deficiency. Mechanistically, NUFIP1 interacted directly with ATF4 and regulated its nuclear translocation. Conclusion These findings suggest that NUFIP1 regulates ER stress through the EIF2AK3–ATF4–DDIT3 pathway, highlighting its critical regulatory role in sepsis. Thus, NUFIP1 represents a new target for sepsis therapy.
{"title":"NUFIP1-mediated ribophagy regulates immune function of dendritic cells in polymicrobial sepsis","authors":"Li-yu Zheng, Peng-yi He, Peng-yue Zhao, Yu Duan, Meng-yao Wu, Shu-ting Wei, Yao Wu, Ning Dong, Lei Zheng, Ren-qi Yao, Yong-ming Yao","doi":"10.1093/burnst/tkaf034","DOIUrl":"https://doi.org/10.1093/burnst/tkaf034","url":null,"abstract":"Background Dendritic cells are crucial in the development of sepsis, yet the effect of ribophagy on dendritic cell activation remains unclear. This study aimed to investigate the potential role of nuclear fragile X mental retardation-interacting protein 1 (NUFIP1), a selective autophagy receptor, on sequestering ribosomes in autophagosomes to maintain dendritic cell function during early stages of sepsis. Methods Splenic dendritic cells were isolated using CD11c+microbeads and treated with lipopolysaccharide. Sepsis models were generated using cecal ligation and puncture. Expression of dendritic cell surface molecules was detected using flow cytometry. Cytokine level was quantified using enzyme-linked immunosorbent assay kits. Laser scanning confocal microscopy was employed to observe ribophagy and endoplasmic reticulum (ER) morphology. Transmission electron microscopy was used to examine autophagosomes containing ribosomes. Western blotting was performed to determine the levels of ribophagy- and ER stress-associated proteins. Results The results showed that NUFIP1-mediated ribophagy was significantly activated under septic challenge and facilitated the functional activation of dendritic cells by mitigating excessive ER stress. Deletion of Nufip1resulted in reduced expression of surface molecules on dendritic cells, inhibited T-cell proliferation, exacerbated peripheral immunosuppression and severe multiple organ damage, and increased mortality. Salubrinal, a specific inhibitor of EIF2A dephosphorylation, rescued dendritic cell dysfunction in septic mice with Nufip1deficiency. Mechanistically, NUFIP1 interacted directly with ATF4 and regulated its nuclear translocation. Conclusion These findings suggest that NUFIP1 regulates ER stress through the EIF2AK3–ATF4–DDIT3 pathway, highlighting its critical regulatory role in sepsis. Thus, NUFIP1 represents a new target for sepsis therapy.","PeriodicalId":9553,"journal":{"name":"Burns & Trauma","volume":"18 1","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144088269","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}
Background Wound healing is a sophisticated biological process characterized by the orchestrated interplay of diverse cellular components, growth factors, and signaling cascades. Recent research has highlighted the pivotal role of fibroblast exosomes in mediating intercellular communication and facilitating tissue regeneration. This investigation aimed to elucidate the therapeutic efficacy of fibroblast exosomes in enhancing wound repair mechanisms, with a particular emphasis on their differential effects in normal and diabetic wound healing paradigms. Methods A mouse full-thickness skin defect model was used to evaluate the effects of fibroblast exosomes on wound re-epithelialization, granulation tissue formation, and epidermal barrier function. Molecular and cellular experiments were conducted to analyze the roles of exosomes in epidermal stem cell proliferation, migration, differentiation, and antioxidant stress, with further validation of the associated signaling pathways. The therapeutic efficacy was additionally confirmed in a type 1 diabetic mouse model. Results Fibroblast exosomes significantly enhanced wound re-epithelialization by promoting the proliferation, migration, and differentiation of epidermal stem cells. Additionally, exosomes increased fibroblast abundance and myofibroblast activation, facilitating granulation tissue formation as well as improving extracellular matrix (ECM) deposition and the biomechanical properties of healed skin. Furthermore, exosomes improved epidermal barrier function by upregulating tight junction proteins (e.g., Claudin-1 and ZO-1) and reducing transepidermal water loss (TEWL). In diabetic mouse models, exosomes accelerated wound closure, restored ECM deposition and biomechanical integrity, and repaired epidermal barrier function. Mechanistically, exosomes target the 3′ untranslated region (UTR) of Keap1 mRNA through miR-29a-3p and activate the KEAP1/Nrf2 antioxidant pathway, mitigating oxidative stress and protecting epidermal stem cells from reactive oxygen species (ROS)-induced damage. Conclusion Fibroblast exosomes alleviate oxidative damage by modulating the KEAP1/Nrf2 pathway through miR-29a-3p and enhancing epidermal stem cell function. These exosomes exhibit remarkable therapeutic potential in accelerating wound healing and improving healing quality under both normal and diabetic conditions, offering a robust foundation for innovative therapeutic strategies.
{"title":"Fibroblast Exosomes Promote Wound Healing and Improve the Quality of Healed Skin via miR-29a-3p-Mediated KEAP1/Nrf2 Pathway Activation","authors":"Lingfeng Yan, Dejiang Fan, Jiacai Yang, Jue Wang, Xiaohong Hu, Xiaorong Zhang, Yong Huang, Hong Wang, Wenjing Yin, Xin Cai, Ruoyu Shang, Canhua Huang, Gaoxing Luo, Weifeng He","doi":"10.1093/burnst/tkaf035","DOIUrl":"https://doi.org/10.1093/burnst/tkaf035","url":null,"abstract":"Background Wound healing is a sophisticated biological process characterized by the orchestrated interplay of diverse cellular components, growth factors, and signaling cascades. Recent research has highlighted the pivotal role of fibroblast exosomes in mediating intercellular communication and facilitating tissue regeneration. This investigation aimed to elucidate the therapeutic efficacy of fibroblast exosomes in enhancing wound repair mechanisms, with a particular emphasis on their differential effects in normal and diabetic wound healing paradigms. Methods A mouse full-thickness skin defect model was used to evaluate the effects of fibroblast exosomes on wound re-epithelialization, granulation tissue formation, and epidermal barrier function. Molecular and cellular experiments were conducted to analyze the roles of exosomes in epidermal stem cell proliferation, migration, differentiation, and antioxidant stress, with further validation of the associated signaling pathways. The therapeutic efficacy was additionally confirmed in a type 1 diabetic mouse model. Results Fibroblast exosomes significantly enhanced wound re-epithelialization by promoting the proliferation, migration, and differentiation of epidermal stem cells. Additionally, exosomes increased fibroblast abundance and myofibroblast activation, facilitating granulation tissue formation as well as improving extracellular matrix (ECM) deposition and the biomechanical properties of healed skin. Furthermore, exosomes improved epidermal barrier function by upregulating tight junction proteins (e.g., Claudin-1 and ZO-1) and reducing transepidermal water loss (TEWL). In diabetic mouse models, exosomes accelerated wound closure, restored ECM deposition and biomechanical integrity, and repaired epidermal barrier function. Mechanistically, exosomes target the 3′ untranslated region (UTR) of Keap1 mRNA through miR-29a-3p and activate the KEAP1/Nrf2 antioxidant pathway, mitigating oxidative stress and protecting epidermal stem cells from reactive oxygen species (ROS)-induced damage. Conclusion Fibroblast exosomes alleviate oxidative damage by modulating the KEAP1/Nrf2 pathway through miR-29a-3p and enhancing epidermal stem cell function. These exosomes exhibit remarkable therapeutic potential in accelerating wound healing and improving healing quality under both normal and diabetic conditions, offering a robust foundation for innovative therapeutic strategies.","PeriodicalId":9553,"journal":{"name":"Burns & Trauma","volume":"1 1","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144083180","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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