Background TBI is one of the leading causes of injury and disability worldwide. Pyroptosis, a specific type of programmed cell death (PCD) triggered by inflammatory signals, plays a significant part in the pathological process after TBI. Copper ions play an important role in anti-inflammation and anti-oxidative stress. There is a more active copper metabolism in neurons after injury, and that neurons may require more copper ions and downstream copper-based enzymes to maintain normal physiological functions. Methods We developed an electrostatic spinning scaffold loaded with copper oxide (CuO@ PCL/gelatin) to achieve small-dose local administration and avoid toxic side effects. The membranes underwent preparation and characterization through various techniques including Fourier transform infrared spectroscopy, measurement of water contact angle, antibacterial experiment, scanning electron microscopy, and assessment of in vitro release of copper. In addition, we used a controlled cortical impact (CCI) to establish a TBI model in mice to examine the effect of CuO@PG on TBI-induced pyroptosis and the ability of the membranes to heal brain injury. Results CuO@PG inhibited TBI-induced neuronal pyroptosis. CuO@PG can inhibit the expression of the pyroptosis-related proteins. Moreover, CuO@PG also alleviates brain edema and the degree of neurodegeneration in the acute phase of TBI. The neuroprotective effect of CuO@PG was further confirmed by wire-grip test, open field test, Morris water maze test. Lastly, the beneficial results were significantly inhibited by the use of the copper chelator TTM. Conclusions In this study, we successfully constructed electrostatically spun scaffolds loaded with copper oxide to achieve slow, continuous and low-dose copper supply to the local brain, which provides a new theoretical basis for the imbalance of copper homeostasis in the brain after TBI.
{"title":"Electrospun Nanofiber Scaffolds Loaded with Copper Oxide for Repairing Traumatic Brain Injury through Restoring Copper Homeostasis and Regulating Pyroptosis pathway","authors":"Yumei An, Sunao Li, Xinqi Huang, Xueshi Chen, Mingyuan Xu, Chen Chen, Xuefeng Zhou, Haiyan Shan, Luyang Tao, Mingyang Zhang","doi":"10.1093/burnst/tkaf030","DOIUrl":"https://doi.org/10.1093/burnst/tkaf030","url":null,"abstract":"Background TBI is one of the leading causes of injury and disability worldwide. Pyroptosis, a specific type of programmed cell death (PCD) triggered by inflammatory signals, plays a significant part in the pathological process after TBI. Copper ions play an important role in anti-inflammation and anti-oxidative stress. There is a more active copper metabolism in neurons after injury, and that neurons may require more copper ions and downstream copper-based enzymes to maintain normal physiological functions. Methods We developed an electrostatic spinning scaffold loaded with copper oxide (CuO@ PCL/gelatin) to achieve small-dose local administration and avoid toxic side effects. The membranes underwent preparation and characterization through various techniques including Fourier transform infrared spectroscopy, measurement of water contact angle, antibacterial experiment, scanning electron microscopy, and assessment of in vitro release of copper. In addition, we used a controlled cortical impact (CCI) to establish a TBI model in mice to examine the effect of CuO@PG on TBI-induced pyroptosis and the ability of the membranes to heal brain injury. Results CuO@PG inhibited TBI-induced neuronal pyroptosis. CuO@PG can inhibit the expression of the pyroptosis-related proteins. Moreover, CuO@PG also alleviates brain edema and the degree of neurodegeneration in the acute phase of TBI. The neuroprotective effect of CuO@PG was further confirmed by wire-grip test, open field test, Morris water maze test. Lastly, the beneficial results were significantly inhibited by the use of the copper chelator TTM. Conclusions In this study, we successfully constructed electrostatically spun scaffolds loaded with copper oxide to achieve slow, continuous and low-dose copper supply to the local brain, which provides a new theoretical basis for the imbalance of copper homeostasis in the brain after TBI.","PeriodicalId":9553,"journal":{"name":"Burns & Trauma","volume":"3 1","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143927326","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}
As the largest organ in the human body, the skin protects the body from pathogens and harmful substances through physical, chemical and immune barrier functions. However, accurately replicating the complex physiology of human skin in mouse models remains a significant challenge. Accurately replicating the complex physiology of human skin in mouse models remains a significant challenge, making the development of bionic artificial skin particularly important. In recent years, skin organoid and skin-on-a-chip technologies have greatly enhanced in vitro skin modeling, overcoming many limitations of traditional approaches. In this review, we comprehensively summarize important advances in research on skin organoids and skin-on-a-chip. First, we present the anatomical structures and functional roles of the different skin layers. We then highlight current construction techniques and research findings on skin organoids and skin-on-a-chip. We then discuss in detail the biomedical applications of these emerging technologies. However, current models of skin organoids and skin-on-a-chip still have limitations. Therefore, we summarize the key challenges and explore strategies to improve the complexity and maturation of skin models via the precise control over the microenvironment. In the future, with the advancement of bioengineering technology, skin organoids and skin-on-a-chip will provide more powerful tools for skin disease research and treatment.
{"title":"Organoids/organs-on-chips towards biomimetic human artificial skin","authors":"Yuting Huang, Xiaoyan Wu, Yongxin Xu, Nengjie Yang, Peipei Xi, Yunan Wang, Yujuan Zhu, Xiaodong Chen","doi":"10.1093/burnst/tkaf029","DOIUrl":"https://doi.org/10.1093/burnst/tkaf029","url":null,"abstract":"As the largest organ in the human body, the skin protects the body from pathogens and harmful substances through physical, chemical and immune barrier functions. However, accurately replicating the complex physiology of human skin in mouse models remains a significant challenge. Accurately replicating the complex physiology of human skin in mouse models remains a significant challenge, making the development of bionic artificial skin particularly important. In recent years, skin organoid and skin-on-a-chip technologies have greatly enhanced in vitro skin modeling, overcoming many limitations of traditional approaches. In this review, we comprehensively summarize important advances in research on skin organoids and skin-on-a-chip. First, we present the anatomical structures and functional roles of the different skin layers. We then highlight current construction techniques and research findings on skin organoids and skin-on-a-chip. We then discuss in detail the biomedical applications of these emerging technologies. However, current models of skin organoids and skin-on-a-chip still have limitations. Therefore, we summarize the key challenges and explore strategies to improve the complexity and maturation of skin models via the precise control over the microenvironment. In the future, with the advancement of bioengineering technology, skin organoids and skin-on-a-chip will provide more powerful tools for skin disease research and treatment.","PeriodicalId":9553,"journal":{"name":"Burns & Trauma","volume":"24 1","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143902962","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}
Bone defect regeneration is a dynamic healing process, which relies on intrinsic ability of the body to repair albeit limited healing. The objective of this research was to synthesize hybrid scaffolds based on natural/synthetic polymers and inorganic nanomaterials (NMs). We prepared three-dimensional (3D) composite scaffolds based on flexible silica-strontium oxide (SiO2-SrO) nanofibers and poly(lactic acid)/gelatin (PG) fibers. These scaffolds displayed an ordered porous structure as well as exhibited biocompatibility and biological activity. In vitro release studies demonstrated that the scaffolds enabled sustained and controlled release of silicon ions (Si4+) and strontium ions (Sr2+). Furthermore, these scaffolds not only upregulated the expression of osteogenic-related genes but also promoted tubule-like network formation in human umbilical vein endothelial cells (HUVECs) in vitro. The scaffold enabled concurrent bone regeneration and vascularization in rat skull defect repair. Taken together, our strategy of leveraging the synergistic effect of SiO2-SrO short fibers and PG fibers may have potential to promote bone regeneration and potentially other bio-related disciplines.
{"title":"Three-Dimensional Composite Aerogel Scaffolds Based on Electrospun Poly(lactic acid)/Gelatin and Silica-Strontium Oxide Short Fibers Promote Bone Defect Healing","authors":"Jie Cui, Lixiang Zhang, Muhammad Shafiq, Panpan Shang, Xiao Yu, Yangfan Ding, Pengfei Cai, JiaHui Song, Binbin Sun, Mohamed EL-Newehy, Meera Moydeen Abdulhameed, Urszula Stachewicz, Xingping Zhou, Yuan Xu, Xiumei Mo","doi":"10.1093/burnst/tkaf028","DOIUrl":"https://doi.org/10.1093/burnst/tkaf028","url":null,"abstract":"Bone defect regeneration is a dynamic healing process, which relies on intrinsic ability of the body to repair albeit limited healing. The objective of this research was to synthesize hybrid scaffolds based on natural/synthetic polymers and inorganic nanomaterials (NMs). We prepared three-dimensional (3D) composite scaffolds based on flexible silica-strontium oxide (SiO2-SrO) nanofibers and poly(lactic acid)/gelatin (PG) fibers. These scaffolds displayed an ordered porous structure as well as exhibited biocompatibility and biological activity. In vitro release studies demonstrated that the scaffolds enabled sustained and controlled release of silicon ions (Si4+) and strontium ions (Sr2+). Furthermore, these scaffolds not only upregulated the expression of osteogenic-related genes but also promoted tubule-like network formation in human umbilical vein endothelial cells (HUVECs) in vitro. The scaffold enabled concurrent bone regeneration and vascularization in rat skull defect repair. Taken together, our strategy of leveraging the synergistic effect of SiO2-SrO short fibers and PG fibers may have potential to promote bone regeneration and potentially other bio-related disciplines.","PeriodicalId":9553,"journal":{"name":"Burns & Trauma","volume":"15 1","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143872687","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 Diabetic wounds represent the most common type of chronic wounds. Persistent inflammation and elevated oxidative stress are hallmark features of chronic wounds, where macrophage phenotypic polarization playing a critical role in the healing process. Although adipose-derived mesenchymal stem cell exosomes (ADSC-exos) have shown therapeutic potential for diabetic wounds, their precise mechanisms remain elucidated. Methods A streptozotocin-induced diabetic mouse model and high glucose-stimulated RAW 264.7 macrophages were utilized to mimic diabetic microenvironments. Wound tissues were collected from patients with diabetic foot ulcer. A skin incision model was established in mice and ADSC-exos were given subcutaneously. Streptozotocin-induced diabetic myeloid-specific sirt1−/− mice SIRT1 siRNA-transfected macrophages were employed to investigate the role of SIRT1 in vivo and in vitro. Wound healing rates were quantified. Mitochondrial function, lysosomal activity, autophagy flux, and inflammation status were systematically assessed. Results In diabetic mice and high glucose-treated macrophages, lysosomal dysfunction preceded mitochondrial and autophagy flux impairments. SIRT1 expression was significantly reduced in both diabetic wound tissues and macrophages, accompanied by M1 macrophage polarization. SIRT1 interference experiments revealed that the impact of ADSC-exos on mitochondrial function, autophagy flux, and inflammatory response were partially dependent on SIRT1. Notably, the therapeutic effects of ADSC-exos on mitochondrial and autophagic pathways were markedly attenuated upon SIRT1 suppression. Conclusions These findings demonstrate that ADSC-exos promotes diabetic wound healing by restoring mitochondrial function and autophagy via SIRT1 activation. These findings highlight the therapeutic potential of ADSC-exos and provide a mechanistic foundation for future exosome engineering strategies.
{"title":"Adipose Mesenchymal Stem Cell-derived Exosomes Rescue Mitochondrial Function through SIRT1 to Improve Diabetic Wound Healing","authors":"Xiaozhi Bai, Yu Li, Peng Wang, Zhigang Xu, Jingtao Wei, Ting He, Juntao Han","doi":"10.1093/burnst/tkaf017","DOIUrl":"https://doi.org/10.1093/burnst/tkaf017","url":null,"abstract":"Background Diabetic wounds represent the most common type of chronic wounds. Persistent inflammation and elevated oxidative stress are hallmark features of chronic wounds, where macrophage phenotypic polarization playing a critical role in the healing process. Although adipose-derived mesenchymal stem cell exosomes (ADSC-exos) have shown therapeutic potential for diabetic wounds, their precise mechanisms remain elucidated. Methods A streptozotocin-induced diabetic mouse model and high glucose-stimulated RAW 264.7 macrophages were utilized to mimic diabetic microenvironments. Wound tissues were collected from patients with diabetic foot ulcer. A skin incision model was established in mice and ADSC-exos were given subcutaneously. Streptozotocin-induced diabetic myeloid-specific sirt1−/− mice SIRT1 siRNA-transfected macrophages were employed to investigate the role of SIRT1 in vivo and in vitro. Wound healing rates were quantified. Mitochondrial function, lysosomal activity, autophagy flux, and inflammation status were systematically assessed. Results In diabetic mice and high glucose-treated macrophages, lysosomal dysfunction preceded mitochondrial and autophagy flux impairments. SIRT1 expression was significantly reduced in both diabetic wound tissues and macrophages, accompanied by M1 macrophage polarization. SIRT1 interference experiments revealed that the impact of ADSC-exos on mitochondrial function, autophagy flux, and inflammatory response were partially dependent on SIRT1. Notably, the therapeutic effects of ADSC-exos on mitochondrial and autophagic pathways were markedly attenuated upon SIRT1 suppression. Conclusions These findings demonstrate that ADSC-exos promotes diabetic wound healing by restoring mitochondrial function and autophagy via SIRT1 activation. These findings highlight the therapeutic potential of ADSC-exos and provide a mechanistic foundation for future exosome engineering strategies.","PeriodicalId":9553,"journal":{"name":"Burns & Trauma","volume":"134 1","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143847130","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}
Programmed cell death, which occurs via modes such as apoptosis, necroptosis and pyroptosis, is an important mechanism for host defence against pathogens and inflammation-mediated immune responses. Recently, interactions between various types of cell death have gradually been discovered. PANoptosis is a newly discovered mode of programmed cell death that involves apoptosis, necroptosis and pyroptosis and is closely related to many diseases. Ischaemia–reperfusion injury (IRI) is common in patients with blood circulation disorders such as those related to burns, traumatic shock, surgery, organ transplantation and thrombus. However, the literature on the role of PANoptosis in IRI is limited. Herein, we systematically described the emergence of PANoptosis as a cell death mode, clinical evidence of its occurrence, the molecular mechanisms of PANoptosis and its role in IRI. This study is expected to provide novel approaches for the prevention and treatment of tissue and organ IRI after severe burns.
{"title":"PANoptosis: a new insight into the mechanism of ischemia–reperfusion injury","authors":"Huapei Song, Fengjun Wang","doi":"10.1093/burnst/tkaf026","DOIUrl":"https://doi.org/10.1093/burnst/tkaf026","url":null,"abstract":"Programmed cell death, which occurs via modes such as apoptosis, necroptosis and pyroptosis, is an important mechanism for host defence against pathogens and inflammation-mediated immune responses. Recently, interactions between various types of cell death have gradually been discovered. PANoptosis is a newly discovered mode of programmed cell death that involves apoptosis, necroptosis and pyroptosis and is closely related to many diseases. Ischaemia–reperfusion injury (IRI) is common in patients with blood circulation disorders such as those related to burns, traumatic shock, surgery, organ transplantation and thrombus. However, the literature on the role of PANoptosis in IRI is limited. Herein, we systematically described the emergence of PANoptosis as a cell death mode, clinical evidence of its occurrence, the molecular mechanisms of PANoptosis and its role in IRI. This study is expected to provide novel approaches for the prevention and treatment of tissue and organ IRI after severe burns.","PeriodicalId":9553,"journal":{"name":"Burns & Trauma","volume":"5 1","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143818962","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}
Yao Wang, Haomin Wu, Yan Pan, Yibo Xiao, Yingying Chen, Shuhao Yang, Jun Wang, Wanyue Feng, Cheng Hu, Xiangke Niu, Xin Yong, Jin Yang, Xulin Hu
Diabetic wounds (DWs), which are complex and challenging to treat due to delayed healing and incomplete regeneration, pose a significant burden on global healthcare systems. Existing clinical interventions, which mainly comprise debridement, decompression, and wound dressings, have limited efficacy. In addition, DW pathogenesis is complex, with diabetic peripheral neuropathy (DPN), diabetic peripheral arterial disease (PAD), and diabetic foot infections (DWIs) further complicating wound management. Owing to their unique versatility, tunability, and hydrophilicity, hydrogels show promise in several biomedical applications, including DW management. They can effectively promote DW healing by loading therapeutic substances for on-demand release. Given the distinct physiological milieu of DWs, hydrogels with tailored attributes can be engineered to enable on-demand drug release, optimize the wound microenvironment, and cater to the diverse stages of wound healing. Based on the clinical status and pathophysiological features of DWs, this review explores hydrogel wound dressings with the following effects: hypoglycemic, nerve regeneration, vascular regeneration, anti-infective, and bone repair. Additionally, the strategy for applying hydrogels to DWs has been comprehensively studied to provide a robust theoretical foundation for DW treatment and pave the way for clinical translation.
{"title":"Innovations in hydrogel therapies for diabetic wound healing: bridging the gap between pathophysiology and clinical application","authors":"Yao Wang, Haomin Wu, Yan Pan, Yibo Xiao, Yingying Chen, Shuhao Yang, Jun Wang, Wanyue Feng, Cheng Hu, Xiangke Niu, Xin Yong, Jin Yang, Xulin Hu","doi":"10.1093/burnst/tkaf025","DOIUrl":"https://doi.org/10.1093/burnst/tkaf025","url":null,"abstract":"Diabetic wounds (DWs), which are complex and challenging to treat due to delayed healing and incomplete regeneration, pose a significant burden on global healthcare systems. Existing clinical interventions, which mainly comprise debridement, decompression, and wound dressings, have limited efficacy. In addition, DW pathogenesis is complex, with diabetic peripheral neuropathy (DPN), diabetic peripheral arterial disease (PAD), and diabetic foot infections (DWIs) further complicating wound management. Owing to their unique versatility, tunability, and hydrophilicity, hydrogels show promise in several biomedical applications, including DW management. They can effectively promote DW healing by loading therapeutic substances for on-demand release. Given the distinct physiological milieu of DWs, hydrogels with tailored attributes can be engineered to enable on-demand drug release, optimize the wound microenvironment, and cater to the diverse stages of wound healing. Based on the clinical status and pathophysiological features of DWs, this review explores hydrogel wound dressings with the following effects: hypoglycemic, nerve regeneration, vascular regeneration, anti-infective, and bone repair. Additionally, the strategy for applying hydrogels to DWs has been comprehensively studied to provide a robust theoretical foundation for DW treatment and pave the way for clinical translation.","PeriodicalId":9553,"journal":{"name":"Burns & Trauma","volume":"8 1","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143813592","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}
Tianqi Wang, Chiew Yong Ng, Bryan Zheng Jie Ng, Wei Seong Toh, James Hoi Po Hui
Osteoarthritis (OA) is a prevalent degenerative joint disorder with significant socioeconomic impact. Despite advances in understanding its pathophysiology, current therapeutic strategies remain largely palliative. Small extracellular vesicles (sEV) have emerged as crucial mediators of intercellular communication in joint tissues, offering new insights into OA pathogenesis and potential therapeutic targets. This review explores the application of multi-omics approaches to sEV research in OA, assessing how these advanced technologies are contributing to our understanding of the disease and their potential to revolutionize OA management. We discuss the latest findings on the role of sEV in OA, the applications of multi-omics technologies in deciphering sEV cargo, the progress towards clinical translation, and the challenges and opportunities in this field. By synthesizing current knowledge and identifying key research gaps, this review provides a roadmap for leveraging sEV multi-omics to bridge the gap between molecular discoveries and clinical applications in OA.
{"title":"Multi-Omics Analysis of Small Extracellular Vesicles in Osteoarthritis: Bridging the Gap between Molecular Insights and Clinical Applications","authors":"Tianqi Wang, Chiew Yong Ng, Bryan Zheng Jie Ng, Wei Seong Toh, James Hoi Po Hui","doi":"10.1093/burnst/tkaf023","DOIUrl":"https://doi.org/10.1093/burnst/tkaf023","url":null,"abstract":"Osteoarthritis (OA) is a prevalent degenerative joint disorder with significant socioeconomic impact. Despite advances in understanding its pathophysiology, current therapeutic strategies remain largely palliative. Small extracellular vesicles (sEV) have emerged as crucial mediators of intercellular communication in joint tissues, offering new insights into OA pathogenesis and potential therapeutic targets. This review explores the application of multi-omics approaches to sEV research in OA, assessing how these advanced technologies are contributing to our understanding of the disease and their potential to revolutionize OA management. We discuss the latest findings on the role of sEV in OA, the applications of multi-omics technologies in deciphering sEV cargo, the progress towards clinical translation, and the challenges and opportunities in this field. By synthesizing current knowledge and identifying key research gaps, this review provides a roadmap for leveraging sEV multi-omics to bridge the gap between molecular discoveries and clinical applications in OA.","PeriodicalId":9553,"journal":{"name":"Burns & Trauma","volume":"34 1","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143666074","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}
Hongyi Li, Huiyun Wen, He Zhang, Xiang Cao, Li Li, Xiaowen Hu, Yanmei Zhang, Xinkun Shen, Quazi T H Shubhra, Hong Yang, Xiaojun Cai
Background The management of chronic diabetic wounds remains a formidable challenge in clinical practice. Persistent hyperglycemia triggers vasculopathy, neuropathy, and immune dysfunction, critically impeding wound repair. We developed a multifunctional hydrogel (DPFI) engineered for sequential therapeutic actions, including antibacterial, anti-inflammatory, antioxidant, pro-vascularization/epithelialization, and glycemic-regulating properties, to address these complications. Methods DPFI hydrogels were prepared by encapsulating dihydromyricetin (DMY) into aldehyde-functionalized Pluronic F127 micelles (DMY@PF127-CHO), followed by a Schiff base reaction with amine-rich polyethyleneimine (PEI), resulting in the formation of a hydrogel for controlled drug release. The antimicrobial, antioxidant, anti-inflammatory, pro-cellular proliferative, and angiogenic properties of the hydrogels were evaluated using various techniques, including structural characterization, bacterial live/dead staining, reactive oxygen species (ROS) assays, antioxidant enzyme assays, reverse transcription–polymerase chain reaction (RT–PCR), cellular immunofluorescence staining, scratch wound healing assays, and angiogenesis assays. In vivo, the effects of the hydrogel on wound healing and glycemic control were assessed in MRSA-infected mice with streptozotocin-induced diabetes. Results The hydrogel exhibits exceptional injectability, bioadhesion, and self-healing properties, facilitating the controlled, sustained release of DMY, which synergistically enhances antimicrobial effects in combination with PEI. The antioxidant activity of DMY is remarkable; it effectively scavenges reactive oxygen species (ROS) and induces the expression of antioxidant enzymes while promoting the phenotypic switch of M1 macrophages to M2 macrophages to mitigate inflammation. Critically, DPFI also contributes to glycemic regulation, reducing hyperglycemia-associated complications and creating a microenvironment conducive to wound repair. Comprehensive in vitro and in vivo analyses corroborate the multifaceted therapeutic capabilities of DPFI, including its antibacterial activity and abilities to clear ROS, reduce inflammation, promote angiogenesis, promote epithelialization, and modulate blood glucose levels. Conclusions DPFI represents a promising, integrative strategy for enhanced diabetic wound management, meriting further exploration for clinical application.
{"title":"A multifunctional Dihydromyricetin-loaded hydrogel for the sequential modulation of diabetic wound healing and Glycemic control","authors":"Hongyi Li, Huiyun Wen, He Zhang, Xiang Cao, Li Li, Xiaowen Hu, Yanmei Zhang, Xinkun Shen, Quazi T H Shubhra, Hong Yang, Xiaojun Cai","doi":"10.1093/burnst/tkaf024","DOIUrl":"https://doi.org/10.1093/burnst/tkaf024","url":null,"abstract":"Background The management of chronic diabetic wounds remains a formidable challenge in clinical practice. Persistent hyperglycemia triggers vasculopathy, neuropathy, and immune dysfunction, critically impeding wound repair. We developed a multifunctional hydrogel (DPFI) engineered for sequential therapeutic actions, including antibacterial, anti-inflammatory, antioxidant, pro-vascularization/epithelialization, and glycemic-regulating properties, to address these complications. Methods DPFI hydrogels were prepared by encapsulating dihydromyricetin (DMY) into aldehyde-functionalized Pluronic F127 micelles (DMY@PF127-CHO), followed by a Schiff base reaction with amine-rich polyethyleneimine (PEI), resulting in the formation of a hydrogel for controlled drug release. The antimicrobial, antioxidant, anti-inflammatory, pro-cellular proliferative, and angiogenic properties of the hydrogels were evaluated using various techniques, including structural characterization, bacterial live/dead staining, reactive oxygen species (ROS) assays, antioxidant enzyme assays, reverse transcription–polymerase chain reaction (RT–PCR), cellular immunofluorescence staining, scratch wound healing assays, and angiogenesis assays. In vivo, the effects of the hydrogel on wound healing and glycemic control were assessed in MRSA-infected mice with streptozotocin-induced diabetes. Results The hydrogel exhibits exceptional injectability, bioadhesion, and self-healing properties, facilitating the controlled, sustained release of DMY, which synergistically enhances antimicrobial effects in combination with PEI. The antioxidant activity of DMY is remarkable; it effectively scavenges reactive oxygen species (ROS) and induces the expression of antioxidant enzymes while promoting the phenotypic switch of M1 macrophages to M2 macrophages to mitigate inflammation. Critically, DPFI also contributes to glycemic regulation, reducing hyperglycemia-associated complications and creating a microenvironment conducive to wound repair. Comprehensive in vitro and in vivo analyses corroborate the multifaceted therapeutic capabilities of DPFI, including its antibacterial activity and abilities to clear ROS, reduce inflammation, promote angiogenesis, promote epithelialization, and modulate blood glucose levels. Conclusions DPFI represents a promising, integrative strategy for enhanced diabetic wound management, meriting further exploration for clinical application.","PeriodicalId":9553,"journal":{"name":"Burns & Trauma","volume":"183 1","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143661359","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}
Foot ulcerations in patients with diabetes are common and severe, typically caused by infection and chronic inflammation. Poor blood circulation and neuropathy impair the body's ability to heal wounds effectively, creating a conducive environment for ulcers. Excessive reactive oxygen species contribute to ulcer development by damaging cellular structures and hindering wound healing. The administration of antioxidants can protect cells from oxidative damage and promote wound recovery. Antioxidants such as epidermal growth factors, flavonoid hesperidin, alpha-lipoic acid, and N-acetylcysteine effectively reduce oxidative stress. Encapsulating various drugs into nanoparticles and targeting carriers such as hydrogels, metal–organic frameworks, and nanohydrogels can improve their therapeutic effects. Nanotechnologies have been shown to boost tissue regeneration by modifying biomaterial properties, modulating signal release, and targeting key factors. Here, we describe the occurrence and development of diabetic foot ulcers (DFUs), emphasizing the role of oxidative damage in these processes. This review summarizes the strategy for targeting oxidative damage in DFUs using nanotechnology-loaded antioxidant drugs. This review advocates for the use of personalized biomaterials in treating DFUs and provides a theoretical basis for their potential clinical and translational applications.
{"title":"Targeting oxidative damage in diabetic foot ulcers: integrative strategies involving antioxidant drugs and nanotechnologies","authors":"Runze Wang, Bowen Li, Mengchao Dong, Huili Zhu, Ping Jin, Yingying Zou","doi":"10.1093/burnst/tkaf020","DOIUrl":"https://doi.org/10.1093/burnst/tkaf020","url":null,"abstract":"Foot ulcerations in patients with diabetes are common and severe, typically caused by infection and chronic inflammation. Poor blood circulation and neuropathy impair the body's ability to heal wounds effectively, creating a conducive environment for ulcers. Excessive reactive oxygen species contribute to ulcer development by damaging cellular structures and hindering wound healing. The administration of antioxidants can protect cells from oxidative damage and promote wound recovery. Antioxidants such as epidermal growth factors, flavonoid hesperidin, alpha-lipoic acid, and N-acetylcysteine effectively reduce oxidative stress. Encapsulating various drugs into nanoparticles and targeting carriers such as hydrogels, metal–organic frameworks, and nanohydrogels can improve their therapeutic effects. Nanotechnologies have been shown to boost tissue regeneration by modifying biomaterial properties, modulating signal release, and targeting key factors. Here, we describe the occurrence and development of diabetic foot ulcers (DFUs), emphasizing the role of oxidative damage in these processes. This review summarizes the strategy for targeting oxidative damage in DFUs using nanotechnology-loaded antioxidant drugs. This review advocates for the use of personalized biomaterials in treating DFUs and provides a theoretical basis for their potential clinical and translational applications.","PeriodicalId":9553,"journal":{"name":"Burns & Trauma","volume":"10 1","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143599840","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}
Wei Dai, Haowei Zhou, Jincheng Du, Ruozu Xiao, Junwei Su, Zhe Liu, Rong Huang, Yuqian Li, Jing Li
Background Diabetic wounds present persistent clinical challenges characterized by disrupted extracellular matrix (ECM) homeostasis, which critically impedes tissue regeneration. While bone marrow-derived mesenchymal stem cells (BMSCs) exhibit therapeutic potential through ECM remodeling, conventional transplantation strategies are limited by suboptimal cell retention and transient therapeutic effects. Methods BMSCs cultured on Flexcell plates were subjected to programmable mechanical stretching using a custom-built spherical cell-stretching system. Strain rate- and duration-dependent effects on paracrine signaling and ECM secretion were longitudinally assessed through Western blotting and ELISA. The optimized mechanical parameters (15% deformation, 1440 cycles, 5-s vertex residence time) were subsequently applied to generate BMSC sheets. Comparative analyses of biological activity and mechanical properties were performed between non-stretched controls and mechanically optimized groups. In vivo therapeutic efficacy was evaluated in diabetic rat models through wound closure kinetics, Masson’s trichrome staining, and immunofluorescence detection of neovascularization markers. Mechanistic insights were obtained via transcriptomic profiling of stretch-activated signaling pathways. Results Mechanical stretching significantly upregulated type I collagen, type III collagen, vascular endothelial growth factor (VEGF), and transforming growth factor-beta (TGF-β) secretion in BMSCs. The optimized stretching parameters (15% deformation, 1440 cycles, and 5 s vertex residence time) promoted BMSC proliferation while reducing apoptosis without compromising stemness. Mechanical stretching facilitated the formation of layered cell sheets with more organized collagen deposition and higher mechanical strength, expediting wound healing in diabetic rats through enhanced re-epithelialization and neovascularization. RNA sequencing analysis revealed that mechanical stretching significantly upregulated mechanosensitive molecules, mechanical stimulation signaling pathways, and cellular behavior regulatory pathways, particularly those associated with mechanical stimuli response, integrin binding, ECM secretion, and intercellular adhesion. Conclusions Mechanically stretched BMSC cell sheets can promote diabetic wound healing by enhancing cellular activity, paracrine of growth factors, and ECM components.
{"title":"Mechanical stretching enhances the cellular and paracrine effects of bone marrow mesenchymal stem cells on diabetic wound healing","authors":"Wei Dai, Haowei Zhou, Jincheng Du, Ruozu Xiao, Junwei Su, Zhe Liu, Rong Huang, Yuqian Li, Jing Li","doi":"10.1093/burnst/tkaf022","DOIUrl":"https://doi.org/10.1093/burnst/tkaf022","url":null,"abstract":"Background Diabetic wounds present persistent clinical challenges characterized by disrupted extracellular matrix (ECM) homeostasis, which critically impedes tissue regeneration. While bone marrow-derived mesenchymal stem cells (BMSCs) exhibit therapeutic potential through ECM remodeling, conventional transplantation strategies are limited by suboptimal cell retention and transient therapeutic effects. Methods BMSCs cultured on Flexcell plates were subjected to programmable mechanical stretching using a custom-built spherical cell-stretching system. Strain rate- and duration-dependent effects on paracrine signaling and ECM secretion were longitudinally assessed through Western blotting and ELISA. The optimized mechanical parameters (15% deformation, 1440 cycles, 5-s vertex residence time) were subsequently applied to generate BMSC sheets. Comparative analyses of biological activity and mechanical properties were performed between non-stretched controls and mechanically optimized groups. In vivo therapeutic efficacy was evaluated in diabetic rat models through wound closure kinetics, Masson’s trichrome staining, and immunofluorescence detection of neovascularization markers. Mechanistic insights were obtained via transcriptomic profiling of stretch-activated signaling pathways. Results Mechanical stretching significantly upregulated type I collagen, type III collagen, vascular endothelial growth factor (VEGF), and transforming growth factor-beta (TGF-β) secretion in BMSCs. The optimized stretching parameters (15% deformation, 1440 cycles, and 5 s vertex residence time) promoted BMSC proliferation while reducing apoptosis without compromising stemness. Mechanical stretching facilitated the formation of layered cell sheets with more organized collagen deposition and higher mechanical strength, expediting wound healing in diabetic rats through enhanced re-epithelialization and neovascularization. RNA sequencing analysis revealed that mechanical stretching significantly upregulated mechanosensitive molecules, mechanical stimulation signaling pathways, and cellular behavior regulatory pathways, particularly those associated with mechanical stimuli response, integrin binding, ECM secretion, and intercellular adhesion. Conclusions Mechanically stretched BMSC cell sheets can promote diabetic wound healing by enhancing cellular activity, paracrine of growth factors, and ECM components.","PeriodicalId":9553,"journal":{"name":"Burns & Trauma","volume":"37 1","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143570443","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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