Yan Zhang,Dan Wu,Chen Zhou,Muran Bai,Yucheng Wan,Qing Zheng,Zhijin Fan,Xianwen Wang,Chun Yang
Extracellular vesicles (EVs) are heterogeneous membrane-like vesicles secreted by living cells that are involved in many physiological and pathological processes and act as intermediaries of intercellular communication and molecular transfer. Recent studies have shown that EVs from specific sources regulate tissue repair and regeneration by delivering proteins, lipids, and nucleic acids to target cells as signaling molecules. Nanotechnology breakthroughs have facilitated the development and exploration of engineered EVs for tissue repair. Enhancements through gene editing, surface modification, and content modification have further improved their therapeutic efficacy. This review summarizes the potential of EVs in tissue repair and regeneration, their mechanisms of action, and their research progress in regenerative medicine. This review highlights their design logic through typical examples and explores the development prospects of EVs in tissue repair. The aim of this review is to provide new insights into the design of EVs for tissue repair and regeneration applications, thereby expanding their use in regenerative medicine.
{"title":"Engineered extracellular vesicles for tissue repair and regeneration.","authors":"Yan Zhang,Dan Wu,Chen Zhou,Muran Bai,Yucheng Wan,Qing Zheng,Zhijin Fan,Xianwen Wang,Chun Yang","doi":"10.1093/burnst/tkae062","DOIUrl":"https://doi.org/10.1093/burnst/tkae062","url":null,"abstract":"Extracellular vesicles (EVs) are heterogeneous membrane-like vesicles secreted by living cells that are involved in many physiological and pathological processes and act as intermediaries of intercellular communication and molecular transfer. Recent studies have shown that EVs from specific sources regulate tissue repair and regeneration by delivering proteins, lipids, and nucleic acids to target cells as signaling molecules. Nanotechnology breakthroughs have facilitated the development and exploration of engineered EVs for tissue repair. Enhancements through gene editing, surface modification, and content modification have further improved their therapeutic efficacy. This review summarizes the potential of EVs in tissue repair and regeneration, their mechanisms of action, and their research progress in regenerative medicine. This review highlights their design logic through typical examples and explores the development prospects of EVs in tissue repair. The aim of this review is to provide new insights into the design of EVs for tissue repair and regeneration applications, thereby expanding their use in regenerative medicine.","PeriodicalId":9553,"journal":{"name":"Burns & Trauma","volume":"30 1","pages":"tkae062"},"PeriodicalIF":5.3,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142488306","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 Hypertrophic scars cause impaired skin appearance and function, seriously affecting physical and mental health. Due to medical ethics and clinical accessibility, the collection of human scar specimens is frequently restricted, and the establishment of scar experimental animal models for scientific research is urgently needed. The four most commonly used animal models of hypertrophic scars have the following drawbacks: the rabbit ear model takes a long time to construct; the immunodeficient mouse hypertrophic scar model necessitates careful feeding and experimental operations; female Duroc pigs are expensive to purchase and maintain, and their large size makes it difficult to produce a significant number of models; and mouse scar models that rely on tension require special skin stretch devices, which are often damaged and shed, resulting in unstable model establishment. Our group overcame the shortcomings of previous scar animal models and created a new mouse model of hypertrophic scarring induced by suture anchoring at the wound edge. Methods We utilized suture anchoring of incisional wounds to impose directional tension throughout the healing process, restrain wound contraction, and generate granulation tissue, thus inducing scar formation. Dorsal paired incisions were generated in mice, with wound edges on the upper back sutured to the rib cage and the wound edges on the lower back relaxed as a control. Macroscopic manifestation, microscopic histological analysis, mRNA sequencing, bioinformatics, and in vitro cell assays were also conducted to verify the reliability of this method. Results Compared with those in relaxed controls, the fibrotic changes in stretched wounds were more profound. Histologically, the stretched scars were hypercellular, hypervascular, and hyperproliferative with disorganized extracellular matrix deposition, and displayed molecular hallmarks of hypertrophic fibrosis. In addition, the stretched scars exhibited transcriptional overlap with mechanically stretched scars, and human hypertrophic and keloid scars. Phosphatidylinositol 3-kinase-serine/threonine-protein kinase B signaling was implicated as a profibrotic mediator of apoptosis resistance under suture-induced tension. Conclusions This straightforward murine model successfully induces cardinal molecular and histological features of pathological hypertrophic scarring through localized suture tension to inhibit wound contraction. The model enables us to interrogate the mechanisms of tension-induced fibrosis and evaluate anti-scarring therapies.
背景增生性疤痕导致皮肤外观和功能受损，严重影响身心健康。由于医学伦理和临床可及性等原因，人类疤痕标本的采集往往受到限制，建立疤痕实验动物模型用于科学研究迫在眉睫。目前最常用的四种增生性疤痕动物模型存在以下缺点：兔耳模型制作时间长；免疫缺陷小鼠增生性疤痕模型需要精心饲养和实验操作；雌性杜洛克猪购买和饲养成本高，且体型较大，难以制作大量模型；依靠拉力的小鼠疤痕模型需要特殊的皮肤拉伸装置，而这种装置经常损坏和脱落，导致模型建立不稳定。我们的研究小组克服了以往疤痕动物模型的缺点，创建了一种通过缝合固定伤口边缘诱导增生性疤痕的新型小鼠模型。方法 我们利用缝合锚定切口伤口，在整个愈合过程中施加定向张力，抑制伤口收缩，生成肉芽组织，从而诱导疤痕形成。小鼠背侧切口成对，上背部伤口边缘与肋骨缝合，下背部伤口边缘放松作为对照。为验证该方法的可靠性，还进行了宏观表现、显微组织学分析、mRNA 测序、生物信息学和体外细胞实验。结果 与松弛对照组相比，拉伸伤口的纤维化变化更为深刻。从组织学角度看，拉伸的疤痕细胞增生、血管增生、增殖旺盛，细胞外基质沉积紊乱，显示出肥厚性纤维化的分子特征。此外，拉伸疤痕与机械拉伸疤痕、人类肥厚性瘢痕和瘢痕疙瘩在转录上有重叠。磷脂酰肌醇 3- 激酶-丝氨酸/苏氨酸蛋白激酶 B 信号转导被认为是缝合线诱导的张力下抵抗细胞凋亡的促组织坏死介质。结论 这种直接的小鼠模型通过局部缝合张力抑制伤口收缩，成功诱导了病理肥厚性瘢痕的主要分子和组织学特征。该模型使我们能够探究张力诱导纤维化的机制并评估抗瘢痕疗法。
{"title":"Suture-anchored cutaneous tension induces persistent hypertrophic scarring in a novel murine model","authors":"Yashu Li, Anqi Liu, Jingyan Wang, Changsheng Yang, Kaiyang Lv, Weifeng He, Jun Wu, Wenbin Chen","doi":"10.1093/burnst/tkae051","DOIUrl":"https://doi.org/10.1093/burnst/tkae051","url":null,"abstract":"Background Hypertrophic scars cause impaired skin appearance and function, seriously affecting physical and mental health. Due to medical ethics and clinical accessibility, the collection of human scar specimens is frequently restricted, and the establishment of scar experimental animal models for scientific research is urgently needed. The four most commonly used animal models of hypertrophic scars have the following drawbacks: the rabbit ear model takes a long time to construct; the immunodeficient mouse hypertrophic scar model necessitates careful feeding and experimental operations; female Duroc pigs are expensive to purchase and maintain, and their large size makes it difficult to produce a significant number of models; and mouse scar models that rely on tension require special skin stretch devices, which are often damaged and shed, resulting in unstable model establishment. Our group overcame the shortcomings of previous scar animal models and created a new mouse model of hypertrophic scarring induced by suture anchoring at the wound edge. Methods We utilized suture anchoring of incisional wounds to impose directional tension throughout the healing process, restrain wound contraction, and generate granulation tissue, thus inducing scar formation. Dorsal paired incisions were generated in mice, with wound edges on the upper back sutured to the rib cage and the wound edges on the lower back relaxed as a control. Macroscopic manifestation, microscopic histological analysis, mRNA sequencing, bioinformatics, and in vitro cell assays were also conducted to verify the reliability of this method. Results Compared with those in relaxed controls, the fibrotic changes in stretched wounds were more profound. Histologically, the stretched scars were hypercellular, hypervascular, and hyperproliferative with disorganized extracellular matrix deposition, and displayed molecular hallmarks of hypertrophic fibrosis. In addition, the stretched scars exhibited transcriptional overlap with mechanically stretched scars, and human hypertrophic and keloid scars. Phosphatidylinositol 3-kinase-serine/threonine-protein kinase B signaling was implicated as a profibrotic mediator of apoptosis resistance under suture-induced tension. Conclusions This straightforward murine model successfully induces cardinal molecular and histological features of pathological hypertrophic scarring through localized suture tension to inhibit wound contraction. The model enables us to interrogate the mechanisms of tension-induced fibrosis and evaluate anti-scarring therapies.","PeriodicalId":9553,"journal":{"name":"Burns & Trauma","volume":"75 1","pages":""},"PeriodicalIF":5.3,"publicationDate":"2024-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142452177","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}
Xuting Bian, Xiao Liu, Mei Zhou, Hong Tang, Rui Wang, Lin Ma, Gang He, Shibo Xu, Yunjiao Wang, Jindong Tan, Kanglai Tang, Lin Guo
Background We previously confirmed that mechanical stimulation is an important factor in the repair of tendon–bone insertion (TBI) injuries and that mechanoreceptors such as transient receptor potential ion-channel subfamily V member 4 (TRPV4; also known as transient receptor potential vanilloid 4) are key to transforming mechanical stimulation into intracellular biochemical signals. This study aims to elucidate the mechanism of mechanical stimulation regulating TRPV4. Methods Immunohistochemical staining and western blotting were used to evaluate cartilage repair at the TBI after injury. The RNA expression and protein expression of mechanoreceptors and key pathway molecules regulating cartilage proliferation were analyzed. TBI samples were collected for transcriptome sequencing to detect gene expression. Calcium-ion imaging and flow cytometry were used to evaluate the function of TPRV4 and cellular communication network factor 2 (CCN2) after the administration of siRNA, recombinant adenovirus and agonists. Results We found that treadmill training improved the quality of TBI healing and enhanced fibrochondrocyte proliferation. The transcriptome sequencing results suggested that the elevated expression of the mechanistically stimulated regulator CCN2 and the exogenous administration of recombinant human CCN2 significantly promoted TRPV4 protein expression and fibrochondrocyte proliferation. In vitro, under mechanical stimulation conditions, small interfering RNA (siRNA)-CCN2 not only inhibited the proliferation of primary fibrochondrocytes but also suppressed TRPV4 protein expression and activity. Subsequently, primary fibrochondrocytes were treated with the TRPV4 agonist GSK1016790A and the recombinant adenovirus TRPV4 (Ad-TRPV4), and GSK1016790A partially reversed the inhibitory effect of siRNA-CCN2. The phosphoinositide 3-kinase/ protein kinase B (PI3K/AKT) signaling pathway participated in the above process. Conclusions Mechanical stimulation promoted fibrochondrocyte proliferation and TBI healing by activating TRPV4 channels and the PI3K/AKT signaling pathway, and CCN2 may be a key regulatory protein in maintaining TRPV4 activation.
{"title":"Mechanical stimulation promotes fibrochondrocyte proliferation by activating the TRPV4 signaling pathway during tendon–bone insertion healing: CCN2 plays an important regulatory role","authors":"Xuting Bian, Xiao Liu, Mei Zhou, Hong Tang, Rui Wang, Lin Ma, Gang He, Shibo Xu, Yunjiao Wang, Jindong Tan, Kanglai Tang, Lin Guo","doi":"10.1093/burnst/tkae028","DOIUrl":"https://doi.org/10.1093/burnst/tkae028","url":null,"abstract":"Background We previously confirmed that mechanical stimulation is an important factor in the repair of tendon–bone insertion (TBI) injuries and that mechanoreceptors such as transient receptor potential ion-channel subfamily V member 4 (TRPV4; also known as transient receptor potential vanilloid 4) are key to transforming mechanical stimulation into intracellular biochemical signals. This study aims to elucidate the mechanism of mechanical stimulation regulating TRPV4. Methods Immunohistochemical staining and western blotting were used to evaluate cartilage repair at the TBI after injury. The RNA expression and protein expression of mechanoreceptors and key pathway molecules regulating cartilage proliferation were analyzed. TBI samples were collected for transcriptome sequencing to detect gene expression. Calcium-ion imaging and flow cytometry were used to evaluate the function of TPRV4 and cellular communication network factor 2 (CCN2) after the administration of siRNA, recombinant adenovirus and agonists. Results We found that treadmill training improved the quality of TBI healing and enhanced fibrochondrocyte proliferation. The transcriptome sequencing results suggested that the elevated expression of the mechanistically stimulated regulator CCN2 and the exogenous administration of recombinant human CCN2 significantly promoted TRPV4 protein expression and fibrochondrocyte proliferation. In vitro, under mechanical stimulation conditions, small interfering RNA (siRNA)-CCN2 not only inhibited the proliferation of primary fibrochondrocytes but also suppressed TRPV4 protein expression and activity. Subsequently, primary fibrochondrocytes were treated with the TRPV4 agonist GSK1016790A and the recombinant adenovirus TRPV4 (Ad-TRPV4), and GSK1016790A partially reversed the inhibitory effect of siRNA-CCN2. The phosphoinositide 3-kinase/ protein kinase B (PI3K/AKT) signaling pathway participated in the above process. Conclusions Mechanical stimulation promoted fibrochondrocyte proliferation and TBI healing by activating TRPV4 channels and the PI3K/AKT signaling pathway, and CCN2 may be a key regulatory protein in maintaining TRPV4 activation.","PeriodicalId":9553,"journal":{"name":"Burns & Trauma","volume":"1 1","pages":""},"PeriodicalIF":5.3,"publicationDate":"2024-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142452179","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}
Tianhao Li, Mingzi Zhang, Yunzhu Li, Yixin Sun, Jiuzuo Huang, Ang Zeng, Nanze Yu, Xiao Long
Background Keloid scarring is caused by a fibroproliferative disorder due to abnormal activation of genes, the underlying mechanism of which is still unclear. The basic helix–loop–helix transcription factor Twist-related protein 1 (TWIST1) controls cell proliferation and differentiation in tissue development and disease processes. In this study, we aimed to clarify the essential role of TWIST1 in the pathogenesis of keloids. Methods Immunohistochemistry, cell counting kit-8 assays, western blotting, PCR, matrigel invasion assays and immunofluorescence assays were applied to demonstrate the effects and mechanisms of TWIST1 in fibroblasts derived from normal skin and keloids. Mass spectrometry, ubiquitination assays, chromatin immunoprecipitation and dual luciferase reporter assay were applied to explore the interaction of TWIST1 with downstream molecules. Results In the present study, we confirmed that TWIST1 was upregulated in keloid tissue of patients and in keloid-derived fibroblasts (KFBs). In vitro, TWIST1 inhibition prevented KFB proliferation, invasion and activation. We also discovered a link between TWIST1 and the transforming growth factor β (TGF-β) signaling related molecules TGF-β receptor 1 (TΒR1), SMAD family member 2 (Smad2) and Smad3, and the fibrosis markers α-smooth muscle actin, collagen type I and collagen type III in KFBs. Mechanistically, we uncovered a brand-new mechanism by which TWIST1 interacts with myocyte enhancer factor 2A (MEF2A) and suppresses its ubiquitination and degradation. Using chromatin immunoprecipitation and dual-luciferase reporter assay, TΒR1 was identified as a novel downstream target of MEF2A, which directly binds to its promoter. Overexpression of TWIST1 promoted the recruitment of MEF2A to the TΒR1 promoter and restored TΒR1 functional expression. Conclusions Our research highlights a significant function of TWIST1 in the development of keloid and its related fibroblasts, partially facilitated by elevated MEF2A-dependent TΒR1 expression. Blocking the expression of TWIST1 in KFBs could potentially pave a novel therapeutic avenue for keloid treatment.
{"title":"Twist-related protein 1 promotes transforming growth factor β receptor 1 in keloid fibroblasts via regulating the stability of myocyte enhancer factor 2A","authors":"Tianhao Li, Mingzi Zhang, Yunzhu Li, Yixin Sun, Jiuzuo Huang, Ang Zeng, Nanze Yu, Xiao Long","doi":"10.1093/burnst/tkae024","DOIUrl":"https://doi.org/10.1093/burnst/tkae024","url":null,"abstract":"Background Keloid scarring is caused by a fibroproliferative disorder due to abnormal activation of genes, the underlying mechanism of which is still unclear. The basic helix–loop–helix transcription factor Twist-related protein 1 (TWIST1) controls cell proliferation and differentiation in tissue development and disease processes. In this study, we aimed to clarify the essential role of TWIST1 in the pathogenesis of keloids. Methods Immunohistochemistry, cell counting kit-8 assays, western blotting, PCR, matrigel invasion assays and immunofluorescence assays were applied to demonstrate the effects and mechanisms of TWIST1 in fibroblasts derived from normal skin and keloids. Mass spectrometry, ubiquitination assays, chromatin immunoprecipitation and dual luciferase reporter assay were applied to explore the interaction of TWIST1 with downstream molecules. Results In the present study, we confirmed that TWIST1 was upregulated in keloid tissue of patients and in keloid-derived fibroblasts (KFBs). In vitro, TWIST1 inhibition prevented KFB proliferation, invasion and activation. We also discovered a link between TWIST1 and the transforming growth factor β (TGF-β) signaling related molecules TGF-β receptor 1 (TΒR1), SMAD family member 2 (Smad2) and Smad3, and the fibrosis markers α-smooth muscle actin, collagen type I and collagen type III in KFBs. Mechanistically, we uncovered a brand-new mechanism by which TWIST1 interacts with myocyte enhancer factor 2A (MEF2A) and suppresses its ubiquitination and degradation. Using chromatin immunoprecipitation and dual-luciferase reporter assay, TΒR1 was identified as a novel downstream target of MEF2A, which directly binds to its promoter. Overexpression of TWIST1 promoted the recruitment of MEF2A to the TΒR1 promoter and restored TΒR1 functional expression. Conclusions Our research highlights a significant function of TWIST1 in the development of keloid and its related fibroblasts, partially facilitated by elevated MEF2A-dependent TΒR1 expression. Blocking the expression of TWIST1 in KFBs could potentially pave a novel therapeutic avenue for keloid treatment.","PeriodicalId":9553,"journal":{"name":"Burns & Trauma","volume":"83 1","pages":""},"PeriodicalIF":5.3,"publicationDate":"2024-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142451453","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 haemostasis is an important part of clinical treatments, especially treatments for patients with avulsion injury, destructive injury and large-scale soft tissue injury. Therefore, developing fast and effective haemostatic materials is critical. This study aimed to design a novel and efficient silk fibroin–gelatine composite haemostatic sponge loaded with thrombin (SFG@TB) to assist in wound haemostasis. Methods The SFG@TB composite haemostatic sponge was formed with gelatine, silk fibroin and thrombin through a freeze-drying technique. First, the material characteristics of SFG@TB were measured, including the elastic modulus, swelling rate and porosity. Second, in vitro cell coculture experiments, in vivo embedding experiments and haemolytic analyses were performed to evaluate the biocompatibility of SFG@TB. Then, coagulation experiments and femoral artery and liver bleeding models were used to evaluate the haemostatic performance of SFG@TB. Finally, the ability of SFG@TB to promote tissue healing was evaluated through experiments with Sprague–Dawley rat models of injury. Results Compared with gelatine sponges, SFG@TB exhibited outstanding mechanical properties and water absorption properties. In addition, the excellent biosafety of the composite haemostatic sponge was confirmed by cell experiments, subcutaneous embedding experiments and haemolytic analysis. Based on the in vitro coagulation test results, SFG@TB exhibited greater adhesion of red blood cells and platelets and a shorter dynamic coagulation time. Compared to the use of silk fibroin–gelatine composite haemostatic sponges or gelatine sponges, the introduction of thrombin resulted in a shorter haemostasis time and a smaller bleeding volume, as revealed by in vivo coagulation tests. The experiments with Sprague–Dawley rat models of injury indicated that SFG@TB accelerated the wound healing process and reduced scar width, which was accompanied by thicker granulation tissue. Conclusions Overall, the SFG@TB composite haemostatic sponge, which exhibits outstanding mechanical properties, good haemostatic performance and high biosafety, promoted wound haemostasis and tissue repair. Therefore, the SFG@TB composite haemostatic sponge could be a promising material for wound haemostasis.
{"title":"Silk fibroin–gelatine haemostatic sponge loaded with thrombin for wound haemostasis and tissue regeneration","authors":"Yajun Zhang, Ming Li, Jing Chang, Chang Li, Yuwen Hui, Yanhua Wang, Weiguo Xu","doi":"10.1093/burnst/tkae026","DOIUrl":"https://doi.org/10.1093/burnst/tkae026","url":null,"abstract":"Background Wound haemostasis is an important part of clinical treatments, especially treatments for patients with avulsion injury, destructive injury and large-scale soft tissue injury. Therefore, developing fast and effective haemostatic materials is critical. This study aimed to design a novel and efficient silk fibroin–gelatine composite haemostatic sponge loaded with thrombin (SFG@TB) to assist in wound haemostasis. Methods The SFG@TB composite haemostatic sponge was formed with gelatine, silk fibroin and thrombin through a freeze-drying technique. First, the material characteristics of SFG@TB were measured, including the elastic modulus, swelling rate and porosity. Second, in vitro cell coculture experiments, in vivo embedding experiments and haemolytic analyses were performed to evaluate the biocompatibility of SFG@TB. Then, coagulation experiments and femoral artery and liver bleeding models were used to evaluate the haemostatic performance of SFG@TB. Finally, the ability of SFG@TB to promote tissue healing was evaluated through experiments with Sprague–Dawley rat models of injury. Results Compared with gelatine sponges, SFG@TB exhibited outstanding mechanical properties and water absorption properties. In addition, the excellent biosafety of the composite haemostatic sponge was confirmed by cell experiments, subcutaneous embedding experiments and haemolytic analysis. Based on the in vitro coagulation test results, SFG@TB exhibited greater adhesion of red blood cells and platelets and a shorter dynamic coagulation time. Compared to the use of silk fibroin–gelatine composite haemostatic sponges or gelatine sponges, the introduction of thrombin resulted in a shorter haemostasis time and a smaller bleeding volume, as revealed by in vivo coagulation tests. The experiments with Sprague–Dawley rat models of injury indicated that SFG@TB accelerated the wound healing process and reduced scar width, which was accompanied by thicker granulation tissue. Conclusions Overall, the SFG@TB composite haemostatic sponge, which exhibits outstanding mechanical properties, good haemostatic performance and high biosafety, promoted wound haemostasis and tissue repair. Therefore, the SFG@TB composite haemostatic sponge could be a promising material for wound haemostasis.","PeriodicalId":9553,"journal":{"name":"Burns & Trauma","volume":"110 1","pages":""},"PeriodicalIF":5.3,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142431376","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}
Vascularization is a major challenge in the field of tissue engineering and regenerative medicine. Mechanical factors have been demonstrated to play a fundamental role in vasculogenesis and angiogenesis and can affect the architecture of the generated vascular network. Through the regulation of mechanical factors in engineered tissues, various mechanical strategies can be used to optimize the preformed vascular network and promote its rapid integration with host vessels. Optimization of the mechanical properties of scaffolds, including controlling scaffold stiffness, increasing surface roughness and anisotropic structure, and designing interconnected, hierarchical pore structures, is beneficial for the in vitro formation of vascular networks and the ingrowth of host blood vessels. The incorporation of hollow channels into scaffolds promotes the formation of patterned vascular networks. Dynamic stretching and perfusion can facilitate the formation and maturation of preformed vascular networks in vitro. Several indirect mechanical strategies provide sustained mechanical stimulation to engineered tissues in vivo, which further promotes the vascularization of implants within the body. Additionally, stiffness gradients, anisotropic substrates and hollow channels in scaffolds, as well as external cyclic stretch, boundary constraints and dynamic flow culture, can effectively regulate the alignment of vascular networks, thereby promoting better integration of prevascularized engineered tissues with host blood vessels. This review summarizes the influence and contribution of both scaffold-based and external stimulus-based mechanical strategies for vascularization in tissue engineering and elucidates the underlying mechanisms involved.
{"title":"Mechanical strategies to promote vascularization for tissue engineering and regenerative medicine.","authors":"Yiran Wang, Meixuan Liu, Wei Zhang, Huan Liu, Fang Jin, Shulei Mao, Chunmao Han, Xingang Wang","doi":"10.1093/burnst/tkae039","DOIUrl":"10.1093/burnst/tkae039","url":null,"abstract":"<p><p>Vascularization is a major challenge in the field of tissue engineering and regenerative medicine. Mechanical factors have been demonstrated to play a fundamental role in vasculogenesis and angiogenesis and can affect the architecture of the generated vascular network. Through the regulation of mechanical factors in engineered tissues, various mechanical strategies can be used to optimize the preformed vascular network and promote its rapid integration with host vessels. Optimization of the mechanical properties of scaffolds, including controlling scaffold stiffness, increasing surface roughness and anisotropic structure, and designing interconnected, hierarchical pore structures, is beneficial for the <i>in vitro</i> formation of vascular networks and the ingrowth of host blood vessels. The incorporation of hollow channels into scaffolds promotes the formation of patterned vascular networks. Dynamic stretching and perfusion can facilitate the formation and maturation of preformed vascular networks <i>in vitro</i>. Several indirect mechanical strategies provide sustained mechanical stimulation to engineered tissues <i>in vivo</i>, which further promotes the vascularization of implants within the body. Additionally, stiffness gradients, anisotropic substrates and hollow channels in scaffolds, as well as external cyclic stretch, boundary constraints and dynamic flow culture, can effectively regulate the alignment of vascular networks, thereby promoting better integration of prevascularized engineered tissues with host blood vessels. This review summarizes the influence and contribution of both scaffold-based and external stimulus-based mechanical strategies for vascularization in tissue engineering and elucidates the underlying mechanisms involved.</p>","PeriodicalId":9553,"journal":{"name":"Burns & Trauma","volume":"12 ","pages":"tkae039"},"PeriodicalIF":6.3,"publicationDate":"2024-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11441985/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142342223","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}
Pub Date : 2024-09-30eCollection Date: 2024-01-01DOI: 10.1093/burnst/tkae060
Luyao Zhang, Lu Ke
{"title":"Beta blockers in critical illness: promising but appropriate subphenotyping is needed.","authors":"Luyao Zhang, Lu Ke","doi":"10.1093/burnst/tkae060","DOIUrl":"10.1093/burnst/tkae060","url":null,"abstract":"","PeriodicalId":9553,"journal":{"name":"Burns & Trauma","volume":"12 ","pages":"tkae060"},"PeriodicalIF":6.3,"publicationDate":"2024-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11442145/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142362684","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}
The cutaneous lymphatic system regulates tissue inflammation, fluid balance and immunological responses. Lymphangiogenesis or lymphatic dysfunction may lead to lymphedema, immune deficiency, chronic inflammation etc. Tissue regeneration and healing depend on angiogenesis and lymphangiogenesis during wound healing. Tissue oedema and chronic inflammation can slow wound healing due to impaired lymphangiogenesis or lymphatic dysfunction. For example, impaired lymphangiogenesis or lymphatic dysfunction has been detected in nonhealing wounds such as diabetic ulcers, venous ulcers and bedsores. This review summarizes the structure and function of the cutaneous lymphatic vessel system and lymphangiogenesis in wounds. Furthermore, we review wound lymphangiogenesis processes and remodelling, especially the influence of the inflammatory phase. Finally, we outline how to control lymphangiogenesis to promote wound healing, assess the possibility of targeting lymphangiogenesis as a novel treatment strategy for chronic wounds and provide an analysis of the possible problems that need to be addressed.
{"title":"Lymphangiogenesis: novel strategies to promote cutaneous wound healing","authors":"Yang Jian, Yanqi Li, Yanji Zhang, Mingyuan Tang, Mingfu Deng, Chenxiaoxiao Liu, Maolin Cheng, Shune Xiao, Chengliang Deng, Zairong Wei","doi":"10.1093/burnst/tkae040","DOIUrl":"https://doi.org/10.1093/burnst/tkae040","url":null,"abstract":"The cutaneous lymphatic system regulates tissue inflammation, fluid balance and immunological responses. Lymphangiogenesis or lymphatic dysfunction may lead to lymphedema, immune deficiency, chronic inflammation etc. Tissue regeneration and healing depend on angiogenesis and lymphangiogenesis during wound healing. Tissue oedema and chronic inflammation can slow wound healing due to impaired lymphangiogenesis or lymphatic dysfunction. For example, impaired lymphangiogenesis or lymphatic dysfunction has been detected in nonhealing wounds such as diabetic ulcers, venous ulcers and bedsores. This review summarizes the structure and function of the cutaneous lymphatic vessel system and lymphangiogenesis in wounds. Furthermore, we review wound lymphangiogenesis processes and remodelling, especially the influence of the inflammatory phase. Finally, we outline how to control lymphangiogenesis to promote wound healing, assess the possibility of targeting lymphangiogenesis as a novel treatment strategy for chronic wounds and provide an analysis of the possible problems that need to be addressed.","PeriodicalId":9553,"journal":{"name":"Burns & Trauma","volume":"33 1","pages":""},"PeriodicalIF":5.3,"publicationDate":"2024-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142325482","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}
Panyang Zhang, Dan Wu, Xule Zha, Sen Su, Yajuan Zhang, Yan Wei, Lin Xia, Shijun Fan, Xi Peng
Background Intestinal stem cells (ISCs) play a pivotal role in maintaining intestinal homeostasis and facilitating the restoration of intestinal mucosal barrier integrity. Glutamine (Gln) is a crucial energy substrate in the intestine, promoting the proliferation of ISCs and mitigating damage to the intestinal mucosal barrier after burn injury. However, the underlying mechanism has not yet been fully elucidated. The objective of this study was to explore the mechanism by which Gln facilitates the proliferation of ISCs. Methods A mouse burn model was established to investigate the impact of Gln on intestinal function. Subsequently, crypts were isolated, and changes in TP53-induced glycolysis and apoptosis regulator (TIGAR) expression were assessed using real-time quantitative polymerase chain reaction (RT-qPCR), western blotting, immunohistochemistry, and immunofluorescence. The effects of TIGAR on cell proliferation were validated through CCK-8, EdU, and clonogenicity assays. Furthermore, the effect of TIGAR on Yes-associated protein (YAP) nuclear translocation and ferroptosis was examined by western blotting and immunofluorescence staining. Finally, dot blot analysis and methylation-specific PCR were performed to evaluate the effect of Gln on TIGAR promoter methylation. Results The mRNA and protein levels of TIGAR decreased after burn injury, and supplementation with Gln increased the expression of TIGAR. TIGAR accelerates the nuclear translocation of YAP, thereby increasing the proliferation of ISCs. Concurrently, TIGAR promotes the synthesis of nicotinamide adenine dinucleotide phosphate (NADPH) and glutathione to suppress ferroptosis in ISCs. Subsequent investigations demonstrated that Gln inhibits TIGAR promoter methylation by increasing the expression of the demethylase ten-eleven translocation. This change increased TIGAR transcription, increased NADPH synthesis, and reduced oxidative stress, thereby facilitating the restoration of intestinal mucosal barrier integrity post-burn injury. Conclusions Our data confirmed the inhibitory effect of Gln on TIGAR promoter methylation, which facilitates YAP translocation into the nucleus and suppresses ferroptosis, ultimately promoting the proliferation of ISCs.
{"title":"Glutamine promotes the proliferation of intestinal stem cells via inhibition of TP53-induced glycolysis and apoptosis regulator promoter methylation in burned mice","authors":"Panyang Zhang, Dan Wu, Xule Zha, Sen Su, Yajuan Zhang, Yan Wei, Lin Xia, Shijun Fan, Xi Peng","doi":"10.1093/burnst/tkae045","DOIUrl":"https://doi.org/10.1093/burnst/tkae045","url":null,"abstract":"Background Intestinal stem cells (ISCs) play a pivotal role in maintaining intestinal homeostasis and facilitating the restoration of intestinal mucosal barrier integrity. Glutamine (Gln) is a crucial energy substrate in the intestine, promoting the proliferation of ISCs and mitigating damage to the intestinal mucosal barrier after burn injury. However, the underlying mechanism has not yet been fully elucidated. The objective of this study was to explore the mechanism by which Gln facilitates the proliferation of ISCs. Methods A mouse burn model was established to investigate the impact of Gln on intestinal function. Subsequently, crypts were isolated, and changes in TP53-induced glycolysis and apoptosis regulator (TIGAR) expression were assessed using real-time quantitative polymerase chain reaction (RT-qPCR), western blotting, immunohistochemistry, and immunofluorescence. The effects of TIGAR on cell proliferation were validated through CCK-8, EdU, and clonogenicity assays. Furthermore, the effect of TIGAR on Yes-associated protein (YAP) nuclear translocation and ferroptosis was examined by western blotting and immunofluorescence staining. Finally, dot blot analysis and methylation-specific PCR were performed to evaluate the effect of Gln on TIGAR promoter methylation. Results The mRNA and protein levels of TIGAR decreased after burn injury, and supplementation with Gln increased the expression of TIGAR. TIGAR accelerates the nuclear translocation of YAP, thereby increasing the proliferation of ISCs. Concurrently, TIGAR promotes the synthesis of nicotinamide adenine dinucleotide phosphate (NADPH) and glutathione to suppress ferroptosis in ISCs. Subsequent investigations demonstrated that Gln inhibits TIGAR promoter methylation by increasing the expression of the demethylase ten-eleven translocation. This change increased TIGAR transcription, increased NADPH synthesis, and reduced oxidative stress, thereby facilitating the restoration of intestinal mucosal barrier integrity post-burn injury. Conclusions Our data confirmed the inhibitory effect of Gln on TIGAR promoter methylation, which facilitates YAP translocation into the nucleus and suppresses ferroptosis, ultimately promoting the proliferation of ISCs.","PeriodicalId":9553,"journal":{"name":"Burns & Trauma","volume":"22 1","pages":""},"PeriodicalIF":5.3,"publicationDate":"2024-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142325483","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}
BackgroundThere are various treatment modalities for chronic subdural hematoma (CSDH) and there is extensive debate surrounding pharmaceutical interventions. There is no consensus regarding the relative efficacy and safety of multiple treatment modalities. This study aims to investigate this issue and offer potential clinical recommendations.MethodsWe searched PubMed, Web of Science, Embase and the Cochrane Library from January 2000 to May 2023 to identify randomized and nonrandomized controlled studies reporting one or more outcomes associated with the pharmacologic management of CSDH. The primary outcomes of interest included recurrence, favorable prognosis and adverse events, while the secondary outcomes included a reduction in hematoma volume and mortality. Pooled estimates, credible intervals and odds ratios were calculated for all outcomes using a fixed effects model. Confidence in network meta-analysis judgments were employed to stratify the evidential quality. This study was registered with PROSPERO: CRD42023406599.ResultsThe search strategy yielded 656 references; ultimately, 36 studies involving 8082 patients fulfilled our predefined inclusion criteria. The findings suggested that statins + glucocorticoids (GCs) ranked highest for preventing recurrence, improving prognosis and facilitating hematoma absorption. Tranexamic acid ranked second highest for preventing recurrence. Statins were found to be the preferred drug intervention for decreasing mortality and preventing adverse events. Antithrombotic agents ranked lowest in terms of decreasing mortality and improving prognosis.ConclusionsOur findings indicate that statins + GCs may be the most effective treatment modality for preventing recurrence, improving patient prognosis and facilitating hematoma absorption. In terms of reducing mortality and preventing adverse events, statins may be superior to other pharmacological interventions. Routine use of GCs is not suggested for patients with CSDH. Further prospective research is needed to directly compare the efficacy and superiority of various pharmaceutical interventions targeting CSDH to reinforce and validate our findings.
{"title":"The pharmacological landscape of chronic subdural hematoma: a systematic review and network meta-analysis of randomized and non-randomized controlled studies.","authors":"Tao Liu,Zhihao Zhao,Mingqi Liu,Shuo An,Meng Nie,Xuanhui Liu,Yu Qian,Ye Tian,Jianning Zhang,Rongcai Jiang","doi":"10.1093/burnst/tkae034","DOIUrl":"https://doi.org/10.1093/burnst/tkae034","url":null,"abstract":"BackgroundThere are various treatment modalities for chronic subdural hematoma (CSDH) and there is extensive debate surrounding pharmaceutical interventions. There is no consensus regarding the relative efficacy and safety of multiple treatment modalities. This study aims to investigate this issue and offer potential clinical recommendations.MethodsWe searched PubMed, Web of Science, Embase and the Cochrane Library from January 2000 to May 2023 to identify randomized and nonrandomized controlled studies reporting one or more outcomes associated with the pharmacologic management of CSDH. The primary outcomes of interest included recurrence, favorable prognosis and adverse events, while the secondary outcomes included a reduction in hematoma volume and mortality. Pooled estimates, credible intervals and odds ratios were calculated for all outcomes using a fixed effects model. Confidence in network meta-analysis judgments were employed to stratify the evidential quality. This study was registered with PROSPERO: CRD42023406599.ResultsThe search strategy yielded 656 references; ultimately, 36 studies involving 8082 patients fulfilled our predefined inclusion criteria. The findings suggested that statins + glucocorticoids (GCs) ranked highest for preventing recurrence, improving prognosis and facilitating hematoma absorption. Tranexamic acid ranked second highest for preventing recurrence. Statins were found to be the preferred drug intervention for decreasing mortality and preventing adverse events. Antithrombotic agents ranked lowest in terms of decreasing mortality and improving prognosis.ConclusionsOur findings indicate that statins + GCs may be the most effective treatment modality for preventing recurrence, improving patient prognosis and facilitating hematoma absorption. In terms of reducing mortality and preventing adverse events, statins may be superior to other pharmacological interventions. Routine use of GCs is not suggested for patients with CSDH. Further prospective research is needed to directly compare the efficacy and superiority of various pharmaceutical interventions targeting CSDH to reinforce and validate our findings.","PeriodicalId":9553,"journal":{"name":"Burns & Trauma","volume":"38 1","pages":"tkae034"},"PeriodicalIF":5.3,"publicationDate":"2024-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142328857","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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