Burns & Trauma最新文献

{"title":"Toward System-Level Integration of Organoids for Regenerative Medicine","authors":"Chuqing Zhou, Yuanli Ye, Jinrui Cai, Mingxuan Li, Yuchun Tang, Qiaoli Xie, Xiao Xiang, Mingxing Lei","doi":"10.1093/burnst/tkag031","DOIUrl":"https://doi.org/10.1093/burnst/tkag031","url":null,"abstract":"Regenerating complex human tissues requires proper cellular assembly and the recapitulation of coordinated functions across multiple biological levels. Organoids, as self-organized three-dimensional cellular structures, provide powerful models for rebuilding organ architecture and studying developmental processes. However, their regenerative potential remains limited by the lack of vascular, neural, and immune integration, which are essential for tissue development, homeostasis and repair. Recent studies indicate that the progression from tissue-level organization to organ-level coordination and ultimately to system-level functionality depends on dynamic intercellular communication, feedback signaling, and niche interactions. The integration of biochemical, biomechanical, and bioelectrical cues enables multicellular systems to achieve synchronized growth, patterning, and functional adaptation. Complementary bioengineering strategies further guide these intrinsic processes by modulating spatial organization, microenvironmental signals, and intercellular connectivity. This review summarizes emerging methodologies and molecular mechanisms underlying system-level integration in organoids and discusses how these biological processes may bridge the gap between in vitro morphogenesis and in vivo functional regeneration.","PeriodicalId":9553,"journal":{"name":"Burns & Trauma","volume":"21 1","pages":""},"PeriodicalIF":5.3,"publicationDate":"2026-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147684672","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Narrative Review of Diagnostic Strategies in Necrotizing Soft Tissue Infections: From Clinical Scores to Multi-Omics and Machine Learning","authors":"Xiaolin Ji, Xinze Li, Zhongqiu Lu","doi":"10.1093/burnst/tkag028","DOIUrl":"https://doi.org/10.1093/burnst/tkag028","url":null,"abstract":"Necrotizing soft tissue infections (NSTIs) represent a group of rapidly progressing, life-threatening infections characterized by widespread tissue necrosis, systemic inflammation, and multiorgan failure. Early diagnosis remains a clinical challenge because of nonspecific initial manifestations and overlapping symptoms with other soft tissue infections. Diagnostic scoring systems such as the Laboratory Risk Indicator for Necrotizing Fasciitis (LRINEC) score and its variants have been widely utilized to facilitate early recognition but are limited by variable sensitivity and insufficient predictive value across diverse clinical populations. Recent advances in multi-omics technologies and machine learning approaches have enabled the identification of molecular biomarkers and predictive patterns associated with NSTI onset and progression. Integration of high-dimensional omics data with clinical and imaging parameters holds potential for dynamic, real-time diagnostic support and individualized risk stratification in the intensive care setting. This review summarizes the evolution of diagnostic strategies for NSTIs, critically appraises the limitations of conventional clinical scoring systems, and examines emerging omics-based and machine learning-driven approaches. Finally, we propose an integrated diagnostic roadmap that aligns clinical assessment, imaging, microbiologic evaluation, host-response biomarkers, and multi-omics data to guide future research and clinical translation.","PeriodicalId":9553,"journal":{"name":"Burns & Trauma","volume":"1 1","pages":""},"PeriodicalIF":5.3,"publicationDate":"2026-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147684673","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Physiologic ‘Action at a Distance’: Neuromodulation, Neuroimmune Signaling, and Limb Preservation in Diabetic Foot Disease","authors":"Ahmed Sami Raihane, Gabriela Morales Deusch, Charles Liu, Bijan Najafi, Wuquan Deng, Natasha G Dark, David G Armstrong","doi":"10.1093/burnst/tkag017","DOIUrl":"https://doi.org/10.1093/burnst/tkag017","url":null,"abstract":"The rising global prevalence of chronic conditions, notably obesity and type 2 diabetes, demands innovative approaches to mitigate their health and economic impacts. Complications, including neuropathy and chronic limb-threatening ischemia (CLTI), dramatically increase the risk of lower limb amputation, cardiovascular events, and cerebrovascular events, underscoring the urgent need for effective interventions. Emerging neuromodulation and regenerative strategies provide novel approaches to addressing diabetes-related complications. High-frequency (10-kHz) spinal cord stimulation (SCS) demonstrates marked pain relief and sensory improvement in patients with refractory painful diabetic neuropathy. Peripheral focused ultrasound (pFUS), including splenic-targeted stimulation, shows promise in reducing systemic inflammation, accelerating wound repair, and enhancing vascular function. Remote ischemic conditioning (RIC) leverages brief controlled ischemic reperfusion cycles to enhance microcirculation and promote diabetic foot ulcer healing. In severe cases, surgical techniques such as tibial transverse transport (TTT) and lateral tibial periosteum distraction (LTPD) stimulate angiogenesis and enhance distal limb perfusion. Integrated wound care protocols, incorporating these procedures alongside debridement, negative pressure wound therapy, and skin grafting, may further optimize outcomes. Collectively, these therapies address both local and systemic pathophysiology, frequently producing physiologic effects at sites distant from the primary intervention. These seemingly disparate therapies represent a single unifying concept: generating a physiologic effect at locations remote from the primary target. This systematic approach, engaging neural, vascular, and immune pathways, may be key to improving outcomes in diabetic foot ulcers and CLTI. Early clinical data appears promising; however, larger randomized trials are required to validate efficacy, refine patient selection, and determine optimal integration with standard care. If confirmed, these strategies may shift management toward patient-centered, regenerative interventions that preserve limbs, reduce recurrence, and enhance quality of life for the expanding global patient population. Further research is warranted to confirm or refute these early promising physiologic effects.","PeriodicalId":9553,"journal":{"name":"Burns & Trauma","volume":"63 1","pages":""},"PeriodicalIF":5.3,"publicationDate":"2026-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147649159","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Single-cell transcriptomic profiling identifies YY1 as a key regulator of fibroblast plasticity in hypertrophic scar formation","authors":"Qian Yu, Zonglin Huang, Lei Cai, Yanze Lv, Lianzhao Wang, Huanhuan Wu, Qiang Dai, Zikai Qiu, Zhigang Yang, Xin Fu, Ran Xiao","doi":"10.1093/burnst/tkag027","DOIUrl":"https://doi.org/10.1093/burnst/tkag027","url":null,"abstract":"Background Hypertrophic scars (HS) are characterised by excessive extracellular matrix deposition and impaired scar remodelling. Fibroblasts are central to HS pathogenesis, yet clinical strategies remain limited by an incomplete understanding of fibroblast heterogeneity and transcriptional regulation. This study aimed to identify a key fibroblast subpopulation and its regulatory transcription factors to address this translational gap. Methods Single-cell RNA sequencing was performed on dermal cells from freshly excised human HS and normal skin (NS) tissues. Fibroblast subsets and transcriptional regulators were identified using Seurat, pseudotime, transcription factor prediction, and cell-cell communication analyses. Functional validation involved lentiviral overexpression of Yin Yang 1 (YY1) in fibroblasts derived from patients with hypertrophic scars, followed by bulk RNA sequencing, western blotting, CUT&Tag and immunofluorescence assays. Results Clinical HS specimens showed characteristic collagen overproduction and vascular hyperplasia. Single-cell analysis of 43,303 cells revealed disease-specific shifts in cellular composition, including pronounced pericyte expansion and reduced fibroblast abundance. Notably, fibroblast subcluster Fib_5 (ADAM12+ COMP+ POSTNhi) increased despite the overall fibroblast decline in HS and exhibited upregulated fibrotic gene expression. Cross-validation using combined public datasets comprising 21 samples indicated that the Fib_5-like subcluster is conserved across fibrotic conditions. Pseudotime analyses placed Fib_5 within a HS-dominant branch, state 6; transcription factor prediction from branch-dependent differentially expressed genes identified YY1 as the only predicted transcription factor also differentially expressed in state 6. Functional validation showed that YY1overexpression in fibroblasts derived from patients with HS reversed fibrotic gene expression profiles, with Fib_5 identified as a primary responder by Scissor. CUT&Tag analysis validated these findings at the epigenomic level. Cell-cell communication analyses further revealed marked reprogramming of fibroblast-pericyte signalling across multiple fibrosis-related pathways in HS. Conclusion This work establishes the Fib_5-YY1 axis as a central hub in HS pathogenesis, with YY1-mediated fibroblast plasticity as a key transcriptional mechanism underlying skin fibrogenesis.","PeriodicalId":9553,"journal":{"name":"Burns & Trauma","volume":"102 1","pages":""},"PeriodicalIF":5.3,"publicationDate":"2026-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147586353","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Large Language Models in Emergency and Critical Care Medicine: A Comprehensive Review of Applications, Challenges, and Future Directions","authors":"Jie Yang, Suibi Yang, Ziyao Shao, Tianqi Chen, Hongjie Shen, Pengmin Zhou, Boming Xia, Xiong Lei, Lihui Wang, Dong Xue, Shaojiang Zheng, Yuetian Yu, Zhongheng Zhang","doi":"10.1093/burnst/tkag026","DOIUrl":"https://doi.org/10.1093/burnst/tkag026","url":null,"abstract":"Emergency and critical care medicine (ECCM) requires the rapid synthesis of heterogeneous clinical data under extreme time constraints. Early artificial intelligence (AI) tools lacked the flexibility to manage real-word patient heterogeneity. Large language models (LLMs) offer a paradigm shift by demonstrating advanced natural language understanding, cross-task generalization, and context-sensitive reasoning, thereby bridging the gap between fragmented algorithms and holistic clinical decision support. The effective deployment of these models is grounded in four methodological pillars: domain adaptation, knowledge integration, multimodal and temporal modeling and transparency. Domain adaptation and knowledge integration specifically empower the context-sensitive reasoning required for high-stakes intensive care. This theoretical framework enables their application across clinical decision support, documentation optimization, medical education, and clinical research. Integrating continuous physiological waveforms with multi-omics data facilitates dynamic risk stratification for complex conditions like sepsis, while natural language-to-structured query language capabilities accelerate clinical data extraction and quality improvement. The transition of LLMs from experimental settings to routine clinical deployment remains constrained by model hallucinations, multimodal integration barriers, and unresolved ethical governance. Sustainable implementation requires a human-in-the-loop copilot design, rigorous multicenter prospective validation, and transparent regulatory frameworks. Addressing these challenges is essential to ensure technological innovations safely translate into measurable improvements in patient survival and clinical outcomes.","PeriodicalId":9553,"journal":{"name":"Burns & Trauma","volume":"14 1","pages":""},"PeriodicalIF":5.3,"publicationDate":"2026-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147502041","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Advances in Hemostatic biomaterials: biomimetic strategies, nanotechnology, and smart therapeutics","authors":"Minrui Ji, Zaixin Yuan, Fei Ju, Jie Sun, Yingying Yan, Qi Ding, Jinling Chen, Qian Qian Yang, You Lang Zhou","doi":"10.1093/burnst/tkag023","DOIUrl":"https://doi.org/10.1093/burnst/tkag023","url":null,"abstract":"Bleeding, a critical complication in trauma, surgery, and conditions such as hemophilia, liver cirrhosis, and thrombocytopenia, often leads to shock or death. The limitations of traditional hemostatic methods—such as compression, suturing, and electrocautery—have prompted the development of advanced biomaterials. In modern research, intelligent, multi-mechanism systems have supplanted basic physical or chemical approaches. Biomimetic designs, such as platelet- and fibrin-inspired materials, alongside nanotechnology (e.g. nanoparticle carriers and electrospun fibers) and stimuli-responsive polymers (e.g. light- or temperature-triggered), enable targeted clotting, controlled drug release, and enhanced wound adhesion. Additionally, 3D printing and microfluidics allow precise material modification, further boosting hemostatic efficiency. Despite these advances, clinical translation faces challenges related to biocompatibility, mass production, and patient-specific customization. Future progress is likely to integrate multidisciplinary technologies, such as AI, genetic engineering, smart regulation, and personalized therapies, to improve hemorrhage management. These innovations aim to bridge the gap between laboratory research and clinical application, offering safer, more effective solutions for trauma and surgical interventions.","PeriodicalId":9553,"journal":{"name":"Burns & Trauma","volume":"7 1","pages":""},"PeriodicalIF":5.3,"publicationDate":"2026-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147492724","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Advances in Microneedle Design for the Delivery of Drugs, Proteins and Cells in the Treatment of Hypertrophic Scars","authors":"Juntong Guo, Qinghan Tang, Zhengping Ge, Qing Xia, Hanmei Liu, Huaikai Shi, Jinlong Huang, Jun Chen, Mark S Cooper, Xin Yan, Chenxi Yang, Yiwei Wang","doi":"10.1093/burnst/tkag025","DOIUrl":"https://doi.org/10.1093/burnst/tkag025","url":null,"abstract":"Hypertrophic scars (HS) represent a significant clinical challenge due to their complex pathophysiology and resistance to conventional therapies, often resulting in persistent symptoms such as itching, pain, and impaired joint mobility that compromise patients’ quality of life. Current treatment modalities, including compression therapy, pharmacological agents, radiation, silicone gel, and laser therapies have face limitations primarily due to inadequate drug penetration into the dense fibrotic scar tissue. In this context, microneedle-mediated controlled delivery systems have emerged as a promising pharmaceutical platform to enhance localized and sustained delivery of therapeutic agents, including small-molecule drugs, biologic proteins, siRNA and living cells, directly into HS. This article critically reviews the biological and formulation-related challenges associated with transdermal delivery in scar tissue and highlights recent innovations in microneedle design, material selection, and drug loading techniques tailored for controlled release applications. Furthermore, it discusses the integration of proteins and cell-based therapies within microneedle platforms and their potential to modulate scar remodeling and inflammation. By addressing current limitations and exploring cutting-edge technologies, this review article aims to guide the development of effective microneedle-mediated strategies for pharmaceutical intervention in hypertrophic scar management.","PeriodicalId":9553,"journal":{"name":"Burns & Trauma","volume":"12 1","pages":""},"PeriodicalIF":5.3,"publicationDate":"2026-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147489740","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mechanism of RNA-Binding Protein ILF2 in Promoting Diabetic Foot Ulcer Wound Healing via Regulating the NPM1/NF-κB Axis","authors":"Hua Ji, Ying Tang, Chenfan Zhang, Yinguang Jia, Murong Xu, Xiaotong Zhao, Mingwei Chen","doi":"10.1093/burnst/tkag021","DOIUrl":"https://doi.org/10.1093/burnst/tkag021","url":null,"abstract":"Background Diabetic foot ulcer (DFU) is a severe diabetic complication characterized by impaired healing, often involving fibroblast senescence and the senescence-associated secretory phenotype (SASP). The role of RNA-binding proteins (RBPs) in this process remains undefined. This study investigates the function and mechanism of the RBP Interleukin enhancer-binding factor 2 (ILF2) in DFU pathogenesis. Methods Differentially expressed RBPs were identified via bioinformatics analysis of public single-cell and bulk transcriptomic datasets. ILF2 downregulation was subsequently validated in clinical DFU samples and diabetic mouse models. Functional assays in high-glucose-treated fibroblasts evaluated proliferation, migration, and SASP. Mechanistically, RNA sequencing, RIP, and RNA pull-down assays identified downstream targets, while co-IP and rescue experiments verified the NPM1/NF-κB axis. Finally, a diabetic mouse model was used to study the effects of ILF2 overexpression/knockdown and NPM1 knockdown on wound healing. Results Bioinformatics analysis identified ILF2 as significantly downregulated in DFU. This reduction was consistently validated in DFU patient tissues, diabetic mouse wounds, and high-glucose-treated fibroblasts. Functionally, ILF2 overexpression promoted fibroblast proliferation and migration while suppressing SASP, whereas knockdown exacerbated senescence. Mechanistically, ILF2 directly bound to Nucleophosmin (NPM1) mRNA to promote its degradation. ILF2 deficiency led to aberrant NPM1 accumulation, enhancing the NPM1-p65 interaction and NF-κB pathway activation. Rescue experiments confirmed that NPM1 knockdown reversed ILF2 deficiency-induced cellular dysfunction. Crucially, these findings were validated in primary fibroblasts isolated from DFU patients. In vivo, ILF2 overexpression accelerated wound healing, while knockdown delayed the process. Furthermore, NPM1 knockdown effectively ameliorated the impaired healing phenotype and reduced SASP levels. Conclusion This study elucidates a novel ILF2-NPM1-NF-κB regulatory axis. ILF2 acts as a critical suppressor of inflammatory senescence by destabilizing NPM1 mRNA, highlighting its potential as a therapeutic target for DFU treatment.","PeriodicalId":9553,"journal":{"name":"Burns & Trauma","volume":"13 1","pages":""},"PeriodicalIF":5.3,"publicationDate":"2026-03-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147489741","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neutrophils and NETs in Ischaemia–Reperfusion Injury: Pathophysiological Roles and Therapeutic Potential","authors":"Yiqiong Zhang, Chaofu Li, Qiuyan Jiang, Yukun Yang, Yingying Jiang, Lin Chen, Xiang Wei, Jun Xiao, Chuanwei Li","doi":"10.1093/burnst/tkag022","DOIUrl":"https://doi.org/10.1093/burnst/tkag022","url":null,"abstract":"Ischaemia–reperfusion injury (IRI) is a fundamental pathological process underlying acute and chronic damage associated with myocardial infarction, ischaemic stroke, and solid organ transplantation. Although timely reperfusion is indispensable for tissue salvage, it paradoxically promotes maladaptive immune activation and oxidative stress, which aggravate microvascular dysfunction and organ failure. Accumulating evidence indicates that sterile inflammation, endothelial injury, and immunothrombosis are the central drivers of IRI progression. Among innate immune effectors, neutrophils act as first responders that integrate chemotactic signalling, adhesion cascades, and metabolic rewiring. Upon activation, neutrophils release damage-associated molecular patterns (DAMPs) and form neutrophil extracellular traps (NETs), which amplify inflammation, promote coagulation, and disrupt tissue repair across organs. However, the organ-specific roles, temporal dynamics, and translational relevance of neutrophils and NETs in IRI remain incompletely understood. In this review, we systematically dissect the neutrophil- and NET-mediated mechanisms involved in IRI across the heart, brain, kidney, liver, and transplanted organs, with a particular emphasis on endothelial crosstalk, immunothrombosis, and metabolic regulation. We further summarize emerging NET-associated biomarkers—including cell-free DNA (cfDNA) and myeloperoxidase–DNA (MPO–DNA) complexes—for IRI diagnosis and prognosis. Finally, we evaluate therapeutic strategies targeting neutrophil recruitment, immune metabolism, and NET clearance, highlighting challenges for clinical translation. In summary, this review provides a mechanistic and translational framework for targeting neutrophils and NETs in precision therapies for IRI.","PeriodicalId":9553,"journal":{"name":"Burns & Trauma","volume":"18 1","pages":""},"PeriodicalIF":5.3,"publicationDate":"2026-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147462185","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting the c-Jun–Irf8–CD36 Axis Attenuates Fibrotic Scar Formation and Promotes Functional Recovery after Spinal Cord Injury","authors":"Min Feng, JiYu Li, Jieying Zhang, Hang Zhang, Wanhua Li, Yili Liu, Xiang Gao, Hanyue Yang, Zeyu Liu, Chong Gao, Ruiyang Xiao, Jianru Xiao, Xiaozhong Zhou, Leilei Gong, Songlin Zhou, Jian Zhao, Caiqi Cheng","doi":"10.1093/burnst/tkag020","DOIUrl":"https://doi.org/10.1093/burnst/tkag020","url":null,"abstract":"Background Fibrotic scar formation constitutes a significant pathological obstacle that impedes neural regeneration and long-term functional recovery following spinal cord injury (SCI). However, the spatial distribution of key pro-fibrotic mediators within lesion scars and the upstream regulatory mechanisms driving fibroblast activation remain inadequately defined. Methods This study integrated single-cell RNA sequencing and spatial transcriptomic profiling to characterize CD36 expression patterns and identify fibroblast subpopulations within SCI scars. Pharmacological interventions were administered in mouse SCI models, using salvianolic acid B (SAB) to inhibit CD36 and T5224 to block AP-1/c-Jun activity. Histological and immunofluorescence analyses were performed to assess fibroblast accumulation, extracellular matrix deposition, angiogenesis, and axonal regeneration, alongside longitudinal behavioral evaluations of locomotor function. Mechanistic validation of the regulatory pathway was achieved through CUT&Tag and dual-luciferase reporter assays to investigate c-Jun–Irf8–CD36 transcriptional regulation, complemented by integrated single-cell/spatial analyses to assess fibroblast subcluster remodeling post-treatment. Results Spatial and single-cell analyses demonstrated that CD36 is predominantly localized within lesion scars, correlating with fibrotic progression and preferentially upregulated in specific fibroblast subclusters. SAB-mediated CD36 inhibition markedly reduced P4HB+ fibroblast accumulation, alleviated fibrotic deposition, enhanced angiogenesis and axonal regeneration, and improved hindlimb functional recovery. Mechanistically, c-Jun was upregulated in scar regions and indirectly promoted CD36 transcription through Irf8 activation, establishing a c-Jun–Irf8–CD36 signaling axis. CUT&Tag and reporter assays confirmed c-Jun binding to the Irf8 promoter, leading to Irf8-driven CD36 transcription. Similarly, T5224 downregulated CD36 expression, reduced fibroblast aggregation and matrix deposition, facilitated vascular remodeling, and promoted early functional recovery. These findings demonstrate that modulating this signaling pathway can significantly inhibit pathological scar formation and facilitate approximately scar-free healing, thereby providing an ideal microenvironment for tissue regeneration. Multi-omic analyses further revealed that T5224 selectively inhibited the aberrant expansion of CD36+ fibroblast subclusters and reprogrammed their transcriptional states toward a less fibrotic phenotype. Conclusions The c-Jun–Irf8–CD36 axis serves as a pivotal regulator of fibrotic scar formation after SCI. Targeting this pathway through CD36 inhibition (SAB) or AP-1/c-Jun blockade (T5224) attenuates fibrosis, remodels the scar microenvironment, enhances tissue repair, and promotes functional recovery, highlighting a promising therapeutic strategy for central nervous system injury.","PeriodicalId":9553,"journal":{"name":"Burns & Trauma","volume":"5 1","pages":""},"PeriodicalIF":5.3,"publicationDate":"2026-03-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147439697","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}