Orthopaedics & Traumatology, Surgery & Research[JOURNAL]
Sun
7 papers
Apoptotic Vesicle Membrane-Mediated Targeted Endothelial Mitochondrial Transplantation-Clearance Therapy for Diabetic Wound Healing.
Hu Z, Qian S, Liao B … +9 more , Wang Y, Lu Q, Mao J, Lu B, Zhang L, Wang F, Wang D, Cui W, Sun X
Research (Wash D C) · 2026 · PMID 42058651 · Full text
Impaired mitophagy and the accumulation of damaged mitochondria are key drivers of endothelial cell (EC) dysfunction in diabetic wounds. While mitochondrial transplantation (MT) has demonstrated therapeutic potential in...
Impaired mitophagy and the accumulation of damaged mitochondria are key drivers of endothelial cell (EC) dysfunction in diabetic wounds. While mitochondrial transplantation (MT) has demonstrated therapeutic potential in such mitochondrial damage-related diseases, its application is still thwarted by elusive mechanisms and practical hurdles such as poor targeting specificity and low delivery efficiency. Here, we reveal that MT acts by reactivating mitophagy to selectively eliminate dysfunctional mitochondria, thereby restoring mitochondrial homeostasis and rescuing EC functionality. To exploit this discovery, we engineer a biomimetic MT strategy through coating EC-derived apoptotic vesicle membrane (AVM) onto the surface of isolated mitochondria. The resulting mitochondria-AVM complex (Mito-AVM) leverages homologous targeting and phosphatidylserine-mediated "eat-me" signaling, achieving a remarkable 150% increase in delivery efficiency to ECs in diabetic wounds. Furthermore, we construct a 3-aminophenylboric acid-modified hyaluronic acid/polyvinyl alcohol hydrogel for the diabetic wound microenvironment, enabling reactive oxygen species/glucose-triggered sustained release of encapsulated Mito-AVM at the wound site. In summary, our work elucidates a fundamental mechanism of MT and provides an efficient and targeted strategy for MT therapy, offering fresh perspectives for diabetic wound treatment.
Clinical Application of Deep Learning for Spine MRI Interpretation: A Multicenter Evaluation of Artificial-Intelligence-Assisted versus Manual Reading on Diagnostic Agreement with the Reference Standard.
Cheng X, Zhang M, Ren Z … +19 more , Tang T, Meng X, Huang Z, Li HB, Li W, Yan Q, Chen H, Jia J, Wang C, Li C, Yang C, Shi G, Li G, Zeng K, Chen W, Gao H, Wang X, Zheng X, Wang Y
Research (Wash D C) · 2026 · PMID 41726766 · Full text
Lumbar spine diseases substantially impact the patients' quality of life, necessitating accurate and efficient diagnostic tools. This study presents Lumbar VNet Pro (LVP), the first real-time artificial-intelligence (AI)...
Lumbar spine diseases substantially impact the patients' quality of life, necessitating accurate and efficient diagnostic tools. This study presents Lumbar VNet Pro (LVP), the first real-time artificial-intelligence (AI)-assisted system embedded within MRI hardware for lumbar spine analysis, integrating deep learning with MRI. LVP was trained on 2,453 MRI datasets and validated both internally and externally across multiple centers. During the training (1,848 MRI datasets) and validation (605 MRI datasets), LVP exhibited outstanding performance in localization (Dice = 0.93), segmentation (Dice = 0.92), labeling (identification rate = 0.90), and timeliness (average inference time = 1.1 s). Following the successful construction of LVP, we conducted comprehensive testing through both internal and external multicenter evaluations. Internal testing involving 100 patients indicated that the recognition accuracy of LVP was as high as 100%, and the consistency between the LVP assessment and the manual assessment using the gold standard reached 97%. In external testing involving 1,522 patients, LVP's diagnostic performance was compared to those of manual and human-machine-assisted methods. The AI-assisted approaches demonstrated better performance across multiple spinal pathologies, including lumbar disc herniation, spinal canal stenosis, and lateral recess stenosis, with area under the receiver operating characteristic curve values >0.95 for deep learning/human-machine approaches and >0.90 for the fully manual approach. The real-time integration of LVP with MRI scanning improved positioning accuracy and reduced interobserver variability, supporting its potential as an adjunct tool for enhancing MRI-based spine diagnostics. However, further studies are warranted to assess its generalizability across diverse clinical settings.
Biosynthesis of Lysosomally Escaped Apoptotic Bodies Inhibits Inflammasome Synthesis in Macrophages.
Mao J, Xia W, Wu Y … +7 more , Li M, Zhao Y, Zhai P, Zhang Y, Zan T, Cui W, Sun X
Research (Wash D C) · 2025 · PMID 39850366 · Full text
Hyperglycemia and bacterial colonization in diabetic wounds aberrantly activate Nod-like receptor protein 3 (NLRP3) in macrophages, resulting in extensive inflammatory infiltration and impaired wound healing. Targeted su...
Hyperglycemia and bacterial colonization in diabetic wounds aberrantly activate Nod-like receptor protein 3 (NLRP3) in macrophages, resulting in extensive inflammatory infiltration and impaired wound healing. Targeted suppression of the NLRP3 inflammasome shows promise in reducing macrophage inflammatory disruptions. However, challenges such as drug off-target effects and degradation via lysosomal capture remain during treatment. In this study, engineered apoptotic bodies (BHB-dABs) derived from adipose stem cells loaded with β-hydroxybutyric acid (BHB) were synthesized via biosynthesis. These vesicles target M1-type macrophages, which highly express the folic acid receptor in the inflammatory microenvironment, and facilitate lysosomal escape through 1,2-distearoyl--propyltriyl-3-phosphatidylethanolamine-polyethylene glycol functionalization, which may enhance the efficacy of NLRP3 inhibition for managing diabetic wounds. In vitro studies demonstrated the biocompatibility of BHB-dABs, their selective targeting of M1-type macrophages, and their ability to release BHB within the inflammatory microenvironment via folic acid and folic acid receptor signaling. These nanovesicles exhibited lysosomal escape, anti-inflammatory, mitochondrial protection, and endothelial cell vascularization properties. In vivo experiments demonstrated that BHB-dABs enhance the recovery of diabetic wound inflammation and angiogenesis, accelerating wound healing. These functionalized apoptotic bodies efficiently deliver NLRP3 inflammasome inhibitors using a dual strategy of targeting macrophages and promoting lysosomal escape. This approach represents a novel therapeutic strategy for effectively treating chronic diabetic wounds.
Intelligent Hydrogel-Assisted Hepatocellular Carcinoma Therapy.
Tang Z, Deng L, Zhang J … +7 more , Jiang T, Xiang H, Chen Y, Liu H, Cai Z, Cui W, Xiong Y
Research (Wash D C) · 2024 · PMID 39691767 · Full text
Given the high malignancy of liver cancer and the liver's unique role in immune and metabolic regulation, current treatments have limited efficacy, resulting in a poor prognosis. Hydrogels, soft 3-dimensional network mat...
Given the high malignancy of liver cancer and the liver's unique role in immune and metabolic regulation, current treatments have limited efficacy, resulting in a poor prognosis. Hydrogels, soft 3-dimensional network materials comprising numerous hydrophilic monomers, have considerable potential as intelligent drug delivery systems for liver cancer treatment. The advantages of hydrogels include their versatile delivery modalities, precision targeting, intelligent stimulus response, controlled drug release, high drug loading capacity, excellent slow-release capabilities, and substantial potential as carriers of bioactive molecules. This review presents an in-depth examination of hydrogel-assisted advanced therapies for hepatocellular carcinoma, encompassing small-molecule drug therapy, immunotherapy, gene therapy, and the utilization of other biologics. Furthermore, it examines the integration of hydrogels with conventional liver cancer therapies, including radiation, interventional therapy, and ultrasound. This review provides a comprehensive overview of the numerous advantages of hydrogels and their potential to enhance therapeutic efficacy, targeting, and drug delivery safety. In conclusion, this review addresses the clinical implementation of hydrogels in liver cancer therapy and future challenges and design principles for hydrogel-based systems, and proposes novel research directions and strategies.
Genetic Engineered Ultrasound-Triggered Injectable Hydrogels for Promoting Bone Reconstruction.
Zhao Z, Ruan H, Chen A … +4 more , Xiong W, Zhang M, Cai M, Cui W
Research (Wash D C) · 2023 · PMID 39830009 · Full text
Genetic engineering technology can achieve specific gene therapy for a variety of diseases, but the current strategy still has some flaws, such as a complex system, single treatment, and large implantation trauma. Herein...
Genetic engineering technology can achieve specific gene therapy for a variety of diseases, but the current strategy still has some flaws, such as a complex system, single treatment, and large implantation trauma. Herein, the genetic engineering injectable hydrogels were constructed by ultrasonic technology for the first time to realize in vivo ultrasound-triggered in situ cross-linking and cell gene transfection, and finally complete in situ gene therapy to promote bone reconstruction. First, ultrasound-triggered calcium release was used to activate transglutaminase and catalyze the transamidation between fibrinogen. Simultaneously, liposome loaded with Zinc-finger E-box-binding homeobox 1 (ZEB1) gene plasmid (Lip-ZEB1) was combined to construct an ultrasound-triggered in situ cross-linked hydrogels that can deliver Lip-ZEB1. Second, ultrasound-triggered injectable hydrogel introduced ZEB1 gene plasmid into endothelial cell genome through Lip-ZEB1 sustained release, and then acted on the ZEB1/Notch signal pathway of cells, promoting angiogenesis and local bone reconstruction of osteoporosis through genetic engineering. Overall, this strategy provides an advanced gene delivery system through genetic engineered ultrasound-triggered injectable hydrogels.
Comprehensive Metabolic Profiling and Genome-wide Analysis Reveal Therapeutic Modalities for Hepatocellular Carcinoma.
Qi F, Li J, Qi Z … +6 more , Zhang J, Zhou B, Yang B, Qin W, Cui W, Xia J
Research (Wash D C) · 2023 · PMID 37040510 · Full text
Understanding the details of metabolic reprogramming in hepatocellular carcinoma (HCC) is critical to improve stratification for therapy. Both multiomics analysis and cross-cohort validation were performed to investigate...
Understanding the details of metabolic reprogramming in hepatocellular carcinoma (HCC) is critical to improve stratification for therapy. Both multiomics analysis and cross-cohort validation were performed to investigate the metabolic dysregulation of 562 HCC patients from 4 cohorts. On the basis of the identified dynamic network biomarkers, 227 substantial metabolic genes were identified and a total of 343 HCC patients were classified into 4 heterogeneous metabolic clusters with distinct metabolic characteristics: cluster 1, the pyruvate subtype, associated with upregulated pyruvate metabolism; cluster 2, the amino acid subtype, with dysregulated amino acid metabolism as the reference; cluster 3, the mixed subtype, in which lipid metabolism, amino acid metabolism, and glycan metabolism are dysregulated; and cluster 4, the glycolytic subtype, associated with the dysregulated carbohydrate metabolism. These 4 clusters showed distinct prognoses, clinical characteristics and immune cell infiltrations, which was further validated by genomic alterations, transcriptomics, metabolomics, and immune cell profiles in the other 3 independent cohorts. Besides, the sensitivity of different clusters to metabolic inhibitors varied depending on their metabolic features. Importantly, cluster 2 is rich in immune cells in tumor tissues, especially programmed cell death protein 1 (PD-1)-expressing cells, which may be due to the tryptophan metabolism disorders, and potentially benefiting more from PD-1 treatment. In conclusion, our results suggest the metabolic heterogeneity of HCC and make it possible to treat HCC patients precisely and effectively on specific metabolic characteristics.
In Situ-Activated Phospholipid-Mimic Artemisinin Prodrug via Injectable Hydrogel Nano/Microsphere for Rheumatoid Arthritis Therapy.
Du Y, Li C, Zhang Y … +8 more , Xiong W, Wang F, Wang J, Zhang Y, Deng L, Li X, Chen W, Cui W
Research (Wash D C) · 2022 · PMID 39290968 · Full text
In situ-activated therapy is a decent option for localized diseases with improved efficacies and reduced side effects, which is heavily dependent on the local conversion or activation of bioinert components. In this work...
In situ-activated therapy is a decent option for localized diseases with improved efficacies and reduced side effects, which is heavily dependent on the local conversion or activation of bioinert components. In this work, we applied a phospholipid-mimic artemisinin prodrug (ARP) for preparing an injectable nano/microsphere to first realize an in situ-activated therapy of the typical systemically administrated artemisinin-based medicines for a localized rheumatoid arthritis (RA) lesion. ARP is simultaneously an alternative of phospholipids and an enzyme-independent activable prodrug, which can formulate "drug-in-drug" co-delivery liposomes with cargo of partner drugs (e.g., methotrexate). To further stabilize ARP/methotrexate "drug-in-drug" liposomes (MTX/ARPL) for a long-term intra-articular retention, a liposome-embedded hydrogel nano/microsphere (MTX/ARPL@MS) was prepared. After the local injection, the MTX/ARPL could be slowly released because of imine hydrolysis and targeted to RA synovial macrophages and fibroblasts simultaneously. ARP assembly is relatively stable before cellular internalization but disassembled ARP after lysosomal escape and converted into dihydroartemisinin rapidly to realize the effective in situ activation. Taken together, phospholipid-mimic ARP was applied for the firstly localized in situ-activated RA therapy of artemisinin-based drugs, which also provided a brand-new phospholipid-mimic strategy for other systemically administrated prodrugs to realize a remodeling therapeutic schedule for localized diseases.
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