Eszter Éva Virág-Tulassay, Noémi Gede, Peter Hegyi, Gábor Skaliczki
{"title":"Response to the Letter to the Editor on “Bankart surgery is the most effective treatment for first-time anterior shoulder dislocation without significant bone loss - Systematic review and network meta-analysis”","authors":"Eszter Éva Virág-Tulassay, Noémi Gede, Peter Hegyi, Gábor Skaliczki","doi":"10.1016/j.jot.2026.101217","DOIUrl":"10.1016/j.jot.2026.101217","url":null,"abstract":"","PeriodicalId":16636,"journal":{"name":"Journal of Orthopaedic Translation","volume":"60 ","pages":"Article 101217"},"PeriodicalIF":9.8,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148958471","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}
{"title":"Hesperetin mitigates IBD-associated bone loss via Akkermansia muciniphila enrichment and IDA-driven gut-bone axis crosstalk","authors":"Yimin Pi, Haodong Zhu, Jian Xie, Furui Tang, Zhuoya Wang, Li Liu, Yuchun Zhong, Zhidong He, Tian Liu, Jiacheng Zheng, Yuwen Tang, Jun Luo, Cihua Zheng","doi":"10.1016/j.jot.2026.101216","DOIUrl":"10.1016/j.jot.2026.101216","url":null,"abstract":"<div><div>Inflammatory bowel disease (IBD) is a chronic inflammatory disorder frequently accompanied by extraintestinal complications such as bone loss, yet effective treatment options remain elusive. In this study, we investigated whether hesperetin mitigates colitis-associated bone loss by modulating the “gut–bone axis.” Using a DSS-induced mouse model of chronic colitis, we found that hesperetin significantly reduced intestinal inflammation, restored mucosal barrier integrity, and suppressed serum inflammatory cytokines. Furthermore, hesperetin effectively alleviated DSS-induced bone microstructure damage, promoted the expression of ALP, Runx2, OCN, and inhibited NFATc1 and CTSK. Fecal microbiota transplantation experiments further confirmed that the intestinal microbiota from hesperetin-treated group attenuated intestinal inflammation and bone loss. 16S rRNA sequencing and metabolomics revealed that hesperetin enriched <em>Akkermansia muciniphila</em> (<em>A. muciniphila</em>) and increased the tryptophan metabolite 3-indoleacrylic acid (IDA). Supplementation with <em>A. muciniphila</em> or IDA alone simulated the therapeutic benefits of hesperetin. Furthermore, RNA-seq revealed that hesperetin regulated bone metabolism-related gene expression by ECM-receptor interaction and PI3K-AKT signaling, while inhibiting the NOD-like receptor pathway. In conclusion, hesperetin mitigates intestinal inflammation and bone homeostasis imbalance by reshaping the gut microbiota, enriching <em>A. muciniphila,</em> and promoting IDA production, thus providing new insights into potential therapies for IBD-related bone loss.</div></div>","PeriodicalId":16636,"journal":{"name":"Journal of Orthopaedic Translation","volume":"60 ","pages":"Article 101216"},"PeriodicalIF":9.8,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149044133","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}
{"title":"MRSA-dominant colonization and synergistic pathogenicity with Pseudomonas aeruginosa in a polymicrobial bone infection model","authors":"Hang Zhou, Wanchang Liu, Xinliang Peng, Maohui Li, Zhongyuan He, Hang Liu, Xingyu Yang, Zhaoyang Guo, Wentao Zhang, Wei Fu, Hanchao Liang, Lei Shi, Rui Deng, Yaohua Chen, Ruixiang Zhang, Yongjun Dang, Chao Xie, Yunying Wang, Zhongliang Deng, Lei Chu, Youliang Ren","doi":"10.1016/j.jot.2026.101222","DOIUrl":"10.1016/j.jot.2026.101222","url":null,"abstract":"<div><h3>Objective</h3><div>Polymicrobial bone infections (PBI) remain difficult to treat due to multi-drug resistance and poorly defined microbial interactions. Co-infection with methicillin-resistant <em>Staphylococcus aureus</em> (MRSA) and <em>Pseudomonas aeruginosa</em> (PA) represents a clinically prevalent subtype of PBI. Using a rat PBI model, this study aimed to elucidate the spatiotemporal dynamics of MRSA-PA co-infection and its impact on host responses, bacterial persistence, and antimicrobial susceptibility.</div></div><div><h3>Methods</h3><div>Titanium screws were pre-contaminated with fluorescently labeled MRSA (mCherry) or PA (green fluorescent protein, GFP) and implanted 5 mm apart into the femoral mid-diaphysis of Sprague–Dawley rats. Animals were assigned to five groups: sterile, MRSA, PA, MRSA + PA, and PA + MRSA. Longitudinal evaluation included hematology, serum biochemistry (CRP, PCT, TNF-α, and IL-6), micro-CT imaging, and hard-tissue sectioning. Colony-forming unit (CFU) counts and histological analyses (H&E, Gram, and DAPI staining) were performed to evaluate bacterial burden, spatiotemporal colonization and biofilm formation. Local inflammation and osteoclast activation were further assessed by TNF-α immunohistochemistry and tartrate-resistant acid phosphatase (TRAP) staining. Antimicrobial susceptibility was evaluated by automated MIC testing and complementary disk diffusion assays. Transcriptomic and whole-genome sequencing analyses were performed to characterize transcriptional adaptations and virulence- and resistance-associated gene profiles.</div></div><div><h3>Results</h3><div>Co-infection induced a synergistic inflammatory response, with a 6.8-fold increase in neutrophil counts relative to baseline, and caused severe osteolysis, with an approximately 80% reduction in bone–implant contact relative to the sterile group. At postoperative day 7, the co-infection groups showed increased local TNF-α-positive and TRAP-positive areas, supporting an association between the amplified inflammatory response and early osteoclast activation. Spatial analyses revealed asymmetric colonization dynamics: MRSA rapidly disseminated to and colonized PA-contaminated sites by postoperative day 7, whereas reciprocal PA dissemination into MRSA-dominant sites was not detected until day 28. Both pathogens concurrently infiltrated the osteocyte lacuno-canalicular network, uncovering a previously unrecognized reservoir for polymicrobial persistence within bone. Multi-omics profiling revealed susceptibility shifts and extensive adaptive reprogramming in PA.</div></div><div><h3>Conclusion</h3><div>MRSA acts as a dominant ecological driver in PBI that amplifies bone destruction and facilitates polymicrobial persistence, emphasizing the need for multi-species therapeutic strategies.</div></div><div><h3>The translational potential of this article</h3><div>This study establishes a reproducible rat model of polymicrobial bone infection and rev","PeriodicalId":16636,"journal":{"name":"Journal of Orthopaedic Translation","volume":"60 ","pages":"Article 101222"},"PeriodicalIF":9.8,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149141033","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}
Emanuel Vitor Appolonio, Vittoria Guerra Altheman, Fernanda de Castro Stievanni, Gustavo dos Santos Rosa, Fernanda Barthelson Carvalho de Moura, Natalia Camargo Faraldo, Carlos Eduardo Fonseca Alves, Camila C. Kaleka, Pedro Debieux, Moises Cohen, Ana Liz Garcia Alves
{"title":"Combining polydioxanone-based scaffold and allogeneic adipose-derived mesenchymal stem cells enhances articular cartilage repair - a pre-clinical study","authors":"Emanuel Vitor Appolonio, Vittoria Guerra Altheman, Fernanda de Castro Stievanni, Gustavo dos Santos Rosa, Fernanda Barthelson Carvalho de Moura, Natalia Camargo Faraldo, Carlos Eduardo Fonseca Alves, Camila C. Kaleka, Pedro Debieux, Moises Cohen, Ana Liz Garcia Alves","doi":"10.1016/j.jot.2026.101193","DOIUrl":"10.1016/j.jot.2026.101193","url":null,"abstract":"<div><h3>Introduction</h3><div>Articular cartilage exhibits limited intrinsic regenerative capacity, making its repair a persistent clinical challenge. Polydioxanone (PDO) scaffolds offer biocompatibility, tunable degradation, and structural support, whereas adipose-derived mesenchymal stem cells (AD-MSCs) possess chondrogenic, immunomodulatory, and regenerative potential. This study evaluated the biocompatibility of the PDO scaffold <em>(Plenum Tissue Ortho)</em> and investigated its effectiveness in enhancing articular cartilage repair when combined with microfracture (MF) or allogeneic ovine adipose-derived mesenchymal stem cells (SadMSCs), in comparison with a collagen scaffold (COL), in a preclinical ovine model.</div></div><div><h3>Methods</h3><div>Twenty-four adult sheep were randomly allocated into six groups. Full-thickness chondral defects were created in the weight-bearing region of the medial femoral condyle and treated according to each group: Control (no treatment), MF alone, MF/COL, MF/PDO, SadMSC/COL, or SadMSC/PDO. SadMSCs were isolated, expanded, and characterized for viability, immunophenotyping, and trilineage differentiation. The biocompatibility of the PDO scaffold was assessed by cell adhesion and proliferation using Live/Dead staining and scanning electron microscopy. After 26 weeks, articular cartilage repair was evaluated macroscopically following ICRS scoring guidelines, histologically using the modified O'Driscoll score, and immunohistochemically for COL I, COL II, COL X, TGF-β2, and TGF-β3.</div></div><div><h3>Results</h3><div>PDO scaffolds supported the survival, adhesion, and proliferation of SadMSCs. Clinically, animals showed good recovery without major complications. At necropsy, no residual membranes, inflammation, or adverse reactions were detected. Macroscopically, the PDO/MF group presented the best repair scores, significantly superior to the Control, MF alone, MF/COL, SadMSC/COL, and SadMSC/PDO groups. Microscopically, SadMSC/PDO achieved the highest O'Driscoll and immunohistochemistry scores, with strong expression of COL II and TGF-β, along with reduced COL I and COL X, indicating hyaline-like cartilage formation. Multivariate analysis confirmed a strong positive correlation between COL II, TGF-β expression, and histological scores.</div></div><div><h3>Conclusion</h3><div>PDO scaffolds demonstrated excellent biocompatibility and, when combined with SadMSCs, promoted superior cartilage repair compared with COL scaffolds or MF alone. While PDO/MF achieved the best macroscopic outcomes, SadMSC/PDO provided the most favorable microscopic and molecular findings, suggesting that allogeneic AdMSCs seeded on PDO scaffolds enhance hyaline-like cartilage formation. These results highlight PDO and AD-MSC-based constructs as a promising alternative for translational strategies in cartilage repair.</div></div><div><h3>The translational potential of this article</h3><div>This study demonstrated that the combination of ","PeriodicalId":16636,"journal":{"name":"Journal of Orthopaedic Translation","volume":"60 ","pages":"Article 101193"},"PeriodicalIF":9.8,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148854621","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}
Xiaowei Zha, Guoli Zheng, Hao Wang, Obada T. Alhalabi, Raban Heller, Maryam Hatami, Thomas Skutella, Marcin Luzarowski, Xingjin Wang, Sandro M. Krieg, Andreas Unterberg, Alexander Younsi
{"title":"Transplantation of LPS, IL-4, and TGF-β-induced reparative-biased macrophages promotes early motor functional recovery after spinal cord injury in rats","authors":"Xiaowei Zha, Guoli Zheng, Hao Wang, Obada T. Alhalabi, Raban Heller, Maryam Hatami, Thomas Skutella, Marcin Luzarowski, Xingjin Wang, Sandro M. Krieg, Andreas Unterberg, Alexander Younsi","doi":"10.1016/j.jot.2026.101219","DOIUrl":"10.1016/j.jot.2026.101219","url":null,"abstract":"<div><h3>Objective</h3><div>Spinal cord injury (SCI) triggers an inflammatory cascade that often culminates in chronic neurological deficits. This study investigates a combined stimulation approach using lipopolysaccharide (LPS), interleukin-4 (IL-4), and transforming growth factor-beta (TGF-β) to generate reparative-biased macrophages and evaluate their early effects after SCI.</div></div><div><h3>Methods</h3><div>Bone marrow-derived macrophages (BMDMs) from Wistar rats were exposed to LPS, IL-4, and TGF-β for 24 h to generate reparative-biased hybrid macrophages (Mi) in vitro. The anti-inflammatory and pro-regenerative markers of Mi were characterised by qPCR, immunocytochemistry, and proteomic analysis via mass spectrometry. <em>In vivo</em>, rats with a T9/10 clip-contusion-compression SCI received either Mi transplantation or direct inducer administration at the lesion site. Histological outcomes and functional recovery were assessed and compared between injured and uninjured controls over a 14-day period.</div></div><div><h3>Results</h3><div>Following 24 h induction, Mi exhibited significantly elevated mRNA and immunofluorescence expression of Arg1, as well as increased IL-10 mRNA levels, compared to naïve BMDMs in vitro, while iNOS expression remained unchanged. Bioinformatic analysis of proteomic data from Mi revealed enrichment in metabolic activity, immune modulation, and phagocytosis pathways. Fluorescent microsphere phagocytosis assays demonstrated that Mi macrophages retained robust phagocytic activity. <em>In vivo</em>, transplantation of Mi resulted in elevated Arg1 expression and reduced iNOS and IL-1β levels 3 days after SCI, suggesting an anti-inflammatory shift. Immunohistochemical analysis demonstrated significantly reduced lesions and demyelinated areas, as well as increased preservation of motor neurons and oligodendrocytes. Mi transplantation was also associated with reduced apoptosis and improved early functional recovery at 14 days after SCI.</div></div><div><h3>Conclusion</h3><div>This study suggests that LPS, IL-4, and TGF-β-induced Mi macrophages display a reparative-biased hybrid profile that modulates inflammation, supports early tissue preservation, and promotes functional recovery after SCI, supporting Mi transplantation as a potential cell-based therapeutic strategy for further investigation.</div></div><div><h3>The translational potential of this article</h3><div>Transplantation of this reparative-biased hybrid macrophage phenotype may provide a potential therapeutic strategy for the treatment of spinal cord injury.</div></div>","PeriodicalId":16636,"journal":{"name":"Journal of Orthopaedic Translation","volume":"60 ","pages":"Article 101219"},"PeriodicalIF":9.8,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148958568","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}
{"title":"From trial counting to clinical interpretation in a network meta-analysis of first-time anterior shoulder dislocation","authors":"Yijie Gao, Lin Peng, Yuhao Guo, Yi Huang","doi":"10.1016/j.jot.2026.101220","DOIUrl":"10.1016/j.jot.2026.101220","url":null,"abstract":"","PeriodicalId":16636,"journal":{"name":"Journal of Orthopaedic Translation","volume":"60 ","pages":"Article 101220"},"PeriodicalIF":9.8,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148958675","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}
Yan Wang, LuLu Zhang, XueZhi Liu, Dong Wang, JianXiong Ma
{"title":"Macrophage immunometabolic reprogramming in inflammatory repair failure in osteonecrosis of the femoral head","authors":"Yan Wang, LuLu Zhang, XueZhi Liu, Dong Wang, JianXiong Ma","doi":"10.1016/j.jot.2026.101212","DOIUrl":"10.1016/j.jot.2026.101212","url":null,"abstract":"<div><div>The classical “vascular occlusion” model does not fully account for osteonecrosis of the femoral head (ONFH). Femoral head collapse may progress despite restored perfusion, and ischemia alone cannot adequately explain steroid-associated ONFH. We propose that ONFH involves disruption of bone-vascular-immune homeostasis, with macrophage immunometabolic reprogramming in response to hypoxic and lipotoxic stress acting as a potential driver of inflammatory repair failure. Among the metabolic mechanisms implicated in ONFH, the strongest disease-specific evidence supports roles for hypoxia, oxidative stress, disordered lipid metabolism, macrophage imbalance, and ferroptosis-associated injury. By contrast, macrophage-specific glycolytic reprogramming, remodeling of the tricarboxylic acid (TCA) cycle, epigenetic fixation, osteomac dysfunction, and cuproptosis remain less well established. Regulated cell death pathways, particularly ferroptosis and pyroptosis, may exacerbate local tissue injury by releasing damage-associated molecular patterns (DAMPs) and inflammatory mediators that disrupt type H vessel-osteogenesis coupling and shift repair toward fibrosis. Establishing causal relationships rather than correlative associations will require lineage-tracing experiments, spatial validation, metabolic flux analyses, and genetic loss-of-function studies in ONFH models.</div></div><div><h3>The translational potential of this article</h3><div>Viewing ONFH as an immunometabolic disorder identifies experimentally tractable targets beyond conventional anti-inflammatory strategies, including SLC7A11/GPX4-dependent ferroptosis defense, NLRP3 inflammasome signaling, and HIF-1α-associated macrophage metabolic adaptation. Extracellular vesicle- or biomaterial-based delivery systems designed for prolonged local retention should currently be considered experimental platforms for assessing lesion-specific target engagement in early-stage ONFH. Their clinical relevance must be established through ONFH-specific studies evaluating efficacy, safety, biodistribution, manufacturability, and long-term structural outcomes.</div></div>","PeriodicalId":16636,"journal":{"name":"Journal of Orthopaedic Translation","volume":"60 ","pages":"Article 101212"},"PeriodicalIF":9.8,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148935448","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}
{"title":"hUC-MSCs transplantation promotes neurological recovery by ameliorating spinal cord injury and hippocampal synaptic remodeling in female mice","authors":"Boya Huang, Jiahao Ren, Xinjie Liu, Mi Zhou, Yilin Pang, Zemin Cao, Xiaofeng Lin, Xiang Gao, Baoyou Fan, Yan Hao, Shen Liu, Hui Shen, Guangzhi Ning, Xue Yao, Shiqing Feng","doi":"10.1016/j.jot.2026.101214","DOIUrl":"10.1016/j.jot.2026.101214","url":null,"abstract":"<div><h3>Introduction</h3><div>Spinal cord injury (SCI) induces not only local spinal cord pathology but also distal brain dysfunction, causing multi-dimensional impairments in motor, emotional, and cognitive functions. Human umbilical cord mesenchymal stem cells (hUC-MSCs) transplantation has emerged as a promising therapeutic strategy for SCI, but whether it concurrently improves pathological alterations in both the spinal cord and brain remains unclear.</div></div><div><h3>Methods</h3><div>After establishing a mouse model of spinal cord contusion, hUC-MSCs were transplanted intrathecally starting 7 d post-injury and administered weekly for 4 wk. This study evaluated the effectiveness of hUC-MSCs transplantation in promoting neurological functional recovery in female mice with SCI through multi-dimensional behavioral tests. In addition, histopathological staining, immunofluorescence staining, and western blotting were performed to evaluate pathological changes in the spinal cord and hippocampus after hUC-MSCs transplantation.</div></div><div><h3>Results</h3><div>hUC-MSCs transplantation significantly improved hindlimb locomotor function and alleviated anxiety-like and depression-like behaviors, as well as long-term memory deficits in female mice with SCI. At the spinal cord level, hUC-MSCs increased IL-10 expression, reduced glial activation, and promoted axonal regeneration. In the hippocampus, hUC-MSCs alleviated neuroinflammation and region-specific abnormalities in synaptic remodeling and microglial synaptic pruning.</div></div><div><h3>Conclusion</h3><div>This study demonstrated that hUC-MSCs transplantation concurrently improved pathological alterations in both the spinal cord and hippocampus after SCI, providing experimental evidence for comprehensive neurorestoration following SCI.</div></div><div><h3>Translational potential</h3><div>This preclinical study demonstrated that subacute sequential hUC-MSCs transplantation is a promising therapeutic strategy for SCI. By improving both motor, emotional, and cognitive outcomes, it supports the concept of “brain-spinal co-repair” and provides a rationale for optimizing cell transplantation regimens to facilitate the clinical translation of hUC-MSC-based therapies for SCI.</div></div>","PeriodicalId":16636,"journal":{"name":"Journal of Orthopaedic Translation","volume":"60 ","pages":"Article 101214"},"PeriodicalIF":9.8,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148958470","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}
{"title":"Chinese expert consensus on the clinical application of stromal vascular fraction combined with bone marrow flushing for osteonecrosis of the femoral head","authors":"Xin Wang, Junming Zhang, Liming Cheng, Jiang Peng","doi":"10.1016/j.jot.2026.101192","DOIUrl":"10.1016/j.jot.2026.101192","url":null,"abstract":"<div><div>Osteonecrosis of the femoral head (ONFH) is a common orthopedic disease that leads to severe dysfunction of the hip joint in young and middle-aged patients. Its core pathological mechanism lies in the interruption of blood supply to the femoral head and an imbalance in bone repair capacity. Traditional hip-preserving treatment methods face many limitations in promoting effective repair of the necrotic area. With the rapid development of regenerative medicine, stromal vascular fraction (SVF) therapy, due to its rich content of various repair cells and growth factors, provides a highly promising new strategy for promoting angiogenesis and bone tissue regeneration in the necrotic area. Bone marrow flushing, as a key auxiliary means to optimize the local repair microenvironment, can further enhance the therapeutic effect when combined with SVF. This expert consensus aims to systematically review the current evidence-based medical evidence and clinical practice experience of SVF combined with bone marrow flushing in the treatment of ONFH, and to clarify the core norms and operational standards for its clinical application. The article will focus on in-depth elaboration of the indications and contraindications for SVF therapy, the standardized preparation and quality control system of cell preparations, key technical points of clinical minimally invasive surgical operations (including bone marrow flushing standards), multi-dimensional efficacy evaluation methods, and prevention and management strategies for potential complications. It is intended to provide clinicians with a set of standardized and scientific practical guidelines, ultimately promoting the safe, standardized, and effective application of SVF combined with bone marrow flushing technology in the field of ONFH treatment.</div></div>","PeriodicalId":16636,"journal":{"name":"Journal of Orthopaedic Translation","volume":"60 ","pages":"Article 101192"},"PeriodicalIF":9.8,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13636308/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149111108","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}
{"title":"Exercise alleviates age-related osteoarthritis associated with PGC-1α activation to suppress chondrocyte senescence and aberrant glycolysis","authors":"Yuting Cao, An Lao, Shijie Zhu, Fangchun Jin, Zhou Sha, Yu Zhuang, Huilu Zhan, Liao Wang, Huiwu Li, Kaili Lin, Rui Zhu","doi":"10.1016/j.jot.2026.101213","DOIUrl":"10.1016/j.jot.2026.101213","url":null,"abstract":"<div><h3>Background</h3><div>Age-related osteoarthritis (OA) is a leading global disability cause. Exercise is recommended as first-line therapy but poorly tolerated by elderly patients. This study elucidated the mechanism of low-intensity exercise in OA and develop a targeted exercise-mimetic nanotherapy.</div></div><div><h3>Methods</h3><div>The effects of low-intensity swimming exercise on age-related OA were investigated using aged mouse models. A senescence-targeted nanoparticle system (NP-B2M) was fabricated via a double-emulsion solvent evaporation method combined with EDC/NHS conjugation. The mechanisms underlying exercise and PGC-1α–mediated metabolic reprogramming were explored using transcriptomic sequencing, glycolysis analysis, RT-qPCR, and Western blotting in IL-1β–induced senescent ATDC5 chondrocytes. The therapeutic efficacy of intra-articular delivery of NP-B2M was systematically evaluated using micro-CT, histological staining, and immunohistochemistry in aged mice.</div></div><div><h3>Results</h3><div>Low-intensity swimming attenuated OA by suppressing chondrocyte senescence and pathological glycolysis via activating PGC-1α, effects that were recapitulated by ZLN005. NP-B2M enabled targeted intra-articular drug release and showed superior efficacy over free ZLN005.</div></div><div><h3>Conclusion</h3><div>This study demonstrates that low-intensity exercise alleviates age-related OA via PGC-1α–mediated metabolic reprogramming. NP-B2M provides a biocompatible, precisely targeted, long-acting platform that mimics exercise benefits, offering promising translational potential as a precision therapeutic strategy for immobile elderly OA patients.</div></div><div><h3>The translational potential of this article</h3><div>In this study, we developed NP-B2M, a PLGA-based nanoplatform, achieves prolonged joint retention and enhanced efficacy versus free drug, representing a promising targeted approach for OA patients with limited mobility.</div></div>","PeriodicalId":16636,"journal":{"name":"Journal of Orthopaedic Translation","volume":"60 ","pages":"Article 101213"},"PeriodicalIF":9.8,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149044075","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}