Journal of Orthopaedic Translation最新文献

{"title":"Establishment of a clinically relevant beagle model for periprosthetic joint infection with 3D-printed prostheses and multimodal evaluation","authors":"Heng Liu , Tingting Fan , Rui Yuan , Shuai Lu , Dadi Sun , Yong Huan , Maoqi Gong , Honghu Xiao , Chongbin Wei , Hao Wang , Shijie Fan , Yilong He , Jialin Hu , Haoran Zhang , Hao Sun , Qi Gu , Yejun Zha , Xieyuan Jiang","doi":"10.1016/j.jot.2025.05.007","DOIUrl":"10.1016/j.jot.2025.05.007","url":null,"abstract":"<div><h3>Objective</h3><div>Periprosthetic joint infection (PJI) poses significant challenges to arthroplasty outcomes, necessitating translational animal models for pathogenesis studies and therapeutic development. This study aimed to establish a standardized Beagle PJI model by integrating species-specific 3D-printed femoral prostheses with quantitative bacterial inoculation, while evaluating the dose-dependent effects of <em>Staphylococcus aureus</em> (<em>S. aureus</em>) on infection progression.</div></div><div><h3>Methods</h3><div>Two titanium alloy prostheses were designed using CT-based anatomical data: BFP-C (canine-optimized) and BFP-H (human-derived). Prostheses underwent mechanical compression tests, finite element analysis (FEA) simulating postoperative and osseointegration phases, and <em>in vivo</em> validation in Beagles. The optimized BFP-C was selected for PJI model construction via hemi-hip arthroplasty (HHA), with intraoperative inoculation of <em>S. aureus</em> ranging from 250 to 10^8 colony-forming units (CFU). Longitudinal evaluation included radiography (X-ray/CT), mechanical pull-out tests, histopathology (H&E/Masson/Giemsa staining), bacterial cultures, and mobility assessments using open-field behavioural tracking.</div></div><div><h3>Results</h3><div>BFP-C exhibited superior biomechanical compatibility, with 12.3-fold higher yield strength (6836 ± 157 N vs. 553 ± 49 N) and 97 % reduction in bone strain (0.71 % vs. 20.32 %) compared to BFP-H. All inoculated groups developed PJI with dose-dependent severity: ultra-high-dose (10^8 CFU) groups displayed severe osteolysis (pull-out strength: 24 ± 8 N vs. 924 ± 45 N in controls), biofilm formation, and mobility impairment (74 % reduction in distance travelled, 2003 ± 276 cm vs. 7976 ± 333 cm in controls), whereas low-dose (250 CFU) groups established PJI with milder manifestations, evidenced by sinus tract formation, 55.1 % reduction in pull-out strength (406 ± 15 N vs. 924 ± 45 N in controls), and concordant radiological/histopathological signs of infection. Imaging examinations revealed differential osteolytic patterns corresponding to bacterial loads. Combined wound evaluation and microbiological analyses confirmed consistent infection establishment across all replicates.</div></div><div><h3>Conclusion</h3><div>This Beagle PJI model successfully recapitulates clinical infection dynamics, emphasizing the critical role of species-specific prosthesis design and standardized bacterial quantification. The integrated multimodal evaluation system (imaging, biomechanical, and behavioural analyses) demonstrated both the reliability of the model and its sensitivity in detecting infection progression. Its modular design supports customization for studying biofilm-resistant implants or antibiotic delivery systems. These findings not only provide a critical tool for mechanistic PJI research but also establish a theoretical foundation for clinical translation, with the quantitativ","PeriodicalId":16636,"journal":{"name":"Journal of Orthopaedic Translation","volume":"53 ","pages":"Pages 274-285"},"PeriodicalIF":5.9,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144548857","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":"Amygdalin and magnesium ions exert synergistic effects on cartilage regeneration by inhibiting chondrocyte ferroptosis via the IL-17/GPX4 axis","authors":"Xuefei Zhao , Hanting Xia , Yiwen Yang , Tianyou Ma , Yichen Lu , Zhefei Xie , Xing Zhou , Jiangyuan Liu , Zhengsheng Bao , Huihui Xu , Jinjin Ma , Houfu Ling , Shuyan Zhang , Taotao Xu , Peijian Tong , Hongting Jin","doi":"10.1016/j.jot.2025.05.006","DOIUrl":"10.1016/j.jot.2025.05.006","url":null,"abstract":"<div><h3>Background/objective</h3><div>Cartilage defects (CDs) present a significant challenge in orthopaedic medicine. Owing to the inherently limited regenerative capacity of cartilaginous tissue, defects usually do not heal via natural repair processes. Consequently, damaged tissue is replaced by fibrocartilage-like tissues instead of the original hyaline cartilage. Therefore, inhibiting fibrocartilage formation while promoting hyalinisation may represent a novel strategy for CD therapy. Although studies have explored the role of interleukin (IL)-17A and ferroptosis in the fibrosis of visceral organs, such as the liver, lungs, and kidneys, their implication in cartilage fibrosis and fibrocartilage formation remains unclear. Herein, we aimed to determine whether IL-17A and ferroptosis are collectively involved in the process of cartilage fibrosis and to investigate the effects of amygdalin (AMD) and magnesium ions (Mg<sup>2+</sup>) in cartilage regeneration and the potential molecular mechanisms underlying these effects.</div></div><div><h3>Methods</h3><div>Cartilage samples were collected from patients with osteoarthritis and subjected to immunohistochemistry analysis to assess fibrocartilage formation indicators within the degenerated areas. Quantitative real-time polymerase chain reaction, western blot, and immunohistochemistry analyses were employed to assess changes in cartilage anabolism and expression of fibrocartilage markers after treatment with different concentrations of AMD. We also treated chondrocytes with an IL-17A/RA antagonist, a ferroptosis inhibitor, a ferroptosis inducer, and AMD, and measured the changes in fibrocartilage-, ferroptosis-, and IL-17 signalling-associated factors. Finally, mice with microfracture (MF)-induced CDs were administered intra-articular injections of either saline, AMD (10 μmol/L), MgCl<sub>2</sub> (0.5 mmol/L), or AMD (10 μmol/mL) plus MgCl<sub>2</sub> (0.5 mmol/L) twice a week. After 4 and 8 weeks, chondral repair was assessed through histological and immunohistochemical analyses in each group.</div></div><div><h3>Results</h3><div>IL-17A activated lipid peroxidation, leading to chondrocyte ferroptosis, while AMD suppressed IL-17 signalling, thereby mitigating the decrease in glutathione peroxidase 4 (GPX4) expression induced by IL-17A or erastin. In mice with MF surgery-induced CD, the combination of AMD and Mg<sup>2+</sup> mitigated oxidative stress, thereby enhancing the positive effects of Mg<sup>2+</sup>. This combination led to a significant improvement in chondrogenesis, activation of anabolic processes, and reduction of catabolic activity in the articular cartilage, ultimately supporting cartilage repair and regeneration.</div></div><div><h3>Conclusions</h3><div>AMD targets IL-17 signalling to inhibit chondrocyte ferroptosis. Furthermore, the combination of AMD and Mg<sup>2+</sup> suppresses IL-17A/GPX4 signalling, suppressing fibrocartilage formation and fostering hyaline cartilage regenera","PeriodicalId":16636,"journal":{"name":"Journal of Orthopaedic Translation","volume":"53 ","pages":"Pages 246-259"},"PeriodicalIF":5.9,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144523963","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":"Regenerative strategies for intervertebral disc degeneration","authors":"Raed H. Ogaili ,&nbsp;Ahmed Alassal ,&nbsp;Nurul Fariha Za'aba ,&nbsp;Izzat Zulkiflee ,&nbsp;Isma Liza Mohd Isa","doi":"10.1016/j.jot.2025.06.003","DOIUrl":"10.1016/j.jot.2025.06.003","url":null,"abstract":"<div><div>Low back pain (LBP) is a global health problem, primarily caused by intervertebral disc (IVD) degeneration. Current treatments focus on symptom relief without addressing the underlying degenerative mechanisms. Regenerative strategies have emerged as promising therapies through the use of functional biomaterials and stem cells capable of modulating key signalling pathways to promote tissue regeneration. However, challenges such as efficient delivery systems, long-term survival of transplanted cells, and hostile disc microenvironment remain. This review focuses on recent advances in regenerative approaches using biomaterials, cells, and therapeutic agents of exosomes, and genes to restore IVD structure and function. We discuss the current understanding of IVD anatomy, physiology and degeneration pathophysiology followed by current treatments. We highlight the rationale for regenerative therapy in halting the degenerative hallmarks tailored to mild, moderate to severe IVD degeneration. Our review emphasizes on the functional biomaterials designed for advanced delivery system, therapeutic intervention and IVD tissue engineering. We discuss the cell-based therapy, highlighting various cell sources, therapeutic effects, clinical trials and its obstacles. We discuss the use of therapeutic agents such as the genes and exosome therapies in IVD regeneration. The clinical translational potential of regenerative therapy is vast and promising, driven by advances in cellular therapies, biomaterials, and cell-free approaches like exosomes, which offer new avenues for regenerating degenerative IVDs. While significant progress has been made in developing safe, effective, and scalable treatments, challenges remain in immune compatibility, manufacturing, and regulatory pathways. Emerging innovations in gene editing, 3D bioprinting, and personalized approaches are poised to accelerate the translation of these therapies into mainstream medicine, with interdisciplinary collaboration and global efforts playing a crucial role in overcoming current bottlenecks and realizing the full potential of regenerative medicine to transform patient care. This article offers a comprehensive framework to guide preclinical research and future clinical translation of effective regenerative therapies, aiming at reducing the global burden of LBP and improving long-term patient outcomes.</div></div>","PeriodicalId":16636,"journal":{"name":"Journal of Orthopaedic Translation","volume":"53 ","pages":"Pages 286-308"},"PeriodicalIF":5.9,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144548856","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":"Bone marrow-derived myeloid cells drive neuroinflammation in Alzheimer's disease: Insights from the FAD4T mouse model","authors":"Yidan Pang ,&nbsp;Dongjing Jia ,&nbsp;Fang Ye ,&nbsp;Fei Liu ,&nbsp;Jiaqi Li ,&nbsp;Siyuan Zhu ,&nbsp;Bingqi Wang ,&nbsp;Meng Yao ,&nbsp;Lin Du ,&nbsp;Chunying Yang ,&nbsp;Guoji Guo ,&nbsp;Cunxiang Ju ,&nbsp;Lufeng Yao ,&nbsp;Changqing Zhang ,&nbsp;Junjie Gao ,&nbsp;Hao Qi","doi":"10.1016/j.jot.2025.06.014","DOIUrl":"10.1016/j.jot.2025.06.014","url":null,"abstract":"<div><h3>Objective</h3><div>Alzheimer's disease (AD) is marked by amyloid β (Aβ) accumulation, neuroinflammation, and cognitive decline. While neuroinflammation is a key feature of AD, the potential involvement of bone marrow-derived cells in its pathology remains unclear. This study aimed to investigate the role of bone marrow-derived myeloid cells in driving neuroinflammation in AD.</div></div><div><h3>Methods</h3><div>We developed a transgenic mouse model (FAD4T) by overexpressing human APPSwe/Ind and PSEN1 M146L/L286V on a C57BL/6J background. FAD^4T mice were characterized for hallmark AD features, including amyloid deposition, glial activation, and cognitive deficits. Additionally, single-cell transcriptomic analysis was performed to profile bone marrow and brain myeloid cells. Bone marrow transplantation experiments were conducted to assess the contribution of bone marrow-derived macrophages to neuroinflammation in AD.</div></div><div><h3>Results</h3><div>FAD^4T mice exhibited hallmark AD phenotypes such as amyloid deposition, glial activation, and cognitive impairment, alongside osteoporosis-like changes. Single-cell transcriptomic analysis identified a significant increase in bone marrow-derived macrophages in the brains of FAD^4T mice. These cells showed upregulation of AD-related genes, including <em>Cst7</em> and <em>Ctsd</em>, suggesting their active role in neuroinflammation. Bone marrow transplantation experiments further confirmed that bone marrow-derived macrophages contributed to the inflammatory processes in the AD brain.</div></div><div><h3>Conclusion</h3><div>Our findings demonstrate that bone marrow-derived myeloid cells infiltrate the brain and might play a critical role in driving neuroinflammation in AD. Targeting these cells may represent a novel therapeutic strategy for mitigating inflammation and disease progression in AD.</div></div><div><h3>The translational potential of this article</h3><div>Our findings suggest that bone marrow-derived inflammation play a critical role in AD-associated inflammation, offering potential targets for therapeutic intervention such as <em>Cst7</em> and <em>Ctsd</em> in bone marrow-derived myeloid cells.</div></div>","PeriodicalId":16636,"journal":{"name":"Journal of Orthopaedic Translation","volume":"53 ","pages":"Pages 309-324"},"PeriodicalIF":5.9,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144571209","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":"Relieving oxidative stress microenvironment and promoting vascularized bone formation to treat femoral head necrosis using 3D-printed scaffold with ultralong-term multienzyme-like activity","authors":"Xiaobo Xie ,&nbsp;Jinwei Zhang ,&nbsp;Jianxiong Shu ,&nbsp;Zhaoran Wu ,&nbsp;Chengqiang Wang ,&nbsp;Zhifei Gao ,&nbsp;Zhenwen Huang ,&nbsp;Lihua Li ,&nbsp;Jieli Chen ,&nbsp;Yao Lu","doi":"10.1016/j.jot.2025.06.010","DOIUrl":"10.1016/j.jot.2025.06.010","url":null,"abstract":"<div><h3>Background</h3><div>Characterized by microcirculatory disorder and oxidative stress microenvironment, the repair of bone defect after hip preservation therapy (such as core decompression) for osteonecrosis of the femoral head (ONFH) remains a clinical challenge. Thus, an ideal bone scaffold for treating ONFH should not only promote bone and vessel formation but also alleviate hypoxia and oxidative stress.</div></div><div><h3>Method</h3><div>We integrated manganese oxides (MnO_x) nanoparticles (NPs) with a 3D-printed poly(lactic-co-glycolic acid) (PLGA) scaffold to achieve this goal. The MnO_x NPs were synthesized using an oxidation reaction and the scaffold was 3D-printed using a fused deposition modeling method. The characterization and the enzyme-like activity of the scaffold was investigated. The biocompatibility and biofunctions of the scaffold were evaluated both in vitro and in vivo, including the antioxidant capacity, the effects on promoting bone formation and vascularization, and the therapeutic effect in animal model.</div></div><div><h3>Results</h3><div>The resultant MnO_x-doped PLGA scaffold could catalyze reactive oxygen species into oxygen through its superoxide dismutase (SOD)-like and catalase (CAT)-like activities. In vitro studies revealed that this multienzyme-like activity of the scaffold could be maintained for more than 30 days, thereby improving cell viability under oxidative stress. The underlying mechanism was shown to involve regulation of the antioxidant activity of cells via PI3K/AKT signaling pathway. The scaffold also significantly improved capabilities of osteogenesis and angiogenesis compared to pure PLGA scaffold. In vivo studies further demonstrated that the combination therapy of core decompression and scaffold implantation efficiently reduced osteoblast necrosis and enhanced vascularized bone formation in a clinically relevant ONFH rabbit model.</div></div><div><h3>Conclusion</h3><div>The 3D-printed MnO_x-doped PLGA scaffold not only relieve oxidative stress to protect osteocytes under ONFH microenvironment but also promote vascularized bone formation, showing the potential for treating ONFH.</div></div><div><h3>Translational potential of this article</h3><div>PLGA has been already applied in clinical bone implants. Mn is an essential trace element for the human body and MnO_x NPs offer the advantage of biocompatibility, ease of large-scale preparation, and low cost. Hence, this scaffold has the potential for clinical translation in the treatment of ONFH.</div></div>","PeriodicalId":16636,"journal":{"name":"Journal of Orthopaedic Translation","volume":"53 ","pages":"Pages 206-220"},"PeriodicalIF":5.9,"publicationDate":"2025-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144501148","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":"Why muscle strengthening exercises should target the quadriceps and gluteus maximus in patients with knee osteoarthritis?: Effects of knee pain on muscle volume and fatty degeneration based on AI-assisted cross-sectional analysis","authors":"Do Kyung Lee ,&nbsp;Hyeon Su Kim ,&nbsp;Kyung Rae Ko ,&nbsp;Jong Pil Yoon ,&nbsp;Jun-Il Yoo","doi":"10.1016/j.jot.2025.06.013","DOIUrl":"10.1016/j.jot.2025.06.013","url":null,"abstract":"<div><h3>Background</h3><div>Sarcopenia, characterized by age-related muscle loss, traditionally presents as systemic muscle atrophy. However, knee osteoarthritis (OA) patients often exhibit localized quadriceps muscle atrophy, suggesting a potential pain-related mechanism distinct from classical sarcopenia. This study aimed to investigate the relationship between knee OA pain and selective muscle atrophy, particularly focusing on its role as a potential aggravating factor for sarcopenia.</div></div><div><h3>Methods</h3><div>Eighty-nine patients scheduled for unilateral primary total knee arthroplasty were analyzed. Preoperative computed tomography was used to compare muscle volume and intramuscular adipose tissue (IMAT) proportion between the more painful limb (Group 1) and the contralateral, less painful limb (Group 2). Analysis included both compartmental evaluation (anterior, medial, and posterior thigh compartments; hip abductors and external rotators) and individual muscle assessment.</div></div><div><h3>Results</h3><div>Group 1 demonstrated significant volume reduction in the anterior thigh compartment (specifically vastus lateralis, intermedius, and medialis) and gluteus maximus, compared to Group 2 (<em>p</em> &lt; 0.05). IMAT proportion was significantly higher in most muscles of Group 1, except for hip abductors, tensor fascia latae, and gluteus minimus (p &lt; 0.05), suggesting widespread fatty degeneration despite selective volume loss.</div></div><div><h3>Conclusion</h3><div>Knee osteoarthritis–related pain induces selective atrophy in the anterior thigh compartment and gluteus maximus while promoting diffuse fatty infiltration throughout the lower extremity. These findings suggest that OA-associated pain may exacerbate sarcopenia by driving both region-specific muscle loss and widespread intramuscular adipose degeneration.</div></div><div><h3>The translational potential of this article</h3><div>These findings underscore the importance of pain control as a primary therapeutic goal in patients with knee osteoarthritis. They also highlight the clinical necessity of targeted strengthening of the quadriceps and gluteus maximus muscles, given the role of knee pain in inducing secondary, selective muscle atrophy. Furthermore, symptoms commonly observed in elderly patients with OA—such as limping, giving way, lower extremity weakness, and patellofemoral knee pain—may not be attributable solely to the aging process. Rather, they may reflect secondary muscular adaptations driven by chronic pain during the progression of osteoarthritis (Figure 1).</div></div>","PeriodicalId":16636,"journal":{"name":"Journal of Orthopaedic Translation","volume":"53 ","pages":"Pages 221-230"},"PeriodicalIF":5.9,"publicationDate":"2025-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144501146","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":"Comparative efficacy of non-vascularized and vascularized bone grafts, with emerging insights into bone biomaterial grafts, in scaphoid fracture nonunion treatment: A systematic review and meta-analysis","authors":"Reza Karimnazhand ,&nbsp;Roshanak Shams ,&nbsp;Ali Behmanesh ,&nbsp;Masoud Vosough ,&nbsp;Azadeh Gharooee Ahangar ,&nbsp;Laura Serrano Barrenechea ,&nbsp;Omid Mahmoudinasab ,&nbsp;Farid Najd Mazhar","doi":"10.1016/j.jot.2025.06.009","DOIUrl":"10.1016/j.jot.2025.06.009","url":null,"abstract":"<div><h3>Background</h3><div>Scaphoid fractures are prevalent wrist injuries with significant treatment challenges, especially when get complicated by nonunion and avascular necrosis. Various grafting techniques, including non-vascularized bone grafts (NVBGs), vascularized bone grafts (VBGs), and bone biomaterial grafts, are utilized to promote healing, but the comparative efficacy of these methods remains unclear.</div></div><div><h3>Objective</h3><div>This systematic review and meta-analysis aim to assess the efficacy of different types of bone grafts (NVBGs, VBGs, and bone biomaterials) in the treatment of scaphoid nonunion, focusing on outcomes including union rates, time to healing, and functional recovery scores.</div></div><div><h3>Methods</h3><div>A systematic search of PubMed, Scopus, Cochrane and Web of Science was conducted to identify eligible studies published between 2000 and 2024. studies were categorized into: (1) comparative studies of NVBG vs. VBG, (2) studies reporting only NVBG outcomes, and (3) studies reporting only VBG outcomes. Bone Biomaterials were assessed separately due to limited data (one study). Meta-analyses were performed on in common reported outcomes for each group including union rates, time to healing, range of motion, grip strength, and Modified Mayo Wrist Scores (MMWS).</div></div><div><h3>Results</h3><div>A total of 62 studies involving 2332 scaphoid nonunion patients were included. VBGs demonstrated significantly higher union rates and shorter healing times compared to NVBGs. VBG-treated patients also showed better functional outcomes, including greater grip strength and MMWS in comparative studies NVBGs were less effective in evaluated cases and required longer healing times. The use of bone biomaterial grafts, although limited in the current literature, showed promising results comparable to NVBGs, but further studies are needed.</div></div><div><h3>Conclusion</h3><div>VBGs demonstrated higher union rates and shorter healing times compared to NVBGs, with better functional outcomes in some cases, though evidence certainty is moderate. Bone biomaterials represent a promising alternative to traditional grafts but require more evidence to support their widespread use. Treatment decision-makers should consider clinical context and case-specific conditions. Further research is needed to confirm these trends.</div><div>Translational potential: This study helps clinical decision-making by evaluating the efficacies of different bone grafts outcomes in complex scaphoid nonunions, potentially reducing treatment failures. It also underscores the emerging role of bone biomaterial grafts as a less invasive alternative, paving the way for personalized orthopedic strategies needing further evaluations to be used for treating scaphoid nonunions.</div></div>","PeriodicalId":16636,"journal":{"name":"Journal of Orthopaedic Translation","volume":"53 ","pages":"Pages 231-245"},"PeriodicalIF":5.9,"publicationDate":"2025-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144501147","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":"PPARγ controls ESCRT-dependent fibroblast-like synoviocyte exosome biogenesis and alleviates chondrocyte osteoarthritis mediated by exosomal ANXA1","authors":"Shuangshuo Jia ,&nbsp;Yue Yang ,&nbsp;Jiabao Liu ,&nbsp;Ziyuan Wang ,&nbsp;Lunhao Bai","doi":"10.1016/j.jot.2025.06.008","DOIUrl":"10.1016/j.jot.2025.06.008","url":null,"abstract":"<div><h3>Background</h3><div>Exercise therapy has been recognized as first line therapy of osteoarthritis (OA). The exercise related exosome involved in the interaction between fibroblast-like synoviocytes (FLSs) and chondrocytes could be a novel nanoparticle strategy for treating OA.</div></div><div><h3>Methods</h3><div>Single-cell transcriptome sequencing was used to investigate the exercise therapy-related gene. Cells were transfected by recombinant adenovirus carrying knockdown or overexpression sequences. Quantitative proteomics of FLS-derived exosomes via data-independent acquisition was used to investigate exosomal cargo.</div></div><div><h3>Results</h3><div>In this study, PPARγ was upregulated in FLSs under exercise stimulation. Our data revealed that overexpression (OE) PPARγ FLSs derived exosome could ameliorate the OA severity <em>in vivo</em> and activate autophagy, inhibit chondrocyte apoptosis, and reduced cartilage degeneration. But knockdown (KD) PPARγ FLSs derived exosome aggravate the OA. Moreover, we found PPARγ controls the endosomal sorting complex required for the transport (ESCRT)-dependent pathway to activate exosome biogenesis. Annexin A1 (ANXA1) was enriched in OE- PPARγ exosome. As a therapeutic cargo, FLSs exosomal ANXA1 was confirmed be internalization by chondrocyte via exosome labeled experiment and ANXA1 could inhibit the phosphorylation of ERK to activate the autophagy and decrease chondrocyte apoptosis.</div></div><div><h3>Conclusions</h3><div>PPARγ controls ESCRT-dependent FLSs exosome biogenesis and alleviates chondrocyte osteoarthritis mediated by exosomal cargo ANXA1 protein.</div></div><div><h3>The translational potential of this article</h3><div>PPARγ/ESCRT – FLSs exosomal ANXA1 – ERK axis provides a deeper theoretical basis for exercise therapy of OA and a new idea for the clinical transformation of nanoparticles into OA therapy.</div></div>","PeriodicalId":16636,"journal":{"name":"Journal of Orthopaedic Translation","volume":"53 ","pages":"Pages 187-205"},"PeriodicalIF":5.9,"publicationDate":"2025-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144489829","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":"Synovial advanced glycosylation end products aggravate periprosthetic infection in diabetes by upregulating Staphylococcus aureus RNAIII","authors":"Tianyu Dai ,&nbsp;Yinxian Wen ,&nbsp;Qingxian Li ,&nbsp;Hui Wang ,&nbsp;Hebin Liao ,&nbsp;Yingying Pu ,&nbsp;Liaobin Chen","doi":"10.1016/j.jot.2025.06.012","DOIUrl":"10.1016/j.jot.2025.06.012","url":null,"abstract":"<div><h3>Background</h3><div>Diabetes mellitus (DM) is a high-risk factor for periprosthetic joint infection (PJI). However, the mechanism how hyperglycemia induces or promotes PJI remains unclear. This study aimed to determine how host hyperglycemia stimulates pathogenic bacteria and thus induces PJI.</div></div><div><h3>Methods</h3><div>The rats were divided into 4 groups: control total knee arthroplasty (TKA) group, control PJI group, DM + TKA group, and DM + PJI group namely treating with high-sugar and high-fat diet + streptozotocin (STZ), and artificially induced PJI. After 3 weeks, bone and joint local inflammatory response, micro-CT, bacterial load, and biofilm formation were analyzed. The effects of advanced glycosylation end products (AGEs) and STF-31 on the biofilm formation of <em>Staphylococcus aureus (S. aureus)</em> were detected by crystal violet and confocal microscopy <em>in vitro</em>. In addition, the mechanism of AGEs promoting biofilm formation was explored by combined proteomics and transcriptomics analysis, and the effect of AGEs on RNAIII was further detected by constructing mutants.</div></div><div><h3>Results</h3><div>In both humans and rats, we found more severe infectious responses in the knee joint specimens of patients and rats with DM + PJI when compared with those without PJI. Moreover, DM + PJI specimens showed higher levels of synovial AGEs and expression of glucose transporter 1 (GLUT1). AGEs exacerbated the localized infectious response of joints <em>in vivo</em> and promoted biofilm formation <em>in vitro</em>, whereas GLUT1 receptor inhibitors attenuated these effects. Finally, RNA-seq and proteomics revealed that RNAIII may be the target of AGEs acting on <em>S. aureus</em>. AGEs directly promoted biofilm formation by enhancing δ-hemolysin translated by RNAIII. In contrast, inhibition of RNAIII effectively attenuated AGEs-induced biofilm formation.</div></div><div><h3>Conclusions</h3><div>In summary, high glucose upregulates <em>S. aureus</em> RNAIII expression by activating the synovial GLUT1-AGEs pathway, thereby promoting <em>S. aureus</em> colonization and biofilm formation on the surface of articular prostheses, contributing to the onset and progression of PJI.</div></div><div><h3>The translational potential of this article</h3><div>Our study shows the great potential of STF-31 as a specific treatment for DM + PJI, and is expected to become a new treatment method combined with antibiotics. RNAIII may be the target of AGEs-induced <em>Staphylococcus aureus</em> biofilm, which provides theoretical support and experimental basis for analyzing the effect of DM on PJI.</div></div>","PeriodicalId":16636,"journal":{"name":"Journal of Orthopaedic Translation","volume":"53 ","pages":"Pages 161-174"},"PeriodicalIF":5.9,"publicationDate":"2025-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144471234","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":"Dumbbell-shaped hydrogel plug for annulus fibrosus repair: From material design to in vivo validation","authors":"Mao-dan Nie ,&nbsp;Bing-kun Bao ,&nbsp;Ning-ze Zhang ,&nbsp;Rong-shan Cheng ,&nbsp;Ling-jie Fu ,&nbsp;Cheng-Kung Cheng","doi":"10.1016/j.jot.2025.06.004","DOIUrl":"10.1016/j.jot.2025.06.004","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Background&lt;/h3&gt;&lt;div&gt;Intervertebral disc (IVD) herniation is a degenerative spine disease, and current treatments often result in reherniation due to iatrogenic annulus fibrosus (AF) defects. Developing effective AF repair strategies is critical to preventing reherniation and improving surgical outcomes. This study aims to develop a novel hydrogel plug to repair significant AF defects, improving surgical outcomes and reducing the risk of reherniation.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;div&gt;Inspired by Dumbbell, a novel hydrogel plug was developed using methacrylate-grafted hyaluronic acid and 4-arm polyethylene glycol. The plug's geometry was optimized via an IVD finite element (FE) model, adjusting the bulbous end's thickness, radius, and curvature. A scanning electron microscope characterized the hydrogel's microstructure. Swelling behavior was assessed through freeze-drying and rehydration, and the mechanical properties were evaluated by compression and tensile testing. Degradation studies were performed in vitro and in vivo. The material's biocompatibility was assessed with cytotoxicity assays and subcutaneous implantation in mice. The repair efficacy of the dumbbell-shaped plug was analyzed using the lumbar spine FE model and was validated through dynamic mechanical testing. Finally, the plugs were inserted into the goat IVD injury model to compare the repair effects with the goat model for non-damaged, non-repaired, and suture-repaired conditions. The harvested samples were assessed using MRI and histological analysis, and the stability of the repair was verified through mechanical testing.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;The hydrogel exhibited rapid swelling, had mechanical properties similar to the natural AF, showed a stable degradation profile, and had excellent biocompatibility. For repairing a 3 mm defect, the FE simulation showed that a plug with an inner bulbous end radius of 2.25 mm, a thickness of 1.5 mm, and a curvature of 20–30° provided the most uniform stress distribution and optimal lumbar stability. The plug was successfully implanted into an ex vivo lumbar model and maintained its position after 10,000 cyclic loads. In the vivo goat model, no marked degeneration of the plug is observed on MRI after 4 weeks. Histological and immunostaining results revealed no significant inflammation, with slight vascular and fibrous tissue formation in both the plug and suture groups. The plug group demonstrated superior compressive strength compared to the suture repair and the untreated group.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusion&lt;/h3&gt;&lt;div&gt;This study developed and tested a novel hydrogel plug system for repairing large AF defects. The hydrogel plug resulted in an AF repair with superior mechanical properties, better biocompatibility, and a more effective defect repair than traditional suturing.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;The translational potential of this article&lt;/h3&gt;&lt;div&gt;Given the current lack of products for repairing significant AF defec","PeriodicalId":16636,"journal":{"name":"Journal of Orthopaedic Translation","volume":"53 ","pages":"Pages 175-186"},"PeriodicalIF":5.9,"publicationDate":"2025-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144480348","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}