Journal of Orthopaedic Translation最新文献

{"title":"Preclinical evaluation of a fully threaded biodegradable magnesium alloy headless compression screw for enhanced fixation in small bones","authors":"Hiroshi Noguchi,&nbsp;Kotaro Hanada,&nbsp;Ryunosuke Watanabe,&nbsp;Yasukazu Totoki,&nbsp;Yohei Tomaru,&nbsp;Akira Ikumi,&nbsp;Akira Kitagawa,&nbsp;Sakiko Orui,&nbsp;Lulu Zhang,&nbsp;Hajime Mishima","doi":"10.1016/j.jot.2026.101201","DOIUrl":"10.1016/j.jot.2026.101201","url":null,"abstract":"<div><h3>Background</h3><div>Biodegradable magnesium (Mg) alloys have attracted attention as alternatives to conventional metallic implants; however, their clinical applicability to fully threaded headless compression (HC) screws has been scarcely investigated.</div></div><div><h3>Methods</h3><div>In this study, a fully threaded biodegradable Mg alloy HC screw was developed, and its mechanical performance, biological safety, and in vivo degradation behavior were systematically evaluated. Mechanical properties were assessed according to ASTM standards and compared with clinically used titanium (Ti) alloy and poly-L-lactic acid/hydroxyapatite (PLLA/HA) screws. Biological safety was evaluated in accordance with ISO 10993 and in compliance with Good Laboratory Practice. In vivo degradation behavior was investigated using a rabbit distal femoral condyle model.</div></div><div><h3>Results</h3><div>The Mg alloy HC screw demonstrated superior torsional strength compared with PLLA/HA screws and comparable insertion performance, along with enhanced fixation strength, compared with Ti alloy screws. No cytotoxicity, sensitization, or intracutaneous reactivity was observed. Although transient gas cavity formation was observed during the early implantation period, it progressively diminished over time and did not adversely affect bone formation or implant stability.</div></div><div><h3>Conclusion</h3><div>These findings indicate that the developed Mg alloy HC screw exhibits favorable mechanical performance, biocompatibility, and in vivo degradation. This study provides preclinical evidence supporting its potential clinical translation, particularly in eliminating the need for secondary implant removal surgery.</div></div><div><h3>The translational potential of this article</h3><div>This article focuses on the preclinical evaluation of a fully threaded Mg-alloy HC screw developed to improve fixation performance for small bone fractures. The results of this study have significant clinical potential for the fully threaded design of biodegradable Mg alloy implants in fracture treatment.</div></div>","PeriodicalId":16636,"journal":{"name":"Journal of Orthopaedic Translation","volume":"60 ","pages":"Article 101201"},"PeriodicalIF":9.8,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148854622","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":"PLPP1 inhibits Wnt/β-catenin signaling via enhancing Caveolin-1/β-catenin interaction and is negatively regulated by c-Myc in osteosarcoma","authors":"Jiangbo Nie,&nbsp;Yang Zhou,&nbsp;Xinsheng Xie,&nbsp;Jinfa Wu,&nbsp;Weilai Tong,&nbsp;Zhiguo Shu,&nbsp;Shijiang Wang,&nbsp;Jiaming Liu,&nbsp;Feng Yang,&nbsp;Zhili Liu","doi":"10.1016/j.jot.2026.101202","DOIUrl":"10.1016/j.jot.2026.101202","url":null,"abstract":"<div><h3>Background</h3><div>Osteosarcoma (OS) is the most common primary malignant bone tumor in adolescents, characterized by rapid progression and poor prognosis. The molecular mechanisms underlying OS malignancy remain incompletely understood. Phospholipid phosphatase 1 (PLPP1) has recently been implicated in cancer biology, yet its role in OS is largely unknown.</div></div><div><h3>Methods</h3><div>RNA sequence data from TARGET-OS and GEO cohorts were downloaded and analyzed for assessing the relationship between PLPP1 expression levels and the OS prognosis. PLPP1 expression levels in OS cells and samples were detected using qRT-PCR, WB and immunohistochemistry. The effects of PLPP1 on proliferation, migration, invasion and chemosensitivity of OS cells were evaluated by up- or down-regulated PLLP1 expression. In <em>vivo</em> subcutaneous and tail-vein xenograft models were used to examine tumor growth and metastasis. Then, transcriptome profiling, luciferase reporter assays, co-immunoprecipitation, immunofluorescence and ChIP-PCR were conducted to elucidate the molecular mechanisms.</div></div><div><h3>Results</h3><div>PLPP1 was markedly down-regulated in OS tissues and cell lines. And low expression level of PLPP1 was correlated with poor prognosis, advanced clinical stage and metastasis. Functionally, PLPP1 overexpression inhibited OS cell proliferation, migration, invasion, and enhanced chemotherapy-induced apoptosis; conversely, silencing PLPP1 produced the opposite effects. In <em>vivo</em>, PLPP1 overexpression suppressed tumor growth and lung metastasis. Mechanistically, overexpression of PLPP1 impaired strength of Wnt/β-catenin signaling without altering β-catenin abundance, but instead inhibited β-catenin nuclear import by enhancing Caveolin-1/β-catenin interaction. Furthermore, PLPP1 was transcriptionally repressed by c-Myc, which directly bound to the PLPP1 promoter. Rescue experiments confirmed that c-Myc promoted OS malignancy by repressing PLPP1, thereby activating Wnt/β-catenin signaling.</div></div><div><h3>Conclusions</h3><div>This study identified PLPP1 as a prognostic suppressor in OS that inhibited β-catenin nuclear import through enhancing Caveolin-1/β-catenin interaction and was transcriptionally repressed by c-Myc. Targeting the c-Myc/PLPP1/β-catenin axis might represent a promising therapeutic strategy for OS.</div></div><div><h3>The translational potential of this article</h3><div>This study revealed the potential of PLPP1 as a novel prognostic biomarker of OS, and suggested its potential for therapeutic applications by specifically activating PLPP1 expression using small-molecule activators.</div></div>","PeriodicalId":16636,"journal":{"name":"Journal of Orthopaedic Translation","volume":"60 ","pages":"Article 101202"},"PeriodicalIF":9.8,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149141032","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":"Biomimetic nanodelivery of antagomiR-155-5p ameliorates wear particle-induced osteolysis by dual regulation of Gas6/Axl-mediated macrophage inflammation","authors":"Taihe Liu,&nbsp;Sipeng Lin,&nbsp;Chenhao Pan,&nbsp;Yifan Yu,&nbsp;Haopeng Sun,&nbsp;Junxi Chen,&nbsp;Muyun Tan,&nbsp;Changchuan Li,&nbsp;Shixun Li,&nbsp;Siyuan Tan,&nbsp;Gang Zeng,&nbsp;Haoxian Liu,&nbsp;Wingcheuk Ko,&nbsp;Jing Xu,&nbsp;Yujun Sun,&nbsp;Phei Er Saw,&nbsp;Yue Ding","doi":"10.1016/j.jot.2026.101198","DOIUrl":"10.1016/j.jot.2026.101198","url":null,"abstract":"<div><h3>Background</h3><div>Aseptic loosening (AL) is the primary cause of prosthesis failure after total joint replacement, which is triggered by wear particle-induced macrophage activation, excessive inflammatory factor secretion and subsequent periprosthetic osteolysis. MicroRNAs (miRNAs) act as key regulators of this pathological cascade, yet the specific functional miRNAs and their precise regulatory mechanisms remain incompletely clarified.</div></div><div><h3>Methods</h3><div>mRNA-seq and miRNA-seq were performed in titanium particle (TiPs)-stimulated macrophages to screen osteolysis-associated miRNAs, with expression validation conducted in clinical periprosthetic osteolytic tissues. In vitro functional and mechanistic assays were used to verify the miR-155-5p/Gas6/Axl regulatory axis, and a mouse calvarial osteolysis model was applied for in vivo validation. Macrophage membrane-camouflaged PLGA-PEI nanoparticles loaded with antagomir-155-5p (Anta-155@MNPs) were constructed, and their local therapeutic efficacy was evaluated in murine osteolysis models.</div></div><div><h3>Results</h3><div>miR-155-5p was significantly upregulated in both TiPs-stimulated macrophages and clinical periprosthetic osteolytic tissues. Functionally, miR-155-5p promoted Stat1/p65 phosphorylation, proinflammatory cytokine production and M1 macrophage polarization by inhibiting the Gas6/Axl pathway via dual mechanisms: Mafb-mediated Gas6 transcriptional repression and Adam10-dependent Axl cleavage inhibition. In vivo, this axis exacerbated TiPs-induced calvarial osteolysis, while local Anta-155@MNPs administration markedly mitigated bone resorption and tissue inflammation.</div></div><div><h3>Conclusion</h3><div>miR-155-5p drives TiPs-induced periprosthetic osteolysis via the Gas6/Axl signaling pathway, and targeted inhibition of miR-155-5p is a promising strategy to prevent artificial joint AL.</div></div><div><h3>The translational potential of this article</h3><div>This study identifies the miR-155-5p/Gas6/Axl axis as a novel therapeutic target for AL, and the targeted Anta-155@MNPs delivery system provides a feasible preclinical strategy for clinical translation to treat wear particle-induced osteolysis.</div></div>","PeriodicalId":16636,"journal":{"name":"Journal of Orthopaedic Translation","volume":"60 ","pages":"Article 101198"},"PeriodicalIF":9.8,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148935198","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":"Collagen epineurial substitute-assisted neurorrhaphy is superior to conventional end-to-end neurorrhaphy in a rat model of peripheral nerve injury","authors":"Yongquan Wang,&nbsp;Zoran Pletikosa,&nbsp;Peilin Chen,&nbsp;Jiayue Li,&nbsp;Ziming Chen,&nbsp;Cameron Bright,&nbsp;Sharon Chu,&nbsp;Alex O'Beirne,&nbsp;David Brogan,&nbsp;Brendan F. Kennedy,&nbsp;Harry Hoyen,&nbsp;Haotian Li,&nbsp;Daohui Li,&nbsp;Clair Lee,&nbsp;Lingqiang Chen,&nbsp;Rui Ruan,&nbsp;Minghao Zheng","doi":"10.1016/j.jot.2026.101197","DOIUrl":"10.1016/j.jot.2026.101197","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Background&lt;/h3&gt;&lt;div&gt;Peripheral nerve injuries (PNIs) are common and may result in profound and persistent functional deficits. Although end-to-end neurorrhaphy remains the gold standard for nerve repair, clinical outcomes are frequently suboptimal. This study aimed to validate a novel surgical method using a collagen epineurial substitute (CES) to minimize the number of sutures and reduce nerve tension at the coaptation site.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;div&gt;Finite element analysis (FEA) was performed to simulate stress distribution and guide suture configuration. Sprague–Dawley (SD) rats underwent sciatic nerve transection and were allocated into six groups: control; end-to-end neurorrhaphy using 1, 3, or 6 epineurial sutures; or epineurial substitute-assisted repair with one or no coaptation-site sutures. Mechanical stability was validated by tensile testing, while the Sciatic Functional Index (SFI) and gastrocnemius muscle weight were used as screening assessments to evaluate functional recovery. Histological outcomes, including vascularization and cellular alignment at the transection site, were also assessed. A further comparison between two representative groups, based on the equivalent mechanical stability was performed using behavioural tests for sensory recovery and electrophysiological testing for motor recovery to precisely track functional outcomes, together with Osmium staining for myelin and Silver staining for nerve fibres, to further investigate nerve tissue regeneration associated with microenvironmental changes.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;To test if CES-assisted repair can stabilize the mechanical strength and reduce nerve tension at the coaptation site, we first used FEA and demonstrated that, under physiological tension (2%), CES-assisted nerve coaptation redistributed mechanical stress along the covering of nerve segment. In contrast, conventional neurorrhaphy showed the concentrated tension of nerve at the coaptation. These computational findings were further supported by biomechanical testing in the rat model. The failure load of constructs repaired with three coaptation-site sutures was not significantly different from that of epineurial substitute-assisted constructs without coaptation-site sutures (p = 0.0635) and was significantly lower than that of CES-assisted constructs incorporating a single coaptation-site suture (p = 0.0022). This optimised mechanical environment offered by CES-assisted neurorrhaphy led to a 63–82% increase in parallel direction ratios relative to suture-only repairs, thereby promoting superior cellular alignment at the nerve transection site, enhancing epineurial and intraneural vascularization and reducing suture-related inflammation. In contrast, excessive suturing impaired early regenerative responses, whereas the epineurial substitute approach facilitated a tension-free microenvironment conducive to axonal regeneration and tissue integration. Repair of transected nerves","PeriodicalId":16636,"journal":{"name":"Journal of Orthopaedic Translation","volume":"60 ","pages":"Article 101197"},"PeriodicalIF":9.8,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149044135","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":"Current status and future prospects of biodegradable magnesium-based implants developed for orthopaedic applications","authors":"Dewei Zhao,&nbsp;Weidan Wang,&nbsp;Ye Li,&nbsp;Frank Witte,&nbsp;Qing Lu,&nbsp;Weirong Li,&nbsp;Tianwei Zhang,&nbsp;Xiuzhi Zhang,&nbsp;Ling Qin","doi":"10.1016/j.jot.2026.101200","DOIUrl":"10.1016/j.jot.2026.101200","url":null,"abstract":"<div><div>Biodegradable magnesium-based implants are the most clinically translated biodegradable metallic biomaterials in orthopaedics, owing to their favorable biocompatibility, bone-matched mechanics, and bioactive degradation behaviour. Through Mg²⁺ release, these implants may support osteogenesis, angiogenesis, and immunomodulation while avoiding permanent implant retention. However, their broader adoption remains constrained by degradation/healing mismatch, gas-associated issues, site-specific mechanical limitations, and insufficient long-term safety evidence. This review summarises the current status of biodegradable magnesium-based orthopaedic implants from a translational perspective by integrating biological mechanisms, preclinical animal models, clinical progress, long-term and regulation-related challenges. We particularly highlight the dual biological effects of Mg-based degradation, the translational relevance of disease-oriented small- and large-animal models, and emerging clinical evidence. By linking mechanistic insight with preclinical and clinical evidence, this review highlights the major opportunities and unresolved barriers that will shape the next stage of clinical translation in this field.</div><div>The translational potential of this article.</div><div>This review summarises biodegradable magnesium-based orthopaedic implants from a translational perspective, linking biological mechanisms, preclinical animal models, clinical evidence, long-term safety, and regulation-related considerations. By identifying key barriers to clinical adoption and highlighting indication-oriented evaluation strategies, it provides a practical reference for the future development, assessment, and translation of magnesium-based implants in orthopaedics.</div></div>","PeriodicalId":16636,"journal":{"name":"Journal of Orthopaedic Translation","volume":"60 ","pages":"Article 101200"},"PeriodicalIF":9.8,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149141034","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":"Exosomes target liver TREM-1 to break the systemic inflammatory cascade and improve spinal cord injury outcomes","authors":"Chengfang Luo,&nbsp;Han Zheng,&nbsp;Xuexiang Wang,&nbsp;Wenxiang Li,&nbsp;Yiming Gao,&nbsp;Zhongze Yuan,&nbsp;Yongfu Lou,&nbsp;Xiaohong Kong,&nbsp;Caorui Lin,&nbsp;Fanshuo Zeng,&nbsp;Ning Ran,&nbsp;Shiqing Feng","doi":"10.1016/j.jot.2026.101221","DOIUrl":"10.1016/j.jot.2026.101221","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Background&lt;/h3&gt;&lt;div&gt;Spinal cord injury (SCI) is a catastrophic neurological disorder characterized by irreversible functional deficits and the absence of effective clinical therapies. Increasing evidence suggests liver inflammation has emerged as a critical contributor to the exacerbation of secondary injury by amplifying systemic inflammatory responses and hindering neurological recovery following SCI, suggesting that mitigating hepatic inflammation may alleviate disease progression. Recently, exosomes have gained attention as promising therapeutic agents due to their ability to mediate intercellular communication and deliver bioactive molecules. Whether exosome-based interventions can modulate liver inflammation and improve SCI outcomes remains to be elucidated.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;div&gt;Functional recovery was assessed using BMS, gait analysis and inclined plane test. Histological and molecular analyses were performed to evaluate spinal cord pathology. Downstream inflammatory signaling pathways were further analyzed through immunohistology staining, flow cytometry and q-RT-PCR to elucidate the cascade involved in liver-mediated secondary injury. Exosomal cargo was characterized by proteomics and western blotting with a focus on heat shock protein 70 (HSP70). Competitive inhibition experiment was used to determine the interaction between exosome-delivered HSP70 and Triggering Receptor Expressed on Myeloid cells-1 (TREM-1) on hepatic macrophages &lt;em&gt;in vitro&lt;/em&gt;.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;Exosomes from different sources significantly improve functional recovery following SCI, as evidenced by enhanced locomotor performance and reduced tissue damage. Importantly, exosome treatment markedly attenuated liver inflammation, characterized by reduced macrophage activation and decreased expression of pro-inflammatory cytokines. Mechanistically, we found that exosomal HSP70 interacts with TREM-1 on hepatic macrophages. This interaction competitively inhibits the binding of HMGB1, a key damage-associated molecular pattern that is persistently elevated after SCI. By blocking the HMGB1-TREM-1 axis, exosomal HSP70 effectively suppresses downstream inflammatory signaling and mitigates the amplification of systemic inflammation originating from the liver.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusion&lt;/h3&gt;&lt;div&gt;This study uncovers a previously unrecognized systemic mechanism by which exosomes promote recovery after SCI through the modulation of liver inflammation. By targeting the HMGB1-TREM-1 signaling pathway in hepatic macrophages via exosomal HSP70 delivery, exosomes effectively suppress the inflammatory cascade that contributes to secondary injury.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;The translational potential of this article&lt;/h3&gt;&lt;div&gt;Targeting systemic inflammation, particularly liver-mediated immune responses, may complement existing neuroprotective strategies and improve therapeutic outcomes. These findings pave the way for future preclinical and clinic","PeriodicalId":16636,"journal":{"name":"Journal of Orthopaedic Translation","volume":"60 ","pages":"Article 101221"},"PeriodicalIF":9.8,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148958569","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":"Author's reply to the Letters regarding “Cysteine metabolism dysregulation promotes ferroptosis in osteoarthritis: Insights from multi-species bioinformatics and experimental validation”","authors":"Luxi Zheng,&nbsp;Zhengmeng Yang,&nbsp;Sihui Chen,&nbsp;Gongli Cai,&nbsp;Nan Hou,&nbsp;Wenxuan Lin,&nbsp;Carina Hey Pui Cheung,&nbsp;Huisheng Zhou,&nbsp;Junjie Chen,&nbsp;Yican Wang,&nbsp;Huifeng Chen,&nbsp;Yaofeng Wang,&nbsp;Micky D. Tortorella,&nbsp;Jinyu Zhu,&nbsp;Lu Feng,&nbsp;Gang Li","doi":"10.1016/j.jot.2026.101215","DOIUrl":"10.1016/j.jot.2026.101215","url":null,"abstract":"","PeriodicalId":16636,"journal":{"name":"Journal of Orthopaedic Translation","volume":"60 ","pages":"Article 101215"},"PeriodicalIF":9.8,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148958674","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":"Letter to the Editor regarding “Cysteine metabolism dysregulation promotes ferroptosis in osteoarthritis: Insights from multi-species bioinformatics and experimental validation”","authors":"Yiyun Ni,&nbsp;Bin Liu","doi":"10.1016/j.jot.2026.101218","DOIUrl":"10.1016/j.jot.2026.101218","url":null,"abstract":"","PeriodicalId":16636,"journal":{"name":"Journal of Orthopaedic Translation","volume":"60 ","pages":"Article 101218"},"PeriodicalIF":9.8,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148952098","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":"Multifunctional ultrafast hydrogel for arthroscopic surgery: An enzymatically cross-linked, nanosilicate-reinforced system promotes dual cartilage and subchondral bone regeneration","authors":"Qiang Lian,&nbsp;Jianqun Wu,&nbsp;Yun Lian,&nbsp;Danfeng Du,&nbsp;Yangyi Yu,&nbsp;Yuanhao Fan,&nbsp;Shenlei Feng,&nbsp;Hang Zhou,&nbsp;Jiawei Li,&nbsp;Chengheng You,&nbsp;Ying Wang,&nbsp;Decheng Wu,&nbsp;Chao Liu,&nbsp;Guangheng Li","doi":"10.1016/j.jot.2026.101104","DOIUrl":"10.1016/j.jot.2026.101104","url":null,"abstract":"<div><h3>Background</h3><div>Arthroscopic repair of osteochondral (OC) defects using injectable hydrogels remains highly challenging due to the high-pressure, water-filled environment of the joint during arthroscopic surgery. Conventional hydrogels exhibit slow gelation kinetics, prolonged setting times, poor adhesion to wet tissues, and insufficient mechanical strength, rendering them prone to washout throughout the procedure.</div></div><div><h3>Methods</h3><div>To address these limitations, we incorporated a small amount of transglutaminase (TG) and synthetic lithium silicate nanoplatelets (SN) into a gelatin–oxidized starch (GelS) precursor and evaluated the regenerative performance of the resulting hydrogel under simulated arthroscopic conditions. In vivo, the hydrogels were implanted into osteochondral defects in rats to assess their repair efficacy.</div></div><div><h3>Results</h3><div>The GelS-TG-SN hydrogel demonstrated ultrafast enzymatic gelation, robust underwater adhesion, and significantly enhanced mechanical strength. It was cytocompatible, displayed anti-inflammatory activity, and supported context-dependent dual-lineage differentiation of Synovial-derived stem cells (SDSCs) chondrogenesis in a cartilage-like niche and PI3K–Akt–mediated osteogenesis in a vascular-like niche. Following 8-week implantation, it enabled coordinated regeneration of cartilage and subchondral bone, recapitulating native osteochondral architecture.</div></div><div><h3>Conclusion</h3><div>The GelS-TG-SN nanocomposite hydrogel offers a compelling strategy for effective osteochondral regeneration in arthroscopic surgical environments.</div></div><div><h3>The Translational Potential of this Article</h3><div>This hydrogel platform offers an elegant and clinically accessible solution for arthroscopic osteochondral repair. Its ultrafast gelation—achieved in under one minute—combined with resilient adhesion under constant irrigation enables seamless intraoperative application without auxiliary instrumentation. By capitalizing on the body's intrinsic osteochondral gradient, a single injection orchestrates synchronized regeneration of cartilage and subchondral bone. Such integration of procedural simplicity with inherent regenerative bioactivity underscores its promise as a genuinely “one-step” therapy ready for clinical translation.</div></div>","PeriodicalId":16636,"journal":{"name":"Journal of Orthopaedic Translation","volume":"59 ","pages":"Article 101104"},"PeriodicalIF":9.8,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13330669/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148391206","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":"GFRα2 identified in TBI-induced bone healing is a novel therapeutic target for osteoporosis via osteogenesis and angiogenesis","authors":"Huibo Ti,&nbsp;Zhenyu Zhang,&nbsp;Huaxin Kang,&nbsp;Yuechun Chen,&nbsp;Keyue Zhang,&nbsp;Shuwen Shi,&nbsp;Xian Wu,&nbsp;Zixin Luo,&nbsp;Xingchen Yao,&nbsp;Xielin Yan,&nbsp;Junjie Wu,&nbsp;Zhengdong Yuan,&nbsp;Hao Nie,&nbsp;Feng-lai Yuan,&nbsp;Xia Li","doi":"10.1016/j.jot.2026.101146","DOIUrl":"10.1016/j.jot.2026.101146","url":null,"abstract":"<div><h3>Background</h3><div>Osteoporosis (OP) is a systemic disease featured by reduced bone mass, deteriorated microstructure and elevated fracture risk. Traditional therapies mainly target direct regulators of bone remodeling. Emerging evidence suggests a critical crosstalk between the skeletal and nervous systems. Traumatic brain injury (TBI) markedly accelerates fracture healing, which holds great potential for OP treatment, yet the underlying mechanism remains unclear.</div></div><div><h3>Methods</h3><div>A mouse TBI plus femoral fracture model was established. Micro-CT, histomorphometry and transcriptome sequencing were performed. In vitro studies included qPCR, Western blot, ALP/Alizarin Red staining, co-culture, ELISA and tube formation assays. Ovariectomized (OVX) mice received tail vein injection of Gfrα2 overexpression plasmid or siRNA for in vivo validation.</div></div><div><h3>Results</h3><div>TBI significantly accelerated fracture healing with elevated GFRα2 in callus BMSCs. GFRα2 promoted BMSC osteogenesis by maintaining iron homeostasis via Ferritin Heavy Chain 1 (FTH1) and enhanced angiogenesis by increasing VEGFD secretion. In OVX mice, GFRα2 overexpression markedly improved bone mineral density, trabecular microstructure, bone formation rate and intraosseous angiogenesis.</div></div><div><h3>Conclusions</h3><div>GFRα2 serves as a key hub linking TBI to accelerated bone formation via dual effects on osteogenesis and angiogenesis. Targeting GFRα2 represents a promising therapeutic strategy against osteoporosis.</div></div><div><h3>The translational potential of this article</h3><div>This study identifis GFRα2 as a key mediator linking traumatic brain injury-accelerated bone formation to osteogenesis and angiogenesis. Targeting GFRα2 effectively ameliorates bone loss in osteoporotic mice by restoring both bone formation and intraosseous vascularization. These findings establish a novel neuro-osteogenic regulatory axis and provide a promising molecular target for developing new therapeutic strategies to treat osteoporosis and improve fracture healing in clinical practice.</div></div>","PeriodicalId":16636,"journal":{"name":"Journal of Orthopaedic Translation","volume":"59 ","pages":"Article 101146"},"PeriodicalIF":9.8,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13380060/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148497727","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}