Journal of Orthopaedic Translation最新文献

{"title":"Development and multi-center validation of a software program, Ofeye 3.0, for automated all-inclusive vertebral fracture detection with chest/abdominal CT images","authors":"Ben-Heng Xiao ,&nbsp;Zhen-Hua Gao ,&nbsp;Cai-Ying Li ,&nbsp;Xiao-Ming Leng ,&nbsp;Er-Zhu Du ,&nbsp;Jian-Bing Ma ,&nbsp;Fu-Shan Liu ,&nbsp;Jing-Shan Gong ,&nbsp;Zhi-Guo Ju ,&nbsp;Ming-Yuan Yuan ,&nbsp;Hui-Ming Zhu ,&nbsp;Michael S.Y. Zhu ,&nbsp;Timothy YC. Kwok ,&nbsp;Yì Xiáng J. Wáng","doi":"10.1016/j.jot.2025.08.011","DOIUrl":"10.1016/j.jot.2025.08.011","url":null,"abstract":"<div><h3>Background</h3><div>Missing report for fragility vertebral fracture (VF) on chest/abdominal CT is common when the indication is not spine disorders. This represents a missed opportunity to alert patients to take preventive measures to improve bone health and prevent further severe fractures. In this study, we aim to develop a software program for automated detection of VF with existing chest/abdominal CT scans and validate its detection performance.</div></div><div><h3>Methods</h3><div>An automated sagittal Central Slab reconstruction (CSR) method for CT axial images was developed. For reference VF reading<em>,</em> VFs inclusive of those of with &lt;20 % vertebral height loss and those of endplate fracture with minimal vertebral height loss were identified. VFs were also differentiated from osteoarthritic wedging and endplatitis short vertebrae. Prior knowledge of VF detection models for lateral radiograph were transferred to a new ‘Ofeye 3.0’ model optimized for VF detection on CT image. Training CT images were obtained from nine centers, totaling 3313 cases without VF and 835 cases with VF. For external validation, CT images were from five centers totaling 732 cases without VF and 224 cases with VF.</div></div><div><h3>Results</h3><div>The automated CSR method showed advantages in demonstrating structural changes of the endplate and adjacent structures. For detecting VF in chest/abdominal CT scans, counting case-by-case and compared with the reference reading, the average performance of Ofeye 3.0 was accuracy 0.967, sensitivity 0.906, and specificity 0.986. Most of false negative or false positive cases were minimal or mild VF, or with image artifacts, or with VF close to the peripheral of CSR images.</div></div><div><h3>Conclusions</h3><div>Despite the challenging requirements for the software to detect all-inclusive VF, our results compare favorably with other published automated VF detection models.</div></div><div><h3>The translational potential of this article</h3><div>We developed a software program for automated all-inclusive VF detection on chest and/or abdominal CT image data and conducted a multi-center external validation study. This software is proved to have high VF detection precision. By alerting patients of the VFs likely related to osteoporosis and in turn the patients taking measures to prevent further fracture, the integration of this software into radiological practice will improve patient outcomes and reduce healthcare costs.</div></div>","PeriodicalId":16636,"journal":{"name":"Journal of Orthopaedic Translation","volume":"55 ","pages":"Pages 192-203"},"PeriodicalIF":5.9,"publicationDate":"2025-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145045683","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":"Multi-scale biomimetic fusion construction of cerium ion hydrogel-scaffold for promoting osteoporotic bone defect repair","authors":"Yesheng Jin ,&nbsp;Shuqing Lv ,&nbsp;Nanning Lv ,&nbsp;Yixue Huang ,&nbsp;Jia Wang ,&nbsp;Yun Xiao ,&nbsp;Xinfeng Zhou ,&nbsp;Yanxia Ma ,&nbsp;Gang Zhao ,&nbsp;Fan He ,&nbsp;Yong Xu","doi":"10.1016/j.jot.2025.08.015","DOIUrl":"10.1016/j.jot.2025.08.015","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Background&lt;/h3&gt;&lt;div&gt;The treatment of bone defects in the context of osteoporosis encounters numerous challenges. In the osteoporotic microenvironment, bone resorption outweighs bone formation, impeding the self-repair of bone defect areas. Furthermore, the deterioration of osteogenesis-angiogenesis coupling function at the defect sites and excessive inflammatory responses further complicate the treatment of bone defects. Hence, an improved approach is urgently needed to enhance the treatment of osteoporotic bone defects.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;div&gt;Our efficient strategy has developed a multi-scale biomimetic fusion alendronate sodium cerium ion hydrogel scaffold, integrating 3D-printed tricalcium phosphate (TCP) scaffolds, collagen-methacrylate (COMA) hydrogel, and nanoparticles of alendronate sodium cerium ions. &lt;em&gt;In vitro&lt;/em&gt;, we intervened osteoporosis rat derived bone marrow stromal cells (BMSCs) with the extract of TCP-H-Alendronate sodium cerium ion nanoparticles (ACNP) scaffold and detected the osteogenesis-related indicators through alkaline phosphatase (ALP) enzymatic activity staining, alizarin red staining, Western Blot, RT-qPCR and immunofluorescence staining to evaluate the osteogenic differentiation effect of TCP-H-ACNP scaffold. Through transcriptome sequencing, we explored the mechanism of TCP-H-ACNP scaffold affecting osteogenic differentiation of osteoporotic BMSCs. We intervened human umbilical vein endothelial cells (HUVECs) with the extract of TCP-H-ACNP scaffold and evaluated the angiogenic effect of TCP-H-ACNP scaffold through tube formation assay and cell scratch assay. &lt;em&gt;In vivo&lt;/em&gt;, we established a distal femoral bone defect model in osteoporotic rats and evaluated the therapeutic effect &lt;em&gt;in vivo&lt;/em&gt; through Mirco CT, Hematoxylin and Eosin (H&amp;E) stainin, Masson staining and immunohistochemical staining.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;The results demonstrated that &lt;em&gt;in&lt;/em&gt; &lt;em&gt;vitro&lt;/em&gt;, TCP-H-ACNP scaffolds could promote osteogenic differentiation of osteoporotic BMSCs from rats and angiogenesis of HUVECs. &lt;em&gt;In vivo&lt;/em&gt;, TCP-H-ACNP scaffolds could promote bone regeneration and repair of distal femoral bone defects in osteoporotic rats and improve local angiogenesis. Mechanistically, TCP-H-ACNP scaffolds could directly promote osteogenic differentiation of osteoporotic BMSCs from rats through the Wnt signaling pathway, and indirectly promote osteogenic differentiation by influencing Ca ion transport and improving mitochondrial function.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusion&lt;/h3&gt;&lt;div&gt;We create a hydrogel scaffold that not only offers adequate mechanical support but also possesses a favorable microenvironment for cell growth and contains biological factors promoting osteogenic and angiogenic differentiation.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;The translational potential of this paper&lt;/h3&gt;&lt;div&gt;This application represents a pioneering aspect of multi-scale biomimetic hydrogel scaffolds in addressing o","PeriodicalId":16636,"journal":{"name":"Journal of Orthopaedic Translation","volume":"55 ","pages":"Pages 172-191"},"PeriodicalIF":5.9,"publicationDate":"2025-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145045684","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":"LOXL2 alleviates post-traumatic knee osteoarthritis and pain","authors":"Faiza Ali ,&nbsp;Rajnikant Dilip Raut ,&nbsp;Chumki Choudhury ,&nbsp;Amit Kumar Chakraborty ,&nbsp;Cheyleann Del Valle-Ponce De Leon ,&nbsp;Pushkar Mehra ,&nbsp;Manish V. Bais","doi":"10.1016/j.jot.2025.08.016","DOIUrl":"10.1016/j.jot.2025.08.016","url":null,"abstract":"<div><h3>Background</h3><div>Cartilage has limited potential for self-regeneration, and damage results in structural, molecular, and functional aberrations, leading to osteoarthritis (OA). Traumatic knee injuries can also lead to cartilage degeneration and post-traumatic OA (PTOA). This study aimed to explore whether lysyl oxidase-like 2 (LOXL2) deletion aggravate PTOA and overexpression alleviate inflammation and pain at mechanical as well as molecular levels.</div></div><div><h3>Methods</h3><div>Modified medial meniscectomy was performed on C57BL/6J mice knee followed by aggrecan promotes specific deletion of <em>Loxl2</em> in cartilage. Transcriptomic aberrations were studied using RNA-seq and qPCR, and biomechanics and allodynia was evaluated using treadmill exhaustion and von Frey nociception test after adenovirus-delivered LOXL2 intra-articular treatment.</div></div><div><h3>Results</h3><div>LOXL2 was found to be downregulated in mouse knee PTOA. <em>Loxl2</em> deletion in knee cartilage, shows OA-like molecular changes, and aggravates PTOA. Transcriptomics analysis revealed the upregulation of cartilage degeneration factors, signatures of inflammatory M1 macrophages, and pain. These <em>Loxl2</em> deleted PTOA mice have a molecular resemblance to the human knee OA pathogenic gene signature. Interestingly, LOXL2 treatment alleviates knee joint function, reduces M1 macrophage infiltration, restores biomechanic capabilities, and reduces mechanical allodynia by relieving knee joint disability and pain.</div></div><div><h3>Conclusion</h3><div>LOXL2 deletion enhances the severity of PTOA, similar to human OA, whereas overexpression mitigates these effects by reducing inflammation and pain, offering LOXL2 as a therapeutic option in OA.</div></div><div><h3>The translational potential of this article</h3><div>LOXL2 modulates inflammation, pain, and degeneration, showing strong translational potential as a disease-modifying therapy for human PTOA.</div></div>","PeriodicalId":16636,"journal":{"name":"Journal of Orthopaedic Translation","volume":"55 ","pages":"Pages 159-171"},"PeriodicalIF":5.9,"publicationDate":"2025-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145045685","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":"Neuropeptide Y1 receptor antagonist alleviated osteoarthritis by restoring chondrocyte autophagy through PI3K/AKT/mTOR signaling pathway","authors":"Song Liu ,&nbsp;Jianqun Wu ,&nbsp;Yucong Lin ,&nbsp;Haifeng Liang ,&nbsp;Yu Cai ,&nbsp;Le Wang ,&nbsp;Zhao Wang ,&nbsp;Hongxun Sang","doi":"10.1016/j.jot.2025.08.003","DOIUrl":"10.1016/j.jot.2025.08.003","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Background&lt;/h3&gt;&lt;div&gt;Osteoarthritis (OA) is a debilitating joint disorder affecting millions worldwide, characterized by progressive cartilage degradation and chronic pain. Emerging evidence suggests that neuropeptide Y (NPY) and its Y1 receptors are involved in OA pathogenesis, although the underlying molecular mechanisms remain poorly understood. This study investigates the role of NPY/Y1R signaling in OA progression through PI3K/AKT/mTOR-mediated regulation of chondrocyte autophagy.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;div&gt;Human cartilage samples were collected from ten OA patients (3 male,7 female, 63–75 years old) undergoing total knee arthroplasty and graded using the Kellgren–Lawrence system. Primary chondrocytes were isolated from neonatal C57BL/6 mice and treated with NPY (0.01–5 μM) or interleukin-1β (IL-1β, 10 ng/mL) to mimic OA-like degeneration. RNA sequencing (RNA-seq) and KEGG pathway analysis were performed to identify NPY-regulated signaling pathways. &lt;em&gt;In vivo&lt;/em&gt;, OA was induced in 8-week-old male C57BL/6 mice via destabilization of the medial meniscus (DMM) or intra-articular injections of NPY (5 μM, every 4 weeks). Mice were treated with the Y1R antagonist (0.1 μM, weekly) or vehicle control. Pain behavior was assessed using von Frey filaments and CatWalk gait analysis. Cartilage degeneration was evaluated via histology (Safranin O/Fast Green, OARSI scoring), immunofluorescence (COLII, MMP13, LC3-II, p62), and micro-CT (subchondral bone remodeling, osteophyte formation). The activation status of the PI3K/AKT/mTOR pathway and autophagy-related markers was determined via Western blotting and immunofluorescence assays under both &lt;em&gt;in vitro&lt;/em&gt; and &lt;em&gt;in vivo&lt;/em&gt; conditions.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;NPY and Y1R expression were significantly elevated in human OA cartilage compared to normal tissue. &lt;em&gt;In vitro&lt;/em&gt;, NPY (5 μM) suppressed chondrocyte proliferation, reduced COLII expression, and increased MMP13 production. RNA-seq revealed NPY-mediated activation of the PI3K/AKT/mTOR pathway and inhibition of autophagy-related genes. NPY treatment enhanced the phosphorylation levels of PI3K, AKT, and mTOR, while concurrently decreasing LC3II expression and increasing p62 accumulation. The Y1R antagonist reversed these effects, restoring autophagy and attenuating cartilage degradation. &lt;em&gt;In vivo&lt;/em&gt;, NPY injections induced OA-like changes, including cartilage thinning, osteophyte formation, and mechanical allodynia. Y1R antagonist treatment mitigated these effects, improving gait parameters and reducing subchondral bone sclerosis. Immunofluorescence confirmed that Y1R inhibition decreased PI3K/AKT/mTOR signaling and enhanced autophagy in chondrocytes.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusion&lt;/h3&gt;&lt;div&gt;This study demonstrates that NPY/Y1R signaling exacerbates OA progression through PI3K/AKT/mTOR-mediated suppression of chondrocyte autophagy. Pharmacological inhibition of Y1R emerges as a novel therapeutic strategy, e","PeriodicalId":16636,"journal":{"name":"Journal of Orthopaedic Translation","volume":"55 ","pages":"Pages 146-158"},"PeriodicalIF":5.9,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145045686","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":"Can alternatives to animal testing yield useful information regarding biological mechanisms and drug discovery?","authors":"Qi Gao,&nbsp;Simon Kwoon-Ho Chow,&nbsp;Issei Shinohara,&nbsp;Masatoshi Murayama,&nbsp;Yosuke Susuki,&nbsp;Mayu Morita,&nbsp;Chao Ma,&nbsp;Stuart B. Goodman","doi":"10.1016/j.jot.2025.08.005","DOIUrl":"10.1016/j.jot.2025.08.005","url":null,"abstract":"<div><div>Establish alternative strategies to standard animal experiments decrease animal utilization and simultaneously enhance the reliability of biological and disease models. This review highlights advancements in three areas: in vitro culture platforms, disease modeling, and in silico simulations. We first discuss the innovative in vitro approaches, including 2D coculture systems, 3D spheroids, organoids, and organ-on-chip models, which facilitate the creation of physiologically relevant environments. Then, we focus on cell selection and characterization in disease modeling, with a particular focus on bone fracture healing and inflammation. We further review the potential of in silico simulations, including molecular docking, machine learning (ML) approaches, and pharmacokinetics-pharmacodynamics (PK/PD) modeling, to predict drug efficacy, interactions, and biological outcomes. These alternative strategies provide the potential for obtaining accurate and consistent results, thereby enhancing biomedical research and decreasing dependence on animal models. The Translational Potential of this Article: This review examines in vitro organoids, microphysiological systems, and computational models as alternatives to animal testing. These methods enhance our understanding of biological mechanisms. They also reduce the requirement for animal models. Ultimately, they help accelerate drug discovery that can directly benefit patients.</div></div>","PeriodicalId":16636,"journal":{"name":"Journal of Orthopaedic Translation","volume":"55 ","pages":"Pages 132-145"},"PeriodicalIF":5.9,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145045687","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Single-cell RNA sequencing reveals early cell dynamics of MSC-based therapy in long bone critical-size defects in mice","authors":"Ning Zhang ,&nbsp;Jie Yuan ,&nbsp;Xueping Li ,&nbsp;Ni Su ,&nbsp;Yiyun Wang ,&nbsp;Shuxian Chen ,&nbsp;Ejun Huang ,&nbsp;Qi Gao ,&nbsp;Fan Yang ,&nbsp;Simon Kwoon-Ho Chow ,&nbsp;Stuart B. Goodman","doi":"10.1016/j.jot.2025.08.007","DOIUrl":"10.1016/j.jot.2025.08.007","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Background&lt;/h3&gt;&lt;div&gt;Bone defects resulting from various causes present significant challenges in obtaining robust bone healing. This clinical scenario is particularly difficult in cases involving large bone defects, often leading to delayed union or non-union. Autogenous bone graft is the gold standard, but it is limited by the quantity and quality of available bone. Mesenchymal stem cells (MSCs) have shown promise in enhancing bone defect healing; however, the mechanisms by which MSCs modify the local bone microenvironment and interact with other cells early in the healing process are not fully understood. Elucidating and modulating the early biological events relevant to the healing of bone defects could lead to novel therapies to obtain a more expeditious and complete outcome.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;div&gt;Critical-size femoral defects were created in 10 to 12-week-old BALB/c male mice and fixed with an external fixation device. Four weeks after the generation of the defect, secondary surgeries were performed. Mice were randomized into three groups based on the secondary surgery: Empty group - surgery was performed without implanting scaffolds or cells. Sc group - a 2 mm diameter cylindrical microribbon (μRB) scaffold was implanted into the defect site. Sc + MSC group - a scaffold embedded with MSCs was implanted into the bone defect site. One week after the secondary surgeries, the entire tissue within the bone defect site was harvested for single-cell RNA sequencing (scRNA-seq).&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;Uniform manifold approximation and projection (UMAP) plots with quality filtered cells from three groups were used to identify the cell distributions in the defects. We identified thirteen populations and annotated each cluster using UMAP with Louvain clustering on combined single cells of three groups based on marker gene expression. Different cell compositions were revealed, especially the proportion of various types of immune cells in the Sc vs Sc + MSC groups. MSCs and osteoblastic lineage cells (MSC/Osteo), and osteoclasts were almost exclusively found in the Sc + MSC group. Differential gene expression and pathway analysis in major cell populations identified immune cell changes and inflammatory changes in the presence of implanted MSCs. Cell–cell communications revealed a greater number of interactions between different cell types in the Sc and Sc + MSC groups. More interactions among MSCs, macrophages, and T cells were observed in Sc + MSC groups. MSC demonstrated the highest outgoing interaction strength in all groups.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusions&lt;/h3&gt;&lt;div&gt;In the critical-size bone defect model, a combination of MSCs with μRB scaffolds showed an increased presence of mesenchymal lineage cells and promoted the further recruitment of macrophages and osteoclasts at 1 week. This alteration in the local immune landscape and microenvironment could enhance the cellular dynamics of critical cell populations tha","PeriodicalId":16636,"journal":{"name":"Journal of Orthopaedic Translation","volume":"55 ","pages":"Pages 121-131"},"PeriodicalIF":5.9,"publicationDate":"2025-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145019904","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":"Natural products in the treatment of osteoarthritis: Current status and prospects","authors":"Chenyue Xu ,&nbsp;Xiaoyu Cui ,&nbsp;Yuhang Shi ,&nbsp;Tianhang Zhang ,&nbsp;Zhengyi Ni ,&nbsp;Kehan Li ,&nbsp;Xiaobo Chen ,&nbsp;Fei Wang","doi":"10.1016/j.jot.2025.07.007","DOIUrl":"10.1016/j.jot.2025.07.007","url":null,"abstract":"<div><div>Osteoarthritis (OA) is a chronic degenerative joint disease characterized by progressive cartilage degradation, synovial inflammation, and subchondral bone remodeling. Existing treatments primarily offer symptomatic relief without effectively delaying OA progression. Recently, natural products have attracted great interest due to their anti-inflammatory, antioxidant, and chondroprotective effects. This review systematically summarized the efficacy and mechanisms of 13 natural products (Curcumin, Resveratrol, Icariin, Sinomenine, Andrographolide, Apigenin, Salvianolic acid, Matrine, Hesperidin, Plumbagin, Pomegranate extract, Thymoquinone, and Madecassoside) in OA treatment, drawing on evidence from in vitro and in vivo animal models, as well as clinical trials. By elucidating the current research status and future prospects, our review seeks to provide robust evidence for innovative and effective treatment strategies based on natural products to improve patient outcomes in OA management.</div></div><div><h3>The translational potential of this article</h3><div>This review enhances our comprehension of the pathological mechanisms underlying OA, delineates the existing therapeutic approaches for OA, their inherent limitations, and elucidates the current status and future prospects of natural products in OA management. With further clinical validation, these natural products may serve as adjunctive or alternative therapies to improve long-term outcomes in OA patients.</div></div>","PeriodicalId":16636,"journal":{"name":"Journal of Orthopaedic Translation","volume":"55 ","pages":"Pages 94-120"},"PeriodicalIF":5.9,"publicationDate":"2025-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145009855","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":"3D bioprinting bone/cartilage organoids: construction, applications, and challenges","authors":"Deju Gao ,&nbsp;Ruipeng Li ,&nbsp;Jie Pan ,&nbsp;Cairong Li ,&nbsp;Wei Zhang ,&nbsp;Ling Qin ,&nbsp;Yuxiao Lai","doi":"10.1016/j.jot.2025.08.008","DOIUrl":"10.1016/j.jot.2025.08.008","url":null,"abstract":"<div><div>Orthopaedic disorders, such as osteoporosis and osteoarthritis, impose substantial suffering upon an increasing population, driving demand for accurate disease models. Bone/cartilage organoids offer a promising solution by replicating complex 3D microstructures and multi-cellular niches, overcoming limitations of 2D models and animal experiments. 3D bioprinting, an additive manufacturing technology, enables the spatially precise deposition of cells and bioactive materials, facilitating efficient construction of organoids with enhanced structural fidelity. Therefore, this review specifically focuses on bone and cartilage organoids constructed using 3D bioprinting technologies. We summarize the prevailing 3D bioprinting techniques and biomaterials employed, critically analyze the unique advantages of bioprinting for creating these organoids, explore current technical challenges, such as standardization and scalability, and discuss future research directions. By addressing current progress and key issues in bioprinting bone/cartilage organoids, this review aims to accelerate their standardization and application as powerful platforms for multiscale disease modeling, drug screening, and regenerative medicine strategies. The translational potential of this article: Bone/cartilage organoids constructed via 3D bioprinting, through precise recapitulation of bone and cartilage tissue microenvironment and physiology, enable multiscale disease modeling from localized pathologies to systemic responses, despite persisting unresolved challenges in reproducibility and stability. This review highlights their clinical translational value and elucidates the driven role of 3D bioprinting in accelerating their clinical adoption, particularly in regenerative medicine.</div></div>","PeriodicalId":16636,"journal":{"name":"Journal of Orthopaedic Translation","volume":"55 ","pages":"Pages 75-93"},"PeriodicalIF":5.9,"publicationDate":"2025-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144997363","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":"Hydrogel adhesives with a hydrodynamically induced liquid–solid transition for annular fissure sealing and inflammation modulation following microdiscectomy","authors":"Huan Wang ,&nbsp;Moyan Li ,&nbsp;Jiaojiao Yang ,&nbsp;Zhao Liu ,&nbsp;Shijie Shi ,&nbsp;Dachuan Liu ,&nbsp;Youzhi Hong ,&nbsp;Hongjian Liu ,&nbsp;Songfeng Chen ,&nbsp;Jiyao Li ,&nbsp;Song Chen ,&nbsp;Bin Li","doi":"10.1016/j.jot.2025.08.004","DOIUrl":"10.1016/j.jot.2025.08.004","url":null,"abstract":"<div><h3>Background</h3><div>Intervertebral disc (IVD) herniation is a major cause of low back pain and disability, with microdiscectomy being the standard surgical treatment. However, microdiscectomy fails to address annulus fibrosus (AF) defects, increasing the risk of recurrent herniation. Current therapeutic strategies for this condition remain limited in efficacy. The lack of repair following injury and unresolved inflammation can further damage the IVD function, ultimately leading to irreversible IVD degeneration. Therefore, the development of an AF adhesive capable of both mechanically stabilizing annular fissures and enabling localized anti-inflammatory drug delivery emerges as a promising strategy to address this clinical challenge.</div></div><div><h3>Methods</h3><div>The developed AF adhesive system, designated as STIG, is formulated from silk fibroin, tannic acid, ibuprofen, and guanidine hydrochloride (GuCl). A comprehensive evaluation is conducted on STIG, encompassing its microstructure, composition, injectability, tissue adhesion, rheological properties, and biocompatibility. To assess anti-inflammatory efficacy, an <em>in vitro</em> inflammatory microenvironment is established via lipopolysaccharide (LPS)-stimulated AF cells. For <em>in vivo</em> validation, a rat model of IVD degeneration is surgically induced through puncturing the AF to simulate nucleus pulposus (NP) herniation. This experimental framework enables evaluation of STIG's ability to prevent NP protrusion, modulate inflammatory responses, and delay IVD degeneration.</div></div><div><h3>Results</h3><div>In the STIG system, GuCl serves the role of a hydrogen bond disruptor, facilitating its release into bodily fluids, which in turn allows for the reformation of hydrogen bonds. This property endows STIG with the ability to transition from an injectable, low-stiffness state to a high-stiffness adhesive gel upon contact with water. The inclusion of ibuprofen in the adhesive effectively curbs the production of inflammatory mediators and the breakdown of extracellular matrix constituents. In a rat tail model, STIG effectively preserves the NP water content, maintains the disc height index, and safeguards the structural integrity of the IVD post-surgery.</div></div><div><h3>Conclusion</h3><div>These findings highlight STIG's potential as a promising therapeutic solution for sealing AF fissures and preventing IVD degeneration.</div></div><div><h3>The translational potential of this article</h3><div>STIG shows significant clinical potential in spinal surgery. It offers a novel approach to reduce the recurrence rate post-microdiscectomy and improving long-term patient outcomes.</div></div>","PeriodicalId":16636,"journal":{"name":"Journal of Orthopaedic Translation","volume":"55 ","pages":"Pages 62-74"},"PeriodicalIF":5.9,"publicationDate":"2025-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144912730","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":"Preclinical validation of finite element models for predicting in vivo residual plate bending using continuous implant sensor data","authors":"Dominic Mischler ,&nbsp;Manuela Ernst ,&nbsp;Peter Varga","doi":"10.1016/j.jot.2025.08.001","DOIUrl":"10.1016/j.jot.2025.08.001","url":null,"abstract":"<div><h3>Background/objective</h3><div>Plate failure, including bending, is a critical issue in orthopedic fracture fixation, with clinical failure rates of 3.5%–19%, burdening patients and healthcare systems. Preclinical ovine models have observed similar plate bending due to overloading. Finite element (FE) models could be capable of predicting failures but lack <em>in vivo</em> loading data for validation. The AO Fracture Monitor is an implantable sensor that can continuously track implant deformation, offering a proxy for implant loading and the potential to bridge this gap. This study aimed to preclinically validate an FE simulation methodology for predicting overloading bending of locking plates in an ovine tibia osteotomy model using AO Fracture Monitor data, emphasizing its potential for clinical translation.</div></div><div><h3>Methods</h3><div>Tibiae of eleven sheep with osteotomy gaps (0.6 – 30 mm) were instrumented with stainless steel or titanium locking plates equipped with AO Fracture Monitors in a prior study. Residual plate bending angles were measured using co-registered CT scans at 0 and 4 weeks post-operation, with bending defined as ≥ 1°. Animal-specific FE models, incorporating virtual AO Fracture Monitors and non-linear implant material properties, were developed to determine sensor signals at the construct's yield point. <em>In vivo</em> sensor signals were compared to the virtual plasticity threshold to predict CT-based residual bending outcomes.</div></div><div><h3>Results</h3><div>Within 4 weeks, plate bending angles ranged from 0.4° to 10.4°, with overloading bending observed in 6 animals. The FE methodology correctly predicted bending/no-bending outcomes in 9 of 11 animals, achieving 100% sensitivity and 60% specificity.</div></div><div><h3>Conclusions</h3><div>This sensor-validated FE methodology robustly predicted <em>in vivo</em> plate bending, offering a promising tool for reducing implant failure. These findings highlight the methodology's ability to detect clinically relevant bending outcomes. By integrating real-time loading data, it supports the development of personalized rehabilitation strategies, enhancing clinical outcomes in fracture fixation.</div></div><div><h3>The Translational Potential of this Article</h3><div>This validated FE methodology, leveraging AO Fracture Monitor data, can be adapted for human use to tailor rehabilitation protocols immediately post-surgery and provide real-time feedback to patients and clinicians if loading exceeds safe thresholds. This approach could minimize implant failure, reduce revision surgeries, and enhance patient recovery.</div></div>","PeriodicalId":16636,"journal":{"name":"Journal of Orthopaedic Translation","volume":"55 ","pages":"Pages 55-61"},"PeriodicalIF":5.9,"publicationDate":"2025-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144906944","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}