Journal of Orthopaedic Translation最新文献

{"title":"Dumbbell-shaped hydrogel plug for annulus fibrosus repair: From material design to in vivo validation","authors":"Mao-dan Nie , Bing-kun Bao , Ning-ze Zhang , Rong-shan Cheng , Ling-jie Fu , Cheng-Kung Cheng","doi":"10.1016/j.jot.2025.06.004","DOIUrl":"10.1016/j.jot.2025.06.004","url":null,"abstract":"<div><h3>Background</h3><div>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.</div></div><div><h3>Methods</h3><div>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.</div></div><div><h3>Results</h3><div>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.</div></div><div><h3>Conclusion</h3><div>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.</div></div><div><h3>The translational potential of this article</h3><div>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}

{"title":"Prevalence, risk factors, prediction of robust callus formation and accelerated fracture healing in traumatic brain injury patients: a five-year study","authors":"Zheyu Jin ,&nbsp;Jiechen Chen ,&nbsp;Zhengming Shan ,&nbsp;Weiyang Liu ,&nbsp;Zhenkang Wen ,&nbsp;Hongwei Shao ,&nbsp;Tongzhou Liang ,&nbsp;Ziyi Chen ,&nbsp;Xuesong Ren ,&nbsp;Dianhui Tan ,&nbsp;Ling Qin ,&nbsp;Jun Hu ,&nbsp;Jiankun Xu","doi":"10.1016/j.jot.2025.05.011","DOIUrl":"10.1016/j.jot.2025.05.011","url":null,"abstract":"<div><h3>Background</h3><div>Traumatic brain injury (TBI) usually induces robust callus formation at early stage and then subsequent acceleration of fracture union, as supported by both clinical and preclinical studies. However, risk factors and predictive tools to identify TBI patients most likely to experience this accelerated healing response are lacking and subject to future development.This study aimed to study the prevalence, risk factors, and develop machine learning (ML) models to predict robust callus formation and healing acceleration of fractures in TBI patients.</div></div><div><h3>Methods</h3><div>Between January 2018 and 2023, patients sustaining concomitant TBI and diaphyseal fractures who were admitted into the First Affiliated Hospital of Shantou University Medical College were evaluated retrospectively. The TBI patients were categorized into robust callus formation group (RCF) and normal callus formation group (NCF) based on follow-up radiographic fracture callus index assessments. Risk factors for RCF occurrence were first identified using traditional univariate and multivariate regression model, and predictive models were developed using 12 ML models (including traditional logistic regression model). The performance and interpretations of ML models were evaluated using the area under the receiver operating characteristic curve (AUC) and Shapley Additive Explanations (SHAP).</div></div><div><h3>Results</h3><div>Of the 723 patients reviewed, 150 cases were enrolled for final analysis. The prevalence of robust callus formation was 40.67 % (61/150) with significantly wider callus index (2.01 ± 0.61 vs 1.17 ± 0.12, P &lt; 0.001) and acceleration in time to initial callus formation (22.92 ± 11.98 days vs 90.18 ± 34.52 days, P &lt; 0.001). Brain contusions (OR 5.914, 95 % CI:2.479–14.108,P &lt; 0.001), greater TBI severity levels evaluated using Glasgow Coma Scale (GCS, OR 3.074, 95 % CI:1.149–8.222,P = 0.025) and Marshall CT classifications (OR 2.845, 95 %CI:1.095–7.390,P = 0.032) were identified as independent risk factors for RCF occurrence. The gradient boosting decision tree (GBDT) algorithm demonstrated optimal predictive performance using TBI-specific variables, achieving an AUC of 0.86 ± 0.03. SHAP analysis revealed brain contusion, GCS scores, and Marshall CT classification scores as the three most influential clinical features.</div></div><div><h3>Conclusions</h3><div>For the first time, this study provided the prevalence and risk factors contributing to RCF occurrence in TBI patients with combined diaphyseal fractures, and also developed ML models for its prediction, for which it may optimize orthopedics treatment strategies and decision making in these unique set of TBI patients.</div></div><div><h3>The translational potential of this article</h3><div>The findings from this study offer crucial insights to enhance clinical decision-making and treatment approaches for managing fractures in TBI patients. Furthermore, our res","PeriodicalId":16636,"journal":{"name":"Journal of Orthopaedic Translation","volume":"53 ","pages":"Pages 151-160"},"PeriodicalIF":5.9,"publicationDate":"2025-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144344636","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":"Letter to the editor regarding “Promotion of bone-tendon healing after ACL reconstruction using scaffold-free constructs comprising ADSCs produced by a bio-3D printer in rabbit models”","authors":"Yuwang Du","doi":"10.1016/j.jot.2025.06.006","DOIUrl":"10.1016/j.jot.2025.06.006","url":null,"abstract":"","PeriodicalId":16636,"journal":{"name":"Journal of Orthopaedic Translation","volume":"53 ","pages":"Pages 149-150"},"PeriodicalIF":5.9,"publicationDate":"2025-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144335948","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":"Oncostatin-M functionalized cryogel microspheres for promoting diabetic bone defects regeneration","authors":"Rui Song ,&nbsp;Xiaojing Yuan ,&nbsp;Zhuo Wan ,&nbsp;Linxue Zhang ,&nbsp;Feng Rao ,&nbsp;Yuming Zhao ,&nbsp;Zuoying Yuan","doi":"10.1016/j.jot.2025.06.002","DOIUrl":"10.1016/j.jot.2025.06.002","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Background/objective&lt;/h3&gt;&lt;div&gt;Bone defects, especially those associated with diabetes, pose a significant challenge due to impaired healing capabilities. &lt;em&gt;In situ&lt;/em&gt; bone tissue engineering harnesses the body's innate self-repair capabilities instead of introducing exogenous cells, and the development of biomaterials with well-designed biophysical and biochemical properties is pivotal for this strategy. Oncostatin M (OSM), a pleiotropic cytokine belonging to the IL-6 family, is responsible for recruiting endogenous cells and bone regeneration. This study focuses on the role of OSM in osteogenesis, angiogenesis, and immunoregulation, as well as developing OSM functionalized cryogel microspheres (OSM/MS) to enhance bone regeneration in diabetic conditions.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;div&gt;We systematically investigated the &lt;em&gt;in vitro&lt;/em&gt; bioactivities of OSM on bone marrow mesenchymal stromal cells (BMSCs), human umbilical vein endothelial cells (HUVEC), and macrophages (RAW264.7). Subsequently, we fabricated OSM-loaded porous GelMA cryogel microspheres (OSM/MS) via the combination of emulsification and gradient freeze-crosslinking techniques. The biocompatibility, osteogenic and angiogenic potentials, and immunomodulatory effects of OSM/MS were evaluated &lt;em&gt;in vitro&lt;/em&gt;. The &lt;em&gt;in vivo&lt;/em&gt; efficacy of OSM/MS was assessed in an inflammatory diabetic rat calvarial defect model.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;50 ng/ml OSM can enhance migration and osteogenic differentiation of BMSCs, and angiogenesis &lt;em&gt;in vitro&lt;/em&gt; without inciting an inflammatory response. OSM/MS, with an average diameter of ∼80 μm and an average pore size of about ∼10 μm, demonstrated excellent biocompatibility and significantly promoted the migration and osteogenic differentiation of BMSCs, as well as the angiogenic potential of HUVEC. Moreover, OSM/MS effectively regulated macrophage polarization towards an anti-inflammatory M2 phenotype. &lt;em&gt;In vivo&lt;/em&gt; studies revealed that OSM/MS reduced osteoclast differentiation and promoted bone regeneration in diabetic rats.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusion&lt;/h3&gt;&lt;div&gt;The multifunctional properties of OSM/MS, including stem cell recruitment, osteogenesis, immunomodulation, and angiogenic induction, make it an effective approach for promoting bone regeneration in challenging diabetic conditions. This research not only lay the groundwork for the clinical utilization of OSM, but also presents a novel bioactive microsphere-based strategy for the management of diabetic bone defects.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;The translational potential of this article&lt;/h3&gt;&lt;div&gt;The ability of OSM/MS to promote endogenous stem cell recruitment, modulate the immune-osteogenesis microenvironment, and induce angiogenesis makes it a potent candidate for diabetic bone defects. The injectable and porous nature of OSM/MS facilitates minimally invasive delivery and integration with the irregular bone defect site. In particular, OSM/MS face fewer ","PeriodicalId":16636,"journal":{"name":"Journal of Orthopaedic Translation","volume":"53 ","pages":"Pages 138-148"},"PeriodicalIF":5.9,"publicationDate":"2025-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144322075","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":"Electric currents in disc health: The role of ion channels in intervertebral disc pathophysiology","authors":"Hengxiang Shu ,&nbsp;Yan Gao ,&nbsp;Qin Zhang ,&nbsp;Haobo Sun ,&nbsp;Huazheng Wang ,&nbsp;Chengnan Jing ,&nbsp;Peng Liu ,&nbsp;Dechun Geng ,&nbsp;Hao Shen ,&nbsp;Minfeng Gan","doi":"10.1016/j.jot.2025.06.007","DOIUrl":"10.1016/j.jot.2025.06.007","url":null,"abstract":"<div><div>Intervertebral disc degeneration (IVDD), which is known as a common global health concern, has been a significant factor in neck and back pain. The intervertebral discs are avascular structures consisting of the nucleus pulposus, annulus fibrosus, and cartilage endplate, which are crucial for regulating the spinal motion, withstanding stress, and buffering vibration. Due to their special anatomical structure and functional role, they are highly susceptible to stimulation by external factors. Ion channels are transmembrane proteins which have attracted significant attention and great progress in cardiovascular diseases and neurological diseases, and the importance of them in the pathophysiology of IVDD is gaining recognition. They function as a receptor to stimulate the influx of calcium within cells, which acts as a second messenger to activate downstream pathways and upregulate the expression of transcriptional protein, thereby triggering IVDD. This review classified the ion channel families into three types based on their primary activation mechanisms, and then described the regulation of ion channels from transcription and translation to trafficking and expression. Subsequently, the function of ion channels in the pathophysiology of IVDD as well as their potential and practicality in treatment were the main topics of this review. We hope this review could help understand and develop new, specific therapies for IVDD.</div></div><div><h3>The translational potential of this article</h3><div>Targeted therapeutic strategies for ion channels are particularly critical in the treatment of IVDD. Ion channel-targeted drugs and tissue engineering strategies for ion channels have emerged as novel therapeutic targets for intervening in IVDD by modulating calcium homeostasis, inflammatory responses, and extracellular matrix metabolism in disc cells. In addition, as the development of nanotechnology, the integration of ion channel-targeted therapies with advanced drug delivery systems represents a promising frontier in the treatment of IVDD. Nanoparticle-based carriers and hydrogel-mediated sustained-release platforms have emerged as complementary strategies to enhance drug bioavailability and spatiotemporal control within the avascular, mechanically stressed intervertebral disc microenvironment. Furthermore, systematic exploration of combination therapies integrating ion channel-targeted drugs with complementary pharmacological agents like anti-inflammatory drugs and growth factors warrants rigorous investigation to enhance therapeutic efficacy in IVDD management.</div></div>","PeriodicalId":16636,"journal":{"name":"Journal of Orthopaedic Translation","volume":"53 ","pages":"Pages 126-137"},"PeriodicalIF":5.9,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144322074","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":"Inhibiting the REV-ERBα expression protects against mechanical overloading-induced cartilage clock disruption and osteoarthritis progression","authors":"Xiaojie Xu ,&nbsp;Dong Wang ,&nbsp;Bowei Ni ,&nbsp;Hailun Xu ,&nbsp;Zixiang Wu ,&nbsp;Ting He ,&nbsp;Yuejiao Zhang ,&nbsp;Xue Hao ,&nbsp;Guangyu Ding ,&nbsp;Xinyu Zhang ,&nbsp;Qing-Jun Meng ,&nbsp;Liu Yang","doi":"10.1016/j.jot.2025.06.005","DOIUrl":"10.1016/j.jot.2025.06.005","url":null,"abstract":"<div><h3>Background</h3><div>The circadian clock maintains homeostasis in peripheral tissues, including articular cartilage. Cartilage as a highly mechanical loaded tissue experiences diurnal rhythmic mechanical loading activity/rest cycle patterns, which gives external time cue on chondrocytes. Given the cartilage clock driven by loading patterns, we hypothesize that abnormal mechanical loading, a major risk factor for osteoarthritis (OA), can disrupt the cartilage clock, further contributing to OA progression.</div></div><div><h3>Methods</h3><div>We used both noninvasive <em>in vivo</em> mechanical loading system and PER2Luc reporter mice for <em>ex vivo</em> bioluminescence recording. RNA sequencing was performed in mouse primary chondrocytes treated with 1.0 MPa static compression, and identified core clock molecule REV-ERBα, which was confirmed in human and murine OA cartilage samples. Chondrocytes were treated with <em>Rev-erbα</em> small interfering RNA (si-<em>Rev-erbα</em>), and adeno-associated virus carrying <em>Rev-erbα</em>-specific short hairpin RNA (AAV-sh<em>Rev-erbα</em>) was injected intra-articularly in mice to knock down <em>Rev-erbα</em>. Relevant signaling pathways regulating REV-ERBα were analyzed by RNA sequencing data. Intraperitoneal injection of SR8278, a specific REV-ERBα antagonist, was performed in mice after mechanical overloading for OA treatment.</div></div><div><h3>Results</h3><div>Excessive mechanical loading disrupted the circadian rhythm of articular cartilage. The core clock molecule REV-ERBα was increased in OA cartilage and knockdown of <em>Rev-erbα</em>alleviated compression-induced chondrocyte dysfunction. Inhibition of MAPK-MYC pathway by U0126 or SB203580 attenuated compression-induced REV-ERBα up-regulation and cartilage clock disruption. Finally, pharmacological inhibition of REV-ERBα expression by SR8278 restored cartilage clock upon abnormal loading and mitigated OA progression.</div></div><div><h3>Conclusions</h3><div>REV-ERBα is a key factor in the association between mechanical overloading-induced circadian disruption and OA pathology. This study illustrates the essential mechanism of impaired circadian rhythm under overloading and provides a possibly impactful therapeutic approach for the treatment of OA.</div></div><div><h3>The Translational Potential of this Article</h3><div>Inhibition REV-ERBα expression by clock-based therapeutic drug SR8278 or MAPK-MYC pathway inhibitors could ameliorate mechanical overloading-induced circadian disruption of cartilage and OA degeneration, indicating a clinical conversion potential for OA treatment.</div></div>","PeriodicalId":16636,"journal":{"name":"Journal of Orthopaedic Translation","volume":"53 ","pages":"Pages 112-125"},"PeriodicalIF":5.9,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144312886","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":"Construction of cartilaginous organoids based on cartilage extracellular matrix microcarriers to promote articular cartilage regeneration through immune regulation","authors":"Hongyu Jiang ,&nbsp;Wei Liu ,&nbsp;Jiajie Chen ,&nbsp;Yue Tian ,&nbsp;Zhibo Jia ,&nbsp;Yanbin Wu ,&nbsp;Yanjun Guan ,&nbsp;Leijia Chen ,&nbsp;Wenjing Xu ,&nbsp;Haoye Meng ,&nbsp;Yingjie Xiong ,&nbsp;Jianting Ye ,&nbsp;Cheng Huang ,&nbsp;Ruichao He ,&nbsp;Sice Wang ,&nbsp;Yufei Ding ,&nbsp;Wei Fan ,&nbsp;Yunkang Yang ,&nbsp;Jiang Peng ,&nbsp;Aiyuan Wang","doi":"10.1016/j.jot.2025.05.005","DOIUrl":"10.1016/j.jot.2025.05.005","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Objective&lt;/h3&gt;&lt;div&gt;To investigate the feasibility of constructing cartilaginous organoids (CORGs) using cartilage extracellular matrix microcarriers (CEMMs), evaluate their ectopic chondrogenic potential, and analyze their impact on &lt;em&gt;in situ&lt;/em&gt; repair and regeneration of knee cartilage in SD rats.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;div&gt;Cartilage extracellular matrix microcarriers (CEMMs) were created through a combination of decellularization, wet milling, and layered sieving methods. The evaluation of their biological function was conducted through live/dead staining, CCK-8 assay, scratch assay, and Transwell assay in a laboratory setting. The immune microenvironment was confirmed to be influenced by CEMMs through a conditioned culture involving rat macrophages. qRT-PCR and secretory function assays was conducted to evaluate the chondrogenic activity of CORGs. Gene expression profiles throughout the development of CORGs were analyzed using transcriptome sequencing. Immunodeficient mouse subcutaneous model to assess the ectopic chondrogenic capacity of CORGs. CORGs were implanted into the knee joint cartilage defects of SD rats to evaluate their effects on cartilage regeneration.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;Successfully developed CEMMs with dimensions of 210.4 ± 56.89 um exhibited strong biocompatibility, the capacity to draw in stem cells, stimulate their growth and migration, and encourage macrophages to shift to the M2 type. Functionalized CORGs were successfully constructed based on CEMMs. Transcriptomics showed that CORGs had a gene expression pattern similar to mesodermal to chondrogenic development. CORGs successfully generated cartilaginous tissue subcutaneously in immunodeficient mice. Specifically, at 1 week postoperatively, CORGs were observed to promote M2 polarization of periarticular macrophages. At 6 and 12 weeks post-surgery, gross observation, micro-CT scanning, and histological analyses collectively revealed that CORGs promoted cartilage regeneration.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusions&lt;/h3&gt;&lt;div&gt;The functionalized CORGs was successfully constructed based on CEMMs, exhibiting robust expression of chondrogenic-related genes and demonstrating the ability to secrete collagen and GAGs. Transcriptomic analysis revealed that CORGs exhibited a gene expression trajectory consistent with the transition from mesodermal to chondrogenic genes, resulting in the successful development of cartilaginous tissues rich in cartilage-specific matrix when implanted subcutaneously in immunodeficient mice. Furthermore, CORGs demonstrated the ability to modulate the immune microenvironment surrounding the knee joint. In SD rat models of knee cartilage defects, CORGs exhibited robust regenerative and repair capacity.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;The translational potential of this article&lt;/h3&gt;&lt;div&gt;This research involved the creation of CORGs utilizing natural biomaterials (ECM) and MSCs, demonstrating significant promise for treating cartilage inj","PeriodicalId":16636,"journal":{"name":"Journal of Orthopaedic Translation","volume":"53 ","pages":"Pages 82-98"},"PeriodicalIF":5.9,"publicationDate":"2025-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144241333","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":"Porous PLGA microspheres loaded with PTH1-34 peptide for long-term treatment of OA","authors":"Wang Diaodiao ,&nbsp;Tang Miaotian ,&nbsp;Ren Pengcheng ,&nbsp;Tian Zhuang ,&nbsp;Zhang Gang ,&nbsp;Liu Yubo ,&nbsp;Sun Yuyang ,&nbsp;Ye Peng ,&nbsp;Sun Wenqiang ,&nbsp;Yao Qi","doi":"10.1016/j.jot.2025.05.003","DOIUrl":"10.1016/j.jot.2025.05.003","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Background&lt;/h3&gt;&lt;div&gt;Osteoarthritis (OA) is a chronic disease characterized by degeneration of articular cartilage, affecting over 530 million patients worldwide. Current oral medications such as non-steroidal anti-inflammatory drugs (NSAIDs) can only alleviate symptoms and are associated with numerous adverse effects. Although teriparatide (PTH&lt;sub&gt;1-34&lt;/sub&gt;) exhibits dual functions of chondroprotection and osteogenic effects, its clinical application is significantly limited by its short biological half-life (30–60 min) and accelerated degradation within the inflammatory microenvironment of joint cavities.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;div&gt;Porous sustained-release microspheres (M@PTH&lt;sub&gt;1-34&lt;/sub&gt;) were fabricated using FDA-approved poly (lactic-co-glycolic acid) (PLGA) as the matrix, encapsulating PTH&lt;sub&gt;1-34&lt;/sub&gt; within their multi-channel porous structure. Uniform microsphere preparation and high-efficiency drug loading were achieved through membrane emulsification and temperature-controlled embedding techniques. To systematically evaluate the sustained-release profile and therapeutic outcomes, both in vitro and in vivo OA models were established, enabling comprehensive analysis of cartilage repair efficacy, anti-inflammatory regulation, and immunomodulatory effects.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;PTH&lt;sub&gt;1-34&lt;/sub&gt; could be efficiently loaded into microspheres after self-healing and achieve consistent release over 30 days with biological activity being maintained. In OA model rats, M@PTH&lt;sub&gt;1-34&lt;/sub&gt; significantly improved behavioral and radiological outcomes, increased cartilage smoothness and thickness, and increased the expression of chondrogenic markers. Additionally, in vitro and in vivo safety tests revealed no significant safety issues. These findings indicate that M@PTH&lt;sub&gt;1-34&lt;/sub&gt; holds promise as a long-lasting, cost-effective, and safe therapeutic approach for OA.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusion&lt;/h3&gt;&lt;div&gt;This study successfully developed a uniform-sized PLGA-based sustained-release microsphere system (M@PTH&lt;sub&gt;1-34&lt;/sub&gt;) that enables continuous drug release for over 30 days following single intra-articular administration. M@PTH&lt;sub&gt;1-34&lt;/sub&gt; exerts its therapeutic effects on osteoarthritis through the following two ways: (1) Promoting cartilage repair by enhancing the chondrogenic differentiation ability of bone marrow mesenchymal stem cells (BMSCs); (2) Improve the inflammatory microenvironment of joints by inhibiting the expression of inflammatory factors (such as IL-1β) and regulating the polarization state of M1/M2 macrophages.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;The translation potential of this article&lt;/h3&gt;&lt;div&gt;The system demonstrates prominent clinical translation advantages: (1) Innovative utilization of FDA-approved PLGA carrier combined with membrane emulsification technique ensures precise size control and standardized production; (2) Localized delivery strategy achieves targeted retention within articular ","PeriodicalId":16636,"journal":{"name":"Journal of Orthopaedic Translation","volume":"53 ","pages":"Pages 99-111"},"PeriodicalIF":5.9,"publicationDate":"2025-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144241635","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":"Regulating inflammation microenvironment and tenogenic differentiation as sequential therapy promotes tendon healing in diabetic rats","authors":"Jingyi Dang ,&nbsp;Zhao Zhang ,&nbsp;Jun Fu ,&nbsp;Liguo Sun ,&nbsp;Yubo Shi ,&nbsp;Lei Wang ,&nbsp;Weidong Tao ,&nbsp;Debin Cheng ,&nbsp;Xiaohe Wang ,&nbsp;Zhenzhou Mi ,&nbsp;Dong Liu ,&nbsp;Hongbin Fan","doi":"10.1016/j.jot.2025.04.015","DOIUrl":"10.1016/j.jot.2025.04.015","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Background&lt;/h3&gt;&lt;div&gt;Chronic tendinopathy with diabetes mellitus (CTDM) poses significant therapeutic challenges due to persistent inflammation and impaired tenogenesis. While the supplementation of tendon stem/progenitor cells (TSPCs) has the potential to facilitate tenogenesis, premature recruitment and proliferation in inflammatory microenvironments risks fibrosis or heterotopic ossification (HO). Consequently, balancing inflammation regulation and tenogenic differentiation is critical for effective healing.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;div&gt;An injectable glucose-responsive dual-drug-sequential delivery hydrogel (GDSH) was developed utilizing oxidized hyaluronic acid-modified dopamine and phenylboronic acid-functionalized carboxymethyl chitosan. Dendritic mesoporous silica nanospheres (DMSNs) encapsulating irisin and connective tissue growth factor (CTGF) were incorporated into the GDSH matrix. A comprehensive characterization of the hydrogel's properties, including rheological, mechanical, adhesive, swelling/degradation, and drug release behaviors, was conducted. In vitro assessments were performed to evaluate cytocompatibility, as well as antioxidant and anti-inflammatory effects, alongside the migration, proliferation, and differentiation of TSPCs. The therapeutic efficacy was further investigated using a collagenase type I/streptozotocin-induced CTDM model in rats, with analyses conducted through histological, biomechanical, and micro-CT methods. Transcriptome sequencing and Western blot analyses were employed to elucidate the involvement of specific signaling pathways in the tissue repair process.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;The GDSH composite hydrogels possess a range of advantageous properties, including exceptional mechanical strength, optimal adhesiveness, superior biocompatibility, and appropriate swelling and degradation rates, in addition to controllable and sequential drug release capabilities. In vitro investigations revealed that these composite hydrogels exhibit antioxidant and anti-inflammatory effects, while also promoting cell proliferation and migration. Furthermore, they facilitate tenogenic differentiation and simultaneously inhibit the aberrant differentiation of TSPCs. In vivo studies demonstrated that the composite hydrogels significantly improved the morphological and biomechanical properties of injured tendons, reduced inflammation, corrected abnormal differentiation, and displayed favorable biosafety profiles. Transcriptome sequencing and Western blotting analysis indicated that the composite hydrogels repaired CTDM through the MAPK, AMPK, Smad, Hippo and PI3K/AKT signaling pathways.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusion&lt;/h3&gt;&lt;div&gt;GDSH achieves spatiotemporal control of inflammation resolution and tenogenesis via glucose-responsive sequential delivery of irisin and CTGF. This strategy restores tendon microstructure, biomechanics, and redox homeostasis in CTDM, offering a translatable platform for diabeti","PeriodicalId":16636,"journal":{"name":"Journal of Orthopaedic Translation","volume":"53 ","pages":"Pages 63-81"},"PeriodicalIF":5.9,"publicationDate":"2025-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144222310","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":"N6-methyladenosine and intervertebral disc degeneration: Advances in detection and pathological insights","authors":"Bin Liu ,&nbsp;Guanhui Song ,&nbsp;Yaosheng Wang ,&nbsp;Changheng Song ,&nbsp;Yiping Cao ,&nbsp;Jinlin Tong ,&nbsp;Yuyao Wang ,&nbsp;Xinrong Fan ,&nbsp;Nannan Shi ,&nbsp;Hongyan Zhao ,&nbsp;Danping Fan","doi":"10.1016/j.jot.2025.05.004","DOIUrl":"10.1016/j.jot.2025.05.004","url":null,"abstract":"<div><div>Intervertebral disc (IVD) degeneration (IDD) is a progressive condition characterized by the deterioration of the intervertebral discs, which serve as cushions between the vertebrae in the spinal column. This degeneration is often associated with aging and can be influenced by various factors, including genetics, mechanical stress, and lifestyle choices. N⁶-methyladenosine (m⁶A) modification has emerged as a critical post-transcriptional regulatory mechanism that influences various biological processes, including cellular differentiation, proliferation, and response to stress. Recent studies suggest that m⁶A modification play significant roles in the pathophysiology of IDD. The dysregulation of m⁶A methylation is linked to the altered expression of genes involved in inflammation, oxidative stress, extracellular matrix remodeling, regulated cell death including apoptosis, autophagy, pyroptosis and ferroptosis, all of which contribute to the IDD. In this review, we summarize the advanced detection technology of m⁶A and the roles of m⁶A in pathological process of IDD, to provide new insights into the molecular mechanisms underlying IDD and identify novel therapeutic targets for intervention.</div></div><div><h3>The translational potential of this article</h3><div>This work underscores the diagnostic and therapeutic potential of targeting m⁶A mechanism in IDD. Clinically, m6A regulators may serve as biomarkers for early IDD detection or progression monitoring. Therapeutically, small-molecule modulators of m⁶A writers/erasers or RNA-based strategies could restore ECM homeostasis, mitigate inflammation, and prevent IVD cell death. Furthermore, advanced m⁶A mapping technologies may enable personalized interventions by decoding patient-specific epitranscriptomic profiles. These insights bridge molecular mechanisms to clinical innovation, offering novel avenues for IDD treatment and regenerative therapies.</div></div>","PeriodicalId":16636,"journal":{"name":"Journal of Orthopaedic Translation","volume":"53 ","pages":"Pages 38-51"},"PeriodicalIF":5.9,"publicationDate":"2025-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144222843","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}