Journal of Orthopaedic Translation最新文献

{"title":"Endowing implants surface with enhanced vascularization and osseointegration via presenting triple-functional peptides","authors":"Wenjie Liu , Qing Wang , Hao Liu , Suqin He , Hongxiang Wang , Chengwei Xu , Chaofan Jin , Na Li , Lianxin Li","doi":"10.1016/j.jot.2025.03.020","DOIUrl":"10.1016/j.jot.2025.03.020","url":null,"abstract":"<div><h3>Background</h3><div>Titanium-based implants have demonstrated good mechanical properties and biocompatibility in clinical applications, however, their inherent low bioactivity and complex biological behaviors during the process of osseointegration have resulted in a high rate of long-term implant failure. Although the immobilization of highly bioactive peptides on the implant surface is an effective strategy to improve osseointegration, the existing mono- and bifunctional peptide-modified implant surfaces can hardly meet the needs of cell behavior regulation and tissue regeneration during the process of osseointegration, and there is an urgent need for the development of more efficient surface modification technologies.</div></div><div><h3>Methods</h3><div>In the present study, a multifunctional peptide-modified implant material, MPN@K6, was successfully prepared by linking one end of a tripeptide system (cell adhesion peptide RGD, osteogenic growth peptide OGP, and pro-angiogenic peptide ang), which possesses a specific biological function, to hexameric lysine, and constructing the tripeptide system on the surface of metal-polyphenol coatings (MPNs) by means of non-covalent interactions between the lysine and the polyphenol, and then the MPN@K6 - RGD/OGP/ang was used as a peptide modification. RGD/OGP/ang.</div></div><div><h3>Results</h3><div>The MPN@K6-RGD/OGP/Ang coating not only supported the early adhesion and migration, late osteogenesis and mineralization of BMSCs, but also promoted the adhesion, migration and vascularization of HUVECs. RT-qPCR results showed that the hybrid peptide up-regulated the expression of key factors in angiogenesis and osteogenesis. In vivo testing further confirmed these findings, with the functional peptide coating being 1.5 to 2 times more effective at inducing new bone formation at an early stage than the other two-peptide combinations, confirming the effectiveness and superiority of the tripeptide synergistic modification strategy.</div></div><div><h3>Conclusions</h3><div>The results showed that the MPN@K6 - RGD/OGP/ang-modified implant exhibited significant advantages at the cellular level compared to different combinations of bifunctional peptide-coated forms. It was able to promote early cell migration and adhesion more efficiently, significantly induced osteoblast differentiation and mineralization, and enhanced the level of local vascularization. In a rat bone defect animal model, the material demonstrated more excellent bone repair effects and achieved better bone healing results, confirming the effectiveness and superiority of the tripeptide synergistic modification strategy.</div></div><div><h3>The translational potential of this article</h3><div>The trifunctional peptide coating (MPN@K6 - RGD/OGP/Ang) constructed in this paper has a mild preparation process, is biologically safe, facilitates large-scale production, has a positive effect on bone tissue repair, and has a great potential for cl","PeriodicalId":16636,"journal":{"name":"Journal of Orthopaedic Translation","volume":"52 ","pages":"Pages 150-166"},"PeriodicalIF":5.9,"publicationDate":"2025-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143854859","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":"Application of biphasic mineralized collagen/polycaprolactone scaffolds in the repair of large load-bearing bone defects: A study in a sheep model","authors":"Meng-Xuan Yao , Jing-Chuan Zheng , Hai-Cheng Wang , Hong-Zhi Lv , Yi-Fan Zhang , Yu-Qin Zhang , Tai-Long Shi , Yan-Ze Zhu , Ying-Ze Zhang , Xiu-Mei Wang , Wei Chen","doi":"10.1016/j.jot.2025.03.014","DOIUrl":"10.1016/j.jot.2025.03.014","url":null,"abstract":"<div><h3>Objective</h3><div>This study aims to evaluate the efficacy of biphasic mineralized collagen/polycaprolactone (bMC/PCL) scaffolds in repairing large load-bearing bone defects, particularly femoral defects, using a sheep model.</div></div><div><h3>Methods</h3><div>The bMC/PCL scaffolds were prepared by combining porous mineralized collagen/polycaprolactone (pMC/PCL) with compact mineralized collagen/polycaprolactone (cMC/PCL). The scaffolds were characterized using scanning electron microscopy to observe the microstructure and compression testing to assess mechanical properties. Twenty female sheep were selected to create a 20 mm femoral defect model, divided into a blank group (no material implanted) and an experimental group (bMC/PCL scaffolds implanted), with 10 sheep in each group. Bone healing and lower limb functional recovery were assessed at 1 month, 3 months, and 6 months postoperatively using Lane-Sandhu scores and visual analog scale scores for lameness. Additionally, bone repair progress was analyzed through X-ray, Micro-CT, and histological analyses.</div></div><div><h3>Results</h3><div>Compared with the blank group, the bMC/PCL scaffold group showed significant improvement in bone defect repair. At 3 and 6 months postoperatively, X-ray, Micro-CT scans, and histological staining indicated stable scaffold integration and gradual new bone formation. The Lane-Sandhu scores in the experimental group were 3.60 ± 0.548 and 4.00 ± 0.707 at 3 and 6 months, respectively, whereas the blank group experienced plate/screw breakage leading to fixation failure, with scores of 1, indicating better bone healing in the experimental group. The lameness scores in the experimental group were 2.71 ± 0.97 and 1.48 ± 0.86 at 3 and 6 months, respectively, significantly lower than those in the blank group (<em>p</em> < 0.0001 and <em>p</em> = 0.0002). Micro-CT analysis showed that bone volume to tissue volume ratio increased from 28.07 ± 9.22 % to 62.02 ± 11.82 %, bone mineral density increased from 0.392 ± 0.032 g/cm<sup>3</sup> to 0.583 ± 0.125 g/cm<sup>3</sup>, trabecular thickness increased from 0.690 ± 0.224 mm to 1.049 ± 0.089 mm, and trabecular separation decreased from 2.766 ± 1.183 mm to 0.501 ± 0.268 mm at 3 and 6 months postoperatively.</div></div><div><h3>Conclusion</h3><div>This study evaluated the efficacy of bMC/PCL scaffolds in repairing large load-bearing bone defects. The bMC/PCL scaffolds demonstrated good bioactivity and mechanical properties, indicating promising clinical application prospects. Future studies should further verify the safety and efficacy of these scaffolds in a wider range of animal models to support their clinical application.</div></div><div><h3>Significance statement</h3><div>The bMC/PCL scaffolds offer a promising solution for large femoral bone defects, with potential for clinical use in orthopedic and trauma surgeries.</div></div><div><h3>The translational potential of this article</h3><div>The applicatio","PeriodicalId":16636,"journal":{"name":"Journal of Orthopaedic Translation","volume":"52 ","pages":"Pages 138-149"},"PeriodicalIF":5.9,"publicationDate":"2025-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143854842","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":"The mitochondrial protectant SS31 optimized decellularized Wharton's jelly scaffold improves allogeneic chondrocyte implantation-mediated articular cartilage repair","authors":"Chao Wang ,&nbsp;Hao Li ,&nbsp;Fakai Li ,&nbsp;Yongkang Yang ,&nbsp;Ziheng Xu ,&nbsp;Tianze Gao ,&nbsp;Runmeng Li ,&nbsp;Ruiyang Zhang ,&nbsp;Yuhao Mu ,&nbsp;Zheng Guo ,&nbsp;Quanyi Guo ,&nbsp;Shuyun Liu","doi":"10.1016/j.jot.2025.03.023","DOIUrl":"10.1016/j.jot.2025.03.023","url":null,"abstract":"<div><h3>Background</h3><div>The process of allogeneic chondrocyte implantation entails obtaining donor chondrocytes, culturing them in a medium enriched with growth factors, and then introducing them-either individually or in conjunction with biocompatible scaffolds-into areas of cartilage damage. While promising, this approach is hindered by mitochondrial dysfunction in the implanted chondrocytes.</div></div><div><h3>Methods</h3><div>This research introduced an innovative approach by creating a new type of scaffold derived from Decellularized Umbilical Cord Wharton's Jelly (DUCWJ) extracted from human umbilical cords. The scaffold was manufactured using procedures involving decellularization and lyophilization. The resulting scaffold demonstrated superior characteristics, including high porosity, hydrophilic properties, and excellent biocompatibility. To enhance its function, SS31 peptides, known for their mitochondrial-protective properties, were chemically bonded to the scaffold surface, creating an SS31@DUCWJ system. This system aims to protect chondrocytes and regulate the mitochondrial respiratory chain (MRC), thereby improving cartilage repair mediated by allogeneic chondrocyte implantation.</div></div><div><h3>Results</h3><div>In vitro studies have shown that SS31 effectively attenuates metabolic dysfunction, extracellular matrix degradation, oxidative stress, inflammation, and mitochondrial damage induced by serial cell passages. Complementary in vivo experiments showed that the SS31@DUCWJ scaffold promoted regeneration of healthy articular cartilage in femoral condylar defects in rabbits.</div></div><div><h3>Conclusions</h3><div>This SS31-modified porous decellularized scaffold represents an innovative biomaterial with anti-inflammatory properties and targeted mitochondrial regulation. It offers a promising new approach for treating articular cartilage injuries.</div></div><div><h3>The translational potential of this article</h3><div>Our study was the first to successfully load the mitochondrial protectant SS31 onto a DUCWJ hydrogel scaffold for localized drug delivery. This method is highly efficacious in repairing cartilage defects and offers a promising new avenue for the treatment of such conditions.</div></div>","PeriodicalId":16636,"journal":{"name":"Journal of Orthopaedic Translation","volume":"52 ","pages":"Pages 126-137"},"PeriodicalIF":5.9,"publicationDate":"2025-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143828966","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":"Ferroptosis-mediated immune responses in osteoporosis","authors":"Wang Xiao ,&nbsp;Wang Yike ,&nbsp;Liu Gongwen ,&nbsp;Xu Youjia","doi":"10.1016/j.jot.2025.03.011","DOIUrl":"10.1016/j.jot.2025.03.011","url":null,"abstract":"<div><div>Osteoporosis is a common systemic metabolic disease, characterized by decreased bone mass and susceptibility to fragility fractures, often associated with aging, menopause, genetics, and immunity. Ferroptosis plays an underestimated yet crucial role in the further impact of immune function changes on osteoporosis. Cell ferroptosis can induce alterations in immune function, subsequently influencing bone metabolism. In this context, this review summarizes several mechanisms of ferroptosis and introduces the latest insights on how ferroptosis regulates immune responses, exploring the interactions between ferroptosis and other mechanisms such as oxidative stress, inflammation, etc. This review elucidates potential treatment strategies for osteoporosis, emphasizing the promising potential of ferroptosis as an emerging target in the treatment of osteoporosis. In conclusion, preparations related to ferroptosis exhibit substantial clinical promise for enhancing bone mass restoration.</div><div>The translational potential of this article: This review elucidates a nuanced conversation between the immune system and osteoporosis, with ferroptosis serving as the connecting link. These findings underscore the potential of ferroptosis inhibition as a therapeutic strategy for osteoporosis.</div></div>","PeriodicalId":16636,"journal":{"name":"Journal of Orthopaedic Translation","volume":"52 ","pages":"Pages 116-125"},"PeriodicalIF":5.9,"publicationDate":"2025-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143823932","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":"PDGF-BB improves cortical bone quality through restoring the osteogenic microenvironment in the steroid-associated osteonecrosis of rabbits","authors":"Huijuan Cao ,&nbsp;Keda Shi ,&nbsp;Jing Long ,&nbsp;Yanzhi Liu ,&nbsp;Xiangbo Meng ,&nbsp;Cuishan Huang ,&nbsp;Jie Hao ,&nbsp;Lingli Li ,&nbsp;Yiqing Zhao ,&nbsp;Tianluo Ye ,&nbsp;Yuxiao Lai ,&nbsp;Ling Qin ,&nbsp;Xinluan Wang","doi":"10.1016/j.jot.2025.03.010","DOIUrl":"10.1016/j.jot.2025.03.010","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Objective&lt;/h3&gt;&lt;div&gt;Steroid-associated osteonecrosis of the femoral head (SONFH) is a refractory disease characterized by progressive bone destruction. Clinical evidence suggests that SONFH may extend beyond the intra-capital region to the femoral neck, metaphysis, and even diaphysis, increasing the risk of subtrochanteric fractures and implant loosening post-surgery. While our previous study demonstrated that platelet-derived growth factor-BB (PDGF-BB) promotes reparative osteogenesis in the femoral head, its effects on cortical bone quality in the extended diaphyseal regions under steroid-associated osteonecrosis (SAON) remain unclear. This study aims to investigate whether PDGF-BB could mitigate cortical bone deterioration in the femoral diaphysis during SAON progression.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;div&gt;SAON was induced by repeated lipopolysaccharide (LPS) and methylprednisolone (MPS) injections in rabbits. At 2, 4, and 6 weeks after SAON induction, PDGF-BB was intramedullary injected into the proximal femur. Xylenol orange and Calcein green were injected subcutaneously into rabbits on days 14 and 4 before euthanasia. At 3 days after last PDGF-BB treatment, micro-fil perfusion was performed for angiography. Then the femur shaft was dissected for micro-computed tomography (μCT)-based angiography, μCT-based cortical bone geometry, and histological analysis. With regard to the macrophage infiltration and activated osteoclast function in osteonecrosis regions during SAON progression, RAW 264.7 cells were utilized to evaluate the effect of PDGF-BB on macrophage polarization and osteoclasts activity &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;In this study, osteonecrosis extended to the femoral diaphysis, accompanied by vascular disruption (reduced CD31+ vessels), sensory nerve degeneration (decreased CGRP + fibers), and cortical bone destruction, at 6 weeks post-SAON induction. While PDGF-BB treatment significantly attenuated SAON progression in the femoral diaphysis, restoring blood supply (angiography) and improving cortical bone geometry (μCT). Histologically, PDGF-BB enhanced periosteal and endosteal osteogenesis while suppressing osteoclastic resorption. &lt;em&gt;In vitro,&lt;/em&gt; PDGF-BB not only could modulate M1-type macrophages polarization to reduce inflammatory response, but also subsequently afford a secondary source of bioactivity factors during osteoclasts formation process to restore the osteogenic microenvironment, suggesting a dual role in resolving inflammation and enhancing bone remodeling.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusion&lt;/h3&gt;&lt;div&gt;SAON progression leads to diaphyseal cortical bone deterioration, while PDGF-BB application could restore the osteogenic microenvironment and drive cortical bone remodeling during SAON progression.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;The translational potential of this article&lt;/h3&gt;&lt;div&gt;These findings suggest that PDGF-BB could serve as a potential candidate for attenuating the progression of SAON. Local","PeriodicalId":16636,"journal":{"name":"Journal of Orthopaedic Translation","volume":"52 ","pages":"Pages 97-115"},"PeriodicalIF":5.9,"publicationDate":"2025-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143823933","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":"Therapeutic potential of stem cell-derived exosomes for bone tissue regeneration around prostheses","authors":"Biwu Wang ,&nbsp;Feng-Juan Lyu ,&nbsp;Zhantao Deng ,&nbsp;Qiujian Zheng ,&nbsp;Yuanchen Ma ,&nbsp;Yujie Peng ,&nbsp;Shujun Guo ,&nbsp;Guihua Lei ,&nbsp;Yonggang Lai ,&nbsp;Qingtian Li","doi":"10.1016/j.jot.2025.03.007","DOIUrl":"10.1016/j.jot.2025.03.007","url":null,"abstract":"<div><div>Artificial joint replacement is a widely recognized treatment for arthritis and other severe joint conditions. However, one of the primary causes of failure in joint replacements is the loosening of the prosthesis. After implantation, wear particles between the implant and the adjacent bone tissue are the principal contributors to this loosening. Recently, exosomes have garnered significant interest due to their low immunogenicity and effective membrane binding. They have shown potential in promoting bone regeneration via the paracrine pathway. This review examines the role and mechanisms of exosomes derived from mesenchymal stem cells (MSCs) in bone regeneration, their impact on the integration of various implants into surrounding bone tissue and current challenges and future directions for the clinical application of exosomes.</div><div>The Translational Potential of this Article: Emerging evidence suggests that mesenchymal stem cell-derived exosomes may offer a promising therapeutic strategy for aseptic prosthesis loosening, potentially mediated through mechanisms such as modulation of inflammatory responses, suppression of osteoclastogenesis, enhancement of osteogenic differentiation and facilitation of bone regeneration. Preclinical studies further indicate that the therapeutic potential of these extracellular vesicles could be optimized through bioengineering strategies, including surface modification and cargo-loading techniques, warranting further investigation to advance their clinical translation.</div></div>","PeriodicalId":16636,"journal":{"name":"Journal of Orthopaedic Translation","volume":"52 ","pages":"Pages 85-96"},"PeriodicalIF":5.9,"publicationDate":"2025-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143816523","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":"The multifaceted roles of extracellular vesicles in osteonecrosis of the femoral head","authors":"Hongxu Li ,&nbsp;Haoyang Liu ,&nbsp;Yu Zhou ,&nbsp;Liming Cheng ,&nbsp;Bailiang Wang ,&nbsp;Jinhui Ma","doi":"10.1016/j.jot.2025.03.009","DOIUrl":"10.1016/j.jot.2025.03.009","url":null,"abstract":"<div><div>Osteonecrosis of the femoral head (ONFH) is a severe disease characterized by bone tissue necrosis due to vascular impairment, often leading to joint collapse and requiring surgical intervention. Extracellular vesicles (EVs) serve as crucial mediators of intercellular communication, influencing osteogenesis, angiogenesis, and immune regulation. This review summarizes the dual role of EVs in both the pathogenesis of ONFH and post-necrosis bone repair, highlighting the impact of various EV-mediated signaling pathways on bone regeneration and the potential crosstalk among these pathways. Additionally, EVs hold promise as diagnostic biomarkers or contrast agents to complement conventional imaging techniques for ONFH detection. By elucidating the role of EVs in osteonecrosis and addressing the current challenges, we aspire to establish a foundation for the timely identification and treatment of ONFH.</div><div>The translational potential of this article: This review comprehensively discusses the role of EVs in ONFH, providing innovative and promising insights for its diagnosis and treatment, which also establishes a theoretical foundation for the future clinical application of EVs in ONFH.</div></div>","PeriodicalId":16636,"journal":{"name":"Journal of Orthopaedic Translation","volume":"52 ","pages":"Pages 70-84"},"PeriodicalIF":5.9,"publicationDate":"2025-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143807421","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":"Near-infrared smart responsive orthopedic implants with synergistic antimicrobial and bone integration-promoting properties","authors":"Ziming Liao ,&nbsp;Luyao Zhang ,&nbsp;Jingxuan Li ,&nbsp;Yujie Zhou ,&nbsp;Yu Cao ,&nbsp;Yan Wei ,&nbsp;Jingjing Du ,&nbsp;Li Lu ,&nbsp;Di Huang","doi":"10.1016/j.jot.2025.03.015","DOIUrl":"10.1016/j.jot.2025.03.015","url":null,"abstract":"<div><h3>Background</h3><div>The decline in antibiotic use has made the treatment of post-implant infections increasingly challenging, especially the problem of bacterial invasion caused by inadequate tissue fusion with the implant in the early stages of the implant. Developing multiple methods to reduce bacterial infections through synergies will be superior to a single model of antimicrobial means.</div></div><div><h3>Methods</h3><div>The composite coating composed of titanium phosphate (TiP)/copper oxide nanoparticles (CuO)/nano-hydroxyapatite (n-HA) named TiP-ua was used to kill <em>Staphylococcus aureus</em> (<em>S. aureus</em>) and <em>Escherichia coli</em> (<em>E. coli</em>) under near infrared (NIR) irradiation by means of photothermal therapy (PTT) and photodynamic therapy (PDT) synergism.</div></div><div><h3>Results</h3><div>The TiP-ua composite coating can reach about 60 °C and produce a certain amount of reactive oxygen species after 15 min irradiation with 980 nm near infrared light with 0.9 W/cm² power. Under the NIR irradiation of 0.9 W/cm² power for 10 min, the composite coating can achieve about 90% killing effect on <em>S. aureus</em> and more than 90% killing effect on <em>E. coli</em>. In terms of mouse pre-osteoblasts (MC3T3-E1), TiP-ua showed more superiority in promoting osteogenic differentiation ability. In the mouse infection model, it also showed good antibacterial effect, and could significantly reduce the expression of inflammatory factors and accelerate wound healing. In the bone defect model, the intervention significantly accelerated the regeneration of neobone tissue and enhanced osseointegration capacity.</div></div><div><h3>Conclusions</h3><div>The experimental results show that TiP-ua coating not only has good photothermal conversion ability, but also has good biosafety, which can accelerate the regeneration and repair of bone tissue around the implant, including accelerating the osteogenic differentiation of cells, and reduce the activity of bacteria to effectively reduce the inflammatory response.</div></div><div><h3>The translational potential of this article</h3><div>The collaborative antibacterial and bone repair coating in this study has a simple preparation process, high repeatability, high biosafety and positive effect on bone tissue repair, and has great clinical application potential in orthopedics and dental implants.</div></div>","PeriodicalId":16636,"journal":{"name":"Journal of Orthopaedic Translation","volume":"52 ","pages":"Pages 55-69"},"PeriodicalIF":5.9,"publicationDate":"2025-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143799355","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":"Chronic motoneuronal activation enhanced axonal regeneration and functional recovery after brachial plexus injury","authors":"Shiqin Lv ,&nbsp;Zizhuo Wu ,&nbsp;Yu Huang ,&nbsp;Pingzhen Wu ,&nbsp;Jianqing Shao ,&nbsp;Jiajia Wu ,&nbsp;Ke Zhong ,&nbsp;Lihua Zhou ,&nbsp;Wutian Wu","doi":"10.1016/j.jot.2025.02.007","DOIUrl":"10.1016/j.jot.2025.02.007","url":null,"abstract":"<div><h3>Background</h3><div>Brachial plexus injury (BPI) leads to significant impairment of upper limb motor function, primarily due to progressive atrophy of denervated muscles resulting from the slow rate of axonal regeneration. Therefore, identifying strategies to accelerate axon extension is of critical importance.</div></div><div><h3>Methods</h3><div>In this study, we first established a mouse model of brachial plexus injury and employed chemogenetic approaches to specifically activate C6 spinal motoneurons. We then assessed axonal regeneration and motor function recovery in the injured mice through behavioral tests, morphological analyses, and electrophysiological detection.</div></div><div><h3>Results</h3><div>We found that the AAV9-hM3Dq virus efficiently transduced motoneurons, and CNO administration robustly activated mature hM3Dq⁺ motoneurons in vivo. Chronic chemogenetic activation significantly enhanced the regeneration of spinal motoneurons injured by ventral root crush, accelerated axon extension, and improved axonal remyelination, resulting in increased axon size. This activation also facilitated the formation of new neuromuscular junctions (NMJs) in adult motoneurons and reduced muscle atrophy. Furthermore, it promoted electrophysiological recovery of the motor unit and improved overall motor function.</div></div><div><h3>Conclusion</h3><div>Chemogenetic activation of adult motoneurons can robustly enhances axon growth and mediate better behavioral recovery. These findings highlight the therapeutic potential of chemogenetic neuronal activation in promoting functional recovery following nerve injury.</div></div><div><h3>The translational potential of this article</h3><div>We have established a chronic chemogenetic method to activate hM3Dq⁺ motor neurons after brachial plexus injury, which accelerates axonal regeneration and enhances functional recovery. This strategy holds promise as a clinical therapeutic approach for treating nervous system injuries.</div></div>","PeriodicalId":16636,"journal":{"name":"Journal of Orthopaedic Translation","volume":"52 ","pages":"Pages 40-54"},"PeriodicalIF":5.9,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143759043","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":"RO5126766 attenuates osteoarthritis by inhibiting osteoclastogenesis and protecting chondrocytes through mediating the ERK pathway","authors":"Han Wang ,&nbsp;Xiwen Yuan ,&nbsp;Jie Han ,&nbsp;Zuoxing Wu ,&nbsp;Zheru Ma ,&nbsp;Fan Shi ,&nbsp;Zhengqiong Luo ,&nbsp;Zihan Chen ,&nbsp;Chenyang Guo ,&nbsp;Guixin Yuan ,&nbsp;Xuemei He ,&nbsp;Zemin Ling ,&nbsp;Lin Meng ,&nbsp;Rong Shen ,&nbsp;Jianming Huang ,&nbsp;Ren Xu","doi":"10.1016/j.jot.2025.03.002","DOIUrl":"10.1016/j.jot.2025.03.002","url":null,"abstract":"<div><h3>Background</h3><div>Osteoarthritis (OA) is a degenerative joint disease that remains challenging to treat due to lack of complete understanding of its pathogenesis. Previous studies have identified RO5126766 (RO) as a small molecule compound that inhibited RAF/MEK-ERK pathway and garnered much interest for its anti-cancer properties. But its role in the treatment of OA remains unclear.</div></div><div><h3>Methods</h3><div>This study employed the anterior cruciate ligament transection (ACLT) procedure to create an OA model in mice. The effects of RO on pathological changes in articular cartilage and subchondral bone were assessed using micro-CT and histological staining. Mice received peritoneal injections of RO at 1 mg/kg and 5 mg/kg biweekly for 4 weeks after ACLT, while control mice received saline. <em>In vitro</em>, bone marrow-derived macrophages were cultured to examine the effects of RO on osteoclast activation using immunofluorescence, TRAP staining, and bone resorption assays. The inflammatory degeneration of chondrocytes and gene expression levels were evaluated using staining and RT-qPCR. Western blot and immunohistochemistry were used to analyze MAPK signaling and autophagy-related protein expression, investigating RO's molecular mechanism in OA treatment. Human single-cell data were also analyzed to identify genes and pathways upregulated in OA tissues.</div></div><div><h3>Results</h3><div>Our findings showed that RO protects subchondral bone by inhibiting osteoclast formation in the ACLT mouse model of OA. <em>In vitro</em>, RO was shown to inhibit osteoclast differentiation and reduce inflammatory degeneration of chondrocytes. Mechanistically, RO counteracted subchondral osteoclast hyperactivation by suppressing the ERK/c-fos/NFATc1 signaling pathway. Additionally, RO inhibited LPS-induced inflammatory degeneration of chondrocytes and enhanced autophagy via the ERK pathway. Single-cell analysis further confirmed significant upregulation of the ERK signaling pathway in human OA tissues.</div></div><div><h3>Conclusions</h3><div>Overall, our findings suggested that RO inhibited osteoclast differentiation and protected articular cartilage, suggesting its potential as a novel treatment for OA.</div></div><div><h3>Translational potential of this article</h3><div>In this study, we have, for the first time, substantiated the therapeutic potential of RO in the treatment of OA. By demonstrating its ability to inhibit osteoclast differentiation and protect articular cartilage, RO could offer a new avenue for disease-modifying treatments in OA. Thus, this paper provides valuable insights into understanding the molecular mechanisms and treatment of OA.</div></div>","PeriodicalId":16636,"journal":{"name":"Journal of Orthopaedic Translation","volume":"52 ","pages":"Pages 27-39"},"PeriodicalIF":5.9,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143715563","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}