Pub Date : 2025-09-08DOI: 10.1016/j.jot.2025.07.007
Chenyue Xu , Xiaoyu Cui , Yuhang Shi , Tianhang Zhang , Zhengyi Ni , Kehan Li , Xiaobo Chen , Fei Wang
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.
The translational potential of this article
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.
{"title":"Natural products in the treatment of osteoarthritis: Current status and prospects","authors":"Chenyue Xu , Xiaoyu Cui , Yuhang Shi , Tianhang Zhang , Zhengyi Ni , Kehan Li , Xiaobo Chen , 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}
Pub Date : 2025-09-05DOI: 10.1016/j.jot.2025.08.008
Deju Gao , Ruipeng Li , Jie Pan , Cairong Li , Wei Zhang , Ling Qin , Yuxiao Lai
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.
{"title":"3D bioprinting bone/cartilage organoids: construction, applications, and challenges","authors":"Deju Gao , Ruipeng Li , Jie Pan , Cairong Li , Wei Zhang , Ling Qin , 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}
Pub Date : 2025-08-29DOI: 10.1016/j.jot.2025.08.004
Huan Wang , Moyan Li , Jiaojiao Yang , Zhao Liu , Shijie Shi , Dachuan Liu , Youzhi Hong , Hongjian Liu , Songfeng Chen , Jiyao Li , Song Chen , Bin Li
Background
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.
Methods
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 in vitro inflammatory microenvironment is established via lipopolysaccharide (LPS)-stimulated AF cells. For in vivo 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.
Results
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.
Conclusion
These findings highlight STIG's potential as a promising therapeutic solution for sealing AF fissures and preventing IVD degeneration.
The translational potential of this article
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.
{"title":"Hydrogel adhesives with a hydrodynamically induced liquid–solid transition for annular fissure sealing and inflammation modulation following microdiscectomy","authors":"Huan Wang , Moyan Li , Jiaojiao Yang , Zhao Liu , Shijie Shi , Dachuan Liu , Youzhi Hong , Hongjian Liu , Songfeng Chen , Jiyao Li , Song Chen , 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}
Pub Date : 2025-08-28DOI: 10.1016/j.jot.2025.08.001
Dominic Mischler , Manuela Ernst , Peter Varga
Background/objective
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 in vivo 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.
Methods
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. In vivo sensor signals were compared to the virtual plasticity threshold to predict CT-based residual bending outcomes.
Results
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.
Conclusions
This sensor-validated FE methodology robustly predicted in vivo 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.
The Translational Potential of this Article
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.
{"title":"Preclinical validation of finite element models for predicting in vivo residual plate bending using continuous implant sensor data","authors":"Dominic Mischler , Manuela Ernst , 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}
Pub Date : 2025-08-26DOI: 10.1016/j.jot.2025.08.009
Tongmeng Jiang , Shibo Su , Ruijiao Tian , Yang Jiao , Shudan Zheng , Tianyi Liu , Yang Yu , Pengbing Hua , Xiuhong Cao , Yanlong Xing , Panli Ni , Rui Wang , Fabiao Yu , Juan Wang
Osteoarthritis (OA) is characterized by the inability of stable and complex joint structures to function as they did, accompanied by inflammation, tissue changes, chronic pain, and neuropathic inflammation. In the past, the primary focus on the causes of joint dysfunction has been on mechanical stress leading to cartilage wear. Further researches emphasize the aging of cartilage and subchondral bone triggered cartilage lesion and osteophyte formation. Recently, the effects of immune cells, particularly macrophages and T cells, have been receiving focused attention. Herein, we primarily discuss the role of macrophages and T cells in the progression of OA and how mild inflammation in cartilage, subchondral bone, synovium, muscles, and nerves influences the progression of OA. Additionally, this review highlights the interaction between mesenchymal stromal cells (MSCs) and macrophages, as well as MSCs and T cells, along with how these interactions affect OA development and treatment. Finally, we explore future research directions and issues that still need to be addressed, providing more insights for the clinical translation of MSC-based therapy for OA.
The translational potential of this article
This review highlights the promising translational potential of MSCs in OA therapy by targeting immunoregulatory networks. MSCs directly modulating macrophage M1/M2 polarization, Th1/Th2 and Th/Treg balance of T cells to suppress inflammation, thereby promoting cartilage repair and subchondral bone remodeling. Their ability to synergize with biomaterials or drug carriers enhances therapeutic precision and efficacy. However, challenges like MSCs survival in inflammatory microenvironments, heterogeneity in immune cell responses, and personalized treatment strategies require further optimization. Advances in genetical engineered strategies, extracellular vesicles, scaffolds/hydrogels or nanoparticle-based approaches may bridge these gaps, offering scalable solutions for clinical translation. This work underscores MSC-based therapies as a transformative approach for OA, pending refinement of delivery systems and patient stratification.
{"title":"Immunoregulatory orchestrations in osteoarthritis and mesenchymal stromal cells for therapy","authors":"Tongmeng Jiang , Shibo Su , Ruijiao Tian , Yang Jiao , Shudan Zheng , Tianyi Liu , Yang Yu , Pengbing Hua , Xiuhong Cao , Yanlong Xing , Panli Ni , Rui Wang , Fabiao Yu , Juan Wang","doi":"10.1016/j.jot.2025.08.009","DOIUrl":"10.1016/j.jot.2025.08.009","url":null,"abstract":"<div><div>Osteoarthritis (OA) is characterized by the inability of stable and complex joint structures to function as they did, accompanied by inflammation, tissue changes, chronic pain, and neuropathic inflammation. In the past, the primary focus on the causes of joint dysfunction has been on mechanical stress leading to cartilage wear. Further researches emphasize the aging of cartilage and subchondral bone triggered cartilage lesion and osteophyte formation. Recently, the effects of immune cells, particularly macrophages and T cells, have been receiving focused attention. Herein, we primarily discuss the role of macrophages and T cells in the progression of OA and how mild inflammation in cartilage, subchondral bone, synovium, muscles, and nerves influences the progression of OA. Additionally, this review highlights the interaction between mesenchymal stromal cells (MSCs) and macrophages, as well as MSCs and T cells, along with how these interactions affect OA development and treatment. Finally, we explore future research directions and issues that still need to be addressed, providing more insights for the clinical translation of MSC-based therapy for OA.</div></div><div><h3>The translational potential of this article</h3><div>This review highlights the promising translational potential of MSCs in OA therapy by targeting immunoregulatory networks. MSCs directly modulating macrophage M1/M2 polarization, Th1/Th2 and Th/Treg balance of T cells to suppress inflammation, thereby promoting cartilage repair and subchondral bone remodeling. Their ability to synergize with biomaterials or drug carriers enhances therapeutic precision and efficacy. However, challenges like MSCs survival in inflammatory microenvironments, heterogeneity in immune cell responses, and personalized treatment strategies require further optimization. Advances in genetical engineered strategies, extracellular vesicles, scaffolds/hydrogels or nanoparticle-based approaches may bridge these gaps, offering scalable solutions for clinical translation. This work underscores MSC-based therapies as a transformative approach for OA, pending refinement of delivery systems and patient stratification.</div></div>","PeriodicalId":16636,"journal":{"name":"Journal of Orthopaedic Translation","volume":"55 ","pages":"Pages 38-54"},"PeriodicalIF":5.9,"publicationDate":"2025-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144904569","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}
Pub Date : 2025-08-26DOI: 10.1016/j.jot.2025.08.002
Guanzhi Li , Tong Li , Ye Deng , Xiao Deng , Chao Chen , Bin Yu , Kairui Zhang
Background
Heterotopic ossification (HO) is a common degenerative disease following trauma. Tendon HO is primarily attributed to osteogenic differentiation of stem/progenitor cells within the tendon. However, the precise mechanism underlying this process remains unclear. Recent studies suggest that PTEN induced kinase 1 (PINK1)/Parkin-mediated mitophagy plays a crucial role in biomineralization. Adenine nucleotide translocase 1 (ANT1), an upstream regulator of the PINK1/Parkin pathway, may influence tendon ossification development by modulating mitophagy.
Methods
This study investigated the role of mitophagy in tendon osteogenesis in clinical specimens, mouse tissues, and cells. The impact of ANT1 on tendon osteogenesis through mitophagy regulation was assessed by knocking down solute carrier family 25 member 4 (Slc25a4) both in vitro and in vivo. Furthermore, elamipretide was identified as a potential targeted drug for ANT1 through computer virtual screening and experimental verification. Its therapeutic efficacy on tendon ossification was validated using mouse cells, tissues, and human cells.
Results
This study found that PINK1/Parkin-mediated mitophagy was activated during tendon ossification, and the regulation of mitophagy could impact the osteogenesis of injured tendon-derived progenitor cells (inTPCs). Loss of Slc25a4 inhibited tendon ossification by downregulating the excessive mitophagy. Elamipretide, a targeted drug for ANT1, showed significant efficacy in treating HO.
Conclusion
Modulating PINK1/Parkin-mediated mitophagy by targeting ANT1 mitigated the progression of trauma-induced tendon HO, indicating ANT1 can be a potential therapeutic target for HO, with elamipretide emerging as a promising drug for its treatment.
The translational potential of this article
This study identifies ANT1 as a therapeutic target and supports elamipretide as a promising treatment strategy for HO.
{"title":"Targeting ANT1 to regulate PINK1/Parkin-mediated mitophagy is an effective treatment of trauma-induced tendon heterotopic ossification","authors":"Guanzhi Li , Tong Li , Ye Deng , Xiao Deng , Chao Chen , Bin Yu , Kairui Zhang","doi":"10.1016/j.jot.2025.08.002","DOIUrl":"10.1016/j.jot.2025.08.002","url":null,"abstract":"<div><h3>Background</h3><div>Heterotopic ossification (HO) is a common degenerative disease following trauma. Tendon HO is primarily attributed to osteogenic differentiation of stem/progenitor cells within the tendon. However, the precise mechanism underlying this process remains unclear. Recent studies suggest that PTEN induced kinase 1 (PINK1)/Parkin-mediated mitophagy plays a crucial role in biomineralization. Adenine nucleotide translocase 1 (ANT1), an upstream regulator of the PINK1/Parkin pathway, may influence tendon ossification development by modulating mitophagy.</div></div><div><h3>Methods</h3><div>This study investigated the role of mitophagy in tendon osteogenesis in clinical specimens, mouse tissues, and cells. The impact of ANT1 on tendon osteogenesis through mitophagy regulation was assessed by knocking down solute carrier family 25 member 4 (<em>Slc25a4)</em> both <em>in vitro</em> and <em>in vivo</em>. Furthermore, elamipretide was identified as a potential targeted drug for ANT1 through computer virtual screening and experimental verification. Its therapeutic efficacy on tendon ossification was validated using mouse cells, tissues, and human cells.</div></div><div><h3>Results</h3><div>This study found that PINK1/Parkin-mediated mitophagy was activated during tendon ossification, and the regulation of mitophagy could impact the osteogenesis of injured tendon-derived progenitor cells (inTPCs). Loss of <em>Slc25a4</em> inhibited tendon ossification by downregulating the excessive mitophagy. Elamipretide, a targeted drug for ANT1, showed significant efficacy in treating HO.</div></div><div><h3>Conclusion</h3><div>Modulating PINK1/Parkin-mediated mitophagy by targeting ANT1 mitigated the progression of trauma-induced tendon HO, indicating ANT1 can be a potential therapeutic target for HO, with elamipretide emerging as a promising drug for its treatment.</div></div><div><h3>The translational potential of this article</h3><div>This study identifies ANT1 as a therapeutic target and supports elamipretide as a promising treatment strategy for HO.</div></div>","PeriodicalId":16636,"journal":{"name":"Journal of Orthopaedic Translation","volume":"55 ","pages":"Pages 1-21"},"PeriodicalIF":5.9,"publicationDate":"2025-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144894810","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}
Pub Date : 2025-08-26DOI: 10.1016/j.jot.2025.08.006
Zhen Peng , Xinting Feng , Jiale Tan , Chunfeng Song , Laimeng Song , Yuting Wu , Lingyi Yuan , Jiwu Chen
Artificial ligaments, as an important implant for Anterior Cruciate Ligament reconstruction (ACLR), offer notable advantages in early return to sport. However, most artificial ligaments currently used in clinical ACLR are made of polyethylene terephthalate (PET), a polymer characterized by a smooth and hydrophobic surface that limits cell adhesion and tissue growth, leading to the formation of fibrous scar tissue at the tendon-bone interface. To address these limitations, various surface coating strategies have been developed, including biocompatible, tissue inductive, osteoconductive, drug delivery, and immunomodulatory coatings. These approaches improve biological performance, promote ligamentization, and enhance integration with host tissues. Additionally, the application of composite functional coatings and smart responsive coatings offers new directions for future research. Despite promising preclinical results, most studies remain at the animal experiment stage, and the underlying mechanisms need further investigation. This review summarizes recent advances in coating strategies for artificial ligaments, highlighting their functional classification, technical development, and potential for clinical translation.
Translational potential statement
To address key challenges in the application of artificial ligaments, such as limited biocompatibility and poor tissue integration, it is essential to understand the current research progress. This review provides a comprehensive overview of the coatings used for ligaments, highlighting the promising role of surface modification in enhancing implant performance. It offers valuable insights for improving the clinical success rate of artificial ligaments and their long term effectiveness in ACLR, thus holding significant clinical translational potential.
{"title":"Artificial ligaments in anterior cruciate ligament reconstruction: Coating strategies for PET-based materials","authors":"Zhen Peng , Xinting Feng , Jiale Tan , Chunfeng Song , Laimeng Song , Yuting Wu , Lingyi Yuan , Jiwu Chen","doi":"10.1016/j.jot.2025.08.006","DOIUrl":"10.1016/j.jot.2025.08.006","url":null,"abstract":"<div><div>Artificial ligaments, as an important implant for Anterior Cruciate Ligament reconstruction (ACLR), offer notable advantages in early return to sport. However, most artificial ligaments currently used in clinical ACLR are made of polyethylene terephthalate (PET), a polymer characterized by a smooth and hydrophobic surface that limits cell adhesion and tissue growth, leading to the formation of fibrous scar tissue at the tendon-bone interface. To address these limitations, various surface coating strategies have been developed, including biocompatible, tissue inductive, osteoconductive, drug delivery, and immunomodulatory coatings. These approaches improve biological performance, promote ligamentization, and enhance integration with host tissues. Additionally, the application of composite functional coatings and smart responsive coatings offers new directions for future research. Despite promising preclinical results, most studies remain at the animal experiment stage, and the underlying mechanisms need further investigation. This review summarizes recent advances in coating strategies for artificial ligaments, highlighting their functional classification, technical development, and potential for clinical translation.</div></div><div><h3>Translational potential statement</h3><div>To address key challenges in the application of artificial ligaments, such as limited biocompatibility and poor tissue integration, it is essential to understand the current research progress. This review provides a comprehensive overview of the coatings used for ligaments, highlighting the promising role of surface modification in enhancing implant performance. It offers valuable insights for improving the clinical success rate of artificial ligaments and their long term effectiveness in ACLR, thus holding significant clinical translational potential.</div></div>","PeriodicalId":16636,"journal":{"name":"Journal of Orthopaedic Translation","volume":"55 ","pages":"Pages 22-37"},"PeriodicalIF":5.9,"publicationDate":"2025-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144895863","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}
Pub Date : 2025-08-19DOI: 10.1016/j.jot.2025.03.017
Chuanlong Wu , Hongyi Wang , Teng Yu , Qiyuan Bao , Junxiang Wen , Jiong Zhang , Zhihong Liu , Jianmin Feng , Weibin Zhang , Chuan He
<div><h3>Background</h3><div>Chronic expanding hematoma (CEH) is an infrequent yet serious complication following total hip arthroplasty (THA). Mismanagement of this condition can result in severe consequences. The purpose of this study is to conduct a retrospective analysis of patients who developed CEH after THA at our institution over the past 20 years, complemented by a review of the existing literature. This comprehensive approach aims to contribute valuable clinical insights into the diagnosis and management of CEH.</div></div><div><h3>Methods</h3><div>In this study, we conducted a retrospective study of patients who had undergone THA within the past two decades and subsequently developed CEH during their follow-up period at our institution. The data collected encompassed fundamental patient demographics, including age, gender, and specifics regarding the primary THA implants. Additionally, we gathered preoperative, postoperative, and follow-up imaging studies. Following the data compilation, a thorough literature review was performed to aggregate and analyze the published cases of CEH occurring post-THA.</div></div><div><h3>Results</h3><div>Our follow-up data identified five patients who developed CEH more than ten years after undergoing THA. In one case, CEH manifested subsequent to a traumatic event, while the remaining four cases were non-traumatic. The outcomes following revision surgery were heterogeneous: two patients showed no indications of recurrence throughout a least follow-up period of over one year, one patient eventually underwent amputation, and two patients developed periprosthetic joint infection (PJI), an ongoing management challenge. Our literature review revealed nine previously reported cases with similar clinical features. A summary is as follows: <strong>Etiology</strong>: While often linked to trauma or surgery, a definitive cause is not always present. It is hypothesized that inadequate hemostasis during the initial procedure may contribute to the development of CEH. <strong>Time Course</strong>: The condition typically evolves slowly over an extended period of years. <strong>Mechanism</strong>: The underlying mechanism remains unclear. <strong>Diagnosis</strong>: <strong>MRI</strong>: T2-weighted sequences exhibits a combination of hypointense and hyperintense signals reflecting a blend of fresh and old blood, indicative of recurrent hemorrhage. Isointense or slightly high signals on T1-weighted sequences. <strong>Histological Features</strong>: Characterized by three distinct aspects: a peripheral wall densely encapsulated in fibrous tissue; fresh and mobile blood clots; and a central zone of loose connective tissue formation. <strong>Differential Diagnosis</strong>: Includes inflammatory pseudotumors, hemophilia, and malignant neoplasms, among others. <strong>Treatment</strong>: The gold standard of care involves complete surgical resection, inclusive of the capsule. Given CEH's propensity for progressive bone r
{"title":"Chronic expanding hematomas arising over a decade post primary total hip arthroplasty","authors":"Chuanlong Wu , Hongyi Wang , Teng Yu , Qiyuan Bao , Junxiang Wen , Jiong Zhang , Zhihong Liu , Jianmin Feng , Weibin Zhang , Chuan He","doi":"10.1016/j.jot.2025.03.017","DOIUrl":"10.1016/j.jot.2025.03.017","url":null,"abstract":"<div><h3>Background</h3><div>Chronic expanding hematoma (CEH) is an infrequent yet serious complication following total hip arthroplasty (THA). Mismanagement of this condition can result in severe consequences. The purpose of this study is to conduct a retrospective analysis of patients who developed CEH after THA at our institution over the past 20 years, complemented by a review of the existing literature. This comprehensive approach aims to contribute valuable clinical insights into the diagnosis and management of CEH.</div></div><div><h3>Methods</h3><div>In this study, we conducted a retrospective study of patients who had undergone THA within the past two decades and subsequently developed CEH during their follow-up period at our institution. The data collected encompassed fundamental patient demographics, including age, gender, and specifics regarding the primary THA implants. Additionally, we gathered preoperative, postoperative, and follow-up imaging studies. Following the data compilation, a thorough literature review was performed to aggregate and analyze the published cases of CEH occurring post-THA.</div></div><div><h3>Results</h3><div>Our follow-up data identified five patients who developed CEH more than ten years after undergoing THA. In one case, CEH manifested subsequent to a traumatic event, while the remaining four cases were non-traumatic. The outcomes following revision surgery were heterogeneous: two patients showed no indications of recurrence throughout a least follow-up period of over one year, one patient eventually underwent amputation, and two patients developed periprosthetic joint infection (PJI), an ongoing management challenge. Our literature review revealed nine previously reported cases with similar clinical features. A summary is as follows: <strong>Etiology</strong>: While often linked to trauma or surgery, a definitive cause is not always present. It is hypothesized that inadequate hemostasis during the initial procedure may contribute to the development of CEH. <strong>Time Course</strong>: The condition typically evolves slowly over an extended period of years. <strong>Mechanism</strong>: The underlying mechanism remains unclear. <strong>Diagnosis</strong>: <strong>MRI</strong>: T2-weighted sequences exhibits a combination of hypointense and hyperintense signals reflecting a blend of fresh and old blood, indicative of recurrent hemorrhage. Isointense or slightly high signals on T1-weighted sequences. <strong>Histological Features</strong>: Characterized by three distinct aspects: a peripheral wall densely encapsulated in fibrous tissue; fresh and mobile blood clots; and a central zone of loose connective tissue formation. <strong>Differential Diagnosis</strong>: Includes inflammatory pseudotumors, hemophilia, and malignant neoplasms, among others. <strong>Treatment</strong>: The gold standard of care involves complete surgical resection, inclusive of the capsule. Given CEH's propensity for progressive bone r","PeriodicalId":16636,"journal":{"name":"Journal of Orthopaedic Translation","volume":"54 ","pages":"Pages 199-213"},"PeriodicalIF":5.9,"publicationDate":"2025-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144863798","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}
Pub Date : 2025-08-14DOI: 10.1016/j.jot.2025.07.010
Xu Lou , Qirong Zhou , Zhenglin Dong , Long Bai , Jiacan Su , Hua Yue
Bone organoids, as three-dimensional (3D) biomimetic constructs, have emerged as a promising platform for studying bone development, disease modeling, drug screening, and regenerative medicine. This review comprehensively explores innovative strategies driving bone organoid advancements, emphasizing the integration of cutting-edge technologies such as bioprinting, artificial intelligence, assembloids, and gene editing. While 3D bioprinting enhances spatial precision and structural complexity, artificial intelligence accelerates organoid optimization through data-driven approaches. Assembloids enable the assembly of multicellular systems to better replicate bone tissue microenvironments, whereas gene editing refines disease modeling and functional modifications. Despite these advancements, challenges remain, including the lack of vascularization, insufficient mechanical stimulation, and standardization issues across different models. Also, the clinical translation of bone organoids necessitates the establishment of rigorous evaluation frameworks, ethical guidelines, and regulatory policies to ensure their reproducibility and safety. Looking ahead, interdisciplinary convergence will be critical for constructing physiologically relevant “ex vivo skeletal systems”, advancing bone biology, precision medicine, and biomaterial testing. This review highlights the transformative potential of bone organoid technology and its future applications in personalized orthopedics and bone disease intervention.
The Translational Potential of this Article
This review provides a comprehensive overview of cutting-edge strategies for constructing bone organoids, emphasizing their integration with advanced technologies such as bioprinting, artificial intelligence, assembloids, and gene editing. By systematically discussing their applications in bone development, disease modeling, drug screening, and regenerative medicine, this article bridges the gap between experimental models and clinical translation. The insights into vascularization, skeletal patterning, and high-throughput screening platforms offer a foundation for developing physiologically relevant bone organoids with enhanced fidelity and functionality. These advancements hold significant potential for accelerating personalized medicine, facilitating preclinical evaluation of therapeutics, and ultimately improving treatment outcomes for skeletal diseases.
{"title":"Innovative strategies for bone organoid: Synergistic application and exploration of advanced technologies","authors":"Xu Lou , Qirong Zhou , Zhenglin Dong , Long Bai , Jiacan Su , Hua Yue","doi":"10.1016/j.jot.2025.07.010","DOIUrl":"10.1016/j.jot.2025.07.010","url":null,"abstract":"<div><div>Bone organoids, as three-dimensional (3D) biomimetic constructs, have emerged as a promising platform for studying bone development, disease modeling, drug screening, and regenerative medicine. This review comprehensively explores innovative strategies driving bone organoid advancements, emphasizing the integration of cutting-edge technologies such as bioprinting, artificial intelligence, assembloids, and gene editing. While 3D bioprinting enhances spatial precision and structural complexity, artificial intelligence accelerates organoid optimization through data-driven approaches. Assembloids enable the assembly of multicellular systems to better replicate bone tissue microenvironments, whereas gene editing refines disease modeling and functional modifications. Despite these advancements, challenges remain, including the lack of vascularization, insufficient mechanical stimulation, and standardization issues across different models. Also, the clinical translation of bone organoids necessitates the establishment of rigorous evaluation frameworks, ethical guidelines, and regulatory policies to ensure their reproducibility and safety. Looking ahead, interdisciplinary convergence will be critical for constructing physiologically relevant “<em>ex vivo</em> skeletal systems”, advancing bone biology, precision medicine, and biomaterial testing. This review highlights the transformative potential of bone organoid technology and its future applications in personalized orthopedics and bone disease intervention.</div></div><div><h3>The Translational Potential of this Article</h3><div>This review provides a comprehensive overview of cutting-edge strategies for constructing bone organoids, emphasizing their integration with advanced technologies such as bioprinting, artificial intelligence, assembloids, and gene editing. By systematically discussing their applications in bone development, disease modeling, drug screening, and regenerative medicine, this article bridges the gap between experimental models and clinical translation. The insights into vascularization, skeletal patterning, and high-throughput screening platforms offer a foundation for developing physiologically relevant bone organoids with enhanced fidelity and functionality. These advancements hold significant potential for accelerating personalized medicine, facilitating preclinical evaluation of therapeutics, and ultimately improving treatment outcomes for skeletal diseases.</div></div>","PeriodicalId":16636,"journal":{"name":"Journal of Orthopaedic Translation","volume":"54 ","pages":"Pages 180-198"},"PeriodicalIF":5.9,"publicationDate":"2025-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144828534","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}
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