Pub Date : 2025-06-28DOI: 10.1016/j.jot.2025.06.010
Xiaobo Xie , Jinwei Zhang , Jianxiong Shu , Zhaoran Wu , Chengqiang Wang , Zhifei Gao , Zhenwen Huang , Lihua Li , Jieli Chen , Yao Lu
Background
Characterized by microcirculatory disorder and oxidative stress microenvironment, the repair of bone defect after hip preservation therapy (such as core decompression) for osteonecrosis of the femoral head (ONFH) remains a clinical challenge. Thus, an ideal bone scaffold for treating ONFH should not only promote bone and vessel formation but also alleviate hypoxia and oxidative stress.
Method
We integrated manganese oxides (MnOx) nanoparticles (NPs) with a 3D-printed poly(lactic-co-glycolic acid) (PLGA) scaffold to achieve this goal. The MnOx NPs were synthesized using an oxidation reaction and the scaffold was 3D-printed using a fused deposition modeling method. The characterization and the enzyme-like activity of the scaffold was investigated. The biocompatibility and biofunctions of the scaffold were evaluated both in vitro and in vivo, including the antioxidant capacity, the effects on promoting bone formation and vascularization, and the therapeutic effect in animal model.
Results
The resultant MnOx-doped PLGA scaffold could catalyze reactive oxygen species into oxygen through its superoxide dismutase (SOD)-like and catalase (CAT)-like activities. In vitro studies revealed that this multienzyme-like activity of the scaffold could be maintained for more than 30 days, thereby improving cell viability under oxidative stress. The underlying mechanism was shown to involve regulation of the antioxidant activity of cells via PI3K/AKT signaling pathway. The scaffold also significantly improved capabilities of osteogenesis and angiogenesis compared to pure PLGA scaffold. In vivo studies further demonstrated that the combination therapy of core decompression and scaffold implantation efficiently reduced osteoblast necrosis and enhanced vascularized bone formation in a clinically relevant ONFH rabbit model.
Conclusion
The 3D-printed MnOx-doped PLGA scaffold not only relieve oxidative stress to protect osteocytes under ONFH microenvironment but also promote vascularized bone formation, showing the potential for treating ONFH.
Translational potential of this article
PLGA has been already applied in clinical bone implants. Mn is an essential trace element for the human body and MnOx NPs offer the advantage of biocompatibility, ease of large-scale preparation, and low cost. Hence, this scaffold has the potential for clinical translation in the treatment of ONFH.
{"title":"Relieving oxidative stress microenvironment and promoting vascularized bone formation to treat femoral head necrosis using 3D-printed scaffold with ultralong-term multienzyme-like activity","authors":"Xiaobo Xie , Jinwei Zhang , Jianxiong Shu , Zhaoran Wu , Chengqiang Wang , Zhifei Gao , Zhenwen Huang , Lihua Li , Jieli Chen , Yao Lu","doi":"10.1016/j.jot.2025.06.010","DOIUrl":"10.1016/j.jot.2025.06.010","url":null,"abstract":"<div><h3>Background</h3><div>Characterized by microcirculatory disorder and oxidative stress microenvironment, the repair of bone defect after hip preservation therapy (such as core decompression) for osteonecrosis of the femoral head (ONFH) remains a clinical challenge. Thus, an ideal bone scaffold for treating ONFH should not only promote bone and vessel formation but also alleviate hypoxia and oxidative stress.</div></div><div><h3>Method</h3><div>We integrated manganese oxides (MnO<sub>x</sub>) nanoparticles (NPs) with a 3D-printed poly(lactic-co-glycolic acid) (PLGA) scaffold to achieve this goal. The MnO<sub>x</sub> NPs were synthesized using an oxidation reaction and the scaffold was 3D-printed using a fused deposition modeling method. The characterization and the enzyme-like activity of the scaffold was investigated. The biocompatibility and biofunctions of the scaffold were evaluated both in vitro and in vivo, including the antioxidant capacity, the effects on promoting bone formation and vascularization, and the therapeutic effect in animal model.</div></div><div><h3>Results</h3><div>The resultant MnO<sub>x</sub>-doped PLGA scaffold could catalyze reactive oxygen species into oxygen through its superoxide dismutase (SOD)-like and catalase (CAT)-like activities. In vitro studies revealed that this multienzyme-like activity of the scaffold could be maintained for more than 30 days, thereby improving cell viability under oxidative stress. The underlying mechanism was shown to involve regulation of the antioxidant activity of cells via PI3K/AKT signaling pathway. The scaffold also significantly improved capabilities of osteogenesis and angiogenesis compared to pure PLGA scaffold. In vivo studies further demonstrated that the combination therapy of core decompression and scaffold implantation efficiently reduced osteoblast necrosis and enhanced vascularized bone formation in a clinically relevant ONFH rabbit model.</div></div><div><h3>Conclusion</h3><div>The 3D-printed MnO<sub>x</sub>-doped PLGA scaffold not only relieve oxidative stress to protect osteocytes under ONFH microenvironment but also promote vascularized bone formation, showing the potential for treating ONFH.</div></div><div><h3>Translational potential of this article</h3><div>PLGA has been already applied in clinical bone implants. Mn is an essential trace element for the human body and MnO<sub>x</sub> NPs offer the advantage of biocompatibility, ease of large-scale preparation, and low cost. Hence, this scaffold has the potential for clinical translation in the treatment of ONFH.</div></div>","PeriodicalId":16636,"journal":{"name":"Journal of Orthopaedic Translation","volume":"53 ","pages":"Pages 206-220"},"PeriodicalIF":5.9,"publicationDate":"2025-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144501148","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 : 2025-06-28DOI: 10.1016/j.jot.2025.06.013
Do Kyung Lee , Hyeon Su Kim , Kyung Rae Ko , Jong Pil Yoon , Jun-Il Yoo
Background
Sarcopenia, characterized by age-related muscle loss, traditionally presents as systemic muscle atrophy. However, knee osteoarthritis (OA) patients often exhibit localized quadriceps muscle atrophy, suggesting a potential pain-related mechanism distinct from classical sarcopenia. This study aimed to investigate the relationship between knee OA pain and selective muscle atrophy, particularly focusing on its role as a potential aggravating factor for sarcopenia.
Methods
Eighty-nine patients scheduled for unilateral primary total knee arthroplasty were analyzed. Preoperative computed tomography was used to compare muscle volume and intramuscular adipose tissue (IMAT) proportion between the more painful limb (Group 1) and the contralateral, less painful limb (Group 2). Analysis included both compartmental evaluation (anterior, medial, and posterior thigh compartments; hip abductors and external rotators) and individual muscle assessment.
Results
Group 1 demonstrated significant volume reduction in the anterior thigh compartment (specifically vastus lateralis, intermedius, and medialis) and gluteus maximus, compared to Group 2 (p < 0.05). IMAT proportion was significantly higher in most muscles of Group 1, except for hip abductors, tensor fascia latae, and gluteus minimus (p < 0.05), suggesting widespread fatty degeneration despite selective volume loss.
Conclusion
Knee osteoarthritis–related pain induces selective atrophy in the anterior thigh compartment and gluteus maximus while promoting diffuse fatty infiltration throughout the lower extremity. These findings suggest that OA-associated pain may exacerbate sarcopenia by driving both region-specific muscle loss and widespread intramuscular adipose degeneration.
The translational potential of this article
These findings underscore the importance of pain control as a primary therapeutic goal in patients with knee osteoarthritis. They also highlight the clinical necessity of targeted strengthening of the quadriceps and gluteus maximus muscles, given the role of knee pain in inducing secondary, selective muscle atrophy. Furthermore, symptoms commonly observed in elderly patients with OA—such as limping, giving way, lower extremity weakness, and patellofemoral knee pain—may not be attributable solely to the aging process. Rather, they may reflect secondary muscular adaptations driven by chronic pain during the progression of osteoarthritis (Figure 1).
{"title":"Why muscle strengthening exercises should target the quadriceps and gluteus maximus in patients with knee osteoarthritis?: Effects of knee pain on muscle volume and fatty degeneration based on AI-assisted cross-sectional analysis","authors":"Do Kyung Lee , Hyeon Su Kim , Kyung Rae Ko , Jong Pil Yoon , Jun-Il Yoo","doi":"10.1016/j.jot.2025.06.013","DOIUrl":"10.1016/j.jot.2025.06.013","url":null,"abstract":"<div><h3>Background</h3><div>Sarcopenia, characterized by age-related muscle loss, traditionally presents as systemic muscle atrophy. However, knee osteoarthritis (OA) patients often exhibit localized quadriceps muscle atrophy, suggesting a potential pain-related mechanism distinct from classical sarcopenia. This study aimed to investigate the relationship between knee OA pain and selective muscle atrophy, particularly focusing on its role as a potential aggravating factor for sarcopenia.</div></div><div><h3>Methods</h3><div>Eighty-nine patients scheduled for unilateral primary total knee arthroplasty were analyzed. Preoperative computed tomography was used to compare muscle volume and intramuscular adipose tissue (IMAT) proportion between the more painful limb (Group 1) and the contralateral, less painful limb (Group 2). Analysis included both compartmental evaluation (anterior, medial, and posterior thigh compartments; hip abductors and external rotators) and individual muscle assessment.</div></div><div><h3>Results</h3><div>Group 1 demonstrated significant volume reduction in the anterior thigh compartment (specifically vastus lateralis, intermedius, and medialis) and gluteus maximus, compared to Group 2 (<em>p</em> < 0.05). IMAT proportion was significantly higher in most muscles of Group 1, except for hip abductors, tensor fascia latae, and gluteus minimus (p < 0.05), suggesting widespread fatty degeneration despite selective volume loss.</div></div><div><h3>Conclusion</h3><div>Knee osteoarthritis–related pain induces selective atrophy in the anterior thigh compartment and gluteus maximus while promoting diffuse fatty infiltration throughout the lower extremity. These findings suggest that OA-associated pain may exacerbate sarcopenia by driving both region-specific muscle loss and widespread intramuscular adipose degeneration.</div></div><div><h3>The translational potential of this article</h3><div>These findings underscore the importance of pain control as a primary therapeutic goal in patients with knee osteoarthritis. They also highlight the clinical necessity of targeted strengthening of the quadriceps and gluteus maximus muscles, given the role of knee pain in inducing secondary, selective muscle atrophy. Furthermore, symptoms commonly observed in elderly patients with OA—such as limping, giving way, lower extremity weakness, and patellofemoral knee pain—may not be attributable solely to the aging process. Rather, they may reflect secondary muscular adaptations driven by chronic pain during the progression of osteoarthritis (Figure 1).</div></div>","PeriodicalId":16636,"journal":{"name":"Journal of Orthopaedic Translation","volume":"53 ","pages":"Pages 221-230"},"PeriodicalIF":5.9,"publicationDate":"2025-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144501146","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}
Scaphoid fractures are prevalent wrist injuries with significant treatment challenges, especially when get complicated by nonunion and avascular necrosis. Various grafting techniques, including non-vascularized bone grafts (NVBGs), vascularized bone grafts (VBGs), and bone biomaterial grafts, are utilized to promote healing, but the comparative efficacy of these methods remains unclear.
Objective
This systematic review and meta-analysis aim to assess the efficacy of different types of bone grafts (NVBGs, VBGs, and bone biomaterials) in the treatment of scaphoid nonunion, focusing on outcomes including union rates, time to healing, and functional recovery scores.
Methods
A systematic search of PubMed, Scopus, Cochrane and Web of Science was conducted to identify eligible studies published between 2000 and 2024. studies were categorized into: (1) comparative studies of NVBG vs. VBG, (2) studies reporting only NVBG outcomes, and (3) studies reporting only VBG outcomes. Bone Biomaterials were assessed separately due to limited data (one study). Meta-analyses were performed on in common reported outcomes for each group including union rates, time to healing, range of motion, grip strength, and Modified Mayo Wrist Scores (MMWS).
Results
A total of 62 studies involving 2332 scaphoid nonunion patients were included. VBGs demonstrated significantly higher union rates and shorter healing times compared to NVBGs. VBG-treated patients also showed better functional outcomes, including greater grip strength and MMWS in comparative studies NVBGs were less effective in evaluated cases and required longer healing times. The use of bone biomaterial grafts, although limited in the current literature, showed promising results comparable to NVBGs, but further studies are needed.
Conclusion
VBGs demonstrated higher union rates and shorter healing times compared to NVBGs, with better functional outcomes in some cases, though evidence certainty is moderate. Bone biomaterials represent a promising alternative to traditional grafts but require more evidence to support their widespread use. Treatment decision-makers should consider clinical context and case-specific conditions. Further research is needed to confirm these trends.
Translational potential: This study helps clinical decision-making by evaluating the efficacies of different bone grafts outcomes in complex scaphoid nonunions, potentially reducing treatment failures. It also underscores the emerging role of bone biomaterial grafts as a less invasive alternative, paving the way for personalized orthopedic strategies needing further evaluations to be used for treating scaphoid nonunions.
舟状骨骨折是一种常见的腕部损伤，具有显著的治疗挑战，特别是当合并骨不连和缺血性坏死时。各种移植技术，包括非血管化骨移植（NVBGs）、血管化骨移植（VBGs）和骨生物材料移植，被用于促进愈合，但这些方法的相对疗效尚不清楚。本系统综述和荟萃分析旨在评估不同类型骨移植物（NVBGs、VBGs和骨生物材料）治疗舟状骨不愈合的疗效，重点关注愈合率、愈合时间和功能恢复评分。方法系统检索PubMed、Scopus、Cochrane和Web of Science，筛选2000 - 2024年间发表的符合条件的研究。研究分为：(1)NVBG与VBG的比较研究，(2)仅报道NVBG结果的研究，以及(3)仅报道VBG结果的研究。由于数据有限（一项研究），骨生物材料被单独评估。对每组常见的报告结果进行荟萃分析，包括愈合率、愈合时间、活动范围、握力和改良梅奥手腕评分（MMWS）。结果共纳入62项研究，涉及舟骨不连患者2332例。与nvbg相比，VBGs具有更高的愈合率和更短的愈合时间。vbg治疗的患者也显示出更好的功能结果，包括在比较研究中更强的握力和MMWS， nvbg在评估病例中效果较差，需要更长的愈合时间。骨生物材料移植物的使用，虽然在目前的文献中有限，但显示出与nvbg相当的有希望的结果，但还需要进一步的研究。结论与nvbg相比，vbbg具有更高的愈合率和更短的愈合时间，在某些情况下具有更好的功能结局，尽管证据确定性中等。骨生物材料是传统移植物的一种很有前途的替代品，但需要更多的证据来支持其广泛应用。治疗决策者应考虑临床背景和病例具体情况。需要进一步的研究来证实这些趋势。转化潜力：本研究通过评估复杂舟状骨不连不同骨移植结果的疗效来帮助临床决策，潜在地减少治疗失败。这也强调了骨生物材料移植物作为一种侵入性较小的替代方法的新兴作用，为个性化矫形策略铺平了道路，需要进一步评估用于治疗舟状骨不连。
{"title":"Comparative efficacy of non-vascularized and vascularized bone grafts, with emerging insights into bone biomaterial grafts, in scaphoid fracture nonunion treatment: A systematic review and meta-analysis","authors":"Reza Karimnazhand , Roshanak Shams , Ali Behmanesh , Masoud Vosough , Azadeh Gharooee Ahangar , Laura Serrano Barrenechea , Omid Mahmoudinasab , Farid Najd Mazhar","doi":"10.1016/j.jot.2025.06.009","DOIUrl":"10.1016/j.jot.2025.06.009","url":null,"abstract":"<div><h3>Background</h3><div>Scaphoid fractures are prevalent wrist injuries with significant treatment challenges, especially when get complicated by nonunion and avascular necrosis. Various grafting techniques, including non-vascularized bone grafts (NVBGs), vascularized bone grafts (VBGs), and bone biomaterial grafts, are utilized to promote healing, but the comparative efficacy of these methods remains unclear.</div></div><div><h3>Objective</h3><div>This systematic review and meta-analysis aim to assess the efficacy of different types of bone grafts (NVBGs, VBGs, and bone biomaterials) in the treatment of scaphoid nonunion, focusing on outcomes including union rates, time to healing, and functional recovery scores.</div></div><div><h3>Methods</h3><div>A systematic search of PubMed, Scopus, Cochrane and Web of Science was conducted to identify eligible studies published between 2000 and 2024. studies were categorized into: (1) comparative studies of NVBG vs. VBG, (2) studies reporting only NVBG outcomes, and (3) studies reporting only VBG outcomes. Bone Biomaterials were assessed separately due to limited data (one study). Meta-analyses were performed on in common reported outcomes for each group including union rates, time to healing, range of motion, grip strength, and Modified Mayo Wrist Scores (MMWS).</div></div><div><h3>Results</h3><div>A total of 62 studies involving 2332 scaphoid nonunion patients were included. VBGs demonstrated significantly higher union rates and shorter healing times compared to NVBGs. VBG-treated patients also showed better functional outcomes, including greater grip strength and MMWS in comparative studies NVBGs were less effective in evaluated cases and required longer healing times. The use of bone biomaterial grafts, although limited in the current literature, showed promising results comparable to NVBGs, but further studies are needed.</div></div><div><h3>Conclusion</h3><div>VBGs demonstrated higher union rates and shorter healing times compared to NVBGs, with better functional outcomes in some cases, though evidence certainty is moderate. Bone biomaterials represent a promising alternative to traditional grafts but require more evidence to support their widespread use. Treatment decision-makers should consider clinical context and case-specific conditions. Further research is needed to confirm these trends.</div><div>Translational potential: This study helps clinical decision-making by evaluating the efficacies of different bone grafts outcomes in complex scaphoid nonunions, potentially reducing treatment failures. It also underscores the emerging role of bone biomaterial grafts as a less invasive alternative, paving the way for personalized orthopedic strategies needing further evaluations to be used for treating scaphoid nonunions.</div></div>","PeriodicalId":16636,"journal":{"name":"Journal of Orthopaedic Translation","volume":"53 ","pages":"Pages 231-245"},"PeriodicalIF":5.9,"publicationDate":"2025-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144501147","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 : 2025-06-27DOI: 10.1016/j.jot.2025.06.008
Shuangshuo Jia , Yue Yang , Jiabao Liu , Ziyuan Wang , Lunhao Bai
Background
Exercise therapy has been recognized as first line therapy of osteoarthritis (OA). The exercise related exosome involved in the interaction between fibroblast-like synoviocytes (FLSs) and chondrocytes could be a novel nanoparticle strategy for treating OA.
Methods
Single-cell transcriptome sequencing was used to investigate the exercise therapy-related gene. Cells were transfected by recombinant adenovirus carrying knockdown or overexpression sequences. Quantitative proteomics of FLS-derived exosomes via data-independent acquisition was used to investigate exosomal cargo.
Results
In this study, PPARγ was upregulated in FLSs under exercise stimulation. Our data revealed that overexpression (OE) PPARγ FLSs derived exosome could ameliorate the OA severity in vivo and activate autophagy, inhibit chondrocyte apoptosis, and reduced cartilage degeneration. But knockdown (KD) PPARγ FLSs derived exosome aggravate the OA. Moreover, we found PPARγ controls the endosomal sorting complex required for the transport (ESCRT)-dependent pathway to activate exosome biogenesis. Annexin A1 (ANXA1) was enriched in OE- PPARγ exosome. As a therapeutic cargo, FLSs exosomal ANXA1 was confirmed be internalization by chondrocyte via exosome labeled experiment and ANXA1 could inhibit the phosphorylation of ERK to activate the autophagy and decrease chondrocyte apoptosis.
Conclusions
PPARγ controls ESCRT-dependent FLSs exosome biogenesis and alleviates chondrocyte osteoarthritis mediated by exosomal cargo ANXA1 protein.
The translational potential of this article
PPARγ/ESCRT – FLSs exosomal ANXA1 – ERK axis provides a deeper theoretical basis for exercise therapy of OA and a new idea for the clinical transformation of nanoparticles into OA therapy.
{"title":"PPARγ controls ESCRT-dependent fibroblast-like synoviocyte exosome biogenesis and alleviates chondrocyte osteoarthritis mediated by exosomal ANXA1","authors":"Shuangshuo Jia , Yue Yang , Jiabao Liu , Ziyuan Wang , Lunhao Bai","doi":"10.1016/j.jot.2025.06.008","DOIUrl":"10.1016/j.jot.2025.06.008","url":null,"abstract":"<div><h3>Background</h3><div>Exercise therapy has been recognized as first line therapy of osteoarthritis (OA). The exercise related exosome involved in the interaction between fibroblast-like synoviocytes (FLSs) and chondrocytes could be a novel nanoparticle strategy for treating OA.</div></div><div><h3>Methods</h3><div>Single-cell transcriptome sequencing was used to investigate the exercise therapy-related gene. Cells were transfected by recombinant adenovirus carrying knockdown or overexpression sequences. Quantitative proteomics of FLS-derived exosomes via data-independent acquisition was used to investigate exosomal cargo.</div></div><div><h3>Results</h3><div>In this study, PPARγ was upregulated in FLSs under exercise stimulation. Our data revealed that overexpression (OE) PPARγ FLSs derived exosome could ameliorate the OA severity <em>in vivo</em> and activate autophagy, inhibit chondrocyte apoptosis, and reduced cartilage degeneration. But knockdown (KD) PPARγ FLSs derived exosome aggravate the OA. Moreover, we found PPARγ controls the endosomal sorting complex required for the transport (ESCRT)-dependent pathway to activate exosome biogenesis. Annexin A1 (ANXA1) was enriched in OE- PPARγ exosome. As a therapeutic cargo, FLSs exosomal ANXA1 was confirmed be internalization by chondrocyte via exosome labeled experiment and ANXA1 could inhibit the phosphorylation of ERK to activate the autophagy and decrease chondrocyte apoptosis.</div></div><div><h3>Conclusions</h3><div>PPARγ controls ESCRT-dependent FLSs exosome biogenesis and alleviates chondrocyte osteoarthritis mediated by exosomal cargo ANXA1 protein.</div></div><div><h3>The translational potential of this article</h3><div>PPARγ/ESCRT – FLSs exosomal ANXA1 – ERK axis provides a deeper theoretical basis for exercise therapy of OA and a new idea for the clinical transformation of nanoparticles into OA therapy.</div></div>","PeriodicalId":16636,"journal":{"name":"Journal of Orthopaedic Translation","volume":"53 ","pages":"Pages 187-205"},"PeriodicalIF":5.9,"publicationDate":"2025-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144489829","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 : 2025-06-25DOI: 10.1016/j.jot.2025.06.012
Tianyu Dai , Yinxian Wen , Qingxian Li , Hui Wang , Hebin Liao , Yingying Pu , Liaobin Chen
Background
Diabetes mellitus (DM) is a high-risk factor for periprosthetic joint infection (PJI). However, the mechanism how hyperglycemia induces or promotes PJI remains unclear. This study aimed to determine how host hyperglycemia stimulates pathogenic bacteria and thus induces PJI.
Methods
The rats were divided into 4 groups: control total knee arthroplasty (TKA) group, control PJI group, DM + TKA group, and DM + PJI group namely treating with high-sugar and high-fat diet + streptozotocin (STZ), and artificially induced PJI. After 3 weeks, bone and joint local inflammatory response, micro-CT, bacterial load, and biofilm formation were analyzed. The effects of advanced glycosylation end products (AGEs) and STF-31 on the biofilm formation of Staphylococcus aureus (S. aureus) were detected by crystal violet and confocal microscopy in vitro. In addition, the mechanism of AGEs promoting biofilm formation was explored by combined proteomics and transcriptomics analysis, and the effect of AGEs on RNAIII was further detected by constructing mutants.
Results
In both humans and rats, we found more severe infectious responses in the knee joint specimens of patients and rats with DM + PJI when compared with those without PJI. Moreover, DM + PJI specimens showed higher levels of synovial AGEs and expression of glucose transporter 1 (GLUT1). AGEs exacerbated the localized infectious response of joints in vivo and promoted biofilm formation in vitro, whereas GLUT1 receptor inhibitors attenuated these effects. Finally, RNA-seq and proteomics revealed that RNAIII may be the target of AGEs acting on S. aureus. AGEs directly promoted biofilm formation by enhancing δ-hemolysin translated by RNAIII. In contrast, inhibition of RNAIII effectively attenuated AGEs-induced biofilm formation.
Conclusions
In summary, high glucose upregulates S. aureus RNAIII expression by activating the synovial GLUT1-AGEs pathway, thereby promoting S. aureus colonization and biofilm formation on the surface of articular prostheses, contributing to the onset and progression of PJI.
The translational potential of this article
Our study shows the great potential of STF-31 as a specific treatment for DM + PJI, and is expected to become a new treatment method combined with antibiotics. RNAIII may be the target of AGEs-induced Staphylococcus aureus biofilm, which provides theoretical support and experimental basis for analyzing the effect of DM on PJI.
{"title":"Synovial advanced glycosylation end products aggravate periprosthetic infection in diabetes by upregulating Staphylococcus aureus RNAIII","authors":"Tianyu Dai , Yinxian Wen , Qingxian Li , Hui Wang , Hebin Liao , Yingying Pu , Liaobin Chen","doi":"10.1016/j.jot.2025.06.012","DOIUrl":"10.1016/j.jot.2025.06.012","url":null,"abstract":"<div><h3>Background</h3><div>Diabetes mellitus (DM) is a high-risk factor for periprosthetic joint infection (PJI). However, the mechanism how hyperglycemia induces or promotes PJI remains unclear. This study aimed to determine how host hyperglycemia stimulates pathogenic bacteria and thus induces PJI.</div></div><div><h3>Methods</h3><div>The rats were divided into 4 groups: control total knee arthroplasty (TKA) group, control PJI group, DM + TKA group, and DM + PJI group namely treating with high-sugar and high-fat diet + streptozotocin (STZ), and artificially induced PJI. After 3 weeks, bone and joint local inflammatory response, micro-CT, bacterial load, and biofilm formation were analyzed. The effects of advanced glycosylation end products (AGEs) and STF-31 on the biofilm formation of <em>Staphylococcus aureus (S. aureus)</em> were detected by crystal violet and confocal microscopy <em>in vitro</em>. In addition, the mechanism of AGEs promoting biofilm formation was explored by combined proteomics and transcriptomics analysis, and the effect of AGEs on RNAIII was further detected by constructing mutants.</div></div><div><h3>Results</h3><div>In both humans and rats, we found more severe infectious responses in the knee joint specimens of patients and rats with DM + PJI when compared with those without PJI. Moreover, DM + PJI specimens showed higher levels of synovial AGEs and expression of glucose transporter 1 (GLUT1). AGEs exacerbated the localized infectious response of joints <em>in vivo</em> and promoted biofilm formation <em>in vitro</em>, whereas GLUT1 receptor inhibitors attenuated these effects. Finally, RNA-seq and proteomics revealed that RNAIII may be the target of AGEs acting on <em>S. aureus</em>. AGEs directly promoted biofilm formation by enhancing δ-hemolysin translated by RNAIII. In contrast, inhibition of RNAIII effectively attenuated AGEs-induced biofilm formation.</div></div><div><h3>Conclusions</h3><div>In summary, high glucose upregulates <em>S. aureus</em> RNAIII expression by activating the synovial GLUT1-AGEs pathway, thereby promoting <em>S. aureus</em> colonization and biofilm formation on the surface of articular prostheses, contributing to the onset and progression of PJI.</div></div><div><h3>The translational potential of this article</h3><div>Our study shows the great potential of STF-31 as a specific treatment for DM + PJI, and is expected to become a new treatment method combined with antibiotics. RNAIII may be the target of AGEs-induced <em>Staphylococcus aureus</em> biofilm, which provides theoretical support and experimental basis for analyzing the effect of DM on PJI.</div></div>","PeriodicalId":16636,"journal":{"name":"Journal of Orthopaedic Translation","volume":"53 ","pages":"Pages 161-174"},"PeriodicalIF":5.9,"publicationDate":"2025-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144471234","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 : 2025-06-25DOI: 10.1016/j.jot.2025.06.004
Mao-dan Nie , Bing-kun Bao , Ning-ze Zhang , Rong-shan Cheng , Ling-jie Fu , Cheng-Kung Cheng
<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
{"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}
Pub Date : 2025-06-23DOI: 10.1016/j.jot.2025.05.011
Zheyu Jin , Jiechen Chen , Zhengming Shan , Weiyang Liu , Zhenkang Wen , Hongwei Shao , Tongzhou Liang , Ziyi Chen , Xuesong Ren , Dianhui Tan , Ling Qin , Jun Hu , Jiankun Xu
Background
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.
Methods
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).
Results
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 < 0.001) and acceleration in time to initial callus formation (22.92 ± 11.98 days vs 90.18 ± 34.52 days, P < 0.001). Brain contusions (OR 5.914, 95 % CI:2.479–14.108,P < 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.
Conclusions
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.
The translational potential of this article
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
{"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 , Jiechen Chen , Zhengming Shan , Weiyang Liu , Zhenkang Wen , Hongwei Shao , Tongzhou Liang , Ziyi Chen , Xuesong Ren , Dianhui Tan , Ling Qin , Jun Hu , 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 < 0.001) and acceleration in time to initial callus formation (22.92 ± 11.98 days vs 90.18 ± 34.52 days, P < 0.001). Brain contusions (OR 5.914, 95 % CI:2.479–14.108,P < 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}
Pub Date : 2025-06-21DOI: 10.1016/j.jot.2025.06.006
Yuwang Du
{"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}
Pub Date : 2025-06-20DOI: 10.1016/j.jot.2025.06.002
Rui Song , Xiaojing Yuan , Zhuo Wan , Linxue Zhang , Feng Rao , Yuming Zhao , Zuoying Yuan
<div><h3>Background/objective</h3><div>Bone defects, especially those associated with diabetes, pose a significant challenge due to impaired healing capabilities. <em>In situ</em> 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.</div></div><div><h3>Methods</h3><div>We systematically investigated the <em>in vitro</em> 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 <em>in vitro</em>. The <em>in vivo</em> efficacy of OSM/MS was assessed in an inflammatory diabetic rat calvarial defect model.</div></div><div><h3>Results</h3><div>50 ng/ml OSM can enhance migration and osteogenic differentiation of BMSCs, and angiogenesis <em>in vitro</em> 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. <em>In vivo</em> studies revealed that OSM/MS reduced osteoclast differentiation and promoted bone regeneration in diabetic rats.</div></div><div><h3>Conclusion</h3><div>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.</div></div><div><h3>The translational potential of this article</h3><div>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
{"title":"Oncostatin-M functionalized cryogel microspheres for promoting diabetic bone defects regeneration","authors":"Rui Song , Xiaojing Yuan , Zhuo Wan , Linxue Zhang , Feng Rao , Yuming Zhao , Zuoying Yuan","doi":"10.1016/j.jot.2025.06.002","DOIUrl":"10.1016/j.jot.2025.06.002","url":null,"abstract":"<div><h3>Background/objective</h3><div>Bone defects, especially those associated with diabetes, pose a significant challenge due to impaired healing capabilities. <em>In situ</em> 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.</div></div><div><h3>Methods</h3><div>We systematically investigated the <em>in vitro</em> 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 <em>in vitro</em>. The <em>in vivo</em> efficacy of OSM/MS was assessed in an inflammatory diabetic rat calvarial defect model.</div></div><div><h3>Results</h3><div>50 ng/ml OSM can enhance migration and osteogenic differentiation of BMSCs, and angiogenesis <em>in vitro</em> 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. <em>In vivo</em> studies revealed that OSM/MS reduced osteoclast differentiation and promoted bone regeneration in diabetic rats.</div></div><div><h3>Conclusion</h3><div>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.</div></div><div><h3>The translational potential of this article</h3><div>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}
Pub Date : 2025-06-19DOI: 10.1016/j.jot.2025.06.007
Hengxiang Shu , Yan Gao , Qin Zhang , Haobo Sun , Huazheng Wang , Chengnan Jing , Peng Liu , Dechun Geng , Hao Shen , Minfeng Gan
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.
The translational potential of this article
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.
{"title":"Electric currents in disc health: The role of ion channels in intervertebral disc pathophysiology","authors":"Hengxiang Shu , Yan Gao , Qin Zhang , Haobo Sun , Huazheng Wang , Chengnan Jing , Peng Liu , Dechun Geng , Hao Shen , 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}
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