Thomas Demirjian, John Crues III, Christopher M. Powers
Individuals who undergo anterior cruciate ligament reconstruction are at elevated risk for developing early-onset patellofemoral joint osteoarthritis. Our objective was to use K-means clustering to ascertain whether individuals at risk for patellofemoral joint osteoarthritis could be identified as determined by the presence of multiple co-existing anatomical and patella alignment risk factors. Forty participants (20 after anterior cruciate ligament reconstruction, 20 healthy controls) underwent magnetic resonance imaging assessment of the patellofemoral joint. Measures of hypothesized risk factors for patellofemoral joint osteoarthritis were obtained including patella alignment (lateral patella displacement and tilt), trochlear morphology (sulcus angle, lateral inclination angle), patella height (Insall-Salvati ratio and patella articulating overlap), and patellofemoral joint contact area. K-means clustering (k = 2) was used to ascertain whether a high-risk group could be identified. Following clustering, two distinct groups were detected. Participants assigned to cluster 1 exhibited features consistent with patellofemoral joint osteoarthritis including greater lateral patellar displacement and tilt, flatter trochlear grooves and lower lateral trochlear inclination, less patella articulating overlap, and reduced contact area. The proportion of females after anterior cruciate ligament reconstruction assigned to cluster 1 was 75% (N = 15) compared to 25% of healthy females (N = 5). K-means clustering was capable of characterizing individuals at elevated risk for patellofemoral joint osteoarthritis based on the presence of multiple co-existing anatomical and patella alignment risk factors. The fact that a significant percentage of females were assigned to the high-risk cluster supports the clinical observation that these individuals may be at higher risk of early-onset patellofemoral joint osteoarthritis.
{"title":"Risk factors for patellofemoral joint osteoarthritis following ACL reconstruction: A cluster analysis of anatomy and alignment","authors":"Thomas Demirjian, John Crues III, Christopher M. Powers","doi":"10.1002/jor.26014","DOIUrl":"10.1002/jor.26014","url":null,"abstract":"<p>Individuals who undergo anterior cruciate ligament reconstruction are at elevated risk for developing early-onset patellofemoral joint osteoarthritis. Our objective was to use K-means clustering to ascertain whether individuals at risk for patellofemoral joint osteoarthritis could be identified as determined by the presence of multiple co-existing anatomical and patella alignment risk factors. Forty participants (20 after anterior cruciate ligament reconstruction, 20 healthy controls) underwent magnetic resonance imaging assessment of the patellofemoral joint. Measures of hypothesized risk factors for patellofemoral joint osteoarthritis were obtained including patella alignment (lateral patella displacement and tilt), trochlear morphology (sulcus angle, lateral inclination angle), patella height (Insall-Salvati ratio and patella articulating overlap), and patellofemoral joint contact area. K-means clustering (<i>k</i> = 2) was used to ascertain whether a high-risk group could be identified. Following clustering, two distinct groups were detected. Participants assigned to cluster 1 exhibited features consistent with patellofemoral joint osteoarthritis including greater lateral patellar displacement and tilt, flatter trochlear grooves and lower lateral trochlear inclination, less patella articulating overlap, and reduced contact area. The proportion of females after anterior cruciate ligament reconstruction assigned to cluster 1 was 75% (<i>N</i> = 15) compared to 25% of healthy females (<i>N</i> = 5). K-means clustering was capable of characterizing individuals at elevated risk for patellofemoral joint osteoarthritis based on the presence of multiple co-existing anatomical and patella alignment risk factors. The fact that a significant percentage of females were assigned to the high-risk cluster supports the clinical observation that these individuals may be at higher risk of early-onset patellofemoral joint osteoarthritis.</p>","PeriodicalId":16650,"journal":{"name":"Journal of Orthopaedic Research®","volume":"43 3","pages":"567-575"},"PeriodicalIF":2.1,"publicationDate":"2024-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142647398","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Augustine Mark Saiz, Maryam Rahmati, Robert Charles Henry Gresham, Tony Daniel Baldini, Jane Burgan, Mark A. Lee, Benjamin Osipov, Blaine A. Christiansen, Thaqif El Khassawna, D. C. Florian Wieland, André Lopes Marinho, Clement Blanchet, Molly Czachor, Zachary M. Working, Chelsea S. Bahney, J. Kent Leach
The field of bone regeneration has primarily focused on investigating fracture healing and nonunion in isolated musculoskeletal injuries. Compared to isolated fractures, which frequently heal well, fractures in patients with multiple bodily injuries (polytrauma) may exhibit impaired healing. While some papers have reported the overall cytokine response to polytrauma conditions, significant gaps in our understanding remain in how fractures heal differently in polytrauma patients. We aimed to characterize fracture healing and the temporal local and systemic immune responses to polytrauma in a murine model of polytrauma composed of a femur fracture combined with isolated chest trauma. We collected serum, bone marrow from the uninjured limb, femur fracture tissue, and lung tissue over 3 weeks to study the local and systemic immune responses and cytokine expression after injury. Immune cell distribution was assessed by flow cytometry. Fracture healing was characterized using microcomputed tomography (microCT), histological staining, immunohistochemistry, mechanical testing, and small angle X-ray scattering. We detected more innate immune cells in the polytrauma group, both locally at the fracture site and systemically, compared to other groups. The percentage of B and T cells was dramatically reduced in the polytrauma group 6 h after injury and remained low throughout the study duration. Fracture healing in the polytrauma group was impaired, evidenced by the formation of a poorly mineralized and dysregulated fracture callus. Our data confirm the early, dysregulated inflammatory state in polytrauma that correlates with disorganized and impaired fracture healing.
骨再生领域主要侧重于研究孤立的肌肉骨骼损伤的骨折愈合和不愈合。与通常愈合良好的孤立性骨折相比,身体多处受伤(多发性创伤)患者的骨折可能会出现愈合障碍。虽然一些论文报道了多发性创伤情况下细胞因子的整体反应,但我们对多发性创伤患者骨折愈合的不同方式的理解仍存在很大差距。我们的目的是在一个由股骨骨折和孤立的胸部创伤组成的多发性创伤小鼠模型中,描述骨折愈合以及对多发性创伤的局部和全身免疫反应的时间特征。我们收集了未受伤肢体的血清、骨髓、股骨骨折组织和肺组织,历时 3 周,以研究受伤后的局部和全身免疫反应及细胞因子表达。流式细胞术评估了免疫细胞的分布。利用微型计算机断层扫描(microCT)、组织学染色、免疫组化、机械测试和小角 X 射线散射对骨折愈合进行了表征。与其他组别相比,我们在多发性创伤组的骨折部位和全身检测到了更多的先天性免疫细胞。多发性创伤组的 B 细胞和 T 细胞比例在受伤 6 小时后急剧下降,并在整个研究期间保持较低水平。多发性创伤组的骨折愈合受损,表现为形成矿化度低、调节失调的骨折胼胝体。我们的数据证实了多发性创伤的早期炎症失调状态与骨折愈合紊乱和受损有关。
{"title":"Polytrauma impairs fracture healing accompanied by increased persistence of innate inflammatory stimuli and reduced adaptive response","authors":"Augustine Mark Saiz, Maryam Rahmati, Robert Charles Henry Gresham, Tony Daniel Baldini, Jane Burgan, Mark A. Lee, Benjamin Osipov, Blaine A. Christiansen, Thaqif El Khassawna, D. C. Florian Wieland, André Lopes Marinho, Clement Blanchet, Molly Czachor, Zachary M. Working, Chelsea S. Bahney, J. Kent Leach","doi":"10.1002/jor.26015","DOIUrl":"10.1002/jor.26015","url":null,"abstract":"<p>The field of bone regeneration has primarily focused on investigating fracture healing and nonunion in isolated musculoskeletal injuries. Compared to isolated fractures, which frequently heal well, fractures in patients with multiple bodily injuries (polytrauma) may exhibit impaired healing. While some papers have reported the overall cytokine response to polytrauma conditions, significant gaps in our understanding remain in how fractures heal differently in polytrauma patients. We aimed to characterize fracture healing and the temporal local and systemic immune responses to polytrauma in a murine model of polytrauma composed of a femur fracture combined with isolated chest trauma. We collected serum, bone marrow from the uninjured limb, femur fracture tissue, and lung tissue over 3 weeks to study the local and systemic immune responses and cytokine expression after injury. Immune cell distribution was assessed by flow cytometry. Fracture healing was characterized using microcomputed tomography (microCT), histological staining, immunohistochemistry, mechanical testing, and small angle X-ray scattering. We detected more innate immune cells in the polytrauma group, both locally at the fracture site and systemically, compared to other groups. The percentage of B and T cells was dramatically reduced in the polytrauma group 6 h after injury and remained low throughout the study duration. Fracture healing in the polytrauma group was impaired, evidenced by the formation of a poorly mineralized and dysregulated fracture callus. Our data confirm the early, dysregulated inflammatory state in polytrauma that correlates with disorganized and impaired fracture healing.</p>","PeriodicalId":16650,"journal":{"name":"Journal of Orthopaedic Research®","volume":"43 3","pages":"603-616"},"PeriodicalIF":2.1,"publicationDate":"2024-11-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jor.26015","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142643785","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Frank C. Ko, Spencer Fullam, Hoomin Lee, Kelly Chan, Shingo Ishihara, Natalie S. Adamczyk, Alia M. Obeidat, Sarah Soorya, Richard J. Miller, Anne-Marie Malfait, Rachel E. Miller
A major barrier that hampers our understanding of the precise anatomic distribution of pain sensing nerves in and around the joint is the limited view obtained from traditional two dimensional (D) histological approaches. Therefore, our objective was to develop a workflow that allows examination of the innervation of the intact mouse knee joint in 3D by employing clearing-enabled light sheet microscopy. We first surveyed existing clearing protocols (SUMIC, PEGASOS, and DISCO) to determine their ability to clear the whole mouse knee joint, and discovered that a DISCO protocol provided the optimal transparency for light sheet microscopy imaging. We then modified the DISCO protocol to enhance binding and penetration of antibodies used for labeling nerves. Using the pan-neuronal PGP9.5 antibody, our protocol allowed 3D visualization of innervation in and around the mouse knee joint. We then implemented the workflow in mice intra-articularly injected with nerve growth factor (NGF) to determine whether changes in the nerve density can be observed. Both 3D and 2D analytical approaches of the light sheet microscopy images demonstrated quantifiable changes in midjoint nerve density following 4 weeks of NGF injection in the medial but not in the lateral joint compartment. We provide, for the first time, a comprehensive workflow that allows detailed and quantifiable examination of mouse knee joint innervation in 3D.
传统的二维(D)组织学方法视野有限,是阻碍我们了解痛觉神经在关节内外精确解剖分布的主要障碍。因此,我们的目标是开发一种工作流程,通过使用支持透明的光片显微镜来检查完整小鼠膝关节的三维神经支配。我们首先调查了现有的清除方案(SUMIC、PEGASOS 和 DISCO),以确定它们清除整个小鼠膝关节的能力,结果发现 DISCO 方案为光片显微成像提供了最佳透明度。我们随后修改了 DISCO 方案,以增强用于标记神经的抗体的结合力和穿透力。通过使用泛神经元 PGP9.5 抗体,我们的方案实现了小鼠膝关节及其周围神经支配的三维可视化。然后,我们在关节内注射神经生长因子(NGF)的小鼠身上实施了这一工作流程,以确定能否观察到神经密度的变化。光片显微镜图像的三维和二维分析方法都表明,注射 NGF 4 周后,关节内侧而非外侧的中关节神经密度发生了可量化的变化。我们首次提供了一个全面的工作流程,可对小鼠膝关节神经支配进行详细的三维量化检查。
{"title":"Clearing-enabled light sheet microscopy as a novel method for three-dimensional mapping of the sensory innervation of the mouse knee","authors":"Frank C. Ko, Spencer Fullam, Hoomin Lee, Kelly Chan, Shingo Ishihara, Natalie S. Adamczyk, Alia M. Obeidat, Sarah Soorya, Richard J. Miller, Anne-Marie Malfait, Rachel E. Miller","doi":"10.1002/jor.26016","DOIUrl":"10.1002/jor.26016","url":null,"abstract":"<p>A major barrier that hampers our understanding of the precise anatomic distribution of pain sensing nerves in and around the joint is the limited view obtained from traditional two dimensional (D) histological approaches. Therefore, our objective was to develop a workflow that allows examination of the innervation of the intact mouse knee joint in 3D by employing clearing-enabled light sheet microscopy. We first surveyed existing clearing protocols (SUMIC, PEGASOS, and DISCO) to determine their ability to clear the whole mouse knee joint, and discovered that a DISCO protocol provided the optimal transparency for light sheet microscopy imaging. We then modified the DISCO protocol to enhance binding and penetration of antibodies used for labeling nerves. Using the pan-neuronal PGP9.5 antibody, our protocol allowed 3D visualization of innervation in and around the mouse knee joint. We then implemented the workflow in mice intra-articularly injected with nerve growth factor (NGF) to determine whether changes in the nerve density can be observed. Both 3D and 2D analytical approaches of the light sheet microscopy images demonstrated quantifiable changes in midjoint nerve density following 4 weeks of NGF injection in the medial but not in the lateral joint compartment. We provide, for the first time, a comprehensive workflow that allows detailed and quantifiable examination of mouse knee joint innervation in 3D.</p>","PeriodicalId":16650,"journal":{"name":"Journal of Orthopaedic Research®","volume":"43 3","pages":"632-639"},"PeriodicalIF":2.1,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142639213","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Rebecca A. Hext, Bart L. Kaptein, James L. Howard, Brent A. Lanting, Matthew G. Teeter
Aseptic loosening remains one of the top causes of revision surgery of total knee arthroplasty (TKA). Radiostereometric analysis (RSA) is used in research to measure implant migration, however limitations prevent its clinical use. New methods have allowed the same measurements as RSA to be performed with computed tomography (CT) scanners (CT-RSA). The objective of this study is to determine inducible displacement measurements from weight-bearing computed tomography (WBCT) and conventional RSA to assess implant stability. Participants (n = 17) completed RSA exams in the supine and standing position, and WBCT exams in the seated (leg extended) and standing position. Double examinations were performed in the seated (WBCT) or supine (RSA) positions. Inducible displacements were measured with model-based RSA (MBRSA) for RSA exams, and a novel CT-RSA software, V3MA, for WBCT exams. Precision of each technique was calculated between double examinations. Precision data for tibial component total translations and rotations were 0.05 mm and 0.118°, respectively with WBCT-RSA, and were 0.108 mm and 0.269°, respectively with MBRSA. MTPM precision was 0.141 mm with WBCT-RSA and was 0.168 mm with MBRSA. Inducible displacement MTPM of the tibial component was 0.244 ± 0.220 mm with WBCT-RSA and 0.662 ± 0.257 mm with MBRSA. Inducible displacement measurements with MBRSA were significantly different from WBCT-RSA for tibial component anterior tilt (p = 0.0002). WBCT-RSA demonstrated comparable precision to MBRSA, and both techniques measured inducible displacements consistent with stable components. Clinical Significance: As the availability of WBCT increases, its use as an alternative to MBRSA is supported to measure the instantaneous fixation of implant components.
{"title":"Inducible displacement of cementless total knee arthroplasty components with conventional and weight-bearing CT-based radiostereometric analysis","authors":"Rebecca A. Hext, Bart L. Kaptein, James L. Howard, Brent A. Lanting, Matthew G. Teeter","doi":"10.1002/jor.26017","DOIUrl":"10.1002/jor.26017","url":null,"abstract":"<p>Aseptic loosening remains one of the top causes of revision surgery of total knee arthroplasty (TKA). Radiostereometric analysis (RSA) is used in research to measure implant migration, however limitations prevent its clinical use. New methods have allowed the same measurements as RSA to be performed with computed tomography (CT) scanners (CT-RSA). The objective of this study is to determine inducible displacement measurements from weight-bearing computed tomography (WBCT) and conventional RSA to assess implant stability. Participants (n = 17) completed RSA exams in the supine and standing position, and WBCT exams in the seated (leg extended) and standing position. Double examinations were performed in the seated (WBCT) or supine (RSA) positions. Inducible displacements were measured with model-based RSA (MBRSA) for RSA exams, and a novel CT-RSA software, V3MA, for WBCT exams. Precision of each technique was calculated between double examinations. Precision data for tibial component total translations and rotations were 0.05 mm and 0.118°, respectively with WBCT-RSA, and were 0.108 mm and 0.269°, respectively with MBRSA. MTPM precision was 0.141 mm with WBCT-RSA and was 0.168 mm with MBRSA. Inducible displacement MTPM of the tibial component was 0.244 ± 0.220 mm with WBCT-RSA and 0.662 ± 0.257 mm with MBRSA. Inducible displacement measurements with MBRSA were significantly different from WBCT-RSA for tibial component anterior tilt (<i>p</i> = 0.0002). WBCT-RSA demonstrated comparable precision to MBRSA, and both techniques measured inducible displacements consistent with stable components. Clinical Significance: As the availability of WBCT increases, its use as an alternative to MBRSA is supported to measure the instantaneous fixation of implant components.</p>","PeriodicalId":16650,"journal":{"name":"Journal of Orthopaedic Research®","volume":"43 3","pages":"640-649"},"PeriodicalIF":2.1,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jor.26017","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142639218","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Issue Information - Editorial Board and TOC","authors":"","doi":"10.1002/jor.25622","DOIUrl":"https://doi.org/10.1002/jor.25622","url":null,"abstract":"","PeriodicalId":16650,"journal":{"name":"Journal of Orthopaedic Research®","volume":"42 12","pages":"2605-2609"},"PeriodicalIF":2.1,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jor.25622","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142664652","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Issue Information - Cover","authors":"","doi":"10.1002/jor.25623","DOIUrl":"https://doi.org/10.1002/jor.25623","url":null,"abstract":"","PeriodicalId":16650,"journal":{"name":"Journal of Orthopaedic Research®","volume":"42 12","pages":""},"PeriodicalIF":2.1,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jor.25623","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142664716","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Diclofenac etalhyaluronate (DF-HA) sustained diclofenac release with the effects of hyaluronic acid (HA), offering long-term analgesia in osteoarthritis. In this study, the effects of DF-HA on pain improvement and osteoarthritis were evaluated in a rat knee monoiodoacetate-induced osteoarthritis model compared to HA. Eight rats per group had been injected with monoiodoacetate (2.0 mg) or saline in the right knee for 4 weeks and were injected with either DF-HA (1.25 mg/kg; 0.5 mg), HA (0.5 mg), vehicle which was a substrate without DF-HA (50 μL), or saline and followed for 4 weeks. Mechanical plantar skin sensitivity was assessed weekly using the von Frey assay. Osteoarthritis changes were monitored with Larsen scores via CT imaging at every 2 weeks. The articular cartilage was analyzed using OARSI scores through H&E, Safranin-O staining at 8 weeks. The percentage of Iba-1 positive microglia in the spinal dorsal horn and of FG + CGRP-labeled cells among FG-positive cells in the dorsal root ganglion were evaluated by immunohistochemical staining. TNF-α and IL-6 mRNA expression levels in the knee synovium were evaluated by PCR. The DF-HA showed significantly improved pain hypersensitivity compared with the HA at 6–8 weeks. The percentage of Iba-1-positive microglia was significantly lower than that in the vehicle and the percentage of FG + CGRP/FG was significantly lower than that in the HA. OARSI scores did not differ among treatment groups, Larsen scores indicated lower in the DF-HA than in the vehicle. DF-HA was as effective as HA in joint protection and significantly improved inflammatory pain compared to HA.
{"title":"Comparison of effects of intra-articular diclofenac etalhyaluronate and hyaluronic acid in a monoiodoacetate rat osteoarthritis model","authors":"Soichiro Tokeshi, Miyako Suzuki-Narita, Ikuko Tajiri, Kazuhide Inage, Jun Takeuchi, Takahito Arai, Yuya Kawarai, Hiroakira Terakawa, Seiji Ohtori, Sumihisa Orita","doi":"10.1002/jor.26012","DOIUrl":"10.1002/jor.26012","url":null,"abstract":"<p>Diclofenac etalhyaluronate (DF-HA) sustained diclofenac release with the effects of hyaluronic acid (HA), offering long-term analgesia in osteoarthritis. In this study, the effects of DF-HA on pain improvement and osteoarthritis were evaluated in a rat knee monoiodoacetate-induced osteoarthritis model compared to HA. Eight rats per group had been injected with monoiodoacetate (2.0 mg) or saline in the right knee for 4 weeks and were injected with either DF-HA (1.25 mg/kg; 0.5 mg), HA (0.5 mg), vehicle which was a substrate without DF-HA (50 μL), or saline and followed for 4 weeks. Mechanical plantar skin sensitivity was assessed weekly using the von Frey assay. Osteoarthritis changes were monitored with Larsen scores via CT imaging at every 2 weeks. The articular cartilage was analyzed using OARSI scores through H&E, Safranin-O staining at 8 weeks. The percentage of Iba-1 positive microglia in the spinal dorsal horn and of FG + CGRP-labeled cells among FG-positive cells in the dorsal root ganglion were evaluated by immunohistochemical staining. TNF-α and IL-6 mRNA expression levels in the knee synovium were evaluated by PCR. The DF-HA showed significantly improved pain hypersensitivity compared with the HA at 6–8 weeks. The percentage of Iba-1-positive microglia was significantly lower than that in the vehicle and the percentage of FG + CGRP/FG was significantly lower than that in the HA. OARSI scores did not differ among treatment groups, Larsen scores indicated lower in the DF-HA than in the vehicle. DF-HA was as effective as HA in joint protection and significantly improved inflammatory pain compared to HA.</p>","PeriodicalId":16650,"journal":{"name":"Journal of Orthopaedic Research®","volume":"43 3","pages":"557-566"},"PeriodicalIF":2.1,"publicationDate":"2024-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142622803","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Peter Schwarzenberg, Jérôme Schlatter, Manuela Ernst, Markus Windolf, Hannah L. Dailey, Peter Varga
Bone fracture healing is a complex physiological process influenced by biomechanical and biomolecular factors. Mechanical stability is crucial for successful healing, and disruptions can lead to delayed healing or nonunion. Bone commonly heals itself through secondary fracture healing, which is governed by the mechanical strain at the fracture site. To investigate these phenomena, a validated methodology for capturing the mechanoregulatory process in specimen-specific models of fracture healing could provide insight into the healing process. This study implemented a prognostic healing simulation framework to predict healing trajectories based on mechanical stimuli. Sixteen sheep were subjected to a 3 mm transverse tibial mid-shaft osteotomy, stabilized with a custom plate, and equipped with displacement transducer sensors to measure interfragmentary motion over 8 weeks. Computed tomography scans were used to create specimen-specific bone geometries for finite element analysis. Virtual mechanical testing was performed iteratively to calculate strains in the callus region, which guided tissue differentiation and consequently, healing. The predicted healing outcomes were compared to continuous in vivo sensor data, providing a unique validation data set. Healing times derived from the in vivo sensor and in silico sensor showed no significant differences, suggesting the potential for these predictive models to inform clinical assessments and improve nonunion risk evaluations. This study represents a crucial step towards establishing trustworthy computational models of bone healing and translating these to the preclinical and clinical setting, enhancing our understanding of fracture healing mechanisms.
Clinical significance: Prognostic bone fracture healing simulation could assist in non-union diagnosis and prediction.
{"title":"Prognostic bone fracture healing simulations in an ovine tibia model validated with in vivo sensors","authors":"Peter Schwarzenberg, Jérôme Schlatter, Manuela Ernst, Markus Windolf, Hannah L. Dailey, Peter Varga","doi":"10.1002/jor.26007","DOIUrl":"10.1002/jor.26007","url":null,"abstract":"<p>Bone fracture healing is a complex physiological process influenced by biomechanical and biomolecular factors. Mechanical stability is crucial for successful healing, and disruptions can lead to delayed healing or nonunion. Bone commonly heals itself through secondary fracture healing, which is governed by the mechanical strain at the fracture site. To investigate these phenomena, a validated methodology for capturing the mechanoregulatory process in specimen-specific models of fracture healing could provide insight into the healing process. This study implemented a prognostic healing simulation framework to predict healing trajectories based on mechanical stimuli. Sixteen sheep were subjected to a 3 mm transverse tibial mid-shaft osteotomy, stabilized with a custom plate, and equipped with displacement transducer sensors to measure interfragmentary motion over 8 weeks. Computed tomography scans were used to create specimen-specific bone geometries for finite element analysis. Virtual mechanical testing was performed iteratively to calculate strains in the callus region, which guided tissue differentiation and consequently, healing. The predicted healing outcomes were compared to continuous in vivo sensor data, providing a unique validation data set. Healing times derived from the in vivo sensor and in silico sensor showed no significant differences, suggesting the potential for these predictive models to inform clinical assessments and improve nonunion risk evaluations. This study represents a crucial step towards establishing trustworthy computational models of bone healing and translating these to the preclinical and clinical setting, enhancing our understanding of fracture healing mechanisms.</p><p><b>Clinical significance:</b> Prognostic bone fracture healing simulation could assist in non-union diagnosis and prediction.</p>","PeriodicalId":16650,"journal":{"name":"Journal of Orthopaedic Research®","volume":"43 2","pages":"370-378"},"PeriodicalIF":2.1,"publicationDate":"2024-11-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142621227","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Karan Vishwanath, Jin Su, Marshall J. Colville, Matthew Paszek, Heidi L. Reesink, Lawrence J. Bonassar
The low friction nature of articular cartilage has been attributed to the synergistic interaction between lubricin and hyaluronic acid in the synovial fluid (SF). Lubricin is a mucinous glycoprotein that lowers the boundary mode coefficient of friction of articular cartilage in a dose-dependent manner. While there have been multiple attempts to produce recombinant lubricin and lubricin mimetic cartilage lubricants over the last two decades, these materials have not found clinical use due to challenges associated with large scale production, manufacturing, and purification. Recently, a novel method using codon scrambling was developed to produce a stable, full-length bioengineered equine lubricin (eLub) in large reproducible quantities. While preliminary frictional analysis of eLub and other recombinantly produced forms revealed they can lubricate cartilage, a complete tribological characterization is lacking, with previous studies evaluating the friction coefficient only at a single dose or a single speed. The objective of this study was to analyze the dose-dependent tribological properties of eLub using the Stribeck framework of tribological analysis. Recombinantly produced eLub at doses greater than 1.5 mg/mL exhibits friction coefficients on par with healthy bovine SF, and a maximal 5 mg/mL dose exhibits a nearly 50% lower friction coefficient than healthy SF. eLub also modulates the shift in lubrication mode of the cartilage from the high friction boundary mode to the low friction minimum mode at high concentrations.
{"title":"Bioengineered lubricin alters the lubrication modes of cartilage in a dose-dependent manner","authors":"Karan Vishwanath, Jin Su, Marshall J. Colville, Matthew Paszek, Heidi L. Reesink, Lawrence J. Bonassar","doi":"10.1002/jor.26009","DOIUrl":"10.1002/jor.26009","url":null,"abstract":"<p>The low friction nature of articular cartilage has been attributed to the synergistic interaction between lubricin and hyaluronic acid in the synovial fluid (SF). Lubricin is a mucinous glycoprotein that lowers the boundary mode coefficient of friction of articular cartilage in a dose-dependent manner. While there have been multiple attempts to produce recombinant lubricin and lubricin mimetic cartilage lubricants over the last two decades, these materials have not found clinical use due to challenges associated with large scale production, manufacturing, and purification. Recently, a novel method using codon scrambling was developed to produce a stable, full-length bioengineered equine lubricin (eLub) in large reproducible quantities. While preliminary frictional analysis of eLub and other recombinantly produced forms revealed they can lubricate cartilage, a complete tribological characterization is lacking, with previous studies evaluating the friction coefficient only at a single dose or a single speed. The objective of this study was to analyze the dose-dependent tribological properties of eLub using the Stribeck framework of tribological analysis. Recombinantly produced eLub at doses greater than 1.5 mg/mL exhibits friction coefficients on par with healthy bovine SF, and a maximal 5 mg/mL dose exhibits a nearly 50% lower friction coefficient than healthy SF. eLub also modulates the shift in lubrication mode of the cartilage from the high friction boundary mode to the low friction minimum mode at high concentrations.</p>","PeriodicalId":16650,"journal":{"name":"Journal of Orthopaedic Research®","volume":"43 3","pages":"531-540"},"PeriodicalIF":2.1,"publicationDate":"2024-11-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142622799","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}