Journal of Orthopaedic Research®最新文献

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.

Post-traumatic osteoarthritis develops following an inciting injury to a joint and results in cartilage degeneration. Mechanical loading, including articulation, drives anabolic responses in cartilage clinically, in vivo, and in vitro. Tribological articulation, or sliding of cartilage on a glass counterface, has long been used as an in vitro tool to study cartilage tissue behavior. However, it is unclear if tribological articulation affects chondrocyte fate following injury, and if the timing of articulation impacts the resultant effect. The goal of this study was to investigate the effect of tribological articulation on injured cartilage tissue at two time points: (i) performed immediately after injury and (ii) 24 h after injury. Neonatal bovine femoral cartilage explants were injured using a rapid spring-loaded impactor and subsequently subjected to tribological articulation. Cell death due to impact injury was highest near the articular surface, suggesting a strain-dependent mechanism. Immediate articulation following injury mitigated cell death compared to injury alone or delayed articulation; markers for both general cell death and early-stage apoptosis were markedly decreased in the explants that were immediately slid. Interestingly, mitigation of cell death due to sliding was most predominant at the cartilage surface. Tribological articulation is known to create fluid flow within the tissue, predominantly at the articular surface, which could drive the protective response seen here. Altogether, this work shows that perturbations to the cellular environment immediately following cartilage injury significantly impact chondrocyte fate.

This study aimed to clarify cervical kinematics during daily activities, including level walking and stair ascending, in patients with cervical ossification of the posterior longitudinal ligament (C-OPLL). Eighteen patients with myelopathy caused by C-OPLL and 18 healthy controls were recruited to participate in the study. The sagittal cervical kinematics during level walking and stair ascent were quantitatively assessed using a motion analysis system based on wearable inertial sensors. The Japanese Orthopaedic Association score, Japanese Orthopaedic Association Cervical Myelopathy Evaluation Questionnaire, Neck Disability Index, and deep sensation in the lower extremities were assessed in all participants. Nine of 18 patients with C-OPLL presented with deep sensory disturbances. Patients with C-OPLL with deep sensory disturbances exhibited different sagittal plane cervical motion patterns than healthy controls during level walking and stair ascent. During the first phase of stair ascent, both patients with C-OPLL and healthy controls flexed their necks to the same degree; however, during the middle and final phases of stair ascent and all phases of level walking, the mean cervical flexion angle of patients with C-OPLL with deep sensory disturbances was significantly higher than that of patients with C-OPLL without deep sensory disturbance and healthy controls. Our data suggest that patients with C-OPLL presenting with deep sensory disturbances are likely to walk with their necks flexed and gaze downward to observe their steps throughout their daily lives. This habitual neck posture may lead to a vicious cycle of cervical kyphosis and worsening of compressive myelopathy.

Vertebral body tethering (VBT) uses a flexible tether affixed across the curve convexity with tension applied at each segment to treat scoliosis. Intraoperative tether tension may be achieved directly with a counter-tensioner or with an extension spring tube. The purpose of this study was to quantify the force generated with and without the extension spring tube using current FDA-approved VBT instrumentation, to understand the variation between surgeons using the same instrumentation, and to define the force range that is generated intra-operatively. Using a benchtop mechanical testing setup to simulate a spinal segment, we affixed the tether and applied tension using a tensioner and counter-tensioner alone (method T1) or by adding an extension spring tube (method T2). Eight orthopedic surgeons used T1 and T2 at six tensioner settings, and one surgeon completed three trials. A two-way ANOVA with a Tukey's HSD post hoc test (p < 0.05) compared the tensioner methods and testing levels. Inter- and intra-rater reliabilities were calculated using intraclass correlation coefficients (ICCs). Methods T1 and T2 exhibited linear tension-setting relationships, with high determination coefficients (R² > 0.93). T2 consistently produced higher forces (increase of 62.1 N/setting), compared to T1 (increase of 50.6 N/setting, p < 0.05). Inter-rater reliability exhibited excellent agreement (ICC = 0.951 and 0.943 for T1 and T2, respectively), as did intra-rater reliability (ICC = 0.971).

There is a lack of validated small animal models for femoroacetabular impingement (FAI) that induce intra-articular lesions and cause osteoarthritis (OA) progression. The gene expression profile of articular cartilage in patients with FAI has not been characterized in animal studies. The purpose of this study is to describe a novel rabbit model for FAI with validated induction of intra-articular lesions and OA progression and to characterize the gene expression pattern in impinged cartilage using this model. Thirty 6-month-old New Zealand White rabbits underwent unilateral endobutton implant placement at the acetabular rim to surgically create overcoverage. Radiological assessment confirmed secure placement of endobutton at the acetabular rim for all operated hips with a mean alteration in lateral center-edge angle (ΔLCEA) of 16.2 ± 6.6°. Gross inspection revealed secondary cartilage injuries in the anterosuperior region of the femoral head for the operated hips. Cartilage injuries were shown to exacerbate with increased impingement duration, as demonstrated by the modified Outerbridge scores and Mankin scores. Immunostaining and quantitative real-time polymerase chain reaction revealed elevated expression of inflammatory, anabolic and catabolic genes in impinged cartilage. RNA sequencing analysis of cartilage tissue revealed a distinct transcriptome profile and identified C-KIT, CD86, and CD68 as central markers. Our study confirmed that the novel rabbit FAI model created acetabular overcoverage and produced articular cartilage injury at the impingement zone. Cartilage from the impingement zone demonstrated a heightened metabolic state, corroborating with the gene expression pattern observed in patients with FAI.

The success of radial head arthroplasty (RHA) relies on the design of the implant and precision of the surgical technique, with preoperative planning potentially playing a crucial role. The accurate establishment of a patient-specific anatomical coordinate system (ACS) is essential for this planning process. This study tested the hypothesis that an innovative automated method would be an accurate, reliable, and efficient framework to determine the ACS of the proximal radius, which would be a step toward improving the precision of RHA planning. We used advanced computational techniques to analyze 50 forearm CT scans, comparing the accuracy, reproducibility, reliability, and efficiency of the automated method with manually derived ACS using expert observers as benchmarks. The results showed that the automated approach was more accurate in identifying anatomical landmarks, with smaller mean distance discrepancies (0.6 mm) than manual observers (1 mm). Its reproducibility was also superior, with narrower reproducibility limits, particularly for ulnar notch landmarks (0.6 to 0.8 mm compared to manual selection 1.2 to 1.4 mm) (p = .01). In addition, the limits of agreement and the mean absolute rotational and translational differences of the axes were narrower for the automated method, which also reduced the construction time to an average of 46 s compared to 150 s manually (p < .001). These findings suggest that the automated method has the potential to enhance the accuracy and efficiency of preoperative and postoperative computer-assisted procedures for RHA. Further research is needed to fully understand the utility of this automated system for enhancing RHA computer-assisted surgical planning.

Computer assisted orthopedic surgery is used to improve precision. Electro-magnetic tracking has been shown to improve precision in mono-planar derotational osteotomies. However, studies are lacking to investigate its use in multiplanar osteotomies. For this purpose, 60 complex (derotation and extension) osteotomies were performed in standardized sawbones. Correction amount was randomly planned before the procedures. In 30 bones, the amount of correction was determined intraoperatively using conventional goniometric measurement while in the other 30 bones electro-magnetic tracking was used to guide the amount of correction. CT-scans were done before and after the procedures in all bones and the amount of correction was determined to compare the precision of the two techniques. Electromagnetic tracking resulted in a precision of 2.25° ± 1.77° for derotation and 1.38° ± 1.29° for extension, while precision for the conventional method was significantly lower. There was a significant relationship between goniometer measurement deviation and the absolute angle change for derotation and extension measurements with larger deviations for greater angle changes. For the electro-magnetic tracking, this correlation was observed only for derotation measurement. Electro-magnetic tracking represents an accurate method to control complex, multiplanar corrective osteotomies with superior precision in comparison to conventional goniometric measurement. Further research is needed to investigate the in-vivo accuracy and the effects on clinical outcome.

Rotator cuff tendinopathy is a common musculoskeletal disorder with limited pharmacological treatment strategies. This study aimed to investigate tenocytes' functional in vitro response from a ruptured supraspinatus tendon to suramin administration and to elucidate whether suramin can enhance tendon repair and modulate the inflammatory response to injury. Tenocytes were obtained from human supraspinatus tendons (n = 6). We investigated the effect of suramin on LPS-induced inflammatory responses and the underlying molecular mechanisms in THP-1 macrophages. Suramin enhanced the proliferation, cell viability, and migration of tenocytes. It also increased the protein expression of PCNA and Ki-67. Suramin-treated tenocytes exhibited increased expression of COL1A1, COL3A1, TNC, SCX, and VEGF. Suramin significantly reduced LPS-induced iNOS, COX2 synthesis, inflammatory cytokine TNF-α production, and inflammatory signaling by influencing the NF-κB pathways in THP-1 cells. Our results suggest that suramin holds great promise as a therapeutic option for treating rotator cuff tendinopathy.

This study aimed to investigate the ultrastructural anatomy of the developing ACL tibial enthesis. We hypothesized that enthesis architecture would progressively mature and remodel, eventually resembling that of the adult by the early postnatal stage. Five fresh-frozen human pediatric cadaveric knees aged 1-36 months underwent anatomical dissection to harvest the ACL insertion and underlying tibial chondroepiphysis. The samples were prepared for scanning electron microscopy (SEM) to examine the ultrastructural anatomy of the enthesis and underwent histological staining for circular polarized light (CPL) and light microscopy imaging. SEM analysis of the 1- and 8-month-old samples revealed a shallow interdigitation between the dense fibrous (ligamentous) tissue and unmineralized chondrogenic tissues, with a minimal transition zone. By 11-month, a more complex transition zone was present. By age 19- and 36-month-old, a progressively more complex and defined fibrocartilage zone was observed. CPL analysis revealed distinct collagen fiber continuity, alignment, and organization changes over time. By 19 and 36 months, the samples exhibited complex fiber arrangements and a progression toward uniform fiber orientation. Similarly, histological analysis demonstrated progressive remodeling of the enthesis with increasing age. Our results suggest that the ACL enthesis of the developing knee begins to mimic that of an adult as early as 19 months of age, as a more complex transition between ligamentous and chondro-epiphyseal tissue can be appreciated. We hypothesize that the observed changes are likely due to mechanical loading of the enthesis with the onset of weightbearing. Future investigations of ACL reconstruction and repair will benefit from improved understanding of the chondro-epiphyseal/ACL regions.

Extracellular vesicles (EVs) derived from endometrial-derived mesenchymal stem/stromal cells (eMSC) play a crucial role in tissue repair due to their immunomodulatory and reparative properties. Given these properties, eMSC EVs may offer potential benefits for meniscal repair. The meniscus, being partly vascularized, relies on diffusivity for solute trafficking. This study focuses on EVs transport properties characterization within fibrocartilage that remains unknown. Specifically, EVs were isolated from Crude and CD146⁺ eMSC populations. Green fluorescence-labeled EVs transport properties were investigated in three structurally distinct layers (core, femoral, and tibial surfaces) of porcine meniscus. Diffusivity was measured via custom fluorescence recovery after photobleaching (FRAP) technique. Light spectrometry was used to determine EVs solubility. Both Crude and CD146⁺ eMSC EVs exhibited high purity (>90% CD63CD9 marker expression) and an average diffusivity of 10.924 (±4.065) µm²/s. Importantly, no significant difference was observed between Crude and CD146⁺ eMSC EV diffusivity on the meniscal layer (p > 0.05). The mean partitioning coefficient was 0.2118 (±0.1321), with Crude EVs demonstrating significantly higher solubility than CD146⁺ EVs (p < 0.05). In conclusion, this study underscores the potential of both Crude and CD146⁺ eMSC EVs to traverse all layers of the meniscus, supporting their capacity to enhance delivery of orthobiologics for cartilaginous tissue healing.