Journal of Orthopaedic Research®最新文献

Hip fracture prevention approaches like prophylactic augmentation devices have been proposed to strengthen the femur and prevent hip fracture in a fall scenario. The aim of this study was to validate the finite element model (FEM) of specimens augmented by prophylactic intramedullary nailing in a simulated sideways fall impact against ex vivo experimental data. A dynamic inertia-driven sideways fall simulator was used to test six cadaveric specimens (3 females, 3 males, age 63-83 years) prophylactically implanted with an intramedullary nailing system used to augment the femur. Impact force measurements, pelvic deformation, effective pelvic stiffness, and fracture outcomes were compared between the ex vivo experiments and the FEMs. The FEMs over-predicted the effective pelvic stiffness for most specimens and showed variability in terms of under- and over-predicting peak impact force and pelvis compression depending on the specimen. A significant correlation was found for time to peak impact force when comparing ex vivo and FEM data. No femoral fractures were found in the ex vivo experiments, but two specimens sustained pelvic fractures. These two pelvis fractures were correctly identified by the FEMs, but the FEMs made three additional false-positive fracture identifications. These validation results highlight current limitations of these sideways fall impact models specific to the inclusion of an orthopaedic implant. These FEMs present a conservative strategy for fracture prediction in future applications. Further evaluation of the modelling approaches used for the bone-implant interface is recommended for modelling augmented specimens, alongside the importance of maintaining well-controlled experimental conditions.

During cementless total knee arthroplasty (TKA), an overlap between the resected tibia and the implant's geometry, termed interference fit, is introduced to facilitate primary stability and direct bone-implant contact. However, little is known about the actual interference achieved and the resulting mechanical response in the surrounding cancellous bone. The aim of this study was (1) to experimentally quantify the actual interference achieved for a commercially available cementless tibial implant and (2) to assess its effect on the post-impaction cancellous bone strain. Seven human cadaveric tibiae were micro-CT scanned intact (23 µm/pixel), once prepared for TKA (46 µm/pixel) and following implantation (46 µm/pixel). The actual interference across the entire bone-implant interface was quantified and, via digital volume correlation, the compressive strains of bone in contact with the implant and at increasing distance, were extracted. An inhomogeneous actual interference was found across the implant pegs and keel (median ± std dev: 0.70 ± 0.27 mm), which was lower than the intended. Limited interference (0.02 ± 0.12 mm) was found directly under the baseplate, with immediate bone-baseplate contact of 54%. The induced compressive strains were related to the actual interference within 3.14 mm from the bone-implant interface (R² = 0.269-0.450, p < 0.001), with higher compressive strains corresponding to higher interference, but not being related to the bone volume fraction. Clinical Significance: Insight is provided into the interaction between the variability of the resection and the resulting mechanical environment. A complex relationship is apparent, whereby the actual interference accounted for up to 45% of the variation in induced compressive strain magnitude.

Flatfoot, a foot deformity characterized by the collapse of the arch, significantly impacts an individual's balance and stability. This study explored postural adjustments and sway excursions in individuals with and without flatfoot using the Time-in-Boundary method. This method assessed relative stability by exploring various center of pressure radius thresholds during three trials of single-leg stance. We observed significant interactions in threshold levels (F = 4.37, p = 0.04) and normalized relative stable times (F = 7.64, p = 0.01), particularly in the initial trials. Initially, the flatfoot group showed marked decreases in stable times at 10 mm, 15 mm, and 20 mm thresholds, which expanded to 25 mm and 30 mm in subsequent trials. Despite a significant decrease in stability at the 30 mm threshold in early trials, participants exhibited improved stability control as trials progressed. This enhancement likely reflects a combination of a learning effect and an increased understanding of the task requirements, underscoring the adaptability of postural control systems to the biomechanical challenges posed by flatfoot. The Time-in-Boundary method has proven to be an effective tool for clinicians to assess postural control, playing a vital role in developing customized rehabilitation strategies for individuals with flatfoot.

The purpose of this study was to compare gait biomechanics between limbs and to matched uninjured controls (i.e., sex, age, and body mass index) preoperatively and at 2, 4, 6, and 12 months following primary unilateral anterior cruciate ligament reconstruction (ACLR). Functional mixed effects models were used to identify differences in gait biomechanics throughout the stance phase between the a) ACLR limb and uninvolved limb, b) ACLR limb and controls, and c) uninvolved limb and controls. Compared with the uninvolved limb, the ACLR limb demonstrated lesser knee extension moment (KEM; within 8-37% range of stance) during early stance as well as lesser knee flexion moment (KFM; 45-84%) and greater knee flexion angle (KFA; 43-90%) during mid- to late stance at all timepoints. Compared with controls, the ACLR limb demonstrated lesser vertical ground reaction force (vGRF; 5-26%), lesser KEM (7-47%), and lesser knee adduction moment (KAM; 12-35%) during early stance as well as greater vGRF (39-63%) and greater KFA (34-95%) during mid- to late stance at all timepoints. Compared with controls, the uninvolved limb demonstrated lesser KFA (1-56%) and lesser KEM (12-54%) during early to mid-stance at all timepoints. While gait becomes more symmetrical over the first 12 months post-ACLR, the ACLR and uninvolved limbs both demonstrate persistent aberrant gait biomechanics compared to controls. Biomechanical waveforms throughout stance can be generally described as less dynamic following ACL injury and ACLR compared with uninjured controls.

Osteoporosis in postmenopausal women is one of the causes of femoral fractures and is prevented by the administration of bisphosphonates. Individual morphologies are considered to increase the risk of atypical fractures associated with long-term administration. To evaluate cortical bone morphology quantitatively, we established a method to measure the distance from the center point of a cross-section to the external and internal borders based on CT images. Using this method, 44 sides of a female femoral skeleton specimen were examined and areas of protrusion and thickening in the medial anterior and lateral posterior regions just below the lesser trochanter were identified. These positions strongly correlated with the anteversion angle, suggesting the involvement of the distribution of the load received from body weight defined by the angle. The finite element method was used to examine the relationships between the positions of these areas with compressive and tensile stress distribution areas in the one-legged standing condition. The medial anterior region and lateral posterior region protruded and thickened in response to compressive and tensile stress, respectively. In addition, a hierarchical relationship was observed between the anteversion angle, tensile stress distribution, protrusion, and thickening in femurs with thinning of cortical bone, indicating that morphogenesis occurs adaptively to loading. The present results demonstrate the usefulness of this method in considering the formation mechanism and function of the femoral diaphysis and suggest that bone remodeling is necessary to maintain adaptability.

Successful tendon healing requires sufficient deposition and remodeling of new extracellular matrix at the site of injury, with this process mediating in part through fibroblast activation via communication with macrophages. Moreover, resolution of healing requires clearance or reversion of activated cells, with chronic interactions with persistent macrophages impairing resolution and facilitating the conversion to fibrotic healing. As such, modulation of the macrophage environment represents an important translational target to improve the tendon healing process. Circulating monocytes are recruited to sites of tissue injury, including the tendon, via upregulation of cytokines including Ccl2, which facilitates recruitment of Ccr2⁺ macrophages to the healing tendon. Our prior work has demonstrated that Ccr2^-/- can modulate fibroblast activation and myofibroblast differentiation. However, this approach lacked temporal control and resulted in healing impairments. Thus, in the current study we have leveraged a Ccr2 antagonist to blunt macrophage recruitment to the healing tendon in a time-dependent manner. We first tested the effects of Ccr2 antagonism during the acute inflammatory phase and found that this had no effect on the healing process. In contrast, Ccr2 antagonism during the early proliferative/granulation tissue period resulted in significant improvements in mechanical properties of the healing tendon. Collectively, these data demonstrate the temporally distinct impacts of modulating Ccr2⁺ cell recruitment and Ccr2 antagonism during tendon healing and highlight the translational potential of transient Ccr2 antagonism to improve the tendon healing process.

Osteoarthritis (OA) prevalence increases as the population ages. Diagnosing osteoarthritis often occurs in the late stages when cartilage degradation is severe, making it difficult to distinguish from other types of arthritis. Accurate differentiation of primary osteoarthritis from other arthritic conditions is crucial for effective treatment planning. A new diagnostic test has been developed that uses a dual-biomarker algorithm to inform osteoarthritis diagnosis. Synovial fluid from patients with confirmed primary osteoarthritis showed elevated levels of cartilage oligomeric matrix protein. However, this biomarker alone could not distinguish primary osteoarthritis from other inflammatory conditions that also cause cartilage deterioration. Therefore, a combinatorial algorithm using cartilage oligomeric matrix protein and Interleukin-8 concentrations was developed to differentiate primary osteoarthritis from inflammatory arthritis. Clinical decision limits for cartilage oligomeric matrix protein concentration and the cartilage oligomeric matrix protein to Interleukin-8 ratio were established and validated using 171 human knee synovial fluid specimens. The osteoarthritis algorithm demonstrated clinical sensitivity and specificity of 87.0% and 88.9%, respectively. This is the first report of a biomarker test that can differentiate primary osteoarthritis from inflammatory arthritis with a high degree of accuracy.

Heterotopic ossification (HO) in Achilles tendon often arises due to endochondral ossification during the healing process following trauma. Retinoic acid receptor γ (RARγ) plays a critical role in this phenomenon. This study aims to elucidate the therapeutic effects of CD1530, an RARγ selective agonist, along with the contributing cells, in Achilles tendon healing, utilizing a cell lineage tracing system. Local injection of CD1530 facilitated histological tendon healing by inhibiting chondrification in a mouse Achilles rupture model. Resident Scleraxis (Scx)⁺ cells in Achilles tendon were not found to be actively involved in HO or　tendon healing following injury. Instead, these processes were primarily driven by tendon stem/progenitor cells (TSPC)-like cells. Furthermore, an in vitro assay revealed that CD1530 attenuated inflammation in injured Achilles tendon-derived tendon fibroblasts (iATF) and inhibited the chondrogenesis of iATF. This dual effect suggests the potential of CD1530 in effectively modulating the healing environment during tendon healing. Together, the present study demonstrated that the local administration of CD1530 accelerated tendon healing by modulating the healing environment, including reducing chondrification via targeting TSPC-like cells in a mouse Achilles tendon rupture model. These results suggest that CD1530 may have the potential to be a novel tendon therapy that offers benefits via the inhibition of chondrogenesis.

Osteoarthritis (OA) is a debilitating disease that impacts millions of individuals and has limited therapeutic options. A significant hindrance to therapeutic discovery is the lack of in vitro OA models that translate reliably to in vivo preclinical animal models. An alternative to traditional inflammatory cytokine models is the matrikine stimulation model, in which fragments of matrix proteins naturally found in OA tissues and synovial fluid, are used to stimulate cells of the joint. The objective of this study was to determine if matrikine stimulation of equine synovial fibroblasts and chondrocytes with fibronectin fragments (FN7-10) would result in an OA phenotype. We hypothesized that FN7-10 stimulation of equine articular cells would result in an OA phenotype with gene and protein expression changes similar to those previously described for human chondrocytes stimulated with FN7-10. Synovial fibroblasts and chondrocytes isolated from four horses were stimulated in monolayer culture for 6 or 18 h with 1 µM purified recombinant 42 kD FN7-10 in serum-free media. At the conclusion of stimulation, RNA was collected for targeted gene expression analysis and media for targeted protein production analysis. Consistent with our hypothesis, FN7-10 stimulation resulted in significant alterations to many important genes that are involved in OA pathogenesis including increased expression of IL-1β, IL-4, IL-6, CCL2/MCP-1, CCL5/RANTES, CXCL6/GCP-2, MMP-1, MMP-3, and MMP13. The results of this study suggest that the equine matrikine stimulation model of OA may prove useful for in vitro experiments leading up to preclinical trials.

Staphylococcus aureus has multiple mechanisms to evade the host's immune system and antibiotic treatment. One such mechanism is the invasion of the osteocyte lacuno-canalicular network (OLCN), which may be particularly important in recurrence of infection after debridement and antibiotic therapy. The aim of this study was to develop an ex vivo model to facilitate further study of S. aureus invasion of the OLCN and early-stage testing of antibacterial strategies against bacteria in this niche. The diameter of the canaliculi of non-infected human, sheep, and mouse bones was measured microscopically on Schmorl's picrothionin stained sections, showing a large overlap in canalicular diameter. S. aureus successfully invaded the OLCN in all species in vitro as revealed by presence in osteocyte lacunae in Brown and Brenn-stained sections and by scanning electron microscopy. Murine bones were then selected for further experiments, and titanium pins with either a wild-type or ΔPBP4 mutant S. aureus USA300 were placed trans-cortically and incubated for 2 weeks in tryptic soy broth. Wild-type S. aureus readily invaded the osteocyte lacunae in mouse bones while the ΔPBP4 showed a significantly lower invasion of the OLCN (p = 0.0005). Bone specimens were then treated with gentamicin, sitafloxacin, R14 bacteriophages, or left untreated. Gentamicin (p = 0.0027) and sitafloxacin (p = 0.0280) significantly reduced the proportion of S. aureus-occupied lacunae, whilst bacteriophage treatment had no effect. This study shows that S. aureus is able to invade the OLCN in an ex vivo model. This ex vivo model can be used for future early-stage studies before proceeding to in vivo studies.