Journal of Orthopaedic Research®最新文献

Glenoid implants used in anatomic total shoulder arthroplasties typically incorporate peripheral pegs as a design feature to support eccentric loads. These peripheral pegs and the implant-cement-bone interface undergo substantial cyclic tensile-compressive loads during normal activity. Therefore, these pegs are of interest in translating the micromechanics of local implant fixation failure to the biomechanics of gross anatomic failure of the glenoid implant after total shoulder arthroplasty. This study used an in vitro peg-cement-bone construct which incorporated bone tissue acquired from osteoarthritic patients undergoing total shoulder arthroplasty. Strain distributions in the peripheral peg-cement-bone interfaces were analyzed under loading conditions emulating glenoid implant edge displacements. It was found that tensile strains in the interfaces were highest near the backside-peg junction and were greater in magnitude than compressive strains. Notably, strains near the peg's fixation channels were relatively low. These results suggest that cracks may initiate around the peg near the backside and travel downward to cause broader fixation failure.

Cell apoptosis or necrosis, extracellular matrix loss, and excessive inflammation may induce tendon graft degeneration. The impairment in the regeneration capability of nerve fibers and blood vessels may be the critical cause. Calcitonin gene-related peptide (CGRP), exhibiting a short half-life, favors cell proliferation, nerve fiber regeneration and angiogenesis. We aimed to investigate the effects of CGRP receptor-mediated signaling on tendon graft integrity and study if the modulation pathways are ascribed to cell proliferation, nerve fiber and blood vessel regeneration. A total of three groups in mice with ACL reconstruction were established: the control group (PBS treatment), the adenovirus vectors expressing CGRP receptor (CALCRL) treated group (Adv-Calcrl treatment), and the adenovirus vectors carrying shRNA targeting Calcrl treated group (Adv-shCalcrl treatment). The histological assessment indicated the Adv-Calcrl treatment was favored while the Adv-shCalcrl significantly impaired tendon graft integrity. TUNEL staining revealed a significant decreased number of apoptotic cells in the Adv-Calcrl group relative to the control group and the adv-shCalcrl group. Compared to the control group and the Adv-shCalcrl group, the Adv-Calcrl group showed significantly enhanced proliferation of nestin positive cells. Of note, the Adv-Calcrl treatment significantly increased EMCN expression at the tendon graft relative to the control and the Adv-shCalcrl groups, which may be ascribed to attenuation of the Hippo signaling pathway. Importantly, the Adv-Calcrl treatment significantly increased sensory nerve fibers and also PIEZO2 levels. Our results demonstrate the activation of CGRP receptor-mediated signaling attenuated tendon graft degeneration, which was ascribed to enhanced proliferation of Nestin positive cells, angiogenesis, and nerve fiber outgrowth.

Joint injury can lead to articular cartilage damage, excessive inflammation, and post-traumatic osteoarthritis (PTOA). Collagen is an essential component for cartilage function, yet current literature has limited understanding of how biochemical and biomechanical factors contribute to collagen loss in injured cartilage. Our aim was to investigate spatially dependent changes in collagen content and collagen integrity of injured cartilage, with an explant model of early-stage PTOA. We subjected calf knee cartilage explants to combinations of injurious loading (INJ), interleukin-1α-challenge (IL) and physiological cyclic loading (CL). Using Fourier transform infrared microspectroscopy, collagen content (Amide I band) and collagen integrity (Amide II/1338 cm⁻¹ ratio) were estimated on days 0 and 12 post-injury. We found that INJ led to lower collagen content near lesions compared to intact regions on day 0 (p < 0.001). On day 12, near-lesion collagen content was lower compared to day 0 (p < 0.05). Additionally, on day 12, INJ, IL, and INJ + IL groups exhibited lower collagen content along most of tissue depth compared to free-swelling control group (p < 0.05). CL groups showed higher collagen content along most of tissue depth compared to corresponding groups without CL (p < 0.05). Immunohistochemical analysis revealed higher MMP-1 and MMP-3 staining intensities localized within cell lacunae in INJ group compared to CTRL group on day 0. Our results suggest that INJ causes rapid loss of collagen content near lesions, which is intensified on day 12. Additionally, CL could mitigate the loss of collagen content at intact regions after 12 days.

Co-administration of mirogabalin besylate and nonsteroidal anti-inflammatory drugs is effective for neuropathic pain; however, mechanism of its action remains unknown. We aimed to evaluate the mechanism of this synergistic effect of the concomitant administration for neuropathic pain using chronic constriction injury model rats. Fifty male Wister rats of 7-week-old were used. Right sciatic nerve ligation was performed in 40 rats and they were sub-divided into four groups: vehicle, mirogabalin, diclofenac sodium and co-administration of them. Ten rats underwent sham surgery. Fluorogold was attached to sciatic nerve during surgery. Von Frey filament and weight bearing tests were performed on postoperative Day 6 as behavioral assessments and drug was administrated intraperitoneally. Half rats in each group underwent behavioral assessment and perfusion fixation using 4% paraformaldehyde on postoperative Day 7 and remaining on postoperative Day 14. Subsequently, dorsal root ganglion at L4 to L6 was collected and examined immunohistochemistry for calcitonin gene-related peptide, and their immunoreactivity in fluorogold-labeled neurons was measured. Spinal cord at lumbar swelling was resected, immunostained for ionized-calcium-binding adapter molecule-1 and glial fibrillary acidic protein, and immunoreactive neurons in dorsal horn of spinal cords were calculated as the occupancy of them. Mirogabalin suppresses the neuropeptide-release from presynaptic afferent neuron directly and it resulted in suppressing glia cells activation. Diclofenac sodium inhibits cyclooxygenase-2 and prostaglandin production, related to allodynia. These effects of mirogabalin and diclofenac sodium, respectively, inhibited glia cells strongly, which is presumed to be one of the mechanisms for the effectiveness of their co-administration for neuropathic pain.

The objective of this study was to evaluate a non-resorbable implant for the focal repair of chondral defects in eight adult horses with 12-month follow-up. The bi-layered construct composed of a polycarbonate-urethane-urea biomaterial which was printed in 3D fashion onto a bone anchor was implanted into surgically created osteochondral defects into the femoropatellar joints of eight horses. The analysis of post-mortem outcomes were compared to defects treated with microfracture in the same animal on the contralateral femoropatellar jointfemoropatellar joint. The overall macroscopic scoring after 12 months yielded higher scores in the OCI-treated stifles compared to MF treatment (p = 0.09) with better quality and filling of the defect. Histology revealed good anchorage of repair tissue growing into the 3D structure of the implant and histopathology scoring for adjacent native cartilage showed no difference between groups. MRI and micro-CT showed overall less sclerotic reactions in the surrounding bone in the implant group and no foreign body reaction was detected. Biomechanical analysis of the repair tissue revealed a significantly higher peak modulus (p < 0.05) in the implant group (0.74 ± 0.45) compared to the microfracture control group (0.15 ± 0.11). Dynamic loading yielded higher values for the repair tissue overgrowing the implant group (0.23 ± 0.17) compared to the microfracture control (0.06 ± 0.06) (p < 0.05). The bi-layered osteochondral implant provided a safe implant for focal repair of full-thickness osteochondral defects, as no adverse reaction was seen within the joints and the level of degeneration of adjacent cartilage to the repair site was not different compared to that seen in defects treated with microfracture after 12 months.

Statistical shape modeling (SSM) offers the potential to describe the morphological differences in similar shapes using a compact number of variables. Its application in orthopedics is rapidly growing. In this study, an SSM of the intramedullary canal of the proximal femur was built, with the aim to better understanding the complexity of its shape which may, in turn, enhance the preoperative planning of total hip arthroplasty (THA). This includes the prediction of the prosthetic femoral version (PFV) which is known to be highly variable amongst patients who have undergone THA. The model was built on three dimensional (3D) models of 64 femoral canals which were generated from pelvic computed tomography images including the proximal femur in the field of view. Principal component analysis (PCA) was performed on the mean shape derived from the model and each segmented canal. Five prominent modes of variations representing approximately 84% of the total 3D variations in the population of shapes were found to capture variability in size, proximal torsion, intramedullary femoral anteversion, varus/valgus orientation, and distal femoral shaft twist/torsion, respectively. It was established that the intramedullary femoral canal is highly variable in its size, shape, and orientation between different subjects. PCA-driven SSM is beneficial for identifying patterns and extracting valuable features of the femoral canal.

This study aimed to investigate the biocompatibility and osseointegration of novel titanium (Ti) implants with a perforated part with high surface roughness (Ra >4 μm) and a smooth solid part (test group), as compared to smooth solid Ti implants (control group; Ra < 0.8 μm). Test and control implants were implanted in rabbit femurs. After 4 and 15 weeks, host tissue reaction and quality of tissue formed were evaluated with histopathology, while micro-CT scans were used to quantitatively assess bone–implant contact (BIC), surrounding bone formation, and bone ingrowth.

After 4 and 15 weeks, minimal host reaction was found in the test group. Histopathological analysis showed new bone formation around the implants in both the test and control groups after 4 weeks. Furthermore, additional bone growth was often observed within the holes of the test implants. After 15 weeks, the test implants showed high bone ingrowth and the presence of mature bone in direct contact with the implant surface, whereas, bone ingrowth was poorer for the control group with 30% of the control implants, showing larger gaps at the bone–implant interface. Quantitative micro-CT analysis revealed comparable BIC and bone formation in both groups at 4 weeks, but higher BIC and more bone formation in the test group than in the control group after 15 weeks. No significant differences were observed in any of the analyses. In conclusion, partially perforated, high-roughness Ti implants showed excellent osseointegration and minimal host reaction, indicating their potential for orthopedic applications in bone repair and regeneration.

Elbow trauma can lead to joint contracture and reduced range of motion (ROM). Nonsurgical interventions can improve ROM, but in some cases capsule release surgery is required. Although surgery can improve ROM, it often does not restore full ROM. Thus, alternatives are needed. One approach is to target activated myofibroblasts, which are commonly associated with fibrotic tissue. Mechanical and biochemical cues drive a feedback loop that can result in normal or pathological healing. We hypothesize that this feedback loop exists in joint contracture and can be manipulated so that myofibroblast activity is reduced, normal healing is achieved, and ROM is improved. We previously demonstrated that blebbistatin can inhibit myofibroblast contractile forces and reduce collagen synthesis in vitro. Thus, the purpose of this study was to assess the use of blebbistatin in an animal model of elbow contracture, which was induced in 7 groups of 4 rats each (n = 28). All elbows were mechanically and histologically tested. The uninjured contralateral elbows of each rat were used as a control group. Capsule release surgery significantly improved (p < 0.01) outcomes 1 week after surgery compared to injury alone and was not significantly different from uninjured elbows. Three weeks after surgery, outcomes worsened, indicating joint stiffening consistent with what is observed clinically. The addition of blebbistatin did not significantly improve outcomes. Future work will investigate relationships among treatment, fibrotic tissue deposition, myofibroblast activity, and biomechanics to determine if blebbistatin is a useful adjunctive therapy for treating joint contracture.

Axial micromotion between bone fragments can stimulate callus formation and fracture healing. In this study, we propose a novel mechanically compliant locking plate which achieves up to 0.6 mm of interfragmentary motion as flexures machined into the plate elastically deflect under physiological load. We investigated the biomechanical performance of three compliant plate variations in comparison to rigid control plates with small and large working lengths in a comminuted bridge plating scenario using humeral diaphysis surrogates. Under static axial loading, average interfragmentary motion was 6 times larger at 100 N (0.38 vs. 0.05 mm) and nearly three times larger at 350 N (0.58 vs. 0.2 mm) for compliant plates than rigid plates, respectively. Compliant plates delivered between 2.5 and 3.4 times more symmetric interfragmentary motion than rigid plates (p < 0.01). The bi-phasic stiffness of compliant pates provided 74%–96% lower initial axial stiffness up to approximately 100 N (p < 0.01), after which compliant plate stiffness was similar to rigid plates with increased working length (p > 0.3). The strength to failure of compliant plates under dynamic loading was on average 48%–55% lower than rigid plate groups (p < 0.01); however, all plates survived cyclic fatigue loading of 100,000 cycles at 350 N. This work characterizes the improvement in interfragmentary motion and the reduction in strength to failure of compliant plates compared to control rigid plates. Compliant plates may offer potential in comminuted fracture healing due to their ability to deliver symmetric interfragmentary motion into the range known to stimulate callus formation while surviving moderate fatigue loading with no signs of failure.

This study applied radiomics to MRI data for automated classification of soft tissue abnormalities near total hip arthroplasty (THA). A total of 126 subjects with 1.5 T MRI of symptomatic THA were included in the analysis. Peri-prosthetic soft tissue regions of interest were manually segmented and classified by an expert radiologist. An established radiomics library was used to extract 96 features from 2D image patches across segmented regions. Logistic regression was employed as the primary radiomic classifier, achieving an average area under curve (AUC) of 0.71 in differentiating tissue classifications spanning normal, infected, and several inflammatory, noninfectious categories. Notably, infection cases were identified with the highest accuracy, attaining an AUC of 0.79. Statement of Clinical Significance: This study demonstrates that radiomics applied to MRI data can effectively automate the classification of soft tissue abnormalities in symptomatic total hip arthroplasty, particularly in differentiating periprosthetic infections.