Journal of Orthopaedic Research®最新文献

Drug-resistant organisms (DROs) necessitate the development of new therapies. Antimicrobial blue light (ABL) is a promising option, utilizing photoexcitation of endogenous bacterial components to generate reactive oxygen species, leading to bacterial death. The aim of this study is to investigate the effects of a novel isotropic optical fiber under in-vitro conditions on multidrug-resistant gram-negative Pseudomonas aeruginosa (MDR-Pa) and methicillin-resistant Staphylococcus aureus (MRSA). Time-to-kill assays were conducted in tubes containing 10 mL of 0.9% NaCl solution with an inoculum of 1 × 10⁵ CFU/mL for MDR-Pa or MRSA. The experiments were repeated at least three times per strain. Experimental tubes had either one (low power, LP) or two (high power, HP) optical fibers delivering five ABL wavelengths (405, 415, 435, 450, and 475 nm) over 60 min. Control tubes lacked optical fibers. Samples were taken at 0, 10, 20, 30, and 60 min, streaked on agar, and incubated to determine CFU/mL. Bactericidal reduction was defined as a ≥ 99.9% (≥ 3 log₁₀) reduction in CFU/mL. One-way ANOVA were conducted. The novel isotropic optical fiber was able to exhibit bactericidal effects for MDR-Pa only under HP-ABL with a log₁₀CFU/mL ± SD difference of −3.71 ± 0.01 at 60 min (p = 0.03). Conversely, the optical fiber exhibited bactericidal effects on MRSA under both LP-ABL and HP-ABL with a log₁₀CFU/mL±SD difference of −3.73 ± 0.08 at 60 min (p = 0.03) and −3.07 ± 0.28 at 20 min (p = 0.02), respectively. The isotropic optical fiber demonstrated bactericidal effects on MRSA and MDR-Pa in in-vitro studies and shows potential as a therapeutic option for DROs.

Ewing sarcoma (ES) is a malignant bone tumor prevalent among children and adolescents. Disulfidptosis represents a novel form of cell death; however, the mechanism of disulfidptosis in ES remains unclear. Our aim is to explore the disulfidptosis-related prognostic signature in ES. Utilizing transcriptomic and clinical data of ES, disulfidptosis-related hub genes (DRHGs) were identified by differential gene expression analysis and Least Absolute Shrinkage and Selection Operator (LASSO) Cox regression analysis. A disulfidptosis-related risk score model (DRRS) was constructed based on these DRHGs. The performance of DRRS was assessed using survival analysis and receiver operating characteristic curve analysis. Immune cell infiltration in different risk subgroups and correlations between DRRS and antitumor reagents were also analyzed. In this study, we developed a disulfidptosis-related prognostic feature based on LRPPRC (leucine rich pentatricopeptide repeat containing), IQGAP1 (IQ motif containing GTPase activating protein 1), NDUFS1 (NADH:ubiquinone oxidoreductase core subunit S1), and TLN1 (talin 1), which may serve as a predictive and independent risk factor for ES. ES patients in the high-risk group exhibited a poorer prognosis, had a higher proportion of myeloid-derived suppressor cells (MDSCs) and M2 type of tumor-associated macrophages, and showed heightened sensitivity to some antitumor agents such as nilotinib and olaparib. This study is the first to construct a disulfidptosis-related prognostic signature that may predict the prognosis and immune response in ES patients, thereby providing a new reference for understanding the mechanisms of ES and guiding immunotherapy.

A high proportion of individuals with Achilles tendinopathy continue to demonstrate long-term symptoms and functional impairments after exercise treatment. Thus, there is a need to delineate patient presentations that may require alternative treatment. The objective of this study was to evaluate if the presence of metabolic risk factors relates to tendon symptoms, psychological factors, triceps surae structure, and lower limb function in individuals with Achilles tendinopathy. One hundred and fifty-eight individuals (88 female) with diagnosed midportion Achilles tendinopathy were divided into three groups based on the number of metabolic risk factors linked to cardiovascular disease present at baseline: two or more factors, one factor, no factors. Metabolic risk factors were determined by clinical evaluation and past medical history. Achilles tendinopathy symptoms (Victorian Institute of Sport Assessment-Achilles, Patient Reported Outcome Measurement Information System, movement-evoked pain ratings), psychological factors (Tampa Scale for Kinesiophobia), triceps surae structure (B-mode ultrasound of tendon and muscle morphology, continuous shear wave elastography of tendon mechanical properties), and lower limb function (test battery) were compared among groups. Individuals with two or more metabolic risk factors had worse symptoms with loading (p = 0.011), smaller Achilles tendon size relative to body mass (p = 0.002), and worse lower limb function compared to individuals without metabolic risk factors (p < 0.02). No differences were observed between individuals with one metabolic risk factor and those without metabolic risk factors. Future consideration of multiple metabolic risk factors for individuals with Achilles tendinopathy could facilitate understanding the underlying impairments of tendon pathology and recovery that may be addressed with treatment.

Patient-specific flanged acetabular components are utilized to treat failed total hip arthroplasties with severe acetabular defects. We previously developed and published a finite element model that investigated the impact of hip joint center lateralization on construct biomechanics during gait conditions. This model consisted of a patient-specific implant designed to address a superior-medial defect created in a standard pelvic geometry. This study aims to utilize the same model and examine how cortical shell thickness and ischial cancellous bone density affect the strain distribution in the bone and bone–implant micromotion. Using published studies and bone density analyses of patients who had undergone total hip arthroplasties with flanged acetabular components, we established a thickness range for the cortical shell (1.5, 1, and 0.75 mm) and two levels of ischial cancellous bone density (100% and 25%). We compared the resulting bone strains against the fatigue strength of the bone (0.3% strain) as a criterion for local bone failure and the bone–implant micromotion against the threshold associated with bone ingrowth (20 µm). A thinner pelvic cortical shell and lower ischial cancellous bone density increased areas of bone at risk of failure, particularly at the ischial screws (from 6% to 38%), and decreased areas compatible with bone ingrowth. These findings agree with our clinical knowledge that compromised ischial bone and inadequate ischial fixation negatively impact the survivorship of flanged acetabular components. This series establishes our modeling approach of a computational model that can be utilized to guide implant design to best treat unique acetabular defects.

Periprosthetic joint infection (PJI) is a leading cause and major complication of joint replacement failure. As opposed to standard-of-care systemic antibiotic prophylaxis for PJI, we developed and tested titanium femoral intramedullary implants with titania nanotubes (TNTs) coated with the antibiotic gentamicin and slow-release agent chitosan through electrophoretic deposition (EPD) in a mouse model of PJI. We hypothesized that these implants would enable local gentamicin delivery to the implant surface and surgical site, effectively preventing bacterial colonization. In the mouse PJI model, C57BL/6 mice received implants with TNTs coated with chitosan (chitosan group; control group) or with TNTs coated with chitosan and gentamicin (chitosan + gentamicin group; experimental group). Following implant placement, the surgical site was inoculated with 1 × 10³ CFUs of Xen36 bioluminescent Staphylococcus aureus. All the mice in the chitosan group and none in the chitosan + gentamicin group had evidence of infection based on CFU analysis and bioluminescence imaging through the 14-day assessment postsurgery. Correspondingly, scanning electron microscopy analysis at the implant surface demonstrated bacterial biofilm only in the chitosan group. Furthermore, periosteal reaction and peri-implant bone loss at the femur were significantly reduced in the chitosan + gentamicin group. The chitosan + gentamicin group had reduced pain behavior, improved weight-bearing, and increased weight compared to the chitosan-control group. This study provides preclinical evidence supporting the efficacy of implants with TNTs coated with chitosan and gentamicin through EPD for preventing bacterial colonization and biofilm formation in a mouse model of PJI.

This study investigates the therapeutic potential of Msx1-overexpressing bone marrow mesenchymal stem cells (BMSCs) in enhancing tendon-bone healing in rotator cuff injuries. BMSCs were genetically modified to overexpress Msx1 and were evaluated in vitro for their proliferation, migration, and differentiation potential. Results demonstrated that Msx1 overexpression significantly increased BMSC proliferation and migration while inhibiting osteogenic and chondrogenic differentiation. In a rat model of acute rotator cuff injury, Msx1-BMSCs embedded in a hydrogel scaffold were implanted at the tendon-bone junction. Micro-CT analysis revealed substantial new bone formation in the Msx1-BMSC group, and histological evaluation showed organized collagen and cartilage structures at the repair site. Biomechanical testing further confirmed enhanced structural strength in the Msx1-BMSC-treated group. These findings suggest that Msx1 modification enhances BMSC-mediated repair by promoting cell proliferation and migration, facilitating tendon-bone integration. This Msx1-based approach presents a promising strategy for advancing regenerative therapies for rotator cuff injuries.