Osteomyelitis is an invasive bone infection that can lead to severe pain and even disability, posing a challenge for orthopedic surgery. Naringin can reduce bone-related inflammatory conditions. This study aimed to elucidate the function and mechanism of naringin in a Staphylococcus aureus-induced mouse model of osteomyelitis. Femurs of S. aureus-infected mice were collected after naringin administration and subjected to microcomputed tomography to analyze cortical bone destruction and bone loss. Bacterial growth in femurs was also assessed. Proinflammatory cytokine levels in mouse femurs were measured using enzyme-linked immunosorbent assays. Pathological changes and bone resorption were analyzed using hematoxylin and eosin staining and tartrate-resistant acid phosphatase staining, respectively. Quantitative reverse transcription polymerase chain reaction and western blot analysis were used to quantify the messenger RNA and protein expression of osteogenic differentiation-associated genes in the femurs. The viability of human bone marrow-derived stem cells (hBMSCs) was determined using cell counting kit-8. Alizarin Red S staining and alkaline phosphatase staining were performed to assess the formation of mineralization nodules and bone formation in vitro. Notch signaling-related protein levels in femur tissues and hBMSCs were assessed using western blot analysis. Experimental results revealed that naringin alleviated S. aureus-induced cortical bone destruction and bone loss in mice by increasing the bone volume/total volume ratio. Naringin suppressed S. aureus-induced bacterial growth and inflammation in femurs. Moreover, it alleviated histopathological changes, inhibited bone resorption, and increased the expression of osteogenic markers in osteomyelitic mice. It increased the viability of hBMSCs and promoted their differentiation and bone mineralization in vitro. Furthermore, naringin activated Notch signaling by upregulating the protein levels of Notch1, Jagged1, and Hes1 in the femurs of model mice and S. aureus-stimulated hBMSCs. In conclusion, naringin reduces bacterial growth, inflammation, and bone resorption while upregulating the expression of osteogenic markers in S. aureus-infected mice and hBMSCs by activating Notch signaling.

Stress-induced premature senescent (SIPS) cells induced by various stresses deteriorate cell functions. Dasatinib and quercetin senolytics (DQ) can alleviate several diseases by eliminating senescent cells. α-tricalcium phosphate (α-TCP) is a widely used therapeutic approach for bone restoration but induces bone formation for a comparatively long time. Furthermore, bone infection exacerbates the detrimental prognosis of bone formation during material implant surgery due to oral cavity bacteria and unintentional contamination. It is essential to mitigate the inhibitory effects on bone formation during surgical procedures. Little is known that DQ improves bone formation in Lipopolysaccharide (LPS)-contaminated implants and its intrinsic mechanisms in the study of maxillofacial bone defects. This study aims to investigate whether the administration of DQ ameliorates the impairments on bone repair inflammation and contamination by eliminating SIPS cells. α-TCP and LPS-contaminated α-TCP were implanted into Sprague-Dawley rat calvaria bone defects. Simultaneously, bone formation in the bone defects was investigated with or without the oral administration of DQ. Micro-computed tomography and hematoxylin-eosin staining showed that senolytics significantly enhanced bone formation at the defect site. Histology and immunofluorescence staining revealed that the levels of p21- and p16-positive senescent cells, inflammation, macrophages, reactive oxygen species, and tartrate-resistant acid phosphatase-positive cells declined after administering DQ. DQ could partially alleviate the production of senescent markers and senescence-associated secretory phenotypes in vitro. This study indicates that LPS-contaminated α-TCP-based biomaterials can induce cellular senescence and hamper bone regeneration. Senolytics have significant therapeutic potential in reducing the adverse osteogenic effects of biomaterial-related infections and improving bone formation capacity.

BACKGROUND: Heel puncture (HP) in neonates can result in osteomyelitis if done non-aseptically or with incorrect technique. This study summarizes clinical experience with heel puncture-related osteomyelitis of the calcaneus (HP-CO) in newborns.
METHODS: We systematically reviewed studies that examined HP-CO in newborn patients using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Our search included the PubMed, Embase, and Cochrane Library databases until December 31, 2023. We used the National Institutes of Health (NIH) assessment scale to evaluate the quality of our analyzed studies.
RESULTS: This study analyzed 15 neonatal calcaneal osteomyelitis (CO) cases due to HP conducted in six countries from 1976 to 2016. The average age of the cases was 8.87 ± 6.13 days, with an average birth weight of 2367.27 ± 947.59 g. The infants had undergone an average of 9.00 ± 8.90 HP, with 93.33% exhibiting swelling. Staphylococcus aureus was present in 80% of cases. Beta-lactam antibiotics were used, with satisfactory outcomes in 53.33% of cases. However, in seven cases, three patients had flatfoot due to calcaneal deformity, and other complications were observed in some patients after 7-8 years.
CONCLUSIONS: This study offers valuable insights into a rare condition, including its epidemiology, clinical and laboratory characteristics, and treatment options for infants with HP-CO. To prevent the risk of osteomyelitis in this vulnerable group of patients, increasing awareness and maintaining strict aseptic techniques is necessary. We recommend that infants presenting with tenderness, redness, purulent discharge, erythema, or fever and with a history of repeated HP and swollen ankles should be evaluated for suspicion of osteomyelitis. A graphical abstract is avilable for this article.

Transarticular external fixation is primarily used for open fractures involving the joint. However, its biggest drawback is the potential forjoint dysfunction. The article reports a successful case with complex open tibial plateau fracture treated using locked plate external fixation technique during bone callus formation stage to replace transarticular external fixation. We present a case of a 55-year-old male who sustained a complex open fracture of the tibial plateau. In addition, he also suffered from multiple rib fractures, a fibula fracture, a clavicle fracture, hemorrhagic shock, and lung contusion. The patient has occurred tibial bone infection after undergoing open reduction and transarticular external fixation for fracture management. Our team skillfully applied locked plate external fixation technique during bone callus formation stage to replace transarticular external fixation. Ultimately, the approach not only successfully controls infection and achieves fracture healing but also preserves knee joint function after five years of follow-up. In conclusion,the application of locked plate external fixation technique during bone callus formation stage to replace transarticular external fixation is a valuable approach that orthopedic clinicians should consider and learn from when managing complex intra-articular fractures.

OBJECTIVE: To develop an ensemble multi-task deep learning (DL) framework for automatic and simultaneous detection, segmentation, and classification of primary bone tumors (PBTs) and bone infections based on multi-parametric MRI from multi-center.
METHODS: This retrospective study divided 749 patients with PBTs or bone infections from two hospitals into a training set (N = 557), an internal validation set (N = 139), and an external validation set (N = 53). The ensemble framework was constructed using T1-weighted image (T1WI), T2-weighted image (T2WI), and clinical characteristics for binary (PBTs/bone infections) and three-category (benign/intermediate/malignant PBTs) classification. The detection and segmentation performances were evaluated using Intersection over Union (IoU) and Dice score. The classification performance was evaluated using the receiver operating characteristic (ROC) curve and compared with radiologist interpretations.
RESULTS: On the external validation set, the single T1WI-based and T2WI-based multi-task models obtained IoUs of 0.71 ± 0.25/0.65 ± 0.30 for detection and Dice scores of 0.75 ± 0.26/0.70 ± 0.33 for segmentation. The framework achieved AUCs of 0.959 (95%CI, 0.955-1.000)/0.900 (95%CI, 0.773-0.100) and accuracies of 90.6% (95%CI, 79.7-95.9%)/78.3% (95%CI, 58.1-90.3%) for the binary/three-category classification. Meanwhile, for the three-category classification, the performance of the framework was superior to that of three junior radiologists (accuracy: 65.2%, 69.6%, and 69.6%, respectively) and comparable to that of two senior radiologists (accuracy: 78.3% and 78.3%).
CONCLUSIONS: The MRI-based ensemble multi-task framework shows promising performance in automatically and simultaneously detecting, segmenting, and classifying PBTs and bone infections, which was preferable to junior radiologists.
CONCLUSIONS: Compared with junior radiologists, the ensemble multi-task deep learning framework effectively improves differential diagnosis for patients with primary bone tumors or bone infections. This finding may help physicians make treatment decisions and enable timely treatment of patients.
CONCLUSIONS: • The ensemble framework fusing multi-parametric MRI and clinical characteristics effectively improves the classification ability of single-modality models. • The ensemble multi-task deep learning framework performed well in detecting, segmenting, and classifying primary bone tumors and bone infections. • The ensemble framework achieves an optimal classification performance superior to junior radiologists\' interpretations, assisting the clinical differential diagnosis of primary bone tumors and bone infections.

Musculoskeletal disorders (MSDs), which include a range of pathologies affecting bones, cartilage, muscles, tendons, and ligaments, account for a significant portion of the global burden of disease. While pharmaceutical and surgical interventions represent conventional approaches for treating MSDs, their efficacy is constrained and frequently accompanied by adverse reactions. Considering the rising incidence of MSDs, there is an urgent demand for effective treatment modalities to alter the current landscape. Phototherapy, as a controllable and non-invasive technique, has been shown to directly regulate bone, cartilage, and muscle regeneration by modulating cellular behavior. Moreover, phototherapy presents controlled ablation of tumor cells, bacteria, and aberrantly activated inflammatory cells, demonstrating therapeutic potential in conditions such as bone tumors, bone infection, and arthritis. By constructing light-responsive nanosystems, controlled drug delivery can be achieved to enable precise treatment of MSDs. Notably, various phototherapy nanoplatforms with integrated imaging capabilities have been utilized for early diagnosis, guided therapy, and prognostic assessment of MSDs, further improving the management of these disorders. This review provides a comprehensive overview of the strategies and recent advances in the application of phototherapy for the treatment of MSDs, discusses the challenges and prospects of phototherapy, and aims to promote further research and application of phototherapy techniques.

Bone infection is one of the most devastating orthopedic outcomes, and overuse of antibiotics may cause drug-resistance problems. Photothermal therapy(PTT) is a promising antibiotic-free strategy for treating infected bone defects. Considering the damage to normal tissues and cells caused by high-temperature conditions in PTT, this study combines the antibacterial property of Cu to construct a multi-functional Cu2 O@MXene/alpha-tricalcium phosphate (α-TCP) scaffold support with internal and external sandwiching through 3D printing technology. On the \"outside\", the excellent photothermal property of Ti3 C2 MXene is used to carry out the programmed temperature control by the active regulation of 808 nm near-infrared (NIR) light. On the \"inside\", endogenous Cu ions gradually release and the release accumulates within the safe dose range. Specifically, programmed temperature control includes brief PTT to rapidly kill early bacteria and periodic low photothermal stimulation to promote bone tissue growth, which reduces damage to healthy cells and tissues. Meanwhile, Cu ions are gradually released from the scaffold over a long period of time, strengthening the antibacterial effect of early PTT, and promoting angiogenesis to improve the repair effect. PTT combined with Cu can deliver a new idea forinfected bone defects through in vitro and vivo application.

Electron transfer plays an important role in various catalytic reactions and physiological activities, whose altered processes may change catalytic efficiency and interfere in physiological metabolic processes. In this study, we design an ultrasound (US)-activated piezoelectric responsive heterojunction (PCN-222-BTO, PCN: porous coordination network), which can change the electron transfer path at the abiotic and abiotic-biotic interfaces under US, thus achieving a rapid (15 min) and efficient bactericidal effect of 99.96%. US-induced polarization of BTO generates a built-in electric field, which promotes the electron transfer excited from PCN-222 to BTO at the PCN-222-BTO interface, thereby increasing the level of reactive oxygen species (ROS) production. Especially, we find that the biological electron transfer from the bacterial membrane to BTO is also activated at the MRSA-BTO interface. This antibacterial mode results in the down-regulated ribosomal, DNA and ATP synthesis related genes in MRSA, while the cell membrane and ion transport related genes are up-regulated due to the synergistic damage effect of ROS and disturbance of the bacterial electron transport chain. This US responsive dual-interface system shows an excellent therapeutic effect for the treatment of the MRSA-infected osteomyelitis model, which is superior to clinical vancomycin therapy.

Elimination of bacterial infections and simultaneously promoting osteogenic differentiation are highly required for infectious bone diseases. Massive reactive oxygen species (ROS) can damage cells, while low ROS concentrations as a molecular signal can regulate cellular fate. In this study, a Janus-ROS healing system is developed for infectious bone regeneration. An alendronate (ALN)-mediated defective metal-organic framework (MOF) sonosensitizer is prepared, which can effectively clear Methicillin-resistant Staphylococcus aureus (MRSA) infections and promote osteogenic differentiation under differential ultrasonic irradiation. In the presence of zirconium-phosphate coordination, the ALN-mediated porphyrin-based MOF (HN25) with a proper defect has great sonodynamic antibacterial efficiency (98.97%, 15 min) and bone-targeting ability. Notably, under low-power ultrasound irradiation, HN25 can increase the chromatin accessibility of ossification-related genes and FOXO1 to promote bone repair through low ROS concentrations. Animal models of paravertebral infection, fracture with infection, and osteomyelitis demonstrate that HN25 successfully realizes the targeted and potent repair of various infectious bone tissues through rapid MRSA elimination, inhibiting osteoclast activity and promoting bone regeneration. The results show that high catalytic efficiency and bioactive MOF can be constructed using pharmaceutical-mediated defect engineering. The Janus-ROS treatment is also a promising therapeutic mode for infectious tissue regeneration.

Staphylococcus aureus (S. aureus) contamination commonly occurs in orthopedic internal fixation operations, leading to a delayed healing of the defected bone tissue. However, antibiotic treatments are ineffective in dealing with S. aureus bone infections due to the rise in multiple antimicrobial resistances. Here, we reported the protective effects of a recombinant five-antigen S. aureus vaccine (rFSAV) in an S. aureus infected bone defect model. In this study, we found the number of M2 macrophages markedly increased in the defect site and played a critical role in the healing of defected bone mediated by rFSAV. Mechanistically, rFSAV mediated increased level of IL-13 in bone defect site predominant M2 macrophage polarization. In summary, our study reveals a key role of M2 macrophage polarization in the bone regeneration process in S. aureus infection induced bone defect, which provide a promising application of rFSAV for the treatment of bone infection for orthopedic applications.