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Osteosarcoma (OS) is the most common type of primary malignant bone tumor. The early lung metastasis of osteosarcoma is one of the main factors of poor prognosis. Therefore, searching for new targets and new mechanisms of osteosarcoma metastasis is essential for the prevention and treatment of osteosarcoma. Our previous studies suggested that fatty acid synthase (FASN) was an oncogene and promoted osteosarcoma. In addition, it is reported that the expression of miR-195 was negatively correlated with osteosarcoma. Aberrant DNA methylation can reversely regulate the expression of miRNAs. However, whether miR-195 could target FASN in osteosarcoma and whether ectopic DNA methylation is the upstream regulatory mechanism of miR-195 in metastasis of osteosarcoma are not fully studied. The expressions were detected by qPCR and western blot, and methylation level was determined by methylation-specific PCR. Luciferase reporter assay, MTT, wound healing, and Transwell assay were used. We found that the expression of miR-195 was low in osteosarcoma. The methylation of miR-195 was high. miR-195 targeted and decreased the expression of FASN. In osteosarcoma, miR-195 inhibited cell proliferation, cell migration, and invasion. The methylation of miR-195 was related to decreased miR-195, it might promote osteosarcoma.

Introduction The relationship between patient expectations and clinical outcomes has recently been of increasing interest in the field of orthopaedics. The objective of this study was to evaluate the relationships between (1) patient pre-treatment expectations and post-treatment clinical outcomes, and (2) fulfillment of expectations and patient satisfaction, following distal radius fracture. Methods This was a prospective multicenter cohort study conducted across three hospitals. A total of 133 patients admitted to hospital between 2016 and 2018 with a distal radius fracture were recruited. Patients were administered the Trauma Expectation Factor (TEF) at baseline to measure expectations of pain and functioning at one-year post-injury. Patients were followed up at 6 and 12 months post-injury and outcomes were measured using the Trauma Outcome Measure (TOM), Shortened Disabilities of the Arm, Shoulder and Hand (QuickDASH) questionnaire, and Short-Form 12-item (SF-12) health survey. Fulfillment of expectations was measured as TEF score minus TOM score at each time point. Patient satisfaction was also measured using the Patient Satisfaction Questionnaire Short Form (PSQ-18). Multivariate regression models were created to evaluate the effect of expectations on outcomes. Results Patient expectations correlated moderately with outcomes at 6 and 12 months post-injury. In the multivariate analysis, patient expectations were predictive of better outcomes at 6 and 12 months. Injury severity, age, mechanism of injury, and whether the injury occurred on duty also contributed significantly to one or more regression models. Patient satisfaction correlated weakly with fulfillment of expectations at 6 months, but moderately with all outcome scores. At 12 months, satisfaction did not correlate significantly with expectations fulfillment but correlated moderately to highly with all outcome scores. Conclusion Patient expectations independently predicted outcomes at 6 and 12 months post-injury. Standardized assessment and management of patient expectations may be relevant to future clinical practice and research to best quantify and optimize patient outcomes.

Background Exosomes derived from stem cells have been widely studied for promoting regeneration and reconstruction of multiple tissues as “cell-free” therapies. However, the applications of exosomes have been hindered by limited sources and insufficient therapeutic potency. Results In this study, a stem cell-mediated gene therapy strategy is developed in which mediator mesenchymal stem cells are genetically engineered by bone morphogenetic protein-2 gene to produce exosomes (MSC-BMP2-Exo) with enhanced bone regeneration potency. This effect is attributed to the synergistic effect of the content derived from MSCs and the up-regulated BMP2 gene expression. The MSC-BMP2-Exo also present homing ability to the injured site. The toxic effect of genetical transfection vehicles is borne by mediator MSCs, while the produced exosomes exhibit excellent biocompatibility. In addition, by plasmid tracking, it is interesting to find a portion of plasmid DNA can be encapsulated by exosomes and delivered to recipient cells. Conclusions In this strategy, engineered MSCs function as cellular factories, which effectively produce exosomes with designed and enhanced therapeutic effects. The accelerating effect in bone healing and the good biocompatibility suggest the potential clinical application of this strategy. Graphical Abstract

Zhenquan Lu,1,* Jian Hou,1,* Xiao Li,2 Jun Zhou,2 Bingfeng Luo,1 Songwu Liang,1 Richard K Lo,1 Tak Man Wong,2 Guan-Ming Kuang2 1Department of Urology, The University of Hong Kong-Shenzhen Hospital, Shenzhen, Guangdong Province, People’s Republic of China; 2Department of Orthopaedics and Traumatology, The University of Hong Kong-Shenzhen Hospital, Shenzhen, Guangdong Province, People’s Republic of China*These authors contributed equally to this workCorrespondence: Guan-Ming Kuang, Email kuanggm@hku-szh.orgAbstract: Purpose: The purpose of this study was to identify the potential exosome-derived microRNAs (miRNAs) related to prostate cancer (Pca) bone metastasis.Methods: Two datasets were collected. One dataset was from the authors’ institute, for which two groups of 10 patients each were designed: in the first one, the patients had early-stage localised Pca without bone metastasis, and in the other, the patients presented with Pca with bone metastasis. Then, the miRNA expression profiles of the blood exosomes were obtained and analysed. The other dataset was a public dataset of the miRNA expression transcriptome (GSE26964), which was downloaded from Gene Expression Omnibus (GEO). The results of both datasets were jointly analysed and the most bone-metastatic-related differentially expressed miRNAs (diff-miRNAs) were identified and further validated. Finally, a series of bioinformatics analyses were performed and the relationship between target genes of the diff-miRNAs and the pathogenesis and progression of bone metastasis of Pca were studied.Results: From the authors’ dataset, in all, 313 diff-miRNAs were identified, of which 205 were up-regulated while 108 were down-regulated. From the GSE26964 dataset, 107 diff-miRNAs were found, of which 44 were up-regulated and 63 were down-regulated. Taking the intersection of the results of both datasets, four diff-miRNAs were identified: hsa-miR-125a-3p, hsa-miR-330-3p, hsa-miR-339-5p and hsa-miR-613. In all, 94 target genes of the four diff-miRNAs were predicted. After considering the intersection of the results from the GSE32269 dataset, we obtained 25 target genes. Although either positive or negative correlations were found among the diff-miRNAs with some of the target genes, there is a lack of evidence on how such correlations regulate the development and promotion of Pca bone metastasis.Conclusion: Hsa-miR-125a-3p, hsa-miR-330-3p, hsa-miR-339-5p and hsa-miR-613 are potential biomarkers for Pca bone metastasis.Keywords: prostate cancer, bone metastasis, exosomes, bioinformatics analysis, miRNAs

Bone grafts are commonly used for the treatment of critical sized bone defects. Since the supply of autologous bone is insufficient, allogeneic bone grafts have been used most of the time. However, the poor osteogenic property of allogeneic bone grafts after pretreatment results in delayed union, non-union, or even occasional deformity. Calcium phosphate cement (CPC) is one of the most promising bone filling materials due to its good biocompatibility and similar chemical components as natural bone. However, clinical applications of CPC were hampered by limited osteogenic effects, undesired immune response which results in resorption, and poor mechanical stability in vivo. Magnesium (Mg) has been proven to trigger bone regeneration through modulating cell behaviors of mesenchymal stem cells and macrophages significantly. Unfortunately, the degradation raters of pure Mg and Mg oxide are extremely fast, resulting in early collapse of Mg contained CPC. In this study, we developed a novel magnesium contained calcium phosphate bone cement (Mg-CPC), possessing long-term mechanical stability and osteogenic effects through sustained release of Mg. Furthermore, in vitro studies showed that Mg-CPC had no cytotoxic effects on hBMMSCs and macrophage RAW 264.7, and could enhance the osteogenic differentiation as determined by alkaline phosphate (ALP) activity and calcium nodule staining, as well as suppress the inflammatory as determined by expression of anti-inflammatory cytokine IL-1RA. We also found that Mg-CPC promoted new bone formation and bone maturation in vivo. These results suggest that Mg-CPC should be a good substitute material for bone grafts in clinical use.

The most critical factor determining the success of biodegradable bone implants is the host tissue response, which greatly depends on their degradation behaviors. Here, a new magnesium‐based implant, namely magnesium–silicon–calcium (Mg–0.2Si–1.0Ca) alloy, that coordinates its biodegradation along with the bone regenerative process via a self‐assembled, multilayered bone–implant interface is designed. At first, its rapid biocorrosion contributes to a burst release of Mg2+, leading to a pro‐osteogenic immune microenvironment in bone. Meanwhile, with the simultaneous intervention of Ca and Si in the secondary phases of the new alloy, a hierarchical layered calcified matrix is rapidly formed at the degrading interface that favored the subsequent bone mineralization. In contrast, pure Mg or Mg–0.2Si alloy without the development of this interface at the beginning will unavoidably induce detrimental bone loss. Hence, it is believed this biomimicking interface justifies its bioadaptability in which it can modulate its degradation in vivo and accelerate bone mineralization., The spontaneously formed degradation layers at the bone–implant interface are the key to the superior performance of Mg–Si–Ca alloy, as they regulate the biodegradation behaviors of the implant to elicit an appropriate host response at different stages of bone healing.

Objective To compare the functional status and quality of life (QoL) between patients who underwent an early mobilization scheme and those who underwent a late mobilization scheme after hip fracture fixation surgery in elderly Chinese patients. Methods This was a prospective cohort study. Patients (≥65 years old) with unstable intertrochanteric fractures treated with intramedullary nails were recruited from nine centers in China. Study centers either performed early mobilization or late mobilization scheme. All patients performed immediate in-bed mobilization after surgery and followed a standardized daily exercise program at home during the first 12 weeks. Functional status was measured by the Modified Barthel Index at postoperative visit, 6 weeks, and 12 weeks. QoL was measured by the EuroQol-5D (EQ-5D) at 12 weeks. Results One hundred and forty-eight patients were enrolled to early mobilization, and 136 to late mobilization. At 6 weeks, early mobilization resulted in a significantly better Modified Barthel Index than late mobilization (mean [SD]: 83.7 [12.0] vs. 67.0 [17.5], p < .001). Adjusted mixed effects model showed significantly higher Modified Barthel Index for early mobilization at postoperative visit, 6 weeks, and 12 weeks (all p < .001). Patients in the early mobilization group had slightly better EQ-5D Index at 12 weeks than patients in the late mobilization group (mean: 0.91 vs 0.87, p = .002). Conclusions Early postoperative mobilization resulted in better functional outcomes up to 12 weeks. QoL was rated statistically significantly better in the early mobilization group, but the difference was small and may not be clinically relevant.

Introduction Our prototype wireless full-HD Augmented Reality Head-Mounted Display (AR-HMD) aims to eliminate surgeon head turning and reduce theater clutter. Learning and performance versus TV Monitors (TVM) is evaluated in simulated knee arthroscopy. Methods 19 surgeons and 19 novices were randomized into either the control group (A) or intervention group (B) and tasked to perform 5 simulated loose-body retrieval procedures on a bench-top knee arthroscopy simulator. A cross-over study design was adopted whereby subjects alternated between devices during trials 1-3, deemed the “Unfamiliar” phase, and then used the same device consecutively in trials 4-5, to assess performance in a more “Familiarized” state. Measured outcomes were time-to-completion and incidence of bead drops. Results In the unfamiliar phase, HMD had 67% longer mean time-to-completion than TVM (194.7 ± 152.6s vs 116.7 ± 78.7s, P < .001). Once familiarized, HMD remained inferior to TVM, with 48% longer completion times (133.8 ± 123.3s vs 90.6 ± 55s, P = .052). Cox regression revealed device type (OR = 0.526, CI 0.391-0.709, P < .001) and number of procedure repetitions (OR = 1.186, CI 1.072-1.311, P = .001) are significantly and independently related to faster time-to-completion. However, experience is not a significant factor (OR = 1.301, CI 0.971-1.741, P = .078). Bead drops were similar between the groups in both unfamiliar (HMD: 27 vs TVM: 22, P = .65) and familiarized phases (HMD: 11 vs TVM: 17, P = .97). Conclusion Arthroscopic procedures continue to be better performed under conventional TVM. However, similar quality levels can be reached by HMD when given more time. Given the theoretical advantages, further research into improving HMD designs is advocated.

Background: Currently dual-energy X-ray absorptiometry (DXA) and phantom-based quantitative computed tomography (PB-QCT) have been utilized to diagnose osteoporosis widely in clinical practice. While traditional phantom-less QCT (PL-QCT) is limited by the precision of manual calibration using body tissues, such as fat and muscle. Objective: The aim of this study is to validate the accuracy and precision of one newly-developed automatic PL-QCT system to measure spinal bone mineral density (BMD) and diagnose osteoporosis. Methods: A total of 36 patients were enrolled for comparison of BMD measurement between DXA and QCT. CT images of 63 patients were analyzed by both PB-QCT and newly developed automatic PL-QCT system, then the BMD results generated by the automatic PL-QCT were utilized to diagnose osteoporosis. The diagnostic outcomes were compared with that of DXA and PB-QCT to assess the performance of the new system. Results: BMD test results showed that the automatic PL-QCT system had higher precision than previous studies performed with QCT, while maintaining similar capability to diagnose osteoporosis as DXA and PB-QCT. Area under curve (AUC) result of PL-QCT was larger than 0.8 for predicting spine DXA T-score in receiver operating characteristic (ROC) analysis. Pearson correlation analysis (r ​= ​0.99) showed strong linear correlation and Bland-Altman analysis (bias ​= ​3.0mg/cc) indicated little difference between the two methods. The precision result (CV ​= ​0.89%) represented good reproducibility of the new system. Conclusion: The traditional PL-QCT system has relatively low reproducibility due to the manual selection of the region of interest (ROI) of body tissues. Automatic selection of ROI in this new system makes the BMD testing more convenient and improves precision significantly. Compared with traditional BMD measurement methods, the automatic PL-QCT system had higher precision in accurate diagnosis of osteoporosis with great potential in translational research and wide clinical application. Translational potential statement: With high accuracy and precision, the automatic PL-QCT system could serve as an opportunistic screening tool for osteoporosis patients in the future. It could also facilitate related researches by providing more reliable data collection, both retrospectively and longitudinally.

Surface topography has been reported to play a key role in modulating cell behaviors, yet the mechanism through which it modulates these behaviors is not fully understood, especially in the case of three-dimensional (3D) topographies. In this study, a series of novel hemispherical 3D imprints ranging from the nanoscale to the microscale were prepared on titanium (Ti) surfaces using a customized interfacial lithography method. Mouse embryo osteoblast precursor cells (MC3T3-E1) were selected to investigate the solitary effect of specific hemispherical 3D imprints on cellular behaviors. The results indicated that varied hemispherical 3D imprints can affect the formation of filopodia and the arrangement of the cytoskeleton in different ways. Specifically, they can alter the spreading morphologies of cells and lead to deformation of the nucleus, which eventually affects cell proliferation and osteogenic differentiation. Cells cultured on different hemispherical 3D imprints exhibited promoted proliferation and osteogenic differentiation to different degrees; for example, cells cultured on 90 and 500 nm hemispherical imprints formed abundant filopodia and exhibited the highest alkaline phosphatase activity and osteogenic gene expression, respectively. Four-week tibia implantation also confirmed that 90 nm hemispherical imprints improved the osteogenic ability in vivo compared with an unpatterned Ti substrate. In addition to promoted proliferation, colonization of more cells on the surface of implants and induction of rapid osteogenic differentiation can occur. Our work provides a rational way to balance cell proliferation and differentiation, which can accelerate bone integration of an implant and host tissue.

Developing an ideal wound dressing that not only accelerates wound healing but also eliminates potential bacterial infections remains a difficult balancing act. This work reports the design of a light-programmable sodium alginate nanocomposite hydrogel loaded with BiOCl/polypyrrole (BOC/PPy) nanosheets for state-switchable wound healing promotion and bacterial infection elimination remotely. The nanocomposite hydrogel possesses programmable photoelectric or photothermal conversion due to the expanded light absorption range, optimized electron transmission interface, promoted photo-generated charge separation, and transfer of the BOC/PPy nanosheets. Under white light irradiation state, the nanocomposite hydrogel induces human umbilical vein endothelial cells migration and angiogenesis, and accelerates the healing efficiency of mouse skin in vivo. Under near-infrared light irradiation state, the nanocomposite hydrogel presents superior antibacterial capability in vitro, and reaches an antibacterial rate of 99.1% for Staphylococcus aureus infected skin wound in vivo. This light-programmable nanocomposite hydrogel provides an on-demand resolution of biological state-switching to balance wound healing and elimination of bacterial infection.

Areal and volumetric BMD (aBMD and vBMD) measured by DXA and quantitative CT (QCT), respectively, are usually employed to predict vertebral fracture risks. In this study, we induced compression and wedge vertebral fractures to test if the types of fracture could influence the selection of bone mineral measures to predict biomechanical properties of vertebral bodies. DXA and QCT were employed to scan twenty-four male cadaveric vertebral bodies of humans for bone mineral content (BMC) and aBMD measures, and vBMD measures, respectively. We computed vBMD measures from three kinds of volumes of interest: intact structures (vertebral body, cortical compartment, and trabecular core), axially middle sections (1.250–1.875 cm height) of the intact structures, and clinically used elliptical regions of trabecular bone. We loaded vertebral bodies to failure for properties of strength ( P u ), failure displacement ( δ u ), and stiffness (K). Thirteen vertebral bodies sustained compression fractures and the remaining sustained wedge fractures. Linear and power regression models were used to test bone mineral predictions for P u , δ u , and K. We also did equality tests of correlation coefficients. Our results showed aBMD, BMC, and vBMD of the middle section of trabecular bone had the strongest correlations with P u (R2 = 0.6420, p δ u (R2 = 0.4619, p P u (R2 = 0.6529, p δ u (R2 = 0.4376, p P u (R2 = 0.5845, p δ u . These results may suggest the type of fracture could influence the determination of bone mineral measures to predict biomechanical properties of vertebral bodies.

Background: Percutaneous insertion of third-generation straight humeral nails is a recent alternative to the conventional open method. Rather than splitting, retracting and subsequently repairing the supraspinatus fibers to visualize the humeral head entry site, the percutaneous approach utilizes a cannulated awl to enter the intramedullary canal through the supraspinatus fibers without visualizing internal shoulder structures. Despite recent evidence demonstrating satisfactory outcomes in the percutaneous method, the potential for iatrogenic injury to the rotator cuff and other shoulder structures is not fully understood. Materials and Methods: We performed an anatomical study of 46 shoulders in 23 cadavers to compare damage caused to internal shoulder structures between the open and percutaneous techniques. Dimensions and morphologies of supraspinatus and humeral head perforations were recorded. Results: The percutaneous technique produced greater latitudinal tearing ( p = 0.002) and less longitudinal tearing ( p < 0.001) of muscle fibers, however there was no difference in supraspinatus hole area ( p = 0.748). The long head biceps tendon was within 3 mm of the bone entry hole in 13 (28%) shoulders, with one shoulder in the open group exhibiting full tendon transection. Conclusions: Percutaneous insertion of intramedullary nails using a cannulated awl appears to produce similar soft tissue and bone entry site morphology as compared to the conventional open technique. The percutaneous method was associated with slightly greater latitudinal tearing, however the effects of this remain to be clarified through clinical studies. External rotation should be avoided during instrumentation to reduce the risk of biceps tendon transection.

Introduction Topical application of tranexamic acid (TXA) has been proposed as an alternative to intravenous administration to reduce perioperative bleeding in orthopaedic surgery. The purpose of this randomised controlled trial was to evaluate the efficacy and safety of 1 g topically applied TXA in patients undergoing fixation of intertrochanteric hip fractures by short femoral nailing. Methods A total of 121 patients were enrolled between May 2018 and January 2020. Patients were randomly allocated (1:1) to receive either 10 mL (1 g) of TXA or 10 mL of normal saline (NS) injected through the subfascial drain following wound closure. Total blood loss, total drain output and blood transfusion requirements up to postoperative day 3 were recorded. Rates of thromboembolic complications and mortality up to 90 days postoperatively were also compared. Results There was no statistically significant difference in total blood loss, total drain output or proportion of patients requiring transfusions. Median total blood loss was 1.088 L (IQR: 0.760-1.795) in the TXA group and 1.078 L (IQR: 0.797-1.722) in the NS group (P = .703). Median total drain output was 60 mL (IQR: 40-140) in the TXA group and 70 mL (IQR: 30-168) in the NS group (P = .696). Blood transfusions were administered in 29 patients (47.5%) in the TXA group and 27 patients (45.0%) in the NS group (P = .782). There was also no difference in frequency of thrombotic complications or mortality within 90 days. There were five thrombotic events in the TXA group and four in the NS group (P = .751). The 90-day mortality rate was 6.6% (4 patients) in the TXA group and 3.3% (2 patients) in the NS group (P = .680). Conclusion A 1 g dose of topically administered TXA did not produce any difference in blood loss, transfusion requirements, thromboembolic complications, or 90-day mortality. Future trials may consider the effect of larger doses in patients undergoing hip fracture fixation surgery.

Proper immune responses are critical for successful biomaterial implantation. Here, four scales of honeycomb-like TiO2 structures were custom made on titanium (Ti) substrates to investigate cellular behaviors of RAW 264.7 macrophages and their immunomodulation on osteogenesis. We found that the reduced scale of honeycomb-like TiO2 structures could significantly activate the anti-inflammatory macrophage phenotype (M2), in which the 90-nanometer sample induced the highest expression level of CD206, interleukin-4, and interleukin-10 and released the highest amount of bone morphogenetic protein-2 among other scales. Afterward, the resulting immune microenvironment favorably triggered osteogenic differentiation of murine mesenchymal stem cells in vitro and subsequent implant-to-bone osteointegration in vivo. Furthermore, transcriptomic analysis revealed that the minimal scale of TiO2 honeycomb-like structure (90 nanometers) facilitated macrophage filopodia formation and up-regulated the Rho family of guanosine triphosphatases (RhoA, Rac1, and CDC42), which reinforced the polarization of macrophages through the activation of the RhoA/Rho-associated protein kinase signaling pathway.

Purpose:To evaluate the quality of reduction and clinical outcomes by using Percutaneous Distractor and Subtalar Arthroscopy Closed Reduction followed by Internal Fixation (PDSA-CRIF) in the intra-articular calcaneal fracture.Methods:A consecutive case series of 453 patients with 507 displaced intra-articular calcaneal fractures was recruited in this retrospective study. We performed PDSA-CRIF to treat intra-articular calcaneal fractures. The quality of reduction was assessed by early postoperative Computed Tomography (CT) scans and measurement of serial Bohler’s angles during follow-ups. Clinical outcomes were evaluated by Visual Analogue Scale (VAS) and the American Foot & Ankle Society ankle-hind foot scale (AOFAS) scoring system.Results:Fifty-nine patients (68 fractures) who had complete clinical data and follow-up of at least 12-months (mean: 14 months, range: 12–59 months) were finally included. Anatomical and near-anatomical reduction in subtalar articular surface which had less than 2 mm gap or step-off was found in 93% fractures. Unsatisfactory reduction was found in 7%.Conclusion:Arthroscopic-assisted percutaneous fixation using a distraction device is effective in achieving positive short-term results in the displaced intra-articular calcaneal fractures. A multicenter, large sample, randomized control trial is needed to fully evaluate the long-term effects of PDSA-CRIF in comparison to other methods.

Intra-articular fibroma of tendon sheath is a rare disease. To our knowledge, less than 20 cases have been reported in the literature, and none of them was a Chinese patient. In this case report, we present a Chinese patient with intra-articular fibroma of tendon sheath of the knee joint which was excised arthroscopically. We also summarized the clinical presentation, diagnosis, and subsequent management of intra-articular fibroma of tendon sheath.

Background: Plate fixation is frequently used to treat displaced midshaft clavicular fractures, however the ideal plate choice remains subject to discussion; reconstruction locking compression plates (RLCPs) are cheaper and can be easily contoured, whereas anatomically pre-contoured locking compression plates (ALCPs) are thought to provide better stability and therefore lower rates of mechanical failure. Objective: To compare the incidence of mechanical failures, functional and radiological outcomes in patients with midshaft clavicular fractures treated with ALCPs versus RLCPs. Methods: A propensity score matched retrospective cohort study was conducted across two trauma centers. 114 consecutively recruited patients with displaced midshaft clavicular fractures, who were treated with plate fixation and had a minimum follow-up of 6 months, were matched on gender, age, fracture grading, energy of injury, and fracture location. The resulting groups included 53 ALCP-treated fractures and 53 matched controls treated with RLCPs. Results: During a mean follow-up of 20.5 months, there were no implant deformities in the ALCP group whereas the RLCP group had 6 patients (11.3%, p=0.012) with implant deformities (5 occurrences of plate bending with fracture union, and 1 plate breakage with nonunion). Despite the higher rate of plate deformities in the RLCP group, there were no statistically significant differences in number of patients recovering full shoulder range of motion (ALCP 90.6%, RLCP 88.7%, p=0.751), incidence of rest pain (ALCP 13.2%, RLCP 9.4%, p=0.542), or implant removals (ALCP 49.1%, RLCP 56.6%, p=0.439). Conclusion: ALCPs may be superior to RLCPs in terms of implant stability but appear to produce similar clinical results. Keywords: anatomical plate; locking plate; clavicle fracture; plate fixation; midshaft clavicle

Background One of the characteristics of osteoporotic bone is the deterioration of trabecular microarchitecture. Previous studies have shown microarchitecture alone can vary the apparent modulus of trabecular bone significantly independent of bone volume fraction (BV/TV) from morphological and topological perspectives. However, modulus is a mechanical quantity and there is a lack of mechanical explanatory parameters. This study aims to propose a novel mechanical parameter to quantify the microarchitecture effect on the apparent modulus of trabecular bone. Materials and methods Fourteen human female cadaveric vertebrae were scanned with a dual-energy X-ray (DXA) equipment followed by a micro-CT (μCT) system at 18 μm isotropic resolution. Four trabecular bone specimens (3.46 × 3.46 × 3.46 mm) were obtained from each vertebral body and converted to voxel-based micro finite element (μFE) models. The apparent modulus (E) of the μFE model was computed using a linear micro finite element analysis (μFEA). The normalized apparent modulus (E*) was computed as E divided by BV/TV. The relationship between E and BV/TV was analyzed by linear, power-law and exponential regressions. Linear regression was performed between E* and BV/TV. Ineffective bone mass (InBM) was defined as the bone mass with a negligible contribution to the load-resistance and represented by elements with von Mises stress less than a certain stress threshold. InBM was quantified as the low von Mises stress ratio (LSVMR), which is the ratio of the number of InBM elements to the total number of elements in the μFE model. An incremental search technique with coarse and fine search intervals of 10 and 1 MPa, respectively, was adopted to determine the stress threshold for calculating LSVMR of the μFE model. Correlation between E* and LSVMR was analyzed using linear and power-law models for each stress threshold. The threshold producing the highest coefficient of determination (R2) in the correlation between E* and LSVMR was taken as the optimal stress threshold for calculating LSVMR. Linear regression was performed between E and LSVMR. Multiple linear regression of E against both BV/TV and LSVMR was further analyzed. Results E significantly (p Conclusion LSVMR can be adopted as the mechanical parameter to quantify the microarchitecture effect on the apparent modulus of trabecular bone.

Study design Cadaveric biomechanical with imaging analysis. Objective This study aims to compare the fixation failure between pedicel screws (PS) and cortical screws (CS), thus to investigate their failure mechanisms under vertical migration. Summary of background data Due to their minimal invasive nature, CS are gaining popularity. However, contradictions exist in the literature regarding whether CS may have superior fixation failure resistance compared to PS under vertical migration. Methods Human vertebral specimens were examined under Dual-energy X-ray. For each specimen, PS were inserted on the left and CS on the right with rods secured. Vertical force-displacement tests were applied to rods. MicroCT images were taken pre and post-MTS® for microstructural analysis. Results The average T-scores of the specimens were −4±0.25. Three phases of force-displacement behaviour featuring different PS and CS failure-resistance were discovered. For phase I, the force required to migrate PS tended to be slightly higher than CS. However, during phase II, a fixation instability occurred for PS and the CS fixation strength was superior. For phase III under large displacement, CS did not require increased force to displace, whereas PS re-stabilised and revealed improved displacement resistance. Both force analysis and microstructural analysis indicated that PS migrated along the direction of the vertical loading, whereas CS had a force component in the longitudinal axis of the screw. Conclusions Different failure mechanisms underlay PS and CS under large vertical displacement. PS fail with trabecular bone compaction possibly altering the initial material property surround the screw. CS fail with screw cut-out due to the force component along the screw axis.

To prevent the attachment of bacteria to implant surfaces, the 1D zinc oxide nanowire-coating has been successfully developed on material surfaces by using a custom-made hydrothermal approach. The chemical nature, surface topography and wettability of spike-like 1D ZnO nanowire-coating are comprehensively investigated. The anti-adhesive and antimicrobial properties of 1D nanowire-coating are tested against Staphylococcus aureus, Pseudomonas aeruginosa and Escherichia coli by using in vitro live/dead staining and scanning electron microscopy. We find that the adhesion of bacteria can be reduced via the special spike-like topography and that the release of Zn(2+) ions can help suppress the growth of attached bacteria. Furthermore, the antimicrobial effect is also evaluated under in vivo conditions by using a rat model infected with bioluminescent S. aureus. The amount of live bacteria in the rat implanted with a nanowire-coated sample is less than that of the control at various time points. Hence, it is believed that the nanowire-coated material is promising for application in orthopaedic implantation after the long-term animal studies have been completed.

Introduction: Osteoporosis is one of the major fundamental causes of fractures in individuals over 50 years old. Preventing the first fragility fracture is the most cost-effective strategy for addressing osteoporosis. Therefore, identifying individuals with a high risk of developing osteoporotic fractures is important to save limited medical resources. The Fracture Risk Assessment Tool (FRAX) has been used globally for assessing fracture risk. However, the accuracy of FRAX still needs to be improved partially because of the differences in race and socioeconomic status among nationalities. Methods: In this study, we evaluated the effectiveness of FRAX in Chinese people. The factors not involved in FRAX were also evaluated for a correlation with osteoporotic fracture risks. Results: Age, smoking status, alcohol intake, family history of osteoporotic fracture, diabetes mellitus type II, Charlson Index, vitamin D intake, calcium intake, muscle strength, modified Barthel Index, the 3-level version of EuroQol five dimensions questionnaire, and bone mineral density demonstrated significant differences between the fracture and control groups. Our results also demonstrated that dual-energy X-ray absorptiometry (DEXA)-diagnosed osteoporosis (T ≤ −2.5) was the independent fracture risk factor. The effects of age, muscle strength, and Charlson Index on DEXA were found to be statistically significant. People old over 60, muscle strength test supine leg lift less than 20 times per minute, aCCI scores greater than or equal to 2, had lower DEXA T values (T ≤ −2.5). Discussion: This work was a single-center study, showed social economic status bias, and featured a limited number of cases. Therefore, multi-center studies are necessary in the future. Conclusions: This study revealed that FRAX should be improved further in combination with other risk factors, including aCCI, calcium intake, and muscle strength.

Side-effects from allograft, limited bone stock, and site morbidity from autograft are the major challenges to traditional bone defect treatments. With the advance of tissue engineering, hydrogel injection therapy is introduced as an alternative treatment. Therapeutic drugs and growth factors can be carried by hydrogels and delivered to patients. Abaloparatide, as an analog of human recombinant parathyroid hormone protein (PTHrp) and an alternative to teriparatide, has been considered as a drug for treating postmenopausal osteoporosis since 2017. Since only limited cases of receiving abaloparatide with polymeric scaffolds have been reported, the effects of abaloparatide on pre-osteoblast MC3T3-E1 are investigated in this study. It is found that in vitro abaloparatide treatment can promote pre-osteoblast MC3T3-E1 cells' viability, differentiation, and mineralization significantly. For the drug delivery system, 3D porous structure of the methacrylated gelatin (GelMA) hydrogel is found effective for prolonging the release of abaloparatide (more than 10 days). Therefore, injectable photo-crosslinked GelMA hydrogel is used in this study to prolong the release of abaloparatide and to promote healing of defected bones in rats. Overall, data collected in this study show no contradiction and imply that Abaloparatide-loaded GelMA hydrogel is effective in stimulating bone regeneration.

Introduction: The purpose of this study was to test whether local filling of a novel strontium-containing hydroxyapatite (Sr-HA) bone cement can augment the fixation of a locking plate system in a cadaveric proximal humeral facture model. Materials and Methods: Twelve pairs of formalin-treated cadaveric humeri were used. One side in each pair was for cemented group, while the other side was for the control group. The bone mineral density (BMD) of the samples was tested. A 3-part facture model was created and then reduced and fixed by a locking plate system. In the cemented group, the most proximal 4 screw holes were filled with 0.5 mL bone cement. In the control group, the screw holes were not filled by cement. Locking screws were inserted in a standard manner before the cement hardened. X-ray was taken before all the specimens being subjected to mechanical study, in which 6 pairs were used for axial loading (varus bending) test, while other 6 pairs were used for axial rotational test. Results: There is no difference in BMD between the cemented side and the control side. The X-ray shows that the implant is in position. Cement filling was noted in the most proximal 4 screws in the cemented group. Better mechanical outcome was seen in the cemented groups, in terms of less maximal displacement per cycle and higher failure point and stiffness in varus bending test. However, no difference was found between the cemented group and the control group in the axial rotation test. Discussion: In similarity with the previous studies, our results showed better mechanical results in the cemented group. However, due to the limitations (e.g. sample size, fracture model, testing protocol, etc), we still cannot directly extrapolate current mechanical results to clinical practice at the present moment. Furthermore, it is still unknown whether better primary outcome may lead to better long-term results, even though the local release of strontium may enhance the local bone formation. Conclusion: The local filling of Sr-HA bone cement augments the fixation of the locking plate system in current proximal humeral fracture model.

Rotational malalignment during femoral nailing is common despite having various intraoperative assessment methods. The cortical step sign and diameter difference sign (CSSDDS) is commonly used because of convenience, yet it lack proper scientific scrutiny and is thought to be error prone. Using a software algorithm, cross-sectional dimensions were obtained from CT scans of 22 intact adult femurs at the proximal, mid and distal diaphysis. With multiple simulated scenarios the sensitivity of CSSDDS was comprehensively determined at all possible C-arm positions. At rotation, cortical width changed most significantly around the thick linea aspera and femoral diameter changed most significantly at the sagittal plane. At 15 degrees of rotation and with the linea aspera in view, CSSDDS thresholds of 0.3mm, 0.6mm and 1mm had sensitivities of 98.8%, 93.1% and 73.8%. With the linea aspera masked behind the femur and out of view, the sensitivities significantly deteriorated to 96.4%, 77.1% and 44.1% respectively. CSSDDS is sufficiently sensitive only when strict rules are followed. It is imperative that the operator position the image intensifier in lateral view under proper magnification so that steps of less than 0.6mm around the linea aspera may be appreciated.

Case: We describe 2 patients who sustained a periprosthetic humeral fracture with a loosened long-stemmed Coonrad-Morrey total elbow prosthesis. As noted in the literature, the success rate for a major revision with use of strut grafts is around 70%; therefore, both cases were managed without revision of the prosthesis. A submuscular locking plate was placed following typical fracture fixation principles. Screws that interfered with the humeral stem and the distal flange stabilized both the distal fragment and the humeral stem. Conclusion: At 2 years postoperatively, both fractures had healed, with increased endosteal bone stock. In each case, the prosthesis was successfully salvaged, and radiographic reconstitution of the implant-bone interface was noted after 2 years.

The association between delayed hip fracture surgery and mortality remains elusive because of strong confounding by comorbidity factors. We designed a study to investigate the effect of small delays in surgery due to holidays.Consecutive hip fractures operated in a high-income, publicly funded healthcare system between 2006 and 2013 were analysed. Age65 years, pathological fractures, history of previous hip operation and time to surgeryseven days were excluded. Patients were grouped according to number of holidays following admission (HFA) as a surrogate for time to surgery, with difference in mean time to surgery tested for statistical significance and baseline characteristics including age, sex, Charlson comorbidity index (CCI) and fracture and operation types assessed. Survival up to two years was compared.Thirty-one thousand five hundred and ninety-two patients were included. Patient groups with zero, one, two or three HFA had significantly different mean time to operation of 2.25, 2.47, 2.67 and 2.84 days, respectively (Kruskal-Wallis test p 0.0001), but baseline characteristics were similar. There was no difference in mortality at six months (p = 0.431) and two years (p = 0.785). Cox's regression analysis identified age, gender and CCI as independent predictors of mortality but not HFA, and the adjusted hazards ratio for each HFA increment was 1.026 [95% confidence interval (CI) 0.999-1.025; p = 0.056] which was not statistically significant.We observed no increase in mortality rate in patients having small delays in surgery because of holidays.

Objectives: This study aims to identify if wintertime surgery increases the mortality of the patients after hip fracture operations. Design: Retrospective observational cohort study. Setting: The data for this citywide retrospective observational cohort study came from Clinical Data Analysis Reporting System. Patient: This study included 35 409 patients with hip fracture operations from July 2005 to December 2013. Main Outcome Measures: Cox regression hazard model was used to estimate the independent effect of operation being performed in winter on the hazard of mortality. The hazard model included covariates found to be independent predictors of mortality: age, sex, surgical delay, and Charlson Comorbidity Index (CCI). Results: There was a seasonal variation with more hip fracture operations happening in the winter months. The 1-month, 6-month, 1-year, and 5-year mortality were 3%, 11%, 17%, and 47%, respectively. Operation performed in winter was associated with a higher hazard of mortality (hazard ratio [HR] 1.040; 95% confidence interval: 1.010-1.072; P = .009). The HR was greater with male sex (HR 1.786; P = .000), advanced age (≥85 years old: HR 2.819; P = .000), the longer surgical delay (HR 1.018; P = .000), and higher CCI (severe CCI group: HR 2.963; P = .000). Conclusion: Wintertime hip fracture surgery was associated with an increased hazard of mortality after adjusting for other known risk factors affecting mortality post hip fracture operations.

Three-dimensional (3-D) printing or additive manufacturing, an advanced technology that 3-D physical models are created, has been wildly applied in medical industries, including cardiothoracic surgery, cranio-maxillo-facial surgery and orthopaedic surgery. The physical models made by 3-D printing technology give surgeons a realistic impression of complex structures, allowing surgical planning and simulation before operations. In orthopaedic surgery, this technique is mainly applied in surgical planning especially revision and reconstructive surgeries, making patient-specific instruments or implants, and bone tissue engineering. This article reviews this technology and its application in orthopaedic surgery.

Cutaneous wounds, especially chronic wounds, remain clinical challenges, and this is partially due to the complex healing process composed of four overlapping but distinct stages including hemostasis, inflammation, proliferation and remodeling. Therefore, wound dressings with spatially designed structures which can temporally regulate certain bioactive components to function at specific healing stages might be able to accelerate the healing process. In this study, nanobioglass incorporated chitosan-PVA (polyvinyl alcohol) trilayer nanofibrous membrane (nBG-TFM) was fabricated via sequential electrospinning. This membrane exhibited excellent biocompatibility, antibacterial activity and regeneration promotion effect. Furthermore, spatially designed structure optimized functions of each component and provided more suitable microenvironment as compared with uniform membrane. Rat full-thickness skin defects model and mice diabetic chronic wound model showed that nBG-TFM could achieve significantly accelerated and enhanced healing, in terms of complete re-epithelialization, improved collagen alignment and formation of skin appendages. It was revealed that nBG-TFM functioned through upregulating growth factors including VEGF and TGF-β. Meanwhile inflammatory cytokines such as TNF-α and IL-1β were downregulated. The technology presented in this study shed new light on designing functional wound dressings which can promote healing of chronic wounds.

Rapid corrosion of biodegradable magnesium alloys under in vivo condition is a major concern for clinical applications. Inspired by the stability and biocompatibility of titanium oxide (TiO2) passive layer, a functionalized TiO2/Mg2TiO4 nano-layer has been constructed on the surface of WE43 magnesium implant by using plasma ion immersion implantation (PIII) technique. The customized nano-layer not only enhances corrosion resistance of Mg substrates significantly, but also elevates the osteoblastic differentiation capability in vitro due to the controlled release of magnesium ions. In the animal study, the increase of new bone formation adjacent to the PIII-treated magnesium substrate is 175% higher at post-operation 12 weeks, whereas the growth of new bone on titanium control and untreated magnesium substrate are only 97% and 29%, respectively. In addition, its Young's modulus can be restored to about 82% as compared with the surrounding matured bone. Furthermore, this specific TiO2/Mg2TiO4 layer even exhibits photoactive bacteria disinfection capability when irradiated by ultraviolet light which is attributed to the intracellular reactive oxygen species (ROS) production. With all these constructive observations, it is believed that the TiO2/Mg2TiO4 nano-layer on magnesium implants can significantly promote new bone formation and suppress bacterial infection, while the degradation behavior can be controlled simultaneously.

Bone and surgical site infections after osteosynthesis are notoriously difficult to manage and pose a tremendous burden in fracture management. In this article, we use the term osteosynthesis-associated infection (OAI) to refer to this clinical entity. While relatively few surgically treated fractures become infected, it is challenging to perform a rapid diagnosis. Optimal management strategies are complex and highly customized to each scenario and take into consideration the status of fracture union, the presence of hardware and the degree of mechanical stability. At present, a high level of relevant evidence is unavailable; most findings presented in the literature are based on laboratory work and non-randomized clinical studies. We present this overview of OAI in two parts: an examination of recent literature concerning OAI pathogenesis, diagnosis and classification and a review of treatment options.

of fragility hip fracture also increases. By 2050, the incidence is predicted to be around 4.5 million.1 Treatment of intracapsular hip fractures depends on many factors including patient age, fracture pattern, degree of fracture displacement and comorbidities. For younger patients (

Double dislocation of carpometacarpal and metacarpo-phalangeal joints of thumb is also called ‘floating thumb metacarpal’. This rare injury usually presents with combined joints dislocation and collateral ligaments rupture, which may be predisposing to joint instability after closed reduction. We report a case of traumatic and chronic dislocation of carpometacarpal and metacarpo-phalangeal joints of left thumb in a 63-year-old housewife. Failure of non-operative treatment was found up to 1 month after injury due to missed follow-up. Closed reduction was tried but failed because of joints stiffness. Open reduction and K-wire fixation were performed and radial collateral ligaments were repaired. Patient restored good functional outcome with no evidence of arthritis or subluxation at 1 year. Open reduction and fixation show good result in our case with delayed surgical intervention. The management of a floating thumb could be non-operative by close reduction and cast immobilization. However, closed monitoring and regular follow-up are critical after non-operative treatment to avoid potential risk of post-operative complications.

We compared the Austin Moore hemiarthroplasty versus cemented hemiarthroplasties using a propensity score matched cased control study. For a consecutive cohort of 450 patients with displaced intracapsular neck of femur fractures, 128 matched cases in each group were selected based on age, gender, walking status, nursing home residency, delays in surgery, ASA score, and the Charlson comorbidity score. At a mean follow-up of 16.3 months, we evaluated their outcomes. Significantly more patients with AMA experienced thigh pain (RR = 3.5, 95% CI: 1.67–7.33, p=0.000), overall complications (RR = 4.47, 95% CI: 1.77–11.3,p=0.000), and implant loosening (RR = 8.42, 95% CI: 2.63–26.95,p=0.000). There were no definite cement related deaths in this series. There was no significant difference in mortality, walking status, and the number of revisions between the groups. We support the routine use of cemented hemiarthroplasty instead of the Austin Moore for treating elderlies with displaced intracapsular neck of femur fractures.