Three Birds, One Stone: An Osteo-Microenvironment Stage-Regulative Scaffold for Bone Defect Repair through Modulating Early Osteo-Immunomodulation, Middle Neovascularization, and Later Osteogenesis.

In order to repair critical-sized bone defects, various polylactic acid-glycolic acid (PLGA)-based hybrid scaffolds are successfully developed as bone substitutes. However, the byproducts of these PLGA-based scaffolds are known to acidify the implanted site, inducing tiresome acidic inflammation. Moreover, these degradation productions cannot offer an osteo-friendly microenvironment at the implanted site, matching natural bone healing. Herein, inspired by bone microenvironment atlas of natural bone-healing process, an osteo-microenvironment stage-regulative scaffold (P80/D10/M10) is fabricated by incorporating self-developed decellularized bone matrix microparticles (DBM-MPs) and multifunctional magnesium hydroxide nanoparticles (MH-NPs) into PLGA with an optimized proportion using low-temperature rapid prototyping (LT-RP) 3D-printing technology. The cell experiments show that this P80/D10/M10 exhibits excellent properties in mechanics, biocompatibility, and biodegradability, meanwhile superior stimulations in osteo-immunomodulation, angiogenesis, and osteogenesis. Additionally, the animal experiments determined that this P80/D10/M10 can offer an osteo-friendly microenvironment in a stage-matched pattern for enhanced bone regeneration, namely, optimization of early inflammation, middle neovascularization, and later bone formation. Furthermore, transcriptomic analysis suggested that the in vivo performance of P80/D10/M10 on bone defect repair is mostly attributed to regulating artery development, bone development, and bone remodeling. Overall, this study reveals that the osteo-microenvironment stage-regulative scaffold provides a promising treatment for bone defect repair.

Post-traumatic distal ulnar bifurcation in children: a case report.

BACKGROUND: Galeazzi fracture dislocation is a compound injury that encompasses fractures of the distal third of the radius and dislocation of the distal radial ulnar joint (DRUJ). Clinically, this condition is rare and often leads to distal ulnar bifurcation. In previous similar reports, patients were effectively managed through surgery. CASE PRESENTATION: In this case report, we describe an 11-year-old male child who presented with an ulnar bifida following trauma to the hand, and was treated with manipulation and conservative treatment without surgery. A follow-up performed over the years demonstrated that the patient recovered well, and had normal wrist movements without significant pain, and the patient expressed great satisfaction. CONCLUSIONS: Ulnar diaphyseal fracture may occur in children or adolescents due to injuries, and may be accompanied with manipulation and repositioning. Conservative treatment can be applied to avoid the trauma associated with surgery especially in the absence of severe joint mobility impairment with good outcomes.

Mg2+ -mediated autophagy-dependent polarization of macrophages mediates the osteogenesis of bone marrow stromal stem cells by interfering with macrophage-derived exosomes containing miR-381.

Magnesium ion (Mg2+ ) has received increased attention due to the roles it plays in promoting osteogenesis and preventing inflammation. This study was designed to investigate the mechanism by which Mg2+ influences the osteoblastic differentiation of bone marrow stromal stem cells (BMSCs). The polarization of Mø (macrophages) was measured after treatment with Mg2+ . Meanwhile, autophagy in Mø was measured by detecting LC3B expression. Mø-derived exosomes were isolated and cocultured with BMSCs; after which, osteogenic differentiation was evaluated by Alizarin Red staining and detection of alkaline phosphatase (ALP). Our results showed that Mg2+ could induce autophagy in macrophages and modulate the M1/M2 polarization of macrophages. Mg2+ -mediated macrophages could facilitate the osteogenic differentiation of BMSCs by regulating autophagy, and this facilitation by Mg2+ -mediated macrophages was closely related to macrophage-derived exosomes, and especially exosomes containing miR-381. However, miR-381 in macrophages did not influence autophagy or the polarization of Mg2+ -mediated macrophages. Furthermore, macrophage-derived exosomes containing miR-381 mainly determined the osteogenic differentiation of BMSCs. Mg2+ -mediated macrophages were shown to promote the osteogenic differentiation of BMSCs via autophagy through reducing miR-381 in macrophage-derived exosomes. In conclusion, our results suggest Mg2+ -mediated macrophage-derived exosomes containing miR-381 as novel vehicles for promoting the osteogenic differentiation of BMSCs.

Three-dimensional mapping of distal humerus fracture.

BACKGROUND: Distal humerus fractures (DHFs) constitute one-third of elbow fractures approximately. In this study, we aim to define and analyze the fracture lines and morphological features of DHFs using mapping technique. METHODS: One hundred and two DHFs were retrospectively reviewed. All the computed tomography (CT) data were used to manually reconstruct and virtually reduce the DHF fragments to fit a standard 3D model. Smooth curves were depicted accurately onto the surface of the template to represent the fracture lines. All the curves were overlapped onto the model to create the 3D fracture map and heat map. RESULTS: Our analysis was based on 102 CT images of DHFs, contributed by 59 male and 43 female patients (mean age, 46 years; range, 18-93 years), and included 15 type A, 25 type B, and 62 type C fractures. On mapping, the hot zones were located in the radial fossa, coronoid fossa, olecranon fossa, and the external part of the trochlear. Conversely, the cold zones were noted in medial condyle, the medial side of the trochlear, and the anterolateral area on the supracondylar ridge. CONCLUSIONS: Our study firstly shows the fracture lines and morphological features of distal humeral fractures by three-dimensional mapping technology. Distal humerus fracture lines are characteristic and highly related to the micro-architecture difference of distal humerus, which may provide some guidance for the treatment plan selection and surgical fixation design.

Mg(OH)2 nanoparticles enhance the antibacterial activities of macrophages by activating the reactive oxygen species.

Infection often causes disastrous consequences in all fields of clinical medicine, especially orthopedics. Hence, critical efforts are being made to engineer novel nanomaterials for the treatment of orthopedic infections due to the high biocompatibility and antibacterial properties they possess. The purpose of this study was to investigate the antibacterial effects of magnesium hydroxide (Mg(OH)2 ) nanoparticles (NPs) in vitro and determine their possible mechanisms of action. In this study, Escherichia coli was selected as the pathogenic bacteria and it was found that Mg(OH)2 NPs significantly inhibited the growth of E. coli by promoting nucleic acid leakage, inhibiting protein synthesis, and suppressing the metabolic activity. The minimum inhibitory concentration for these bacteria was determined to be 4.4 µg/ml. In vitro flow cytometry and immunofluorescence tests indicated that Mg(OH)2 NPs induced the macrophages to generate reactive oxygen species to kill the bacteria. To understand the mechanisms involved in this process, western blotting was performed and it was found that Mg(OH)2 NPs activated the phosphatidylinositol-3-kinase/serine-threonine kinase (PI3K/Akt) signaling pathway of macrophages to enhance their phagocytosis with no obvious cytotoxicity. Thus, Mg(OH)2 NPs are a suitable choice to develop promising agents or coating materials for the treatment of clinically widespread infections in view of their safety, biocompatibility, and powerful antibacterial properties.

The association between CD31hiEmcnhi endothelial cells and bone mineral density in Chinese women.

Osteoporosis is the most common bone disease in humans. During bone remodeling, specialized blood vessels influenced by the endothelial cells (CD31hiEmcnhi, also called type H cells) are formatted to supply nutrients. Reductions in vascular supply are associated with bone loss resulting in osteoporosis. Therefore, the objective of the present study was to explore the association between the CD31hiEmcnhi endothelial cells and bone mineral density (BMD). In this prospective study, 134 Chinese women were enrolled and examined. BMD was measured by DEXA method while the percentage of CD31hiEmcnhi endothelial cells in the intertrochanteric part was measured by flow cytometry. The percentage of CD31hiEmcnhi endothelial cells in postmenopausal subjects was significantly lower compared with premenopausal women (8.7 ± 4.0% vs 13.2 ± 5.6%, P < 0.01). Meanwhile, the CD31hiEmcnhi endothelial cell levels in osteopenia and osteoporosis were significantly lower compared with subjects with normal BMD (9.84 ± 4.2% in osteopenia and 7.11 ± 3.2% in osteoporosis vs 12.7 ± 5.6% in subjects with normal T score, P < 0.01). Multiple regression analyses showed that the CD31hiEmcnhi endothelial cells level was positively associated with femur neck and total hip BMD, but not with lumbar BMD. Our study suggests a significantly positive association between CD31hiEmcnhi endothelial cells and local BMD in Chinese women. The proportion of CD31hiEmcnhi endothelial cells is a marker of bone quality and represents a potential target for treatment of bone loss.

Evaluation of the mechanisms and effects of Mg-Ag-Y alloy on the tumor growth and metastasis of the MG63 osteosarcoma cell line.

Osteosarcoma is a malignant primary bone tumor, which often associates with pulmonary metastasis. The radical surgery of osteosarcoma often requires internal orthopedic implants. Therefore, implants with antitumor properties should be developed. Magnesium (Mg) and its alloys possess great potential as orthopedic materials, given their biodegradable properties, superior osteogenesis performance, and antitumor features. However, problems arise with their uncontrolled degradation rates and their unknown antitumor mechanisms. In our study, when compared with pure Mg, the rare element silver alloyed with yttrium (Ag-Y) could extremely enhance the corrosion resistance of these elements, giving the Ex-Mg-1Ag-1Y alloy better anticorrosion rates. Here, we implanted the Ex-Mg-1Ag-1Y alloy and pure Mg and Ti alloy in vivo around tumors in nude mice (BALB/c). Notably, the local tumor weight in Mg alloy and pure Mg groups were much smaller than that in Ti alloy group in 36 days after surgery (6.59 ± 0.70, 6.76 ± 0.62, and 8.54 ± 0.56 g), while the general scores of lung metastasis in Mg alloy and pure Mg groups were also lower than Ti alloy group (64.50 ± 7.64, 62.73 ± 7.84, and 87.60 ± 9.43). Therefore, the Mg and Ex-Mg-1Ag-1Y alloy, both demonstrated resisting effects against local tumor growth and pulmonary metastasis, which could be performed by changing the extracellular acidosis microenvironment, elevating the Mg concentration, suppressing C-X-C chemokine receptor type 4 (CXCR4) levels, and increasing prostacyclin (PGI2 ) synthesis. Our work revealed that the Ex-Mg-1Ag-1Y alloy may be a promising orthopedic implant for treating osteosarcoma due to its better corrosion resistance and antitumor attributes. © 2019 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 107B:2537-2548, 2019.

CXCR4-mediated osteosarcoma growth and pulmonary metastasis is suppressed by MicroRNA-613.

Osteosarcoma is the most common primary bone malignancy. Recently, studies showed chemokine receptor 4 (CXCR4) played a critical role in osteosarcoma. However, the regulation of CXCR4 is not fully understood. microRNAs are short, non-coding RNAs that play an important roles in post-transcriptional regulation of gene expression in a variety of diseases including osteosarcoma. miR-613 is a newly discovered miRNA and has been reported to function as a tumor suppressor in many cancers. In this study, we confirmed that both Stromal Cell-Derived Factor (SDF-1) and CXCR4 could be prognostic markers for osteosarcoma. Meanwhile this study found that SDF-1/CXCR4 pathway regulated osteosarcoma cells proliferation, migration and reduced apoptosis. Besides, we demonstrated that miR-613 was significantly downregulated in osteosarcoma patients. Elevated expression of miR-613 directly suppressed CXCR4 expression and then decreased the proliferation, migration and induced apoptosis of osteosarcoma cells. Moreover, our study found that CXCR4 promoted the development of lung metastases and inhibition of CXCR4 by miR-613 reduced lung metastases. These data indicated that CXCR4 mediated osteosarcoma cell growth and lung metastases and this effect can be suppressed by miR-613 through directly downregulating CXCR4.

miR-139-5p Represses BMSC Osteogenesis via Targeting Wnt/ß-Catenin Signaling Pathway.

Osteogenesis of mesenchymal stem cells (MSCs) has played a necessary role in the repair of bone. According to some reports, microRNAs participate in different physiological activity of the cells, including cell differentiation. This study investigated the function that miR-139-5p plays in the osteogenic differentiation of human bone marrow MSCs (hBMSCs). In addition to miR-139-5p, the effects of alkaline phosphatase (ALP), a membrane-bound metalloenzyme that is considered an early osteogenic differentiation marker, have also been investigated. Calcium-rich deposit (mineralization) is also a typical osteogenic differentiation marker that could be visualized by alizarin red S (ARS) staining. Inhibiting miR-139-5p notably promotes the hBMSC osteoblast differentiation, which, however, will be reduced by overexpressed miR-139-5p. This result has been made based on the alternations of ALP activity, ARS staining, as well as expression of osteogenic genes, including runt-related gene-2 (Runx2), collagen I (Col-1), and osteocalcin (OCN). miR-139-5p exerts its role in BMSC osteogenesis most probably through the Wnt/ß-catenin pathway, by direct targeting CTNNB1 and frizzled 4 (FZD4), essential factors of Wnt/ß-catenin pathway. In conclusion, according to the present study, inhibiting miR-139-5p could be a promising strategy in hBMSC osteogenesis.

[Establishement for regional pelvic trauma database in Hunan Province].

OBJECTIVE: To establish a database for pelvic trauma in Hunan Province, and to start the work of multicenter pelvic trauma registry.
 Methods: To establish the database, literatures relevant to pelvic trauma were screened, the experiences from the established trauma database in China and abroad were learned, and the actual situations for pelvic trauma rescue in Hunan Province were considered. The database for pelvic trauma was established based on the PostgreSQL and the advanced programming language Java 1.6.
 Results: The complex procedure for pelvic trauma rescue was described structurally. The contents for the database included general patient information, injurious condition, prehospital rescue, conditions in admission, treatment in hospital, status on discharge, diagnosis, classification, complication, trauma scoring and therapeutic effect. The database can be accessed through the internet by browser/servicer. The functions for the database include patient information management, data export, history query, progress report, video-image management and personal information management.
 Conclusion: The database with whole life cycle pelvic trauma is successfully established for the first time in China. It is scientific, functional, practical, and user-friendly.

The efficacy of a multimodal analgesia protocol in preventing heterotopic ossification after acetabular fractures surgery.

Background Heterotopic ossification (HO) after joint surgery is always a disturbing problem for patients and surgeons. Prophylaxis is the most effective therapy. Objective To assess the efficacy and safety of a multimodal analgesia protocol that included parecoxib and celecoxib in preventing HO after acetabular fracture surgery. Setting Selecting patients from trauma registry of our hospital. Method We identified 259 patients who had acetabular fracture surgery between January 2008 and December 2014. Hundredsixty-three patients received parecoxib and celecoxib (Group A) and 96 patients received no prophylaxis (Group B). The presence of HO was assessed according to the classification of Brooker et al. at the 12 month postoperative visit. Main outcome measure The differences in HO incidence and severity between the two groups. Results 49 patients (30.0%) developed HO in the Group A and 44(45.8%) in Group B. The difference in total HO incidence between the two groups was significant (P = 0.011 < 0.05, χ2 = 6.530, OR 0.508, 95% CI (0.301-0.857). Severe HO (Brooker grade III or IV) developed in 15 patients (9.2%) in Group A and 17 patients (17.7%) in Group B. Brooker grade I + II was 34(20.9%) and 27(28.1%) in each group. The difference in the severity of HO between the two Groups was significant (P = 0.008 < 0.05). Conclusion A short-term administration of parecoxib and celecoxib aids in the prevention of HO after acetabular fractures surgery.

Percutaneous compression plate versus dynamic hip screw for treatment of intertrochanteric hip fractures: A overview of systematic reviews and update meta-analysis of randomized controlled trials.

PURPOSE: Intertrochanteric hip fractures lead to high morbidity and mortality rates. As a minimally invasive technique, many studies reported the efficacy of PCCP for the treatment of intertrochanteric fractures, but the controversy still existed in some outcomes. The purpose of this study was to evaluate the efficacy of PCCP and DHS by a overview of systematic reviews and well-designed, comprehensive update meta-analysis. METHODS: PUBMED, SCOPUS, CCRCT, WANFANG and CNKI database were searched in all languages published up to April 2016. Systematic reviews and randomized controlled trials reporting outcomes of PCCP and DHS for intertrochanteric fractures were included. Meta-analyses comparing the two techniques were performed according to the Cochrane Handbook. RESULTS: Five original trials and four systematic reviews met the inclusion criteria. Meta-analyses showed that the blood loss [SMD = -2.35, 95%CI(-4.26--0.44)], transfusion volume [SMD = -0.26, 95%CI(-0.47--0.06)] and complications [RR = 0.33, 95%CI(0.14-0.77)] was statistically less in PCCP group than DHS group while there was no significant difference between two groups in mortality rate, transfusion rate and length of hospital day. CONCLUSIONS: PCCP is recommended to treat intertrochanteric hip fractures as an alternative minimally invasive method. More high-quality, randomized controlled trials that are adequately powered are needed to further evaluate the efficacy of PCCP and DHS.

Exploration of the effect of mmu-miR-142-5p on osteoblast and the mechanism.

The objective of this study is to explore the effect of mmu-miR-142-5p on osteoblast and the mechanism. Neonatal New Zealand rabbits were selected to collect and culture primary osteoblasts after being killed. The agonists agomiR-142-5p, agomiR-NC and inhibitors antagomiR-142-5p, antagomiR-NC were transfected to establish mmu-miR-142-5p osteoblast model. 48 h after transfection, total RNA was extracted, ELISA was used to detect ALP level, Western Blot was used to detect HSP27 level, and RT-PCR was used to detect levels of RunX2 and OC. Rabbit osteoblasts showed triangle shape and grew adhering to the wall, cytoplasm extended and protruded. As the culture time prolonged, the cell volume was increased, and the amount showed exponential growth. After transfection, the abundance was significantly increased in agonist group and significantly decreased in inhibitor group, indicating that exogenous agonist can successfully up-regulate mmu-miR-142-5p level and exogenous inhibitor can down-regulate mmu-miR-142-5p level in osteoblast. Compared with control group, ALP level was significantly increased in agonist group and decreased in inhibitor group. Transfection of exogenous agonist can up-regulate HSP27 level in osteoblast, and transfection of exogenous inhibitor can decrease HSP27 level in osteoblast; however, there was no effect on HSP27 mRNA level. RunX2 mRNA and OC mRNA were significantly increased in agonist group and decreased in inhibitor group. Transfection of exogenous nucleic acid agomiR-142-5p can up-regulate the abundance and activity of mmu-miR-142-5p, and transfection of antagomiR-142-5p can down-regulate the abundance and activity of mmu-miR-142-5p, indicating that mmu-miR-142-5p can effectively helps the mineralization of osteoblast.

Posterior wall reconstruction using intertrochanteric crest strut graft in comminuted posterior acetabular wall fractures.

Posterior wall fractures are the most common acetabular fractures. Despite being frequently the easiest to treat, posterior acetabular wall reconstruction following such injuries can be challenging. A prospective study was conducted to evaluate the efficacy of a new surgical technique using gluteus medius muscle-pedicled intertrochanteric crest graft for the reconstruction of comminuted posterior acetabular wall fractures where primary comminuted fragments were beyond fixation. This technique has been performed on six patients from 2010 to 2012. The radiologic (Matta score) and clinical evaluation (modified Merle d'Aubigne and Postel score) were recorded at their final follow-up. 
The mean follow-up was 15.2 months. The radiological outcome by plain radiographs was graded as anatomical in all six patients, the clinical outcome by modified Merle d'Aubigne and Postel score was considered to be excellent in two patients, good in four. 
Reconstruction of the posterior acetabular wall using gluteus medius muscle-pedicled intertrochanteric crest graft may be appropriate in some instances. The early radiological and clinical results of this new technique were promising.

Which treatment is the best for giant cell tumors of the distal radius? A meta-analysis.

BACKGROUND: Intralesional excision and en bloc resection are used to treat giant cell tumors (GCTs) of the distal radius. However, it is unclear whether one provides lower rates of recurrences and fewer complications, and whether the use of polymethylmethacrylate (PMMA) after curettage reduces the risk of recurrence. QUESTIONS/PURPOSES: We examined whether curettage was associated with lower rates of recurrence and fewer major complications compared with en bloc excision, and whether PMMA resulted in lower rates of recurrence compared with a bone graft. METHODS: We systematically searched the literature using the criteria, "giant cell tumor" AND "curettage" OR "intralesional excision" OR "resection". Six relevant articles were identified that reported data for 80 curettage cases (PMMA, n = 49; bone graft, n = 26; no PMMA or bone grafts, n = 5) and 59 involving en bloc excision. A meta-analysis was performed using these data. RESULTS: Overall, patients in the intralesional excision group had a higher recurrence rate (relative risk [RR], 2.80; 95% CI, 1.17-6.71), especially for Campanacci grade 3 GCTs (RR, 4.90; 95% CI, 1.36-17.66), yet fewer major complications (RR, 0.21; 95% CI, 0.09-0.54) than the en bloc resection group. The use of PMMA versus bone graft did not affect the recurrence rate (RR, 0.98; 95% CI, 0.44-2.17). CONCLUSIONS: Based on data obtained from the limited number of studies available, intralesional excision appears to be more appropriate for the treatment of local lesions (e.g., grades 1 and 2) than grade 3 GCTs of the distal radius. Moreover, PMMA was not additionally effective as an adjuvant. LEVEL OF EVIDENCE: Level III, therapeutic study (systematic review). See Guidelines for Authors for a complete description of levels of evidence.