Titanium alloys with various porous structures can be fabricated by advanced additive manufacturing techniques, which are attractive for use as scaffolds for bone defect repair. However, modification of the scaffold surfaces, particularly inner surfaces, is critical to improve the osteointegration of these scaffolds. In this study, a biomimetic approach was employed to construct polydopamine-assisted hydroxyapatite coating (HA/pDA) onto porous Ti6Al4V scaffolds fabricated by the electron beam melting method. The surface modification was characterized with the field emission scanning electron microscopy, energy dispersive spectroscopy, water contact angle measurement, and confocal laser scanning microscopy. Attachment and proliferation of MC3T3-E1 cells on the scaffold surface were significantly enhanced by the HA/pDA coating compared to the unmodified surfaces. Additionally, MC3T3-E1 cells grown on the HA/pDA-coated Ti6Al4V scaffolds displayed significantly higher expression of runt-related transcription factor-2, alkaline phosphatase, osteocalcin, osteopontin, and collagen type-1 compared with bare Ti6Al4V scaffolds after culture for 14 days. Moreover, microcomputed tomography analysis and Van-Gieson staining of histological sections showed that HA/pDA coating on surfaces of porous Ti6Al4V scaffolds enhanced osteointegration and significantly promoted bone regeneration after implantation in rabbit femoral condylar defects for 4 and 12 weeks. Therefore, this study provides an alternative to biofunctionalized porous Ti6Al4V scaffolds with improved osteointegration and osteogenesis functions for orthopedic applications.

Background: There is a controversy in terms of the efficacy of vitamin D supplementation in improving asthma symptom control. Moreover, whether there is a difference in the treatment effect with respect to baseline vitamin D status remains unknown. This meta-analysis was to assess the correlations of vitamin D status with asthmarelated respiratory outcomes. Methods: PubMed, EMBASE, and Cochrane Library were searched for randomized controlled trials of vitamin D supplementation in patients with asthma. Primary outcomes were the rate of asthma exacerbation and predicted percentage of forced expiratory volume in first second (FEV 1 %). Secondary outcomes were asthma control test (ACT) scores, fractional exhaled nitric oxide (FeNO), interleukin-10 (IL-10) and adverse events. Results: A total of 14 randomized controlled trials (1421 participants) fulfilled the inclusion. Vitamin D supplementation was associated with a significant reduction in the rate of asthma exacerbation by 27% (RR: 0.73 95%Cl (0.58-0.92)). In subgroup analysis, the protective effect of exacerbation was restricted in patients with vitamin D insufficiency (vitamin D < 30 ng/ml) (RR: 0.76 95%Cl (0.61-0.95)). An improvement of FEV 1 % was demonstrated in patients with vitamin D insufficiency and air limitation (FEV 1 % < 80%) (MD: 8.3 95%Cl (5.95-10.64). No significant difference was observed in ACT scores, FeNO, IL-10 and adverse events. Conclusions: Vitamin D supplementation reduced the rate of asthma exacerbation, especially in patients with vitamin D insufficiency. Additionally, the benefit of vitamin D had a positive effect on pulmonary function in patients with air limitation and vitamin D insufficiency.

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BackgroundThe Western Ontario Rotator Cuff Index (WORC) is a scale designed to evaluate the impact of rotator cuff (RC) disorders on patients’ general quality of life. Our study aims to adapt the WORC for Chinese patients and to assess its reliability, validity, and responsiveness in Chinese patients with RC disorders.MethodsFirst, we developed the Chinese version of the WORC (C-WORC) in a five-step procedure of translation and cross-cultural adaptation. Next, the recruiting patients finished all three rounds of scales of the C-WORC, the Medical Outcomes Study Short-Form 36 (SF-36), and the Oxford Shoulder score (OSS). Then we calculated Cronbach’s alpha, the intra-class correlation coefficient (ICC), Pearson’s or Spearman’s correlation coefficient (r or r s), the effect size (ES), and the standardized response mean (SRM) to evaluate the reliability, validity and responsiveness of the C-WORC, respectively.ResultsOverall, 124 patients with RC disorders successfully completed the first two rounds of the scales, and 108 patients completed the last round of the scales. Good or excellent internal consistency (Cronbach’s alpha = 0.872–0.954) was found in the overall scale and subscales of C-WORC, as well as good or excellent test-retest reliability (ICC = 0.828–0.961). Moderate or good correlations (r/r s  = 0.472–0.787) were obtained between the physical subscales of the C-WORC and the OSS and the physical subscales of SF-36; the results were also obtained for the emotions subscale of the C-WORC and the mental subscales of SF-36 (r/r s  = 0.520–0.713), which, adequately illustrated that good validity was included in the C-WORC. In addition, good responsiveness was also observed in the overall scale and subscales of the C-WORC (ES = 1.57–2.27, SRM = 1.52–2.28).ConclusionsThe C-WORC scale is reliable, valid and responsible for the evaluation of Chinese-speaking patients with RC disorders and would be an effective instrument.

There is no consensus on how to establish models of osteonecrosis of the femoral head (ONFH) in large mammals. The aim of this study was to investigate the effectiveness of a novel canine model of ONFH, induced by a navigated injection of absolute ethanol. Using three-dimensional reconstruction and rapid prototyping manufacturing techniques, a new template was designed and processed to navigate the ethanol injection. The femoral heads of 18 adult dogs were injected with ethanol. Macroscopic, X-ray and histological examinations were performed at 3, 6, and 9 weeks after the operation. Further, computed tomography (CT), magnetic resonance imaging (MRI), and radionuclide scans were performed 6 weeks postoperatively. Three weeks after the operation, the femoral heads showed evidence of osteonecrosis including increasing numbers of empty lacunae, decreased hematopoietic cells, and destroyed adipose tissue in the medullary cavity, which increased in severity at the subsequent follow-up evaluations at 6 and 9 weeks. Fractured trabeculae and fibrous tissue were noted 9 weeks postoperatively. Image analysis also revealed evidence of osteonecrosis, such as several osteopenic areas with sclerotic rims on the X-ray, several areas of low bone mineral density with sclerosis on the CT scan, increased uptake of the nuclide species in MRI, and an inhomogeneous long T2 signal on the radioisotopic images. Ethanol injection navigated by our novel template was successful in establishing a canine model of ONFH. This model can be used to test new treatment modalities for human ONFH.

Instruments made of porous titanium alloy and fabricated with a 3D printed technique are increasingly used in experimental and clinical research. To date, however, few studies have assessed their use in early-stage osteonecrosis of the femoral head (ONFH). In this study, porous titanium alloy rods (Ti-Rod) with diamond crystal lattice, fabricated using an electron beam melting (EBM) technique, were implanted into sheep models (n=9) of early-stage ONFH for 6 months. Bone ingrowth and integration were investigated and compared with those of sheep (n=9) undergoing core decompression (CD) alone. Following Ti-Rod implantation, femoral heads showed fine osteointegration, with X-ray evaluation showing compact integration between peripheral bone and rods without radiolucent lines encircling the rods, as well as new bone growth along the metal trabeculae without the intervention of fibrous tissue. The regions of interest (ROIs) of femoral heads showed fine bone ingrowth after Ti-Rod implantation than CD alone. By micro-CT evaluation, the ratios of bone volume to total volume (BV/TV) of ROIs in Rod group was 930 % and 452 % higher than CD group after 3 (0.206 ± 0.0095 vs. 0.020 ± 0.0058, p < 0.05, n=3) and 6 (0.232 ± 0.0161 vs. 0.042 ± 0.0061, p < 0.05, n=3) months respectively. By histological evaluation, the BV/TV of ROIs in Rod group was 647 % and 422 % higher than CD group after 3 (0.157 ± 0.0061 vs. 0.021 ± 0.0061, p < 0.05, n=3) and 6 (0.235 ± 0.0145 vs. 0.045 ± 0.0059, p < 0.05, n=3) months respectively. The new bone grew along metal trabeculae into the center of the rod with a rapid bone ingrowth in Rod gorup. Whereas in CD group, new bone grew mainly at the periphery of the decompressive channel with a slow bone ingrowth. Mechanical analysis showed that maximum load on the femoral head-necks was 31 % greater 6 months after Ti-Rod implantation than after CD alone when the vertical press reached the apex (3751.75 ± 391.96 vs. 2858.25 ± 512.91 N, p < 0.05, n=3). The association of rod implantation with fine bone ingrowth, osteointegration, and favorable mechanical properties suggests that implantation of the porous titanium alloy rod with the diamond crystal lattice may be a beneficial intervention for patients with early-stage ONFH.

Type 2 diabetes mellitus (T2DM) is a chronic metabolic disease characterized by lack of insulin and high glucose levels. T2DM can cause bone loss and fracture, thus leading to diabetic osteoporosis. Promoting osteogenic differentiation of osteoblasts may effectively treat diabetic osteoporosis. We previously reported that Sirtuin 1 (Sirt1), a NAD+-dependent deacetylase, promotes osteogenic differentiation through downregulation of peroxisome proliferator-activated receptor (PPAR) γ. We also found that miR-132 regulates osteogenic differentiation by downregulating Sirt1 in a PPARβ/δ-dependent manner. The ligand-activated transcription factor, PPARα, is another isotype of the peroxisome proliferator-activated receptor family that helps maintain bone homeostasis and promot bone formation. Whether the regulatory role of PPARα in osteogenic differentiation is mediated via Sirt1 remains unclear. In the present study, we aimed to determine this role and the underlying mechanism by using high glucose (HG) and free fatty acids (FFA) to mimic T2DM in MC3T3-E1 cells. The results showed that HG-FFA significantly inhibited expression of PPARα, Sirt1 and osteogenic differentiation, but these effects were markedly reversed by PPARα overexpression. Moreover, siSirt1 attenuated the positive effects of PPARα on osteogenic differentiation, suggesting that PPARα promotes osteogenic differentiation in a Sirt1-dependent manner. Luciferase activity assay confirmed interactions between PPARα and Sirt1. These findings indicate that PPARα promotes osteogenic differentiation via the Sirt1-dependent signaling pathway.