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Bone regeneration and mineralization can be achieved by means of distraction osteogenesis (DO). In the present study, we investigated the effect of stromal cell-derived factor 1 (SDF-1) and vascular endothelial growth factor (VEGF) on the new bone formation during DO in rats. Forty-eight Sprague–Dawley rats were randomized into four groups of 12 rats each. We established the left femoral DO model in rats and performed a mid-femoral osteotomy, which was fixed with an external fixator. DO was performed at 0.25 mm/12 h after an incubation period of 5 days. Distraction was continued for 10 days, resulting in a total of 5 mm of lengthening. After distraction, the solution was locally injected into the osteotomy site, once a day 1 ml for 1 week. One group received the solvent alone and served as the control, and the other three groups were treated with SDF-1, VEGF, and SDF-1with VEGF in an aqueous. Sequential X-ray radiographs were taken two weekly. The regeneration was monitored with the use of micro-CT analysis, mechanical testing, and histology. Radiographs showed accelerated regenerate ossification in the SDF-1, VEGF, and SDF-1 with the VEGF group, with a larger amount of new bone compared with the control group, especially SDF-1 with the VEGF group. Micro-CT analysis and biomechanical tests showed Continuous injection of the SDF-1, VEGF, and SDF-1 with VEGF during the consolidation period significantly increased bone mineral density bone volume, mechanical maximum loading, and bone mineralization of the regenerate. Similarly, the expression of osteogenic-specific genes, as determined by real-time polymerase chain reaction , was significantly higher in SDF-1 with the VEGF group than in the other groups. Histological examination revealed more new trabeculae in the distraction gap and more mature bone tissue for the SDF-1 with the VEGF group. SDF-1 and VEGF promote bone regeneration and mineralization during DO, and there is a synergistic effect between the SDF-1 and VEGF. It is possible to provide a new and feasible method to shorten the period of treatment of DO.

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BACKGROUND: Arthroplasty has been the most effective treatment for the end-stage osteoarthritis. However, aseptic loosening is the main long-term complication of arthroplasty. How to ameliorate aseptic loosening is an issue of concern. OBJECTIVE: To investigate the biological behavior of preosteoblasts induced with cobalt-chromium particles during aseptic loosening process. METHODS:(1) In vitro experiment: preosteoblasts were cultured in an osteoblast-induction medium and induced with different doses(0.3 or 1.25 g/L) of cobalt-chromium particles.(2) In vivo experiment: titanium screws were implanted to proximal tibia of server combined with immune-deficiency mice to simulate knee joint arthroplasty. Cobalt-chromium particles inducing MC3 T3-E1(5×105) were intra-articularly injected into the implanted knee at 1 week after surgery. Stable group(n=6): screw implanted mice without local particle insertion and cells transfusion; loosening group(n=6): mice were given an intra-articular injection of cobalt-chromium particles(4×104) before screw implantation; cobalt-chromium group: mice were given an intra-articular injection of preosteoblasts induced by cobalt-chromium particles and cobalt-chromium particles(4×104) before screw implantation. RESULTS AND CONCLUSION:(1) In vitro experiment: with the increasing of cobalt-chromium particles, alkaline phosphatase and osteogenic gene expression was decreasing.(2) In vivo experiment: intra-articular injection of cobalt-chromium particles inducing MC3 T3-E1 cells resulted in thicker peri-implant pseudomembrane, reduced the shear strength of bone-implant, decreased bone mineral density and bone volume, and increased the number of positive cells for tartrate-resistant acid phosphatase.(3) These results indicate that cobalt-chromium particles inhibit the growth, maturation and functions of preosteoblastic cells. Cobalt-chromium particles inducing preosteoblasts may aggravate periprosthetic inflammation and promote osteoclastogenesis. [ABSTRACT FROM AUTHOR]

This study investigated the interactive behavior of the particulate and ion forms of cobalt–chromium (Co–Cr) alloy challenged preosteoblasts during the process of prosthetic implant loosening. Preosteoblasts were challenged with Co–Cr particles or Co(II) ions for 72 h, followed by the proliferation and PCR assays. For in vivo test, a titanium pin was implanted into proximal tibia of SCID mice to mimic knee replacement. Co–Cr particles or Co(II) ion challenged preosteoblasts (5 × 105) were intra‐articularly injected into the implanted knee. The animals were sacrificed 5 weeks post‐op, and the prosthetic knees were harvested for biomechanical pin‐pullout testing, histological evaluations, and microCT assessment. In vitro study suggested that Co–Cr particles and Co(II) ions significantly suppressed the proliferation of preosteoblasts in a dose‐dependent manner. RT‐PCR data on the challenged cells indicated overexpression of receptor activator of nuclear factor kappa‐B ligand (RANKL) and inhibited osteoprotegerin (OPG) gene expression. Introduction of the differently challenged preosteoblasts to the pin‐implant mouse model resulted in reduced implant interfacial shear strength, thicker peri‐implant soft‐tissue formation, more TRAP+ cells, lower bone mineral density, and bone volume fraction. In conclusion, both Co–Cr particles and Co(II) ions interfered with the growth, maturation, and functions of preosteoblasts, and provides evidence that the metal ions as well play an important role in effecting preosteoblasts in the pathogenesis of aseptic loosening. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 107A: 187–194, 2019. [ABSTRACT FROM AUTHOR]

This study compared the particulate and ion forms of a cobalt-chrome (Co-Cr) alloy on the differentiation/activation of preosteoblasts. Mouse preosteoblasts (MC3T3-E1) were cultured in an osteoblast-induction medium in the presence of particulate and ion forms of a Co-Cr alloy, followed by cell proliferation and cytotoxicity evaluations. The maturation and function of osteoblasts were assessed by alkaline phosphatase (ALP) assay and related gene expressions. Both particulate and ion forms of the metals significantly reduced the proliferation of MC3T3-E1 cells in a dose-dependent manner. Similarly, cells challenged with high concentrations of particles and ions exhibited a marked cytotoxic effect and diminished expression of ALP. Real-time (RT) polymerase chain reaction (PCR) data have suggested that cells with Co-Cr particles dramatically promoted over-expression of monocyte chemo-attractant protein-1 ( MCP-1), tumor necrosis factor-α ( TNF-α), and interleukin-6 ( IL-6), whereas Co2+ ions treatment predominately up-regulated expressions of receptor activator of nuclear factor kappa-B ligand ( RANKL), nuclear factor of activated T-cells cytoplasmic 1 ( NFATc1), and down-regulated expression of osteoprotegerin ( OPG) and Osterix ( Osx). Overall, this study provides evidence that both Co-Cr alloy particles and metal ions interfered with the MC3T3-E1 cells for their growth, maturation, and functions. Further, Co-Cr particles exhibited stronger effects on inflammatory mediators, while metal ions showed more influence on inhibition of osteoblast differentiation and promotion of osteoclastogenesis. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 103A: 3564-3571, 2015. [ABSTRACT FROM AUTHOR]

Coronaviruses (CoVs) are important pathogens for humans and other vertebrates, causing severe respiratory and intestinal infections that have become a threat to public health because of the potential for interspecies transmission between animals and humans. Therefore, the development of safe, effective vaccines remains a top priority for the control of CoV infection. The unique immunological characteristics of vaccines featuring messenger RNA (mRNA) present an advantageous tool for coronavirus vaccine development. Here, we designed two lipid nanoparticle (LNP)-encapsulated mRNA (mRNA-LNP) vaccines: one encoding full-length spike (S) protein and the other encoding the spike ectodomain (Se) from porcine deltacoronavirus (PDCoV). Fourteen days after primary immunization, both mRNA vaccines induced high levels of immunoglobulin G and neutralizing antibodies in mice, with the S vaccine showing better performance than the Se vaccine. Passive immune protection of the S mRNA vaccine in suckling piglets was confirmed by the induction of robust PDCoV-specific humoral and cellular immune responses. The S mRNA vaccine also showed better protective effects than the inactivated vaccine. Our results suggest that the novel PDCoV-S mRNA-LNP vaccine may have the potential to combat PDCoV infection., Importance: As an emerging porcine enteropathogenic coronavirus, porcine deltacoronavirus (PDCoV) has the potential for cross-species transmission, attracting extensive attention. Messenger RNA (mRNA) vaccines are a promising option for combating emerging and re-emerging infectious diseases, as evidenced by the demonstrated efficacy of the COVID-19 mRNA vaccine. Here, we first demonstrated that PDCoV-S mRNA-lipid nanoparticle (LNP) vaccines could induce potent humoral and cellular immune responses in mice. An evaluation of passive immune protection of S mRNA vaccines in suckling piglets confirmed that the protective effect of mRNA vaccine was better than that of inactivated vaccine. This study suggests that the PDCoV-S mRNA-LNP vaccine may serve as a potential and novel vaccine candidate for combating PDCoV infection., Competing Interests: The authors declare no conflict of interest.

Objective: To explore the feasibility of establishment of a artificial joint aseptic loosening mouse model by cobalt-chromium particles stimulation., Methods: Twenty-four 8-week-old male severe combined immunodeficient (SCID) mice were divided into experimental group ( n =12) and control group ( n =12). The titanium nail was inserted into the tibial medullary cavity of mouse in the two groups to simulate artificial joint prosthesis replacement. And the cobalt-chromium particles were injected into the tibial medullary cavity of mouse in experimental group. The survival of the mouse was observed after operation; the position of the titanium nail and the bone mineral density of proximal femur were observed by X-ray film, CT, and Micro-CT bone scanning; and the degree of dissolution of the bone tissue around the tibia was detected by biomechanical test and histological staining., Results: Two mice in experimental group died, and the rest of the mice survived until the experiment was completed. Postoperative imaging examination showed that there was no obvious displacement of titanium nails in control group, and there were new callus around the titanium nails. In experimental group, there was obvious osteolysis around the titanium nails. The bone mineral density of the proximal tibia was 91.25%±0.67%, and the maximum shear force at the tibial nail-bone interface was (5.93±0.85) N in experimental group, which were significantly lower than those in control group [102.07%±1.87% and (16.76±3.09) N] ( t =5.462, P =0.041; t =3.760, P =0.046). Histological observation showed that a large number of inflammatory cells could be seen around the titanium nails in experimental group, while there was no inflammatory cells, and obvious bone tissue formation was observed in control group., Conclusion: The artificial joint aseptic loosening mouse model can be successfully established by cobalt-chromium particles stimulation.

Objective: To investigate the effectiveness and advantages of skeletal tractor in closed reduction and proximal femoral nail antirotation (PFNA) internal fixation of intertrochanteric fracture compared with traction table., Methods: The clinical data of 86 patients with intertrochanteric fractures, who were treated with closed reduction and PFNA internal fixation between October 2016 and March 2018 and met the selection criteria, was retrospectively analysed. Among them, 44 cases were treated with skeletal tractor (trial group) and 42 cases were treated with traction table (control group). There was no significant difference between the two groups in gender, age, cause of injury, fracture side, AO classification, and degree of osteoporosis ( P >0.05). The preoperative position time, operation time, intraoperative fluoroscopy times, intraoperative blood loss, fracture healing time, intraoperative and postoperative complications, and postoperative Harris score were compared between the two groups., Results: The operation was successfully completed in both groups. Compared with the control group, the patients in the trial group had shorter preoperative position time and operation time, fewer intraoperative fluoroscopy times, and less intraoperative blood loss ( P <0.05). The patients were followed up 12-21 months in trial group (mean, 14.2 months) and 12-22 months in control group (mean, 14.3 months). Venous thrombosis of lower extremity occurred in 8 patients (3 cases of trial group and 5 cases of control group) after operation. Internal fixation failure occurred in 5 patients (2 cases of trial group and 3 cases of control group) during 1 year after operation. All fractures healed except for those with internal fixation failure, the fracture healing time was (11.6±2.9) weeks in trial group and (12.4±3.6) weeks in control group; and there was no significant difference between the two groups ( t =1.250, P =0.214). At 1 year after operation, Harris score of the trial group was 86.2±5.9 and that of the control group was 84.1±6.1. There was no significant difference between the two groups ( t =1.768, P =0.080)., Conclusion: Compared with traction table, skeletal tractor in closed reduction and PFNA internal fixation of intertrochanteric fracture can significantly shorten the preoperative position time and operation time, reduce the intraoperative fluoroscopy times, improve the operation efficiency, and have similar effectiveness.