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When treating ankle fractures, the question of syndesmosis complex involvement often arises. So far, there is no standardized method to reliably detect syndesmosis injuries in the surgical treatment of ankle fractures. For this reason, an intraoperative syndesmosis-test-tool (STT) was developed and compared to the recommended and established hook-test (HT). Tests were performed on cadaveric lower legs (n = 20) and the diastasis was visualized by 3D camera. Tests were performed at 50, 80, and 100 N in native conditions and four instability levels. Instability was induced from anterior to posterior and the reverse on the opposite side. The impact on diastasis regarding the direction, the force level, the instability level, and the device used was checked using a general linear model for repeated measurement. The direction of the induced instability showed no influence on the diastasis during the stability tests. The diastasis measured with the STT increased from 0.5 to 3.0 mm depending on the instability, while the range was lower with the HT (1.1 to 2.3 mm). The results showed that the differentiation between the instability levels was statistically significantly better for the developed STT. The last level of maximum instability was significantly better differentiable with the STT compared to the HT. An average visualizable diastasis of more than 2 mm could only be achieved at maximum instability. In conclusion, the newly developed STT was superior to the commonly used HT to detect instability. [ABSTRACT FROM AUTHOR]

Purpose: Surgical procedures to prevent osteomyelitis after trauma can be supported by local application of antibiotics. This in-vitro study investigated the release and impact of antibiotics from implant coatings against bacteria associated with combat-related osteomyelitis.Methods: K-wires were coated with poly(D,L-lactide) and ciprofloxacin, gentamicin, colistin, daptomycin or cefoxitin in different concentrations. The release was quantified and antimicrobial activity tested for different gram-positive or gram-negative bacteria, alone and in combination. To exclude toxic effects, primary osteoblast-like cells were exposed to antibiotic coating concentrations.Results: All antibiotics alone and in combination showed an initial burst release with dose dependent antimicrobial activity and no negative effects on osteoblast-like cells, except for cefoxitin.Conclusions: Implant coatings can be customized with single or double antibiotic coatings to effectively fight different bacteria and also mixed infections in the treatment of a combat-acquired osteomyelitis. However, optimal drug load and degradation behaviour of individual antibiotics have to be considered. [ABSTRACT FROM AUTHOR]

Purpose: The reason for the formation of an atrophic non-union is not clear and an altered vascularization as well as a deregulation of endogenous growth factors is hypothesized. To obtain more information, we analysed human non-union tissue regarding the histology and quantity of several growth factors. Methods: Tissue from patients with an atrophic non-union ( n = 44) or with a healed fracture ( n = 13) was analysed. Using histological and immunohistochemical methods the tissue composition was investigated. On the protein level the amount of several growth factors important for bone healing was analysed. Results: The tissue composition was very inhomogeneous containing fibrous, cartilaginous and bony tissue. Vessels were present in all investigated samples without a difference between the tissue from non-union and control patients. The growth factor BMP-2 was below the detection limit in all samples, whereas IL-6 and IGF-I were measured only in a few samples of both groups. TGF-ß1, VEGF-A and BMP-4 were detectable in the majority of the samples of both groups with a high variability in the amount but no difference between the groups. The quantity of both growth factors, BMP-7 and PDGF-AB, was significantly lower in the non-union tissue compared to the healed controls. Conclusion: The reduced quantity of BMP-7 and PDGF-AB might be responsible for the impaired healing. Further studies analysing material from more patients and investigating the early healing phases, however, are necessary to obtain further information and consequently improve healing strategies. [ABSTRACT FROM AUTHOR]

Purpose: The aim of the study was to compare two different demineralised bone matrices used clinically regarding their ability to induce bone healing in a critical-size-defect rat model. Methods: We stabilised 4 mm femur defects with a custom-made plate and filled them either with demineralised bone matrix (DBM) or DBX (DBX Putty®). Bone morphogenetic protein 2 (BMP-2)-loaded collagen and an empty defect served as controls. The outcome was followed after 21 and 42 days by radiology (Faxitron; microCT) and histology. Results: Defect healing did not occur in any animal from the empty control, DBM or DBX group. Residuals of the implanted material were still found after six weeks, but only limited callus formation was visible. In contrast, the BMP-2 control demonstrated enhanced formation of callus tissue and undisturbed healing. After 21 days, 11 out of 16 and after 42 days, 7 out of 8 BMP-2-treated animals showed complete defect bridging by cancellous bone tissue. Conclusions: Demineralised bone grafts were not capable of defect reconstruction; only BMP-2 was able to provide sufficient stimulus to induce uneventful bridging under the specific experimental conditions. [ABSTRACT FROM AUTHOR]

Patients with chronic liver diseases frequently exhibit decreased bone mineral densities (BMD), which is defined as hepatic osteodystrophy (HOD). HOD is a multifactorial disease whose regulatory mechanisms are barely understood. Thus, an early diagnosis and therapy is hardly possible. Therefore, the aim of our study consisted in characterizing a mouse model reflecting the human pathomechanism. Serum samples were collected from patients with chronic liver diseases and 12-week old C57Bl6/N mice after 6-week treatment with carbon tetrachloride (CCl). Repetitive injections of CCl induced liver damage in mice, resembling liver fibrosis in patients, as assessed by serum analysis and histological staining. Although CCl did not affect primary osteoblast cultures, μCT analysis revealed significantly decreased BMD, bone volume, trabecular number and thickness in CCl-treated mice. In both HOD patients and CCl-treated mice, an altered vitamin D metabolism with decreased CYP27A1, CYP2R1, vitamin D-binding protein GC and increased 7-dehydrocholesterol reductase hepatic gene expression, results in decreased 25-OH vitamin D serum levels. Moreover, both groups exhibit excessively high active transforming growth factor-beta (TGF-β) serum levels, inhibiting osteoblast function in vitro. Summarizing, our mouse model presents possible mediators of HOD, e.g. altered vitamin D metabolism and increased active TGF-β. Liver damage and significant changes in bone structure and mineralization are already visible by μCT analysis after 6 weeks of CCl treatment. This fast response and easy transferability makes it an ideal model to investigate specific gene functions in HOD. [ABSTRACT FROM AUTHOR]

Bony allografts are used frequently in the clinic for bone defect filling, however, less comparative data concerning their osteoinductive potential are available. The purpose of the present study was the comparative analysis of different allograft preparations. From five donors, we investigated fresh-frozen cancellous bone (native), peracetic acid–ethanol sterilized (PES) cancellous bone, cortical bone and demineralised bone matrix (DBM). In addition, two commercially available DBM products from five different donors were analyzed: Allomatrix® (Wright Medical Technology Inc.) and DBX putty® (Synthes GmbH). For positive control and as a clinically used growth factor, BMP-2 was chosen. To investigate the osteoinductivity C2C12 cells were cultured with the different materials and the effect on cell proliferation and alkaline phosphatase activity were measured. Proliferation was significantly enhanced by the native cancellous bone, Allomatrix, and BMP-2 and decreased by the PES-processed cancellous bone. The osteogenic differentiation was significantly enhanced by BMP-2 and the two commercial DBM products and decreased by PES-sterilized cancellous bone. All tested materials revealed a high donor-dependent variability. This is the first comparative study on the osteoinductivity of bony allografts frequently used in clinic. [ABSTRACT FROM AUTHOR]

Bone morphogenetic proteins (BMPs) have been applied successfully in the clinic for the treatment of spinal fusion, fracture healing, and delayed and non-unions. Demographic data reveal that because of the steadily rising age of the population, complications related to the musculoskeletal system will increase during the coming years. Multiple in vitro and in vivo studies, as well as clinical trials, clearly show a strong osteoinductive effect of BMP-2 and BMP-7. In comparison to the "gold standard" autologous bone graft, BMPs seem to be as good as the iliac crest bone graft (ICBG) or even more effective, and the side effects are moderate. Today BMPs play an increasingly important role in orthopedic practice. Further improvement of application systems might lower the risk of side effects and could improve outcome parameters. [ABSTRACT FROM AUTHOR]

Introduction: Formation of new blood vessels is essential for the process of fracture healing. Materials and methods: We investigated the expression of the angiogenic factor pleiotrophin/HB-GAM in a closed fracture model in rats by immunohistochemical methods. Results: Histologically, 5 days after fracture the callus was predominantly composed of fibrous tissue. On day 10 a prominent chondral callus connected both ends of the fractured tibia. There was a continuous transition from the chondral callus to the newly formed bone adjacent to the corticalis of the tibia. On day 15 the amount of woven bone had increased, and in 3 of 5 animals the proximal and distal tibiae were connected by a bridge of woven bone. Pleiotrophin could be immunostained in fibroblasts and endothelial cells of the fibrous tissue between the fractured tibia ends. The chondral callus remained largely pleiotrophin-negative. Only single chondrocytes adjacent to the newly formed bone were pleiotrophin-positive. On days 10 and 15 strong immunoreactivity for pleiotrophin in the well vascularized, newly formed, woven bone was detectable. Osteoblasts, endothelial cells and fibroblasts were strongly pleiotrophin-positive. Conclusions: These results show the presence of the angiogenic peptide pleiotrophin during fracture healing. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this study was to develop a clinically relevant standardized closed tibial fracture model in the rat and to characterize the healing process at different time points using radiologic, biomechanical, and histological methods. Material and Methods: The tibia and fibula were fractured in a closed manner using a guillotine-like device under standardized conditions. After closed reduction, the tibia was stabilized with an intramedullary titanium Kirschner wire. To evaluate the soft tissue trauma, the compartment pressure was measured postoperatively. To follow the healing process, X-ray examinations were performed and bridging of the calluses was scored throughout the experimental period. At 28, 42, and 84 days after fracture, animals were killed and the tibiae prepared for biomechanical torsional testing or histological and histomorphological analyses. Results: Only four of the 69 animals subjected to this procedure showed a complex fracture configuration. The remaining animals showed a transverse midshaft fracture (AO A2-A3) with minimal soft tissue trauma. The healing process could be detected in the radiologic investigations and showed comparable scoring parameters in all animals. The biomechanical strength increased with the healing time and showed the highest values after 84 days. The callus was composed of soft tissue, cartilage and newly formed trabecular bone after 4 weeks. At the later time points, a remodeling process was detectable with a decrease in cartilage and an increase in mineralized tissue. Conclusion: Since this model does not require prepinning of the bone prior to fracture, it mimics a clinical trauma setting. Using this model, the basic cellular events of fracture healing can be investigated and the effects of local or systemic factors or conditions assessed. [ABSTRACT FROM AUTHOR]

Formation of new blood vessels is essential for the process of wound and fracture healing. Little is known about the time-dependent expression and the involved splice variants of the vascular endothelial growth factor (VEGF). We therefore quantified and differentiated the angiogenic factor VEGF and its receptors (VEGFR) in a rat fracture model by immunohistochemical, biochemical and molecular biological methods. VEGF could be immunostained in chondrocytes and osteoblasts of the callus, but not in fibrous callus. In the capillaries, VEGFR-1 (flt-1) and VEGFR-2 (flk-1/KDR) were also visualized. Both receptors were also detectable in some chondrocytes and in osteoclasts. Enzyme-linked immunosorbent assay (ELISA) measurements showed high levels of VEGF in fractured tibiae and negligible ones in non-injured bone. Reverse transcriptase-polymerase chain reaction (RT-PCR) revealed expression of the rat splice variants VEGF120 and VEGF164 during the course of fracture healing, which corresponds to human VEGF121 and VEGF165 splice variants. VEGF plays the most important role during the early phase of fracture healing, but VEGF concentrations decrease further after day 5. [ABSTRACT FROM AUTHOR]

During embryogenesis in insects, the axonscaffold of the brain is built around the embryonic foregut which separates the anlagen of the brain hemispheres. Here, we investigate this process in Drosophila and show that the major longitudinal and horizontal tracts of the embryonic brain form superficially near the interface between the foregut and embryonic brain hemispheres. We identify three types of cellular structures which might be involved in tract formation. These are rows of glial cells at the medial brain margin, cellular bridges composed of neuronal somata and the epithelial surface of the foregut itself. The close proximity to the outgrowing axons suggests that the structures at the brain-foregut interface may play a role in the morphogenesis of embryonic brain tracts in Drosophila. [ABSTRACT FROM AUTHOR]