The effective management of tissue integration and immunological responses to transplants decisively co-determines the success of soft and hard tissue reconstruction. The aim of this in vivo study was to evaluate the eligibility of extracorporeal shock wave therapy (ESWT) with respect to its ability to modulate angiogenesis and immune response to a collagen matrix (CM) for tissue engineering in the chorioallantoic membrane (CAM) assay, which is performed with fertilized chicken eggs. CM were placed on the CAM on embryonic development day (EDD) 7; at EDD-10, ESWT was conducted at 0.12 mJ/mm² with 500 impulses each. One and four days later, angiogenesis represented by vascularized area, vessel density, and vessel junctions as well as HIF-1α and VEGF gene expression were evaluated. Furthermore, immune response (iNOS2, MMP-9, and MMP-13 via qPCR) was assessed and compared between ESWT- and non-ESWT-groups. At EDD-14, the vascularized area (+115% vs. +26%) and the increase in vessel junctions (+751% vs. +363%) were significantly higher in the ESWT-group. ESWT significantly increased MMP-9 gene expression at EDD-11 and significantly decreased MMP-13 gene expression at EDD-14 as compared to the controls. Using the CAM assay, an enhanced angiogenesis and neovascularization in CM after ESWT were observed. Furthermore, ESWT could reduce the inflammatory activity after a latency of four days.

Background: Animal models of posttraumatic joint stiffness (PTJS) are helpful in understanding underlying mechanisms, which is important for developing specific treatments and prophylactic therapies. Existing rat models of PTJS in the knee failed to show that the created contracture does not resolve through subsequent remobilization. Our objective was to establish a rat model of persisting PTJS of the knee and compare it to existing models. Methods: Thirty skeletally immature male Sprague Dawley rats underwent surgical intervention with knee hyperextension, extracartilaginous femoral condyle defect, and Kirschner (K)-wire transfixation for 4 weeks with the knee joint in 146.7 degrees +/- 7. 7 degrees of flexion (n = 10 per group, groups I-III). After K-wire removal, group I underwent joint angle measurements and group II and group III were allowed for 4 or 8 weeks of free cage activity, respectively, before joint angles were measured. Eighteen rats (n = 6 per group, groups Ic-IIIc) served as untreated control. Results: Arthrogenic contracture was largest in group I (55.2 degrees). After 4 weeks of remobilization, the contracture decreased to 25.7 degrees in group II (p < 0.05 vs. group I), whereas 8 weeks of remobilization did not reduce the contracture significantly (group III, 26.5 degrees, p = 0.06 vs. group I). Between 4 and 8 weeks of remobilization, no increase in extension (26.5 degrees in group III, p = 0.99 vs. group II) was observed. Interestingly, muscles did not contribute to the development of contracture. Conclusion: In our new rat model of PTJS of the knee joint, we were able to create a significant joint contracture with an immobilization time of only 4 weeks after trauma. Remobilization of up to 8 weeks alone did not result in full recovery of the range of motion. This model represents a powerful tool for further investigations on prevention and treatment of PTJS. Future studies of our group will use this new model to analyze medical treatment options for PTJS.

Skeletal muscle atrophy is characterized by a decrease in muscle fiber size as a result of a decreased protein synthesis, which leads to degradation of contractile muscle fibers. It can occur after denervation and immobilization, and glucocorticoids (GCs) may also increase protein breakdown contributing to the loss of muscle mass and myofibrillar proteins. GCs are already used in vitro to induce atrophic conditions, but until now no studies with primary human skeletal muscle existed. Therefore, this study deals with the effects of the GC dexamethasone (dex) on primary human myoblasts and myotubes. After incubation with 1, 10, and 100 µM dex for 48 and 72 h, gene and protein expression analyses were performed by qPCR and Western blot. Foxo, MuRF-1, and MAFbx were significantly upregulated by dex, and there was increased gene expression of myogenic markers. However, prolonged incubation periods demonstrated no Myosin protein degradation, but an increase of MuRF-1 expression. In conclusion, applying dex did not only differently affect primary human myoblasts and myotubes, as differences were also observed when compared to murine cells. Based on our findings, studies using cell lines or animal cells should be interpreted with caution as signaling transduction and functional behavior might differ in diverse species.

The bioactive coating of calcium phosphate cement (CPC) is a promising approach to enhance the bone-healing properties of bone substitutes. The purpose of this study was to evaluate whether coating CPCs with bone sialoprotein (BSP) results in increased bone formation. Forty-five female C57BL/6NRj mice with an average age of six weeks were divided into three groups. Either a BSP-coated or an uncoated three-dimensional plotted scaffold was implanted into a drilled 2.7-mm diameter calvarial defect, or the defect was left empty (control group; no CPC). Histological analyses revealed that BSP-coated scaffolds were better integrated into the local bone stock eight weeks after implantation. Bone volume/total volume (BV/TV) ratios and bone thickness at the bone–implant contact were analyzed via micro computed tomography (µCT) after eight weeks. BSP-coated scaffolds and uncoated CPC scaffolds increased bone thickness in comparison to the control (CPC + BSP: 691.1 ± 253.5 µm, CPC: 603.1 ± 164.4 µm, no CPC: 261.7 ± 37.8 µm, p < 0.01). Accordingly, BV/TV was enhanced in both scaffold groups (CPC + BSP: 1.3 ± 0.5%, CPC: 0.9 ± 0.5%, no CPC: 0.2 ± 0.3%, p < 0.01). The BSP coating showed a tendency towards an increased bone thickness (p = 0.18) and BV/TV (p = 0.18) in comparison to uncoated CPC scaffolds. However, a significant increase in bone formation through BSP coating was not found.

Background: The increasing incidence of spondylodiscitis and its potentially severe consequences when not promptly diagnosed highlight the need for further research to improve treatment guidelines, reduce mortality and morbidity and improve the quality of life in patients who suffer from persistent physical limitations. Methods: We collected data from 103 patients, with 8 patients lost to follow-up, who were diagnosed with vertebral osteomyelitis, disk infection or discitis between 2009 and 2018. The primary outcome was the 1-year mortality rate in patients treated with either conservative or surgical intervention, with both groups receiving antibiotic treatment. A standardized questionnaire was used to assess health-related quality of life after treatment by evaluating the European Quality of Life 5 Dimension 5 Level version (EQ-5D-5L) and the European Quality of Life Visual Analog Scale (EQ-VAS). In addition, we used the Oswestry Disability Index (ODI) and the Parker Mobility Score to identify backpain-related limitations after treatment. Results: The group receiving surgical treatment had a significantly lower 1-year mortality rate (22%) than did those who were treated conservatively, who had a 4-fold greater risk for death after a year following first diagnosis of SD and treatment. With respect to quality of life, 39 patients answered the standardized questionnaires during follow-up, and the questionnaire results revealed no significant difference in limitations in daily life or in health-related quality of life, with a median Parker Mobility Score of 9 for the conservatively treated patients compared with 7.5 for the surgically treated patients. This difference between the groups was not statistically significant, with a p value of 0.216 > α. A similar result was obtained in the evaluation of the ODI, with a medial index of 30% in the conservatively treated group compared with 24% in the surgical group, which was not statistically significant as indicated by a p value of 0.360 > α. Conclusions: The early surgical approach when treating spondylodiscitis is advantageous for identifying the underlying infection and initiating appropriate antibiotic therapy, therefore reducing mortality and resulting in a greater likelihood of full recovery than the conservative treatment does.