Proliferating and differentiating effects of three different growth factors on pluripotent mesenchymal cells and osteoblast like cells

Growth factors are in clinical use to stimulate bone growth and regeneration. BMP-2 is used in long bone and spinal surgery, PDGFbb for the treatment of periodontal defects and children with growth hormone receptor deficiency are treated with IGF-I

Management of an extended clivus fracture: a case report

Background: Clivus fractures are highly uncommon. The classification by Corradino et al. divides the different lesions in longitudinal, transverse and oblique fractures. Longitudinal types are associated with the highest mortality rate between 67 – 80%. Clivus fractures are often found after high velocity trauma, especially traffic accidents and falls. The risk of neurologic lesions is high, because of the anatomic proximity to neurovascular structures like the brainstem, the vertebrobasilar artery, and the cranial nerves. Longitudinal clivus fractures have a special risk of causing entrapment of the basilar artery and thus ischemia of the brainstem. Case presentation: This lesion in our patient was a combination-fracture of the craniocervical junction with a transverse clivus fracture. In this case, the primary closed reduction of the clivus fracture and the immobilization with a halo device was the therapy of choice and led to consolidation of the fracture. Conclusion: Therapy advices and examples in the literature are scarce. We present a patient with a clivus fracture, who could be well treated by a halo device. Through detailed research of the literature a therapy algorithm has been developed.<br

Cooperative effects in differentiation and proliferation between PDGF-BB and matrix derived synthetic peptides in human osteoblasts

Background: Enhancing osteogenic capabilities of bone matrix for the treatment of fractures and segmental defects using growth factors is an active area of research. Recently, synthetic peptides like AC- 100, TP508 or p-15 corresponding to biologically active sequences of matrix proteins have been proven to stimulate bone formation. The platelet-derived growth factor (PDGF) BB has been identified as an important paracrine factor in early bone healing. We hypothesized that the combined use of PDGF-BB with synthetic peptides could result in an increase in proliferation and calcification of osteoblast-like cells. Methods: Osteoblast-like cell cultures were treated with PDGF and synthetic peptides, singly and as combinations, and compared to non-treated control cell cultures. The cultures were evaluated at days 2, 5, and 10 in terms of cell proliferation, calcification and gene expression of alkaline phosphate, collagen I and osteocalcin. Results: Experimental findings revealed that the addition of PDGF, p-15 and TP508 and combinations of PDGF/AC-100, PDGF/p-15 and PDGF/TP508 resulted in an increase in proliferating osteoblasts, especially in the first 5 days of cultivation. Proliferation did not significantly differ between single factors and factor combinations (p > 0.05). The onset of calcification in osteoblasts occurred earlier and was more distinct compared to the corresponding control or PDGF stimulation alone. Significant difference was found for the combined use of PDGF/p-15 and PDGF/AC-100 (p < 0.05). Conclusions: Our findings indicate that PDGF exhibits cooperative effects with synthetic peptides in differentiation and proliferation. These cooperative effects cause a significant early calcification of osteoblast-like cells (p < 0.05). We suggest the combination of synthetic peptides and PDGF as a potential clinical approach for accelerating bone healing or coating osteosynthesis materials.

Radiographic and safety details of vertebral body stenting : results from a multicenter chart review

Background: Up to one third of BKP treated cases shows no appreciable height restoration due to loss of both restored height and kyphotic realignment after balloon deflation. This shortcoming has called for an improved method that maintains the height and realignment reached by the fully inflated balloon until stabilization of the vertebral body by PMMA-based cementation. Restoration of the physiological vertebral body height for pain relief and for preventing further fractures of adjacent and distant vertebral bodies must be the main aim for such a method. A new vertebral body stenting system (VBS) stabilizes the vertebral body after balloon deflation until cementation. The radiographic and safety results of the first 100 cases where VBS was applied are presented. Methods: During the planning phase of an ongoing international multicenter RCT, radiographic, procedural and followup details were retrospectively transcribed from charts and xrays for developing and testing the case report forms. Radiographs were centrally assessed at the institution of the first/senior author. Results: 100 patients (62 with osteoporosis) with a total of 103 fractured vertebral bodies were treated with the VBS system. 49 were females with a mean age of 73.2 years; males were 66.7 years old. The mean preoperative anterior-middle-posterior heights were 20.3-17.6-28.0 mm, respectively. The mean local kyphotic angle was 13.1°. The mean preoperative Beck Index (anterior edge height/posterior edge height) was 0.73, the mean alternative Beck Index (middle height/posterior edge height) was 0.63. The mean postoperative heights were restored to 24.5-24.6-30.4 mm, respectively. The mean local kyphotic angle was reduced to 8.9°. The mean postoperative Beck Index was 0.81, the mean alternative one was 0.82. The overall extrusion rate was 29.1%, the symptomatic one was 1%. In the osteoporosis subgroup there were 23.8% extrusions. Within the three months followup interval there were 9% of adjacent and 4% of remote new fractures, all in the osteoporotic group. Conclusions: VBS showed its strengths especially in realignment of crush and biconcave fractures. Given that fracture mobility is present, the realignment potential is sound and increases with the severity of preoperative vertebral body deformation

Experimentally induced incomplete burst fractures - a novel technique for calf and human specimens

Background: Fracture morphology is crucial for the clinical decision-making process preceding spinal fracture treatment. The presented experimental approach was designed in order to ensure reproducibility of induced fracture morphology. Results: The presented method resulted in fracture morphology, found in clinical classification systems like the Magerl classification. In the calf spine samples, 70% displayed incomplete burst fractures corresponding to type A3.1 and A3.2 fractures. In all human samples, superior incomplete burst fractures (Magerl A3.1) were identified by an independent radiologist and spine surgeon. Conclusions: The presented set up enables the first experimental means to reliably model and study distinct incomplete burst fracture patterns in an in vitro setting. Thus, we envisage this protocol to facilitate further studies on spine fracture treatment of incomplete burst fractures

Bone Regeneration: A Novel Osteoinductive Function of Spongostan by the Interplay between Its Nano- and Microtopography.

Vordemvenne T, Wähnert D, Koettnitz J, et al. Bone Regeneration: A Novel Osteoinductive Function of Spongostan by the Interplay between Its Nano- and Microtopography. Cells. 2020;9(3): 654.Scaffold materials for bone regeneration are crucial for supporting endogenous healing after accidents, infections, or tumor resection. Although beneficial impacts of microtopological or nanotopological cues in scaffold topography are commonly acknowledged, less consideration is given to the interplay between the microscale and nanoscale. Here, micropores with a 60.66 ± 24.48 m diameter ordered by closely packed collagen fibers are identified in pre-wetted Spongostan, a clinically-approved collagen sponge. On a nanoscale level, a corrugated surface of the collagen sponge is observable, leading to the presence of 32.97 ± 1.41 nm pores. This distinct micro- and nanotopography is shown to be solely sufficient for guiding osteogenic differentiation of human stem cells in vitro. Transplantation of Spongostan into a critical-size calvarial rat bone defect further leads to fast regeneration of the lesion. However, masking the micro- and nanotopographical cues using SiO2 nanoparticles prevents bone regeneration in vivo. Therefore, we demonstrate that the identified micropores allow migration of stem cells, which are further driven towards osteogenic differentiation by scaffold nanotopography. The present findings emphasize the necessity of considering both micro- and nanotopographical cues to guide intramembranous ossification, and might provide an optimal cell- and growth-factor-free scaffold for bone regeneration in clinical settings

A Role for NF-κB in Organ Specific Cancer and Cancer Stem Cells

Kaltschmidt C, Banz-Jansen C, Benhidjeb T, et al. A Role for NF-κB in Organ Specific Cancer and Cancer Stem Cells. Cancers. 2019;11(5): 655.Cancer stem cells (CSCs) account for tumor initiation, invasiveness, metastasis, and recurrence in a broad range of human cancers. Although being a key player in cancer development and progression by stimulating proliferation and metastasis and preventing apoptosis, the role of the transcription factor NF-κB in cancer stem cells is still underestimated. In the present review, we will evaluate the role of NF-κB in CSCs of glioblastoma multiforme, ovarian cancer, multiple myeloma, lung cancer, colon cancer, prostate cancer, as well as cancer of the bone. Next to summarizing current knowledge regarding the presence and contribution of CSCs to the respective types of cancer, we will emphasize NF-κB-mediated signaling pathways directly involved in maintaining characteristics of cancer stem cells associated to tumor progression. Here, we will also focus on the status of NF-κB-activity predominantly in CSC populations and the tumor mass. Genetic alterations leading to NF-κB activity in glioblastoma, ependymoma, and multiple myeloma will be discussed

Differentiation of Traumatic Osteoporotic and Non-Osteoporotic Vertebral AO A3 Fractures by Analyzing the Posterior Edge Morphology—A Retrospective Feasibility Study

Background: Differentiation between traumatic osteoporotic and non-osteoporotic vertebral fractures is crucial for optimal therapy planning. We postulated that the morphology of the posterior edge of the cranial fragment of A3 vertebral fractures is different in these entities. Therefore, the purpose of this study is to develop and validate a simple method to differentiate between osteoporotic and non-osteoporotic A3 vertebral fractures by morphological analysis. Methods: A total of 86 computer tomography scans of AO Type A3 (cranial burst) vertebral body fractures (52 non-osteoporotic, 34 osteoporotic) were included in this retrospective study. Posterior edge morphology was analyzed using the sagittal paramedian slice with the most prominent shaped bulging. Later, the degree of bulging of the posterior edge fragment was quantified using a geometric approach. Additionally, the Hounsfield units of the broken vertebral body, the vertebra above, and the vertebra below the fracture were measured. Results: We found significant differences in the extent of bulging comparing osteoporotic and non-osteoporotic fractures in our cohort. Using the presented method, sensitivity was 100%, specificity was 96%. The positive predictive value (PPV) was 94%. In contrast, by evaluating the Hounsfield units, sensitivity was 94%, specificity 94% and the PPV was 91%. Conclusions: Our method of analysis of the bulging of the dorsal edge fragment in traumatic cranial burst fractures cases allows, in our cases, a simple and valid differentiation between osteoporotic and non-osteoporotic fractures. Further validation in a larger sample, including dual-energy X-ray absorptiometry (DXA) measurements, is necessary

Instability of the posterior pelvic ring: introduction of innovative implants

Grüneweller N, Wähnert D, Vordemvenne T. Instability of the posterior pelvic ring: introduction of innovative implants. Journal of Orthopaedic Surgery and Research. 2021;16(1):625.BACKGROUND: Increasing numbers of posterior pelvic ring fractures, especially in elderly patients, demonstrate the need for soft tissue protecting surgical techniques. Standard of care is iliosacral screw osteosynthesis. This type of osteosynthesis has its limitations especially in patients with reduced bone properties. Therefore, the development of new and straightforward surgical techniques and implant designs is favorable.; METHODS: Introducing this modular system for the posterior pelvic ring, known complications of iliosacral screw osteosynthesis, such as implant loosening and malpositioning may be reduced, due to innovative mechanical characteristics.; RESULTS: The shown cases demonstrate the potential benefits of the system with a wide range of treatment options due to its modularity.; CONCLUSION: The modular implant system presented here can significantly facilitate and improve the stabilization of posterior pelvic ring instabilities. © 2021. The Author(s)

Analysis of risk factors in thoracic trauma patients with a comparison of a modern trauma centre: a mono-centre study.

OBJECTIVES Thoracic trauma (TT) is the third most common cause of death after abdominal injury and head trauma in polytrauma patients. Its management is still a very challenging task. The purpose of this study was to analyse the risk factors affecting the outcome in a high-volume trauma centre and the efficacy of a specialised trauma team in level 1 trauma centres. PATIENTS AND METHODS Between January 2003 and December 2012, data of all patients admitted to the accident and emergency (A&E) department were prospectively collected at the German Trauma Registry (GTR) and thereafter retrospectively analysed. Patients with chest trauma, an Injury Severity Score (ISS) ≥ 18 and an Abbreviated Injury Scale (AIS) > 2 in more than one body region were included. Patients were divided into two groups: group I included patients presenting with thoracic trauma between January 2003 and December 2007. The results of this group were compared with the results of another group (group II) in a later 5-year period (Jan. 2008-Dec. 2012). Univariate and multivariate analyses were performed, and differences with p < 0.05 were considered statistically significant. RESULTS There were 630 patients (56%) with thoracic trauma. A total of 540 patients (48%) had associated extrathoracic injuries. Group I consisted of 285 patients (197 male, mean age 46 years). Group II consisted of 345 patients (251 male, mean age 49 years). Overall 90-day mortality was 17% (n = 48) in group I vs. 9% (n = 31) in group II (p = 0.024). Complication rates were higher in group I (p = 0.019). Higher Injury Severity Scores (ISSs) and higher Abbreviated Injury Acale (AIS) scores in the thoracic region yielded a higher rate of mortality (p < 0.0001). Young patients (< 40 years) were frequently exposed to severe thoracic injury but showed lower mortality rates (p = 0.014). Patients with severe lung contusions (n = 94) (15%) had higher morbidity and mortality (p < 0.001). Twenty-three (8%) patients underwent emergency thoracotomy in group I vs. 14 patients (4%) in group II (p = 0.041). Organ replacement procedures were needed in 18% of patients in group I vs. 31% of patients in group II (p = 0.038). CONCLUSIONS The presence of severe lung contusion, a higher ISS and AISthoracic score and advanced age are independent risk factors that are directly related to a higher mortality rate. Management of blunt chest trauma with corrective chest tube insertion, optimal pain control and chest physiotherapy results in good outcomes in the majority of patients. Optimal management with better survival rates is achievable in specialised centres with multidisciplinary teamwork and the presence of thoracic surgical experience