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.

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

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

Complex biomechanical properties of non-augmented and augmented pedicle screws in human vertebrae with reduced bone density

Background: In osteoporotic bone, the quality of the bone-to-implant interface is decreased, which may lead to early implant failure. Screw anchorage can be improved by augmentation. This effect is mainly investigated with a pull-out test. To our knowledge, the effect of cement augmentation in an in vivo physiological setup focusing on screw movement has not been investigated to date. The aim of this work was to investigate and compare augmented and native screw behavior in a physiologically related setup. Methods: Twelve fresh-frozen human lumbar vertebrae were divided into two groups. Each vertebra was bilaterally instrumented with either non-augmented or augmented pedicle screw systems and loaded in a recently developed test setup that provided cyclic conditions comparable to a physiological gait. The cyclic loading should test the primary implant stability, comparable to the postoperative period of two months in a worst-case scenario in the absence of osseous remodeling. Screws were tracked optically, and screw movement and failure patterns were observed. Results: Mutual influence between the left and right sides resulted in a successive, rather than simultaneous, failure. Augmentation of the screws in vertebrae with poor bone quality reduced screw subsidence and thus improved the rigidity of the screw-to-implant interface by up to six-fold. The non-augmented condition was significantly related to early screw failure. Conclusions: Pedicle screw system failure involves a complex bilateral-coupled mechanism. The cyclic loading based on physiological conditions during walking has allowed the postoperative conditions and clinical failure mechanisms to be simulated in vitro and clarified. Future implant systems should be investigated with a physiologically related setup