Developing stem cell-based therapeutic strategies in orthopaedic surgery

open5siEDITORIAL - Developing Stem Cell-Based Therapeutic Strategies in Orthopaedic SurgeryopenAtesok, Kivanc; Ochi, Mitsuo; Baldini, Nicola; Schemitsch, Emil; Liebergall, MeirAtesok, Kivanc; Ochi, Mitsuo; Baldini, Nicola; Schemitsch, Emil; Liebergall, Mei

Current Strategies in Prevention of Postoperative Infections in Spine Surgery.

Study Design: Narrative review. Objectives: Postoperative surgical site infections (SSIs) are among the most common acute complications in spine surgery and have a devastating impact on outcomes. They can lead to increased morbidity and mortality as well as greater economic burden. Hence, preventive strategies to reduce the rate of SSIs after spine surgery have become vitally important. The purpose of this article was to summarize and critically analyze the available evidence related to current strategies in the prevention of SSIs after spine surgery. Methods: A literature search utilizing Medline database was performed. Relevant studies from all the evidence levels have been included. Recommendations to decrease the risk of SSIs have been provided based on the results from studies with the highest level of evidence. Results: SSI prevention occurs at each phase of care including the preoperative, intraoperative, and postoperative periods. Meticulous patient selection, tight glycemic control in diabetics, smoking cessation, and screening/eradication of Conclusions: Although preventive strategies are already in use alone or in combination, further high-level research is required to prove their efficacy in reducing the rate of SSIs in spine surgery before evidence-based standard infection prophylaxis guidelines can be built

Multilayer scaffolds in orthopaedic tissue engineering

Abstract Purpose The purpose of this study was to summarize the recent developments in the field of tissue engineering as they relate to multilayer scaffold designs in musculoskeletal regeneration. Methods Clinical and basic research studies that highlight the current knowledge and potential future applications of the multilayer scaffolds in orthopaedic tissue engineering were evaluated and the best evidence collected. Studies were divided into three main categories based on tissue types and interfaces for which multilayer scaffolds were used to regenerate: bone, osteochondral junction and tendon-to-bone interfaces. Results In vitro and in vivo studies indicate that the use of stratified scaffolds composed of multiple layers with distinct compositions for regeneration of distinct tissue types within the same scaffold and anatomic location is feasible. This emerging tissue engineering approach has potential applications in regeneration of bone defects, osteochondral lesions and tendon-to-bone interfaces with successful basic research findings that encourage clinical applications. Conclusions Present data supporting the advantages of the use of multilayer scaffolds as an emerging strategy in musculoskeletal tissue engineering are promising, however, still limited. Positive impacts of the use of next generation scaffolds in orthopaedic tissue engineering can be expected in terms of decreasing the invasiveness of current grafting techniques used for reconstruction of bone and osteochondral defects, and tendon-to-bone interfaces in near future

The Use of Endothelial Progenitor Cells to Promote Bone Healing in a Defect Model in the Rat Femur

The objective of this project was to evaluate the effects of local endothelial progenitor cell (EPC) therapy on bone regeneration in a segmental defect in the rat femur. Animals from the EPC-treated (N=28) and control (N=28) groups were sacrificed at 1, 2, 3, and 10 weeks post-operatively. Bone healing was evaluated with radiographic, histological, and micro computed tomography (micro-CT) scans. Radiographically; mean scores of the EPC group at 1, 2, and 3 weeks were significantly higher compared to control group. At 10 weeks, all the animals in the EPC group had complete union (7/7), but in the control group none achieved union (0/7). Histologically, specimens from EPC-treated animals had abundant new bone formation compared to controls. Micro-CT assessment showed significantly improved parameters of bone healing for the EPC group compared to control group. In conclusion, local EPC therapy significantly enhanced bone regeneration in a segmental bone defect in rat femur.MAS

The Use of Endothelial Progenitor Cells for the Regeneration of Musculoskeletal and Neural Tissues

Endothelial progenitor cells (EPCs) derived from bone marrow and blood can differentiate into endothelial cells and promote neovascularization. In addition, EPCs are a promising cell source for the repair of various types of vascularized tissues and have been used in animal experiments and clinical trials for tissue repair. In this review, we focused on the kinetics of endogenous EPCs during tissue repair and the application of EPCs or stem cell populations containing EPCs for tissue regeneration in musculoskeletal and neural tissues including the bone, skeletal muscle, ligaments, spinal cord, and peripheral nerves. EPCs can be mobilized from bone marrow and recruited to injured tissue to contribute to neovascularization and tissue repair. In addition, EPCs or stem cell populations containing EPCs promote neovascularization and tissue repair through their differentiation to endothelial cells or tissue-specific cells, the upregulation of growth factors, and the induction and activation of endogenous stem cells. Human peripheral blood CD34(+) cells containing EPCs have been used in clinical trials of bone repair. Thus, EPCs are a promising cell source for the treatment of musculoskeletal and neural tissue injury

Expression of VEGF gene isoforms in a rat segmental bone defect model treated with EPCs

Angiogenesis and osteogenesis are essential for bone growth, fracture repair, and bone remodeling. Vascular endothelial growth factor (VEGF) has an important role in bone repair by promoting angiogenesis and osteogenesis. In our previous study, endothelial progenitor cells (EPCs) promoted bone healing in a rat segmental bone defect as confirmed by radiological, histological, biomechanical and microCT evaluations. While EPCs have demonstrated effectiveness in animal models of fracture healing, the mechanism by which EPCs enhance fracture healing remains unclear. We hypothesized a possible paracrine mechanism of action, where the secretion of growth factors critical to the processes of fracture healing (such as VEGF), is responsible for the positive effects of EPC therapy. The purpose of this study was to evaluate VEGF gene expression after local EPC therapy for a rat segmental bone defect. Methods: Rat bone marrow-derived EPCs were isolated by the Ficoll-paque gradient centrifuge technique. The EPCs were cultured for 7 to 10 days in endothelial cell growth medium with supplements and collected for treatment of the rat segmental bone defect. EPCs were identified by immunocytochemistry staining with primary antibodies for CD34, CD133, FLK-1, and vWF. A total of fifty six rats were studied. A five millimeter segmental bone defect was created in the middle 1/3 of each femur followed by mini plate fixation. The treatment group received 1x106 EPCs locally at the bone defect on a gelfoam scaffold and control animals received the gelfoam scaffold only. Seven control and seven EPC treated rats were included in each group at 1, 2, 3 and 10 weeks. Animals were sacrificed at the end of the treatment period, and specimens from the fracture gap 4 area were collected and immediately frozen. Rat VEGF mRNA was measured by reverse transcriptase-polymerase chain reaction (RT-PCR) and quantified by VisionWorksLS. All measurements were performed in triplicate. Results: Cultured EPCs at 1 week showed positive staining for CD34, CD133, Flk-1 and vWf markers. The EPC group had a greater VEGF expression than the control group at weeks 1, 2 and 3, but not at week 10. Three VEGF isoforms were detected in this rat model: VEGF120, VEGF164 and VEGF188. VEGF120 and VEGF164 levels peaked at two weeks, while VEGF188 levels peaked at three weeks. All three VEGF isoform levels were low at ten weeks. Discussion and Conclusion: EPC-based therapy for a segmental bone defect results in increased VEGF expression during the early period of fracture repair. In addition, the specific VEGF isoform may be a key regulator of the bone healing process. These findings demonstrate that EPCs may promote fracture healing by increasing VEGF levels and thus stimulating angiogenesis, a process that is essential for early callus formation and bone regeneration

Pathology and Treatment of Traumatic Cervical Spine Syndrome: Whiplash Injury

Traumatic cervical syndrome comprises the various symptoms that occur as a result of external force such as that of a traffic accident. In 1995, the Quebec Task Force on whiplash-associated disorders (WAD) formulated the Quebec classification, with accompanying clinical practice guidelines. These guidelines were in accordance with the stated clinical isolated or combined symptoms of the syndrome: neck pain, headaches, dizziness, numbness of head or face, eye pain, vision loss, double vision, tinnitus, hearing loss, nausea, and numbness and/or weakness of extremities. In recent years, cerebrospinal fluid hypovolemia or fibromyalgia has been recognized as a major notable cause of a variety of symptoms, although many clinical questions remain regarding the pathology of this syndrome. Therefore, its diagnosis and treatment should be conducted extremely carefully. While the Quebec classification and its guidelines are very useful for the normalization and standardization of symptoms of traumatic cervical syndrome, in the future, we would like to see the emergence of new guidelines that better address the diversity of this disease

Traumatic Lumbosacral Dislocation: Current Concepts in Diagnosis and Management

Traumatic lumbosacral dislocation is a rare, high-energy mechanism injury characterized by displacement of the fifth lumbar vertebra in relation to the sacrum. Due to the violent trauma typically associated with this lesion, there are often severe, coexisting injuries. High-quality radiographic studies, in addition to appropriate utilization of CT scan and MRI, are essential for proper evaluation and diagnosis. Although reports in the literature include nonoperative and operative management, most authors advocate for surgical treatment with open reduction and decompression with instrumentation and fusion. Despite advances in early diagnosis and management, this injury type is associated with significant morbidity and mortality, and long-term patient outcomes remain unclear