Percutaneous kyphoplasty in the treatment of Kümmell disease in lumbar scoliosis: A case report.

BACKGROUND: Due to mechanical imbalance in the spine, elderly scoliosis patients tend to develop vertebral fracture nonunion, i.e., Kümmell disease, when osteoporotic vertebral compression fractures occur. However, accompanying vertebral rotational deformities make surgical procedures challenging risky. Such patients are usually compelled to undergo conservative treatment and there are very few reports on minimally invasive surgeries for them. We first-time report a patient with Kümmell disease and lumbar scoliosis treated with percutaneous kyphoplasty (PKP) under O-arm guidance. CASE SUMMARY: An 89-year-old female was admitted to the hospital due to delayed low back pain after a fall. She was diagnosed with Kümmell disease based on physical and radiologic examinations. The patient experienced severe scoliosis and subsequently underwent O-arm-guided kyphoplasty, resulting in a significant alleviation of low back pain. CONCLUSION: PKP has good efficacy in treating Kümmell disease. However, surgical risks are elevated in scoliosis patients with Kümmell disease due to the abnormal anatomical structure of the spine. O-arm assisted operations play a crucial role in decreasing surgical risks.

Comparison of three techniques in the surgical management of metastatic vertebral fracture with posterior wall damage: a retrospective study.

BACKGROUND: To retrospectively compare the safety and efficacy of percutaneous kyphoplasty (PKP), internal fixation (IF), and kyphoplasty combined with internal fixation (KP + IF) in treating metastatic vertebral fracture (MVF) with posterior wall damage. METHODS: 87 patients with MVF with posterior wall damage underwent surgery. In Group PKP, 36 patients underwent PKP; in Group IF, 20 patients underwent pedicle screw fixation; and in Group KP + IF, 31 patients underwent kyphoplasty combined with pedicle screw fixation. Operative time, intraoperative blood loss, clinical and radiological results, and complication rate in each group were evaluated and compared. RESULTS: Significant improvement on the VAS, ODI scores, vertebral height and local kyphotic angle (LKA) was noted in each group (P < 0.001). Group PKP and Group KP + IF achieved better pain relief than Group IF (P < 0.05). At postoperative 3 days, Group PKP had better pain relief than Group KP + IF (P < 0.05). At other follow-up time points, there were no differences between Group PKP and KP + IF (P > 0.05). Group KP + IF and Group IF were more efficacious than Group PKP in terms of height restoration and LKA correction (P < 0.05). Group KP + IF had a higher incidence of postoperative complications than Group PKP and Group IF(P < 0.05). CONCLUSIONS: PKP was safe and effective in treating MVF with posterior wall damage. It can achieve similar clinical outcomes compared to KP + IF, but associated with less operative time, less blood loss and fewer complications. IF alone should not be the first treatment option for its poorer analgesic effect.

GDNF-Loaded Polydopamine Nanoparticles-Based Anisotropic Scaffolds Promote Spinal Cord Repair by Modulating Inhibitory Microenvironment.

Spinal cord injury (SCI) is a devastating injury that causes permanent loss of sensation and motor function. SCI repair is a significant challenge due to the limited regenerating ability of adult neurons and the complex inflammatory microenvironment. After SCI, the oxidative stress induced by excessive reactive oxygen species (ROS) often leads to prolonged neuroinflammation that results in sustained damage to the spinal cord tissue. Polydopamine (PDA) shows remarkable capability in scavenging ROS to treat numerous inflammatory diseases. In this study, glial cell-derived neurotrophic factor (GDNF)-loaded PDA nanoparticle-based anisotropic scaffolds for spinal cord repair are developed. It is found that mesoporous PDA nanoparticles (mPDA NPs) in the scaffolds efficiently scavenge ROS and promote microglia M2 polarization, thereby inhibiting inflammatory response at the injury site and providing a favorable microenvironment for nerve cell survival. Furthermore, the GDNF encapsulated in mPDA NPs promotes corticospinal tract motor axon regeneration and its locomotor functional recovery. Together, findings from this study reveal that the GDNF-loaded PDA/Gelatin scaffolds hold potential as an effective artificial transplantation material for SCI treatment.

Mesenchymal Stromal Cell Therapy in Spinal Cord Injury: Mechanisms and Prospects.

Spinal cord injury (SCI) often leads to severe motor, sensory, and autonomic dysfunction in patients and imposes a huge economic cost to individuals and society. Due to its complicated pathophysiological mechanism, there is not yet an optimal treatment available for SCI. Mesenchymal stromal cells (MSCs) are promising candidate transplant cells for use in SCI treatment. The multipotency of MSCs, as well as their rich trophic and immunomodulatory abilities through paracrine signaling, are expected to play an important role in neural repair. At the same time, the simplicity of MSCs isolation and culture and the bypassing of ethical barriers to stem cell transplantation make them more attractive. However, the MSCs concept has evolved in a specific research context to encompass different populations of cells with a variety of biological characteristics, and failure to understand this can undermine the quality of research in the field. Here, we review the development of the concept of MSCs in order to clarify misconceptions and discuss the controversy in MSCs neural differentiation. We also summarize a potential role of MSCs in SCI treatment, including their migration and trophic and immunomodulatory effects, and their ability to relieve neuropathic pain, and we also highlight directions for future research.

Magnesium Oxide/Poly(l-lactide-co-ε-caprolactone) Scaffolds Loaded with Neural Morphogens Promote Spinal Cord Repair through Targeting the Calcium Influx and Neuronal Differentiation of Neural Stem Cells.

Because of the limited regenerative ability of the central nervous system (CNS), effective treatments for spinal cord injury (SCI) are still lacking. After SCI, neuron loss and axon regeneration failure often result in irreversible functional impairment. The calcium overload induced by the N-methyl-D-aspartate receptor (NMDAR) overactivation is critical for cell death in SCI. It has been reported that the magnesium ion (Mg2+ ) can competitively block the NMDAR and reduce the calcium influx, and that sonic hedgehog (Shh) and retinoic acid (RA) are the critical regulators of neuronal differentiation of endogenous neural stem cells (NSCs). Here, magnesium oxide (MgO)/poly (l-lactide-co-ε-caprolactone) (PLCL) scaffold loaded with purmorphamine (PUR, a Shh signaling agonist) and RA is developed and its feasibility in SCI repair is tested. The results showed that the Mg2+ released from MgO attenuated cell apoptosis by blocking the calcium influx, and the PUR/RA promoted the recruitment and neuronal differentiation of endogenous NSCs, thereby reducing the glial scar formation at the SCI lesion site. Furthermore, implantation of PUR/RA-loaded MgO/PLCL scaffold facilitates the partial recovery of a locomotor function of SCI mouse in vivo. Together, findings from this study imply that PUR/RA-loaded MgO/PLCL scaffold may be a promising biomaterial for the clinical treatment of SCI.

Collagen Modified Anisotropic PLA Scaffold as a Base for Peripheral Nerve Regeneration.

Reconstruction of damaged nerves remains a significant unmet challenge in clinical medicine. Topographical and mechanical stimulations play important roles to repair peripheral nerve injury. The synergistic effects of topography and mechanical rigidity may significantly accelerate nerve regeneration. In this work, a nerve-guiding collagen/polylactic acid (PLA) electrospun scaffold is developed to facilitate peripheral nerve repair. The obtained anisotropic PLA electrospun scaffolds simulate the directional arranged structure of nerve realistically and promote axonal regeneration after sciatic nerve injury when compared with the isotropic PLA electrospun scaffolds. Moreover, the collagen-modified PLA electrospun scaffolds further provide sufficient mechanical support and favorable microenvironment for axon regeneration. In addition, it is observed that collagen-modified PLA electrospun scaffolds facilitate the axon regeneration by regulating Yes-associated protein (YAP) molecular pathway. Taken together, the engineered collagen-modified anisotropic PLA electrospun scaffolds may be a potential candidate to combine topography and mechanical rigidity for peripheral nerve regeneration is engineered.

Deletion of Krüppel-like factor-4 promotes axonal regeneration in mammals.

Axonal regeneration plays an important role in functional recovery after nervous system damage. However, after axonal injury in mammals, regeneration is often poor. The deletion of Krüppel-like factor-4 (Klf4) has been shown to promote axonal regeneration in retinal ganglion cells. However, the effects of Klf4 deletion on the corticospinal tract and peripheral nervous system are unknown. In this study, using a mouse model of sciatic nerve injury, we show that the expression of Klf4 in dorsal root ganglion sensory neurons was significantly reduced after peripheral axotomy, suggesting that the regeneration of the sciatic nerve is associated with Klf4. In vitro, dorsal root ganglion sensory neurons with Klf4 knockout exhibited significantly enhanced axonal regeneration. Furthermore, the regeneration of the sciatic nerve was enhanced in vivo following Klf4 knockout. Finally, AAV-Cre virus was used to knockout the Klf4 gene in the cortex. The deletion of Klf4 enhanced regeneration of the corticospinal tract in mice with spinal cord injury. Together, our findings suggest that regulating KLF4 activity in neurons is a potential strategy for promoting axonal regeneration and functional recovery after nervous system injury. This study was approved by the Animal Ethics Committee at Soochow University, China (approval No. SUDA20200316A01).

Inhibition of PTEN activity promotes IB4-positive sensory neuronal axon growth.

Traumatic nerve injuries have become a common clinical problem, and axon regeneration is a critical process in the successful functional recovery of the injured nervous system. In this study, we found that peripheral axotomy reduces PTEN expression in adult sensory neurons; however, it did not alter the expression level of PTEN in IB4-positive sensory neurons. Additionally, our results indicate that the artificial inhibition of PTEN markedly promotes adult sensory axon regeneration, including IB4-positive neuronal axon growth. Thus, our results provide strong evidence that PTEN is a prominent repressor of adult sensory axon regeneration, especially in IB4-positive neurons.

Preparation and characterization of a silk fibroin/calcium sulfate bone cement.

This study aimed to prepare and characterize a silk fibroin/calcium sulfate (SF/CS) bone cement. SF solutions of the following concentrations 3, 4.5, 6, 7.5, and 9 g/L were used to prepare bone cement samples with SF-to-CS ratios of 0.35, 0.40, 0.45, 0.50, and 0.55 mL of SF solutions (or water as control) per g of CS. Compressive strength, setting time, degradation when immersed in phosphate-buffered saline, X-ray diffraction, Fourier infrared spectroscopy, and scanning electron microscopy were used to characterize the SF/CS bone cement. Biocompatibility was determined using rat bone mesenchymal stem cells (rBMSCs) and the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. The optimal bone cement was obtained with 0.4 mL of 6 g/L SF solution per g of α-hemihydrate CS powder. Compared with CS bone cement, compressive strength of SF/CS bone cement was 19.7% higher (p = 0.003). Samples prepared with SF had less degradation in phosphate-buffered saline than the ones prepared with deionized water. Using SF solution as the solidifying liquid increases the initial setting and final setting time of CS compared with deionized water. Using extracts from SF/CS bone cement, all cell relative proliferation rates were >100%, showing no cytotoxicity for any sample. In conclusion, using the 6 g/L SF solution at 0.40 mL/g of CS increased the cement compressive strength. SF solution added to CS achieved a bone cement with increased durability compared with CS bone cement. The SF/CS cement had no cytotoxicity on rBMSCs. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 512-519, 2018.

Anti-osteoporosis activity of Sanguinarine in preosteoblast MC3T3-E1 cells and an ovariectomized rat model.

Sanguinarine, a benzophenanthridine alkaloid, has been previously demonstrated to exert antimicrobial, anti-inflammatory, and anti-tumor activities. A previous study has identified Sanguinarine as a potential drug candidate for osteoporosis treatment by computational bioinformatics analysis. This study further evaluated the effects of Sanguinarine on the differentiation of murine preosteoblast MC3T3-E1 cells and its anti-osteoporosis activity in an ovarietomized rat model. Sanguinarine treatment (0.25, 0.5, 1, and 2 µm) of MC3T3-E1 cells significantly increased alkaline phosphatase (ALP) activity and the phoshporalyation of AMP-activated protein kinase α subunit (AMPKα), but did not affect cell proliferation. The induction effects of Sanguinarine treatment (2 µm) on ALP activity, AMPKα phosphorylation, Smad1 phosphorylation, and the expression of three osteoblast differentiation-regulators (bone morphogenetic protein 2 [BMP2], osterix [OSX], and osteoprotegerin [OPG]) were partially reversed by Compound C treatment. More importantly, Sanguinarine treatment promoted bone tissue growth in an ovariectomized (OVX) osteoporosis rat model as evaluated by histological examination, micro-CT analysis, and serum parameter detection. In conclusion, these results indicate that Sanguinarine induces the differentiation of MC3T3-E1 cells through the activation of the AMPK/Smad1 signaling pathway. Sanguinarine can stimulate bone growth in vivo and may be an effective drug for osteoporosis treatment.