Double crosslinked biomimetic composite hydrogels containing topographical cues and WAY-316606 induce neural tissue regeneration and functional recovery after spinal cord injury.

Spinal cord injury (SCI) is an overwhelming and incurable disabling condition, for which increasing forms of multifunctional biomaterials are being tested, but with limited progression. The promising material should be able to fill SCI-induced cavities and direct the growth of new neurons, with effective drug loading to improve the local micro-organism environment and promote neural tissue regeneration. In this study, a double crosslinked biomimetic composite hydrogel comprised of acellularized spinal cord matrix (ASCM) and gelatin-acrylated-ß-cyclodextrin-polyethene glycol diacrylate (designated G-CD-PEGDA) hydrogel, loaded with WAY-316606 to activate canonical Wnt/ß-catenin signaling, and reinforced by a bundle of three-dimensionally printed aligned polycaprolactone (PCL) microfibers, was constructed. The G-CD-PEGDA component endowed the composite hydrogel with a dynamic structure with a self-healing capability which enabled cell migration, while the ASCM component promoted neural cell affinity and proliferation. The diffusion of WAY-316606 could recruit endogenous neural stem cells and improve neuronal differentiation. The aligned PCL microfibers guided neurite elongation in the longitudinal direction. Animal behavior studies further showed that the composite hydrogel could significantly recover the motor function of rats after SCI. This study provides a proficient approach to produce a multifunctional system with desirable physiological, chemical, and topographical cues for treating patients with SCI.

Notoginsenoside R1 counteracts mesenchymal stem cell-evoked oncogenesis and doxorubicin resistance in osteosarcoma cells by blocking IL-6 secretion-induced JAK2/STAT3 signaling.

Tumor microenvironment is a critical participant in the initiation, progression and drug resistance of carcinomas, including osteosarcoma. Notoginsenoside R1 (NGR1) is a proverbial active ingredient of the traditional Chinese medicine Panax notoginseng (PN) and possess undeniable roles in several cancers. Nevertheless, its function in osteosarcoma and tumor microenvironment remains elusive. In the current study, exposure to NGR1 dose-dependently inhibited osteosarcoma cell viability and migration, and induced apoptosis. Furthermore, osteosarcoma cells that were incubated with conditioned medium (CM) from bone marrow mesenchymal stem cells (BMSCs) exhibited greater proliferation, migration capacity and MMP-2 and MMP-9 expression relative to control cells, which was reversed when BMSCs were treated with NGR1. Notably, administration with NGR1 antagonized CM-evoked doxorubicin resistance in osteosarcoma cells by decreasing cell viability and increasing cell apoptosis and caspase-3/9 activity. Mechanically, NGR1 suppressed IL-6 secretion from BMSCs, as well as the subsequent activation of the JAK2/STAT3 signaling in osteosarcoma cells. In addition, blocking the JAK2 pathway by its antagonist AG490 reversed CM-induced osteosarcoma cell proliferation, migration and doxorubicin resistance. Moreover, exogenous supplementation with IL-6 engendered not only the reactivation of the JAK2/STAT3 signaling but also muted NGR1-mediated efficacy against osteosarcoma cell malignancy and doxorubicin resistance. Collectively, NGR1 may directly restrain osteosarcoma cell growth and migration, or indirectly antagonize MSC-evoked malignancy and drug resistance by interdicting IL-6 secretion-evoked activation of the JAK2/STAT3 pathway. Consequently, the current study may highlight a promising therapeutic strategy against osteosarcoma by regulating tumor cells and the tumor microenvironment.

Effects of soybean isoflavone on metabolism of rat osteoblasts and cytokines in vitro.

The effects and mechanisms of soybean isoflavone on osteoblast (OB) proliferation in vitro were investigated. Fifty female Wistar rats were randomly divided into five groups with 10 rats in each group. Rat OBs were separated and cultured. The first generation of OBs cultured for 48 hr at various concentrations of isoflavone were set as the experimental groups, the OBs exposed to estradiol (E2 ) culture were considered as positive control group. The biological characterization of OBs was investigated by phase contrast microscopy and alkaline phosphatase (ALP) histochemistry. The concentrations of interleukin (IL-1), osteoprotegerin (OPG), transforming growth factor (TGF), granulocyte-macrophage colony-stimulating factor (GM-CSF), and vascular endothelial growth factor (VEGF) in isoflavone culture solutions were determined. Proliferation rate of OBs was increased in experimental group comparing that in the blank group. ALP activity in experimental group was higher than that in blank group. No significant differences of ALP activity were observed between E2 culture group and isoflavone group at concentrations of 10-5 and 10-7 mM (P > 0.05). Furthermore, in the experimental groups at low isoflavone concentrations, the concentrations of OPG, TGF, and VEGF were increased and positively correlated with OB proliferation. However, the concentrations of IL-1, GM-CSF were decreased at higher concentration of isoflavone and were negatively correlated with OB proliferation. Soybean isoflavone could promote the growth and proliferation of rat OB, it might act as the stimulator of OPG, TGF, and VEGF pathway, and the inhibitor of IL-1, GM-CSF pathway as well.

Right infraaxillary thoracotomy approach for upper thoracic vertebral decompression and fusion at T2-T6 levels: a technical note.

PURPOSE: Disorders of the upper thoracic spine can lead to serious disability and morbidity. However, operating on the upper thoracic vertebrae T2-T5 remains challenging because of the anatomical features of the thoracic spine. We describe a novel anterolateral upper thoracic approach, which is safe and reproducible and allows direct access to the upper thoracic spine from T2 to T6 inclusive, obviating the risk of damaging complex anatomical structures inherent in the anterior trans-sternal approach. METHODS: Three patients with upper thoracic spinal-related spinal cord compression disease, presented with progressive thoracic myelopathy and upper back pain. Magnetic resonance imaging showed direct spinal cord compression due to upper thoracic vertebral destruction. In addition preoperative computed tomography also revealed vertebral erosion and collapse. The surgical management of the three patients involved decompression and reconstruction via the right infraaxillary thoracotomy approach, and fixation with a titanium mesh cage and an anterior plate in each. RESULTS: Clinical outcome measures including pre- and postoperative radiographic parameters were assessed. There were no complications associated with this technique. The back pain and neural function gradually improved, and plate placement was achieved in all patients. None of the patients experienced clinical symptoms or screw loosening or breakage in this study. CONCLUSIONS: The technique described is a safe and novel right infraaxillary thoracotomy approach to provide direct access from vertebral bodies T2-T6 and to provide adequate room for upper thoracic vertebral decompression and fusion surgery. However, a suitable fixation implant should be designed. These slides can be retrieved under Electronic Supplementary Material.

Correction to: Right infraaxillary thoracotomy approach for upper thoracic vertebral decompression and fusion at T2-T6 levels: a technical note.

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