Biomimetic and osteogenic 3D silk fibroin composite scaffolds with nano MgO and mineralized hydroxyapatite for bone regeneration.

Artificial bioactive materials have received increasing attention worldwide in clinical orthopedics to repair bone defects that are caused by trauma, infections or tumors, especially dedicated to the multifunctional composite effect of materials. In this study, a weakly alkaline, biomimetic and osteogenic, three-dimensional composite scaffold (3DS) with hydroxyapatite (HAp) and nano magnesium oxide (MgO) embedded in fiber (F) of silkworm cocoon and silk fibroin (SF) is evaluated comprehensively for its bone repair potential in vivo and in vitro experiments, particularly focusing on the combined effect between HAp and MgO. Magnesium ions (Mg2+) has long been proven to promote bone tissue regeneration, and HAp is provided with osteoconductive properties. Interestingly, the weak alkaline microenvironment from MgO may also be crucial to promote Sprague-Dawley (SD) rat bone mesenchymal stem cells (BMSCs) proliferation, osteogenic differentiation and alkaline phosphatase (ALP) activities. This SF/F/HAp/nano MgO (SFFHM) 3DS with superior biocompatibility and biodegradability has better mechanical properties, BMSCs proliferation ability, osteogenic activity and differentiation potential compared with the scaffolds adding HAp or MgO alone or neither. Similarly, corresponding meaningful results are also demonstrated in a model of distal lateral femoral defect in SD rat. Therefore, we provide a promising 3D composite scaffold for promoting bone regeneration applications in bone tissue engineering.

[Treatment of floating knee injury in children with elastic intramedullary nail].

OBJECTIVE: To observe the clinical effect of elastic intramedullary nail in minimally invasive treatment of floating knee injury in children. METHODS: From January 2009 to September 2017, 11 children with floating knee injury were treated with one-off open reduction and elastic intramedullary nail or external fixator fixation, including 7 males and 4 females, aged 5.0 to 11.0 years, with an average age of 8.3 years. The treatment results were evaluated according to karlstrom's standard. RESULTS: Eleven patients were followed up for 8 to 48 months, with an average of 28 months. All the fractures healed at one time, and there were no complications such as nonunion, malunion and serious dysfunction of knee joint. The length of the affected limb in 2 cases was 1.2 to 1.5 cm longer than that in the opposite side without shortening. According to Karlstrom scoring standard, 8 cases were excellent, 1 case was good and 2 cases were middle. CONCLUSION: Elastic intramedullary nail minimally invasive treatment of floating knee injury in children is a safe and effective treatment, which can effectively reduce the fracture and promote bone healing, which is conducive to early functional recovery.

Research Progress on Diagnosis and Treatment of Chronic Osteomyelitis.

We review the representatives literatures on chronic osteomyelitis, sum up the new insights in recent years into diagnostic options and treatment regimens, analyze the advantages and disadvantages of various diagnostic approaches and treatment strategies, and propose areas of interest to make current diagnostic and treatment strategies more specific.

Diazoxide ameliorates severity of experimental osteoarthritis by activating autophagy via modulation of the osteoarthritis-related biomarkers.

Accumulating evidence suggests that autophagy plays a protective role in chondrocytes and prevents cartilage degeneration in osteoarthritis (OA). The objective of this study was to investigate the effect of diazoxide on chondrocyte death and cartilage degeneration and to determine whether these effects are correlated to autophagy in experimental OA. In this study, a cellular OA model was established by stimulating SW1353 cells with interleukin 1ß. A rat OA model was generated by transecting the anterior cruciate ligament combined with the resection of the medial menisci, followed by treatment with diazoxide or diazoxide combination with 3-methyladenine. The percentage of viable cells was evaluated using calcein-acetoxymethyl/propidium iodide double staining. The messenger RNA expression levels of collagen type II alpha 1 chain (COL2A1), matrix metalloproteinase 13 (MMP-13), TIMP metallopeptidase inhibitor 1 (TIMP-1), and a disintegrin and metalloproteinase with thrombospondin motifs 5 (ADAMTS5) were determined using quantitative real-time polymerase chain reaction. The cartilage thickness and joint space were evaluated using ultrasound. SW1353 cell degeneration and autophagosomes were observed using transmission electron microscopy. The expression levels of microtubule-associated protein 1 light chain 3 (LC3), beclin-1, P62, COL2A1, and MMP-13 were evaluated using immunofluorescence staining and Western blot analysis. Diazoxide significantly attenuated articular cartilage degeneration and SW1353 cell death in experimental OA. The restoration of autophagy was observed in the diazoxide-treated group. The beneficial effects of diazoxide were markedly blocked by 3-methyladenine. Diazoxide treatment also modulated the expression levels of OA-related biomarkers. These results demonstrated that diazoxide exerted a chondroprotective effect and attenuated cartilage degeneration by restoring autophagy via modulation of OA-related biomarkers in experimental OA. Diazoxide treatment might be a promising therapeutic approach to prevent the development of OA.

Diazoxide prevents H2O2-induced chondrocyte apoptosis and cartilage degeneration in a rat model of osteoarthritis by reducing endoplasmic reticulum stress.

Osteoarthritis (OA) is a common disease affecting elderly individuals. Its incidence rises sharply with age, and chondrocyte apoptosis plays a vital role in its pathogenesis. Diazoxide opens mitochondrial ATP-sensitive potassium (mitoKATP) channels and exerts multiple pharmacological effects, including reductions in blood pressure and blood sugar levels. It also exerts anti-apoptotic activities, but the cellular and molecular mechanisms by which diazoxide inhibits chondrocyte apoptosis are unknown, as is whether apoptosis is related to endoplasmic reticulum stress (ERS). In the present study, we explored the mechanism underlying the chondroprotective effect of diazoxide on hydrogen peroxide (H2O2)-stimulated chondrocyte apoptosis in rats with surgically induced OA. A cell counting kit-8 (CCK-8) assay showed that the viability of H2O2-stimulated chondrocytes was enhanced in a dose-dependent manner. However, at a concentration ≥400µM, diazoxide had other, negative effects. The protective effect of diazoxide in vitro included inhibition of the ERS response and of mitochondrial dysfunction induced by H2O2 stimulation. These responses were related to activation of the PERK1/2 and ERK1/2 signaling pathways; the prevention of chondrocyte apoptosis; the down-regulation of caspase-3, Bax, ATF-6 and C/EBP-homologous protein (CHOP) expression; and the up-regulation of Bcl-2 and Col II. In vivo, histological and immunohistochemical analyses of caspase-3 and CHOP expression revealed that diazoxide ameliorated cartilage degeneration in a rat model of OA, as revealed by histological and immunohistochemical analyses of caspase-3 and CHOP expression. Diazoxide suppressed H2O2-triggered chondrocyte apoptosis, and ameliorated cartilage degeneration, by inhibiting the development of ERS.

Research progress on osteoarthritis treatment mechanisms.

Osteoarthritis is a common disease and is frequently encountered in the older population; the incidence rises sharply with age. It is estimated that more than 360 million people suffer from OA. However, the pathogenesis of osteoarthritis remains unclear, and we cannot effectively prevent the progression of OA. The aim of this review was to explore the molecular markers and signaling pathways that induce chondrocyte apoptosis in OA. We searched, using the key words osteoarthritis, chondrocyte apoptosis, autophagy, endoplasmic reticulum stress, molecular targets, and biomarkers, in PubMed, Web of Science, and Google Scholar from 1994 to 2017. We also reviewed the signaling pathways and molecular markers associated with chondrocyte apoptosis and approaches aimed at inhibiting the apoptosis-inducing mechanism to at least delay the progression of cartilage degeneration in OA. This article provides an overview of targeted therapies and the related signaling pathways in OA.