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Introduction: With an average of 6.8 million fractures per year in the United States, the current method for surgical intervention involves bioinert materials that do not promote osteogenesis and can have inflammatory reactions that hinder bone healing. Magnesium has emerged in research due to the material’s biodegradability and biocompatibility; however, it has a low corrosion resistance, which can lead to hydrogen gas evolution and tissue necrosis. Therefore, magnesium is typically alloyed with rare earth elements (REEs) to increase corrosion resistance. The main goal of this study involves fabricating a magnesium (Mg)-based metal matrix nanocomposite (MMNC) containing scandium (Sc) and strontium (Sr) as alloying elements, as well as diopside (CaMgSi2O6) -based bioactive glass-ceramic nanoparticles for reinforcement. Methods: MMNCs were processed using ultrasonic melt processing and hot rolling to disperse nanoparticles and refine their microstructure. These MMNCs have undergone detailed tests to determine microstructure and degradation properties, followed by in vitro and in vivo tests to determine the MMNC’s biodegradation and biocompatibility characteristics. Results: Through cell culture with human bone marrow-derived mesenchymal stem cells (hBM-MSCs) we determined that MMNCs provide in vitro cytocompatibility of >80%. Next, MMNC pins were implanted into rat femoral defects and monitored for 3 months post-implantation with the WE43 Mg alloy used as a control. Utilizing in vivo and ex vivo X-ray imaging and histology of these defects implanted with MMNC or WE43 pins, we found that our composite allows for no or minimal hydrogen gas evolution and fibrotic body response with osteointegration and new bone formation. Discussion: This allows for an understanding of potential applications of our composite as a biomaterial. 

A novel magnesium (Mg)-based metal matrix nanocomposite (MMNC) was fabricated using ultrasonic melt treatment to promote the de-agglomeration of the bioactive glass–ceramic nanoparticles and the homogenization of the melt. The cast samples were then heat treated, machined, and hot rolled to reduce grain size and remove structural defects. Standard mechanical and electrochemical tests were conducted to determine the effect of fabrication and processing on the mechanical and corrosion properties of MMNCs. Compression tests, potentiodynamic polarization tests, electrochemical impedance spectroscopy, and static immersion testing were conducted to determine the characteristics of the MMNCs. The results showed that the combination of ultrasonic melt processing and thermomechanical processing caused the corrosion rate to increase from 8.7 mmpy after 10 days of immersion to 22.25 mmpy when compared with the ultrasonicated MMNCs but remained stable throughout the immersion time, showing no statistically significant change during the incubation periods. These samples also experienced increased yield stress (135.5 MPa) and decreased elongation at break (21.92%) due to the significant amount of grain refinement compared to the ultrasonicated MMNC (σY = 59.6 MPa, elongation = 40.44%). The MMNCs that underwent ultrasonic melt treatment also exhibited significant differences in the corrosion rate calculated from immersion tests. 

This study aims to present an ultrasound-mediated nanobubble (NB)-based gene delivery system that could potentially be applied in the future to treat bone disorders such as osteoporosis. NBs are sensitive to ultrasound (US) and serve as a controlled-released carrier to deliver a mixture of Cathepsin K (CTSK) siRNA and cerium oxide nanoparticles (CeNPs). This platform aimed to reduce bone resorption via downregulating CTSK expression in osteoclasts and enhance bone formation via the antioxidant and osteogenic properties of CeNPs. CeNPs were synthesized and characterized using transmission electron microscopy and X-ray photoelectron spectroscopy. The mixture of CTSK siRNA and CeNPs was adsorbed to the surface of NBs using a sonication method. The release profiles of CTSK siRNA and CeNPs labeled with a fluorescent tag molecule were measured after low-intensity pulsed ultrasound (LIPUS) stimulation using fluorescent spectroscopy. The maximum release of CTSK siRNA and the CeNPs for 1 mg/mL of NB-(CTSK siRNA + CeNPs) was obtained at 2.5 nM and 1 µg/mL, respectively, 3 days after LIPUS stimulation. Then, Alizarin Red Staining (ARS) was applied to human bone marrow-derived mesenchymal stem cells (hMSC) and tartrate-resistant acid phosphatase (TRAP) staining was applied to human osteoclast precursors (OCP) to evaluate osteogenic promotion and osteoclastogenic inhibition effects. A higher mineralization and a lower number of osteoclasts were quantified for NB-(CTSK siRNA + CeNPs) versus control +RANKL with ARS (p < 0.001) and TRAP-positive staining (p < 0.01). This study provides a method for the delivery of gene silencing siRNA and CeNPs using a US-sensitive NB system that could potentially be used in vivo and in the treatment of bone fractures and disorders such as osteoporosis. 

Magnesium (Mg) and its alloys are considered to be biodegradable metallic biomaterials for potential orthopedic implants. While the osteogenic properties of Mg alloys have been widely studied, few reports focused on developing a bifunctional Mg implant with osteogenic and angiogenic properties. Herein, a Mg-Sc-Sr alloy was developed, and this alloy’s angiogenesis and osteogenesis effects were evaluated in vitro for the first time. X-ray Fluorescence (XRF), X-ray diffraction (XRD), and metallography images were used to evaluate the microstructure of the developed Mg-Sc-Sr alloy. Human umbilical vein/vascular endothelial cells (HUVECs) were used to evaluate the angiogenic character of the prepared Mg-Sc-Sr alloy. A mix of human bone-marrow-derived mesenchymal stromal cells (hBM-MSCs) and HUVEC cell cultures were used to assess the osteogenesis-stimulating effect of Mg-Sc-Sr alloy through alkaline phosphatase (ALP) and Von Kossa staining. Higher ALP activity and the number of calcified nodules (27% increase) were obtained for the Mg-Sc-Sr-treated groups compared to Mg-treated groups. In addition, higher VEGF expression (45.5% increase), tube length (80.8% increase), and number of meshes (37.9% increase) were observed. The Mg-Sc-Sr alloy showed significantly higher angiogenesis and osteogenic differentiation than pure Mg and the control group, suggesting such a composition as a promising candidate in bone implants. 

There exists a gap in terms of the signals provided by pacemakers (i.e., intracardiac electrogram (EGM)) and the signals doctors use (i.e., 12-lead electrocardiogram (ECG)) to diagnose abnormal rhythms. Therefore, the former, even if remotely transmitted, are not sufficient for doctors to provide a precise diagnosis, let alone make a timely intervention. To close this gap and make a heuristic step towards real-time critical intervention in instant response to irregular and infrequent ventricular rhythms, we propose a new framework dubbed RT-RCG to automatically search for (1) efficient Deep Neural Network (DNN) structures and then (2) corresponding accelerators, to enable R eal- T ime and high-quality R econstruction of E C G signals from E G M signals. Specifically, RT-RCG proposes a new DNN search space tailored for ECG reconstruction from EGM signals and incorporates a differentiable acceleration search (DAS) engine to efficiently navigate over the large and discrete accelerator design space to generate optimized accelerators. Extensive experiments and ablation studies under various settings consistently validate the effectiveness of our RT-RCG. To the best of our knowledge, RT-RCG is the first to leverage neural architecture search (NAS) to simultaneously tackle both reconstruction efficacy and efficiency.