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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. 

Magnesium (Mg) alloys are being investigated as a biodegradable metallic biomaterial because of their mechanical property profile, which is similar to the human bone. However, implants based on Mg alloys are corroded quickly in the body before the bone fracture is fully healed. Therefore, we aimed to reduce the corrosion rate of Mg using a double protective layer. We used a magnesium-aluminum-zinc alloy (AZ91) and treated its surface with micro-arc oxidation (MAO) technique to first form an intermediate layer. Next, a bioceramic nanocomposite composed of diopside, bredigite, and fluoridated hydroxyapatite (FHA) was coated on the surface of MAO treated AZ91 using the electrophoretic deposition (EPD) technique. Our in vivo results showed a significant enhancement in the bioactivity of the nanocomposite coated AZ91 implant compared to the uncoated control implant. Implantation of the uncoated AZ91 caused a significant release of hydrogen bubbles around the implant, which was reduced when the nanocomposite coated implants were used. Using histology, this reduction in the corrosion rate of the coated implants resulted in an improved new bone formation and reduced inflammation in the interface of the implants and the surrounding tissue. Hence, our strategy using a MAO/EPD of a bioceramic nanocomposite coating (i.e., diopside-bredigite-FHA) can significantly reduce the corrosion rate and improve the bioactivity of the biodegradable AZ91 Mg implant. 

Cryo‐hydrogels (cryogels) are polymer hydrogels formed at sub‐zero temperatures. Bioscaffolds created from cryogels have interconnected macropores which allow for cell migration, tissue‐ingrowth, unhindered diffusion of solutes and mass transport of therapeutics. In this study, we developed collagen based cryogel bioscaffolds and coated them with polydopamine using a simple two‐step technique. Cryogel bioscaffolds were synthesized by collagen crosslinking at −20°C and exhibited a macroporous interconnected architecture with 75% ± 3% porosity. Two groups of pore sizes were observed: 300 ± 50 µm and 30 ± 10 µm in diameter. The addition of a polydopamine coating to cryogel bioscaffolds was confirmed using composition analysis. This resulted in a 41% ± 5% decrease in water uptake, 81% ± 10% decrease in swelling rate and 12% ± 3% decrease in their degree of dissolution (p < 0.05), with a 48% ± 2% increase in stiffness and 57% ± 5% increase in compressive strength (p < 0.05). Seeding adipose tissue‐derived mesenchymal stem cells (AD‐MSCs) into polydopamine coated‐cryogel bioscaffolds resulted in cells demonstrating a 52% ± 4% increase in viability and 33% ± 3% increase in proliferation when compared to AD‐MSCs seeded into uncoated‐cryogel bioscaffolds (p < 0.05). In summary, our novel polydopamine coated‐cryogel bioscaffold represents an efficient and low‐cost bioscaffold platform to support MSC therapies. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 2213‐2228, 2018.

 

The aim of this study was to develop a novel biodegradable magnesium (Mg) alloy for bone implant applications. We used scandium (Sc; 2 wt %) and strontium (Sr; 2 wt %) as alloying elements due to their high biocompatibility, antibacterial efficacy, osteogenesis, and protective effects against corrosion. In the present work, we also examined the effect of a heat treatment process on the properties of the Mg‐Sc‐Sr alloy. Alloys were manufactured using a metal casting process followed by heat treatment. The microstructure, corrosion, mechanical properties, antibacterial activity, and osteogenic activity of the alloy were assessed in vitro. The results showed that the incorporation of Sc and Sr elements controlled the corrosion, reduced the hydrogen generation, and enhanced mechanical properties. Furthermore, alloying with Sc and Sr demonstrated a significantly enhanced antibacterial activity and decreased biofilm formation compared to control Mg. Also, culturing Mg‐Sc‐Sr alloy with human bone marrow‐derived mesenchymal stromal cells showed a high degree of biocompatibility (>90% live cells) and a significant increase in osteoblastic differentiation in vitro shown by Alizarin red staining and alkaline phosphatase activity. Based on these results, the Mg‐Sc‐Sr alloy heat‐treated at 400°C displayed optimal mechanical properties, corrosion rate, antibacterial efficacy, and osteoinductivity. These characteristics make the Mg‐Sc‐Sr alloy a promising candidate for biodegradable orthopedic implants in the fixation of bone fractures such as bone plate‐screws or intramedullary nails.

 

The aim of this article is to develop, characterize, and test a novel 3D bioscaffold matrix that can accommodate pancreatic islets and provide them with a continuous, controlled, and steady source of oxygen to prevent hypoxia‐induced damage following transplantation. Hence, a collagen‐based cryogel bioscaffold that incorporates calcium peroxide (CPO) into its matrix is made. The optimal concentration of CPO integrated into bioscaffolds is 0.25 wt% and this generates oxygen at 0.21 ± 0.02 × 10^‐3mday^‐1(day 1), 0.19 ± 0.01 × 10^‐3mday^‐1(day 6), 0.13 ± 0.03 × 10^‐3md^‐1(day 14), and 0.14 ± 0.02 × 10^‐3md^‐1(day 21). Accordingly, islets seeded into cryogel‐CPO bioscaffolds have a significantly higher viability and function compared to islets seeded into cryogel alone bioscaffolds; these findings are supported by data from quantitative computational modeling. When syngeneic islets are transplanted into the epididymal fat pad (EFP) of diabetic mice, the cryogel‐0.25 wt%CPO bioscaffold improves islet function with diabetic animals re‐establishing glycemic control. Mice transplanted with cryogel‐0.25 wt%CPO bioscaffolds show faster responses to intraperitoneal glucose injections and have a higher level of insulin content in their EFP compared to those transplanted with islets alone (P< 0.05). The novel oxygen‐generating bioscaffold (i.e., cryogel‐0.25 wt%CPO) therefore provides a biostable and biocompatible 3D microenvironment for islets which can facilitate islet survival and function at extra‐hepatic sites of transplantation.