Search

In vivo use of biodegradable magnesium (Mg) metal can be plagued by too rapid a degradation rate that removes metal support before physiological function is repaired. To advance the use of Mg biomedical implants, the degradation rate may need to be adjusted. We previously demonstrated that pure Mg filaments used in a nerve repair scaffold were compatible with regenerating peripheral nerve tissues, reduced inflammation, and improved axonal numbers across a short—but not long—gap in sciatic nerves in rats. To determine if the repair of longer gaps would be improved by a slower Mg degradation rate, we tested, in vitro and in vivo, the effects of Mg filament polishing followed by anodization using plasma electrolytic oxidation (PEO) with non-toxic electrolytes. Polishing removed oxidation products from the surface of as-received (unpolished) filaments, exposed more Mg on the surface, produced a smoother surface, slowed in vitro Mg degradation over four weeks after immersion in a physiological solution, and improved attachment of cultured epithelial cells. In vivo, treated Mg filaments were used to repair longer (15 mm) injury gaps in adult rat sciatic nerves after placement inside hollow poly (caprolactone) nerve conduits. The addition of single Mg or control titanium filaments was compared to empty conduits (negative control) and isografts (nerves from donor rats, positive control). After six weeks in vivo, live animal imaging with micro computed tomography (micro-CT) showed that Mg metal degradation rates were slowed by polishing vs. as-received Mg, but not by anodization, which introduced greater variability. After 14 weeks in vivo, functional return was seen only with isograft controls. However, within Mg filament groups, the amount of axonal growth across the injury site was improved with slower Mg degradation rates. Thus, anodization slowed degradation in vitro but not in vivo, and degradation rates do affect nerve regeneration.

Brain-on-a-chip is a miniaturized engineering platform to mimic the structural and functional aspects of brain tissue. We describe a method to construct a three-dimensional (3D) brain-on-a-chip in this chapter. We firstly portray the method of a brain-on-a-chip model with cocultured mice neurons, microglia, and astrocytes to mimic brain tissue and membrane-free perfusion with endothelial cells, in which we successfully build the blood-brain barrier to screen neurotoxicity. Then we describe a method to construct a brain-on-a-chip with human induced pluripotent stem cell (iPSC)-derived neurons and astrocytes to simulate human brain behavior. This platform consists of neuronal tissue with extracellular matrix (ECM)-embedded GABAergic neurons and astrocytes and a perfusion channel with dynamic flow. We also include the broader applicability test of this model using an organophosphate (OP), malathion, to induce acute and chronic neurotoxicity, and then using butyrylcholinesterase (BuChE) as an exogenous bioscavenger of OP. Following the methods listed in this chapter, we are able to measure the neurotoxic effects on construct integrity, viability, and total AChE and BuChE activity.

Magnesium (Mg)-based alloys have the potential for bone repair due to their properties of biodegradation, biocompatibility, and structural stability, which can eliminate the requirement for a second surgery for the removal of the implant. Nevertheless, uncontrolled degradation rate and possible cytotoxicity of the corrosion products at the implant sites are known current challenges for clinical applications. In this study, we assessed in vitro cytotoxicity of different concentrations (0 to 50 mM) of possible corrosion products in the form of magnesium oxide (MgO) and magnesium hydroxide (Mg(OH)2) nanoparticles (NPs) in human fetal osteoblast (hFOB) 1.19 cells. We measured cell proliferation, adhesion, migration, and cytotoxicity using a real-time, label-free, non-invasive electric cell-substrate impedance sensing (ECIS) system. Our results suggest that 1 mM concentrations of MgO/Mg(OH)2 NPs are tolerable in hFOB 1.19 cells. Based on our findings, we propose the development of innovative biodegradable Mg-based alloys for further in vivo animal testing and clinical trials in orthopedics.

Low-density, high porous bioactive fibrous scaffolds have attracted significant attention for tissue engineering. However, fabrication of biomimetic fibrous scaffolds having three-dimensional architecture along with bioactive materials still remains a challenging task for biomaterial scientists. Herein, for the first time, we developed a novel strategy to fabricate highly porous s-tricalcium phosphate (s-TCP) incorporated Poly ( l -lactide) (PLLA) fibrous scaffold for bone tissue engineering. Blending of PLLA with its monomer, lactic acid (LA) produced the fluffy type highly porous nanofibrous mesh. The mass composition of the constituents of the blend solution was varied to control the morphology and packing of the nanofibers in the scaffold. The results showed that LA played the vital role in the generation of the 3D fluffy type fibrous mesh. s-TCP particles were incorporated in the blend solution prior to the electrospinning solution, to fabricate s-TCP incorporated PLLA fibrous scaffold. Later, LA was leached out by washing with distilled water, to avoid its adverse effect on biocompatibility. Digital and SEM images revealed the formation of spongy, low-density fibrous mesh. TEM images, IR, and TGA analysis confirmed the presence of s-TCP nanoparticles in the nanofibers after leaching of LA. Incorporation of the s-TCP enhanced the water uptake ability, in vitro bio-mineralization, and bioactivity of the fibrous scaffold. Confocal microscopy images showed that the pre-osteoblast cells seeded on the fluffy type fibrous mesh infiltrated throughout the depth of the scaffold, compared to no penetrating growth for the 2D scaffold. In vitro biocompatibility evaluated by CCK assay showed significantly higher growth for cells on the fluffy type scaffold, compared to the 2D scaffold. We demonstrated scaffolds suitability for biocompatibility and osteogenic differentiation of hMSCs as well. We believe that the fabrication of bioactive particle incorporated highly porous 3D fibrous scaffold will open a new avenue for tissue engineering applications.

Predicting degradation behavior of biodegradable metals in vivo is crucial for the clinical success of medical devices. This paper reports on the effect of long-term static stress on degradation of magnesium alloys and further changes in mechanical integrity. AZ31B (H24) and ZE41A (T5) alloys were tested to evaluate stress corrosion cracking (SCC) in a physiological solution for 30 days and 90 days (ASTM G39 testing standard). Scanning electron microscopy (SEM) with energy-dispersive X-ray spectroscopy (EDX) and micro-computed tomography (micro-CT) were used to characterize surface morphology and micro-structure of degraded alloys. The results show the different mechanisms of stress corrosion cracking for AZ31B (transgranular stress corrosion cracking, TGSCC) and ZE41A (intergranular stress corrosion cracking, IGSCC). AZ31B was more susceptible to stress corrosion cracking under a long term static load than ZE41A. In conclusion, we observed that long-term static loading accelerated crack propagation, leading to the loss of mechanical integrity.

Biodegradable magnesium (Mg) alloys have potential applications in orthopedic implants due to their mechanical and osseointegration properties. However, the surface characteristics, biocompatibility, and toxicity of the released corrosion products in the form of magnesium oxide (MgO) and magnesium hydroxide (Mg(OH)2) nanoparticles (NPs) at the junction of implants and in the surrounding tissue are not completely understood. Here, we investigated in vitro cytotoxicity and morphological changes in human fetal osteoblast (hFOB) 1.19 cells in response to various concentrations (1 mM, 5 mM, 10 mM, and 50 mM) of MgO/Mg(OH)2 NPs by live/dead assay and scanning electron microscopy (SEM). In this study, we performed a surface characterization of MgO/Mg(OH)2 NPs to evaluate the size of the NPs. Further, an immersion test was performed in Dulbecco&rsquo, s Modified Eagle&rsquo, s Medium (DMEM) with randomly selected various concentrations (1 mM, 5 mM, 10 mM, 50 mM, and 100 mM) of MgO/Mg(OH)2 NPs to understand the degradation behavior of the NPs, and the change in the pH values from days 1 to 7 was measured. After conducting an immersion test for seven days, the highest concentration (100 mM) of MgO/Mg(OH)2 NPs was selected to study the element depositions on nanoparticles through scanning electron microscopy&ndash, energy-dispersive X-ray spectroscopy (SEM&ndash, EDX) mapping. The results from this in vitro cytotoxicity study suggest that less than or equal to 5-mM concentrations of MgO/Mg(OH)2 NPs are tolerable concentrations for hFOB 1.19 cells. This study provides a foundational knowledge of MgO/Mg(OH)2 NP cytotoxicity in hFOB 1.19 cells that can help to develop future sustainable biodegradable magnesium-based alloys for orthopedic applications.

Adoptive Cell Transfer (ACT) using Chimeric Antigen Receptor (CAR) T-cells shows promising results in treating metastatic melanoma and B cell malignancies. However, the detailed mechanism of CAR T-...

Carbon fiber reinforced plastic (CFRP) materials are the future lightweight materials, being well-received in all industries, including the automotive industry, better than other lightweight materials. However, CFRP-based devices are expensive because of the raw material, carbon fiber. There are also industrial challenges, since industry still uses the existing steel-based automobile manufacturing facilities. In this chapter, we review recent trends in carbon fiber composite materials and development of carbon fiber-reinforced thermoset/thermoplastic composites in the automobile industry in terms of raw materials use and their processing methods. In particular, we introduce the CFRP manufacturing processes that the Korea Institute of Carbon Convergence Technology (KCTECH) has developed for a decade based on the molding equipment and process base of the carbon industry. KCTECH is a specialized research institute established for research and development in the Korean carbon industry, including: (1) multitow spreading machine, (2) hybrid braiding machine, (3) manufacturing system of thermoplastic carbon prepreg with multifunction, (4) automated fiber placement machine, (5) carbon fiber preform (tape) manufacturing system, (6) high-pressure resin transfer molding system, (7) high precision compression molding press with high temperature, (8) winding machine of carbon fiber (filament winding), (9) vacuum microwaves kiln for fast CFRP curing, (10) 3D dynamic waterjet cutting system for CFRP, and (11) machining center for high-strength composite parts reinforced carbon fiber. We provide a case example of lightweight automobile parts using CFRP, such as a side impact beam, acoustic cover for a car engine, CFRP stabilizer bar for automobiles, CFRP leaf spring, CFRP roof rail, and hybrid composite pressure vessel. We further compare current CFRP-based technology with future CNT sheet and yarn technology in terms of current challenges, such as cost reduction and manufacturability. This chapter discusses recent use of various resins used in CFRP manufacturing and examines the development trends of thermoplastic materials suitable for automotive applications in CFRP products and future carbon nanotube (CNT)-based carbon fiber composite technology.

Vascular stent design continues to evolve to further improve the efficacy and minimize the risks associated with these devices. Drug-eluting coatings have been widely adopted and, more recently, biodegradable stents have been the focus of extensive evaluation. In this report, biodegradable elastomeric polyurethanes were synthesized and applied as drug-eluting coatings for a relatively new class of degradable vascular stents based on Mg. The dynamic degradation behavior, hemocompatibility and drug release were investigated for poly(carbonate urethane) urea (PCUU) and poly(ester urethane) urea (PEUU) coated magnesium alloy (AZ31) stents. Poly(lactic-co-glycolic acid) (PLGA) coated and bare stents were employed as control groups. The PCUU coating effectively slowed the Mg alloy corrosion in dynamic degradation testing compared to PEUU-coated, PLGA-coated and bare Mg alloy stents. This was confirmed by electron microscopy, energy-dispersive x-ray spectroscopy and magnesium ion release experiments. PCUU-coating of AZ31 was also associated with significantly reduced platelet adhesion in acute blood contact testing. Rat vascular smooth muscle cell (rSMC) proliferation was successfully inhibited when paclitaxel was released from pre-loaded PCUU coatings. The corrosion retardation, low thrombogenicity, drug loading capacity, and high elasticity make PCUU an attractive option for drug eluting coating on biodegradable metallic cardiovascular stents.

An in-situ and real-time electrochemical study in a vascular bioreactor was designed to analyze corrosion mechanism of magnesium alloy (MgZnCa) under mimetic hydrodynamic conditions. Effect of hydrodynamics on corrosion kinetics, types, rates and products was analyzed. Flow-induced shear stress (FISS) accelerated mass and electron transfer, leading to an increase in uniform and localized corrosions. FISS increased the thickness of uniform corrosion layer, but filiform corrosion decreased this layer resistance at high FISS conditions. FISS also increased the removal rate of localized corrosion products. Impedance-estimated and linear polarization-measured polarization resistances provided a consistent correlation to corrosion rate calculated by computed tomography.

The study describes the design and synthesis of an implantable smart magnetic nanofiber device for endoscopic hyperthermia treatment and tumor-triggered controlled drug release. This device is achieved using a two-component smart nanofiber matrix from monodisperse iron oxide nanoparticles (IONPs) as well as bortezomib (BTZ), a chemotherapeutic drug. The IONP-incorporated nanofiber matrix was developed by electrospinning a biocompatible and bioresorbable polymer, poly ( d , l -lactide-co-glycolide) (PLGA), and tumor-triggered anticancer drug delivery is realized by exploiting mussel-inspired surface functionalization using 2-(3,4-dihydroxyphenyl)ethylamine (dopamine) to conjugate the borate-containing BTZ anticancer drug through a catechol metal binding in a pH-sensitive manner. Thus, an implantable smart magnetic nanofiber device can be exploited to both apply hyperthermia with an alternating magnetic field (AMF) and to achieve cancer cell-specific drug release to enable synergistic cancer therapy. These results confirm that the BTZ-loaded mussel-inspired magnetic nanofiber matrix (BTZ-MMNF) is highly beneficial not only due to the higher therapeutic efficacy and low toxicity towards normal cells but also, as a result of the availability of magnetic nanoparticles for repeated hyperthermia application and tumor-triggered controlled drug release. Statement of Significance The current work report on the design and development of a smart nanoplatform responsive to a magnetic field to administer both hyperthermia and pH-dependent anticancer drug release for the synergistic anticancer treatment. The iron oxide nanoparticles (IONPs) incorporated nanofiber matrix was developed by electrospinning a biocompatible polymer, poly ( d , l -lactide-co-glycolide) (PLGA), and tumor-triggered anticancer drug delivery is realized by surface functionalization using 2-(3,4-dihydroxyphenyl)ethylamine (dopamine) to conjugate the boratecontaining anticancer drug bortezomib through a catechol metal binding in a pH-sensitive manner. This implantable magnetic nanofiber device can be exploited to apply hyperthermia with an alternating magnetic field and to achieve cancer cell-specific drug release to enable synergistic cancer therapy, which results in an improvement in both quality of life and patient compliance.

Polymeric coatings can provide temporary stability to bioresorbable metallic stents at the initial stage of deployment by alleviating rapid degradation and providing better interaction with surrounding vasculature. To understand this interfacing biocompatibility, this study explored the endothelial-cytocompatibility of polymer-coated magnesium (Mg) alloys under static and dynamic conditions compared to that of non-coated Mg alloy surfaces. Poly (carbonate urethane) urea (PCUU) and poly (lactic-co-glycolic acid) (PLGA) were coated on Mg alloys (WE43, AZ31, ZWEKL, ZWEKC) and 316L stainless steel (316L SS, control sample), which were embedded into a microfluidic device to simulate a vascular environment with dynamic flow. The results from attachment and viability tests showed that more cells were attached on the polymer-coated Mg alloys than on non-coated Mg alloys in both static and dynamic conditions. In particular, the attachment and viability on PCUU-coated surfaces were significantly higher than that of PLGA-coated surfaces of WE43 and ZWEKC in both static and dynamic conditions, and of AZ31 in dynamic conditions (P

Organophosphate-based compounds (OPs) represent a significant threat to warfighters (nerve agents) and civilian populations (pesticides). There is a pressing need to develop in vitro brain models that correlate to the in vivo brain to rapidly study OPs for neurotoxicity. Here we report on a microfluidic-based three-dimensional, four-cell tissue construct consisting of 1) a blood-brain barrier that has dynamic flow and membrane-free culture of the endothelial layer, and 2) an extracellular matrix (ECM)-embedded tissue construct with neuroblastoma, microglia, and astrocytes. We demonstrated this platform’s utility by measuring OP effects on barrier integrity, acetylcholinesterase (AChE) inhibition, viability and residual OP concentration with four model OPs. The results show that the OPs penetrate the blood brain barrier (BBB) and rapidly inhibit AChE activity, and that in vitro toxicity was correlated with available in vivo data. This paper demonstrates the potential utility of a membrane-free tetra-cultured brain on chip that can be scaled to high throughput as a cost-effective alternative method to animal testing.

Free-standing thin carbon nanotube (CNT) sheets are challenging to handle and control for device fabrication. In this paper, we report on the inverse-ordered fabrication method from thick CNT sheets to thin free-standing CNT sheets. As proof of the concept, thin CNT sheets for a supercapacitor were fabricated from 200 thick layers. The results show that the thin CNT sheet was electrochemically stable and had enhanced capacitive performance. The smaller the number of layers is, the larger the specific capacitances we have (from 10.10 F g(-1) to 51.37 F g(-1)). Energy and power density were increased from 0.50 to 2.57 Wh kg(-1) and from 0.33 to 2.31 kW kg(-1), respectively. This simple and scalable inverse-ordered method is capable to fabricate CNT sheets in various forms, allowing fast trials on various applications.

Anodization is known to be an effective way to slow down the initial corrosion rate of magnesium (Mg) and its alloys. Here, we investigated the specific use of oxy-salts to improve the corrosion resistance of anodizing coatings. Oxy-salts of silicate, phosphate, and carbonate were added separately to a sodium hydroxide alkaline electrolyte used to anodize Mg alloy AZ91D. The process was investigated in terms of anodizing behavior, the surface properties, and the corrosion behavior of AZ91D. Anodizing AZ91D using the silicate- containing electrolyte generated sparks, and produced a thicker and more corrosion-resistant layer than the other oxy-salts. In the process, MgO and SiO 2 formed Mg 2 SiO 4 at high temperatures. Coatings from the phosphate- and carbonate- containing electrolyte anodizations did not contain phosphorus or carbon. We also studied the effects of silicate concentration on the corrosion resistance and properties of the surface.

We report on the development of a new photoactive material via titania (TiO2) nanoparticle deposition on free-standing aligned carbon nanotube (CNT) sheets. Controlling homogeneous dispersion of negatively charged TiO2 nanoparticles, achieved by adjusting pH higher than the point of zero charge (PZC), influenced electrochemical deposition of TiO2 on CNT sheets substrate. Varying deposition time with constant voltage, 5 V allowed different thickness of TiO2 to be deposited layer on the CNT sheets. The thickness and morphology of CNT–TiO2 sheets was verified by scanning electron microscopy (SEM), energy dispersive X-ray spectroscopy (EDS) and X-ray diffraction (XRD). Electrochemical experiments show that diffusion coefficient of Fe ( CN ) 6 3 - was 5.56 × 10−6 cm2s−1 at pristine CNT sheets and 2.19 × 10−6 cm2 s−1 at the CNT–TiO2 sheets. Photocatalytic activity for CNT–TiO2 sheets exhibits high photocurrent density (when deposition time = 30 min, 4.3 μA cm−2 in N2, 13.4 μA cm−2 in CO2). This paper proved a possibility to use CNT–TiO2 sheets based on highly-aligned CNT sheets substrate as new photoactive material.

Osteocalcin (bone gamma-carboxyglutamate protein; BGLAP) is a highly conserved molecule associated with mineralization of bone matrix. It regulates the dynamics of new bone formation and bone resorption. The synthesis of osteocalcin by osteoblasts is regulated by the active form of vitamin D. In this paper, we report the use of two fluorescent-based assays, one bead-based and a second involving an amino-silane surface pre-treatment, to obtain binding constants of 3.53×10 6 M −1 and 3.19×10 6 M −1 , respectively, for the binding of BGLAP to fluorescently labeled monoclonal-anti BGLAP-clone 2D5. These simple microfluidic techniques demonstrate the feasibility of developing microsphere-based and surface electrostatically-attached binding assays to study peptide–antibody interactions. Both techniques utilize sub-microliter volumes of material an important consideration when studying bone turnover markers (BTMs) like BGLAP.

Here we systematically assess the degradation of biodegradable magnesium pins (as-drawn pure Mg, as-cast Mg-Zn-Mn, and extruded Mg-Zn-Mn) in a bioreactor applying cyclical loading and simulated body fluid (SBF) perfusion. Cyclical mechanical loading and interstitial flow accelerated the overall corrosion rate, leading to loss of mechanical strength. When compared to the in vivo degradation (degradation rate, product formation, uniform or localized pitting, and stress distribution) of the same materials in mouse subcutaneous and dog tibia implant models, we demonstrate that the in vitro model facilitates the analysis of the complex degradation behavior of Mg-based alloys in vivo. This study progresses the development of a suitable in vitro model to examine the effects of mechanical stress and interstitial flow on biodegradable implant materials.

We report the enhanced mechanical properties of AZ31 magnesium alloys by plasma electrolytic oxidation (PEO) coating in NaOH, Na2SiO3, KF and NaH2PO4·2H2O containing electrolytes. Mechanical properties including wear resistance, surface hardness and elastic modulus were increased for PEO-coated AZ31 Mg alloys (PEO-AZ31). DC polarization in Hank's solution indicating that the corrosion resistance significantly increased for PEO-coating in KF-contained electrolyte. Based on these results, the PEO coating method shows promising potential for use in biodegradable implant applications where tunable corrosion and mechanical properties are needed.

Melting and alloying operations were performed in a low carbon steel crucible in an inert ultra-high purity argon environment, preventing the oxidation reactions of molten Mg. High purity Mg (99.97%) was heated to 710°C for 10 minutes until the slug was completely melted. Each alloying element was added separately and kept for 10 minutes before additional alloy was added to ensure complete dissolution of all alloying elements. Automated stirring was applied for 15 minutes to ensure a homogeneous distribution of elements throughout the melt. The melt was then raised to 730 °C, held for 15 minutes and then poured into a steel tube mold. A solution heat treat was carried out on the as-cast alloy at 510 °C for 10 h before it was extruded. The extrusion was conducted with an extrusion ratio 10, extrusion temperature 400 ºC and ramp speed 1 mm/s.

A bioresorbable metallic helical stent was explored as a new device opportunity (magnesium scaffold), which can be absorbed by the body without leaving a trace and simultaneously allowing restoration of vasoreactivity with the potential for vessel remodeling. In this study, developed Mg-based helical stent was inserted and expanded in vessels with subsequent degradation in various environments including static, dynamic, and porcine ex vivo models. By assessing stent degradation in three different environments, we observed: (1) stress- and flow-induced degradation; (2) a high degradation rate in the dynamic reactor; (3) production of intermediate products (MgO/Mg(OH)2 and Ca/P) during degradation; and (4) intermediate micro-gas pocket formation in the neighboring tissue ex vivo model. Overall, the expandable Mg-based helical stent employed as a scaffold performed well, with expansion rate (>100%) in porcine ex vivo model.

Carbon nanotube (CNT)-modified silver titania (Ag–TiO2) nanoparticle composites were synthesized by photochemical reduction. Characterization of the composites was performed using field emission-scanning electron microscopy (FE-SEM), scanning transmission electron microscopy (STEM), energy dispersive X-ray spectroscopy (EDX), X-ray diffraction (XRD), UV–Vis diffuse reflectance spectroscopy (DRS), and Raman spectroscopy. It was found that TiO2 particles were uniformly distributed on CNTs, and the silver particles were decorated on the surface of the TiO2. The photocatalytic activity of Ag–TiO2–CNT nanoparticle composites synthesized with various concentrations of CNTs was investigated using methylene blue (MB) dye solution. Adsorption and recovery of MB showed that Ag–TiO2–CNT nanoparticle composites have a higher absorption efficiency than unadorned CNTs. The higher absorption demonstrates a synergistic effect between the CNTs and silver titania. Overall, novel photocatalytic nanoparticle composites that adsorb organic molecules, absorb light energy, and separate long-lived electron–hole pairs through spatial separation were developed. Minimization of electron–hole recombination allows efficient transfer of photochemical energy which affects the redox chemistry across the interfaces in the composites. The new composites were designed for environmental cleanup of organic pollutants.

We controlled the morphologies of copper (Cu) nanostructure on aligned carbon nanotube (CNT) sheets, influencing the efficiency of the electrocatalytic reduction of CO2. Functionalized CNT sheets affected the pulsed electrodeposition of copper in terms of 3D growth, bonding, and electrochemical activity. CNT/Cu sheet electrocatalyst shows high performance in electrochemical reduction of CO2 to hydrocarbons at room temperature and atmospheric pressure. Reduction products were carbon monoxide (CO), methane (CH4), and ethylene (C2H4) gases. Carbon monoxide yields (178 μmol cm2 mA−1 h−1) and methane yields (346 μmol cm2 mA−1 h−1) at oxygen-plasma-treated CNT/Cu sheet electrodes were remarkably higher than other CNT/Cu and CNT sheets. Experimental results also show 3D morphology of copper growth on CNT sheets may play a critical role in hydrocarbon products from CO2.

Simulated physiological solutions mimicking human plasma have been utilized to study the in vitro corrosion of biodegradable metals. However, corrosion and corrosion product formation are different for different solutions with varied responses and, hence, the prediction of in vivo degradation behavior is not feasible based on these studies alone. This paper reports the role of physiologically relevant salts and their concentrations on the corrosion behavior of a magnesium alloy (AZ31B) and subsequent corrosion production formation. Immersion tests were performed for three different concentrations of Ca(2+), HPO4(2-), HCO3(-) to identify the effect of each ion on the corrosion of AZ31B assessed at 1, 3 and 10 days. Time-lapse morphological characterization of the samples was performed using X-ray computed tomography and scanning electron microscopy. The chemical composition of the surface corrosion products was determined by electron dispersive X-ray spectroscopy and X-ray diffraction. The results show that: (1) calcium is not present in the corrosion product layer when only Cl(-) and OH(-) anions are available; (2) the presence of phosphate induces formation of a densely packed amorphous magnesium phosphate corrosion product layer when HPO4(2-) and Cl(-) are present in solution; (3) octacalcium phosphate and hydroxyapatite (HAp) are deposited on the surface of the magnesium alloy when HPO4(2-) and Ca(2+) are present together in NaCl solution (this coating limits localized corrosion and increases general corrosion resistance); (4) addition of HCO3(-) accelerates the overall corrosion rate, which increases with increasing bicarbonate concentration; (5) the corrosion rate decreases due to the formation of insoluble HAp on the surface when HCO3(-), Ca(2+), and HPO4(2-) are present together.

In recent times, magnesium alloys have emerged as a possible biodegradable implant material. Plasma electrolytic oxidation (PEO) has been used in the past as a useful surface treatment technique to improve wear resistance and corrosion resistance of magnesium alloys by forming protective coatings. This study focuses on the effect of electrolyte solution on the microstructural and nanomechanical behavior of PEO coatings for possible use in biodegradable implants. Microstructural characterization of the coating was carried out by X-ray diffraction (XRD), scanning electron microscopy followed by image analysis and energy dispersive X-ray spectroscopy. Furthermore, nanoindentation was used to evaluate nanohardness of the PEO coatings. The results show beneficial effects of the PEO coating to improve the hardness of the uncoated AZ31 magnesium alloy. The XRD pattern shows that the crystal structures of the film vary based on electrolyte solution and the effect that has on nanomechanical behavior. In conclusion, this article shows the possible benefit of PEO coating for biodegradable implant use.

Current in vitro models fail in predicting the degradation rate and mode of magnesium (Mg) stents in vivo . To overcome this, the microenvironment of the stent is simulated here in an ex vivo bioreactor with porcine aorta and circulating medium, and compared with standard static in vitro immersion and with in vivo rat aorta models. In ex vivo and in vivo conditions, pure Mg wires were exposed to the aortic lumen and inserted into the aortic wall to mimic early- and long-term implantation, respectively. Results showed that: 1) Degradation rates of Mg were similar for all the fluid diffusion conditions ( in vitro static, aortic wall ex vivo and in vivo ); however, Mg degradation under flow condition (i.e. in the lumen) in vivo was slower than ex vivo ; 2) The corrosion mode in the samples can be mainly described as localized ( in vitro ), mixed localized and uniform ( ex vivo ), and uniform ( in vivo ); 3) Abundant degradation products (MgO/Mg(OH) 2 and Ca/P) with gas bubbles accumulated around the localized degradation regions ex vivo , but a uniform and thin degradation product layer was found in vivo . It is concluded that the ex vivo vascular bioreactor provides an improved test setting for magnesium degradation between static immersion and animal experiments and highlights its promising role in bridging degradation behavior and biological response for vascular stent research. Statement of Significance Magnesium and its alloys are candidates for a new generation of biodegradable stent materials. However, the in vitro degradation of magnesium stents does not match the clinical degradation rates, corrupting the validity of conventional degradation tests. Here we report an ex vivo vascular bioreactor, which allows simulation of the microenvironment with and without blood vessel integration to study the biodegradation of magnesium implants in comparison with standard in vitro test conditions and with in vivo implantations. The bioreactor did simulate the corrosion of an intramural implant very well, but showed too high degradation for non-covered implants. It is concluded that this system is in between static incubation and animal experiments concerning the predictivity of the degradation.

Background Phase-change ultrasound contrast agents (PCCAs) offer a solution to the inherent limitations associated with using microbubbles for sonoporation; they are characterized by prolonged circulation lifetimes, and their nanometer-scale sizes may allow for passive accumulation in solid tumors. As a first step towards the goal of extravascular cell permeabilization, we aim to characterize the sonoporation potential of a low-boiling point formulation of PCCAs in vitro. Methods Parameters to induce acoustic droplet vaporization and subsequent microbubble cavitation were optimized in vitro using high-speed optical microscopy. Sonoporation of pancreatic cancer cells in suspension was then characterized at a range of pressures (125–600 kPa) and pulse lengths (5–50 cycles) using propidium iodide as an indicator molecule. Results We achieved sonoporation efficiencies ranging from 8 ± 1% to 36 ± 4% (percent of viable cells), as evidenced by flow cytometry. Increasing sonoporation efficiency trended with increasing pulse length and peak negative pressure. Conclusions We conclude that PCCAs can be used to induce the sonoporation of cells in vitro, and our results warrant further investigation into the use of PCCAs as extravascular sonoporation agents in vivo. Electronic supplementary material The online version of this article (doi:10.1186/s40349-017-0085-z) contains supplementary material, which is available to authorized users.

Polydeoxyribonucleotides (PDRN) have been explored as an effective treatment for tissue repair in peripheral artery occlusive disease, diabetic foot ulcers, and eye lotion. We report on the effect of polydeoxyribonucleotides (PDRN) on wound healing by using the electric cell-substrate impedance sensing (ECIS) system and viability testing. Human osteoblasts (U2OS) and primary human dermal fibroblasts (HDF) were used to study the effect of PDRN on migration and proliferation. ECIS allowed the creation of a wound by applying high current, and then monitoring the healing process by measuring impedance in real time. The traditional culture-insert gap-closure migration assay was performed and compared with the ECIS wound assay. PDRN-treated U2OS and HDF cells affected cell motilities to wounding site. Viability test results show that HDF and U2OS proliferation depended on PDRN concentration. Based on the results, a PDRN compound can be useful in wound healing associated with bone and skin.

Here, we report on carbon nanotube paper-based electroanalytical devices. A highly aligned-carbon nanotube (HA-CNT) array, grown using chemical vapor deposition (CVD), was processed to form bi-layered paper with an integrated cellulose-based Origami-chip as the electroanalytical device. We used an inverse-ordered fabrication method from a thick carbon nanotube (CNT) sheet to a thin CNT sheet. A 200-layered HA-CNT sheet and a 100-layered HA-CNT sheet are explored as a working electrode. The device was fabricated using the following methods: (1) cellulose-based paper was patterned using a wax printer, (2) electrical connection was made using a silver ink-based circuit printer, and (3) three electrodes were stacked on a 2D Origami cell. Electrochemical behavior was evaluated using electrochemical impedance spectroscopy (EIS) and cyclic voltammetry (CV). We believe that this platform could attract a great deal of interest for use in various chemical and biomedical applications.

Ca(2+) signaling controls activation and effector functions of T lymphocytes. Ca(2+) levels also regulate NFAT activation and CD40 ligand (CD40L) expression in T cells. CD40L in activated memory T cells binds to its cognate receptor, CD40, on other cell types resulting in the production of antibodies and pro-inflammatory mediators. The CD40L/CD40 interaction is implicated in the pathogenesis of autoimmune disorders and CD40L is widely recognized as a therapeutic target. Ca(2+) signaling in T cells is regulated by Kv1.3 channels. We have developed lipid nanoparticles that deliver Kv1.3 siRNAs (Kv1.3-NPs) selectively to CD45RO(+) memory T cells and reduce the activation-induced Ca(2+) influx. Herein we report that Kv1.3-NPs reduced NFAT activation and CD40L expression exclusively in CD45RO(+) T cells. Furthermore, Kv1.3-NPs suppressed cytokine release and induced a phenotype switch of T cells from predominantly memory to naive. These findings indicate that Kv1.3-NPs operate as targeted immune suppressive agents with promising therapeutic potentials.

Solid contact (SC) ion-selective electrodes (ISEs) have been recognized as the next generation of ISEs. In this work, the electrical conductivity and mechanical strength of a carbon nanotube (CNT) tower enable it to play the dual roles of transducer and substrate for micro SC-ISEs. The electrode had a close to Nernstian slope of 35 mV/decade aCa2+, a linear range of four orders of magnitude of calcium ion activity (10−5.6 to 10−1.8 M), and a detection limit of 1.6×10−6 M. The simplified fabrication by a one-step drop casting makes miniaturizing SC-ISEs and fabricating sensor arrays easier to achieve.

Magnesium (Mg) and its alloys have numerous potential applications as biodegradable implants, but the fast degradation rate of Mg alloys at the initial implanted stage could be a problem. This paper describes the modification of the water-based bis-[triethoxysilyl] ethane (BTSE) silane applied to the surface of magnesium–yttrium (Mg–4Y) to increase its corrosion resistance. Surface characterization by SEM, FTIR, and EDX showed that the hydrolysis and condensation of the silane resulted in a covalent bonding to the Mg–4Y surface. Corrosion behavior of the uncoated and coated Mg–4Y alloy was evaluated in different environments by using a novel self-developed corrosion probe. Based on the electrochemical results of DC polarization and electrochemical impedance spectroscopy (EIS), we conclude that the epoxy-modified BTSE silane coating successfully increases the corrosion resistance at the initial stage of implantation. The corrosion rates in the flesh of dead mice environments such as body cavity and subcutaneous tissue of the mice were lower than the corrosion rates in in vitro environments.

Electrochemical impedance spectroscopy (EIS), open circuit potential and pH changes were used to examine the corrosion of magnesium 4% yttrium alloy (Mg4Y) with and without a silane-epoxy-coating (SEC) in a stirred 0.154 M NaCl solution at 37 °C. For a good quality SEC we find a relatively low non-Faradaic resistance of 266 Ω cm 2 . The quality of the SEC was affected by the curing temperature. In this article we compare the electrochemical measurements taken during corrosion of bare Mg4Y, Mg4Y with a SEC that remained intact, and a SEC that did not protect the Mg from corrosion.

The response of T cells to antigens (T cell activation) is marked by an increase in intracellular Ca2+ levels. Voltage-gated and Ca2+-dependent K+ channels control the membrane potential of human T cells and regulate Ca2+influx. This regulation is dependent on proper accumulation of K+ channels at the immunological synapse (IS) a signaling zone that forms between a T cell and antigen presenting cell. It is believed that the IS provides a site for regulation of the activation response and that K+ channel inhibition occurs at the IS, but the underlying mechanisms are unknown. A mathematical model was developed to test whether K+ efflux through K+ channels leads to an accumulation of K+ in the IS cleft, ultimately reducing K+ channel function and intracellular Ca2+ concentration ([Ca2+]i). Simulations were conducted in models of resting and activated T cell subsets, which express different levels of K+ channels, by varying the K+ diffusion constant and the spatial localization of K+ channels at the IS. K+ accumulation in the IS cleft was calculated to increase K+ concentration ([K+]) from its normal value of 5.0 mM to 5.2–10.0 mM. Including K+ accumulation in the model of the IS reduced calculated K+ current by 1–12% and consequently, reduced calculated [Ca2+]i by 1–28%. Significant reductions in K+ current and [Ca2+]i only occurred in activated T cell simulations when most K+ channels were centrally clustered at the IS. The results presented show that the localization of K+ channels at the IS can produce a rise in [K+] in the IS cleft and lead to a substantial decrease in K+ currents and [Ca2+]i in activated T cells thus providing a feedback inhibitory mechanism during T cell activation.