The disruption of the blood–brain barrier (BBB) in Alzheimer’s Disease (AD) is largely influenced by amyloid beta (Aβ). In this study, we developed a high-throughput microfluidic BBB model devoid of a physical membrane, featuring endothelial cells interacting with an extracellular matrix (ECM). This paper focuses on the impact of varying concentrations of Aβ1–42 oligomers on BBB dysfunction by treating them in the luminal. Our findings reveal a pronounced accumulation of Aβ1–42 oligomers at the BBB, resulting in the disruption of tight junctions and subsequent leakage evidenced by a barrier integrity assay. Additionally, cytotoxicity assessments indicate a concentration-dependent increase in cell death in response to Aβ1–42 oligomers (LC50 ~ 1 µM). This study underscores the utility of our membrane-free vascular chip in elucidating the dysfunction induced by Aβ with respect to the BBB.
Magnesium (Mg) alloys are gaining interest for biodegradable medical implant devices due to a good combination of mechanical properties and biocompatibility. Nevertheless, the fast degradation rates of Mg and its biocompatible alloys in the aggressive physiological environment impose limitations on their clinical applications. This necessitates the development of Mg based implants with controlled degradation rates to match the kinetics of the bone and tissue healing process and to avoid any complications or issues that might negatively impact surrounding tissues. The current study presents alloy design and thermomechanical processing to optimize the mechanical and biological properties of a new proprietary Mg based alloy. Its corrosion profiles have been evaluated by a combination of in vitro and in vivo experimental studies. The corrosion rates of laboratory samples and prototype devices have been examined via long term immersion studies by measuring the cumulative amount of hydrogen (H2) that is emitted by samples. The cumulative H2 measurements have a direct correlation to the mass loss that the Mg alloy samples undergo during the duration of the tests. The results of the current in vitro corrosion studies are compared to 52 week small animal studies to develop predictive models for designing future biomedical devices.
Few studies have investigated the effect of a monosaturated diet high in ω-9 on osteoporosis. We hypothesized that omega-9 (ω-9) protects ovariectomized (OVX) mice from a decline in bone microarchitecture, tissue loss, and mechanical strength, thereby serving as a modifiable dietary intervention against osteoporotic deterioration. Female C57BL/6J mice were assigned to sham-ovariectomy, ovariectomy, or ovariectomy + estradiol treatment prior to switching their feed to a diet high in ω-9 for 12 weeks. Tibiae were evaluated using DMA, 3-point-bending, histomorphometry, and microCT. A significant decrease in lean mass (p = 0.05), tibial area (p = 0.009), and cross-sectional moment of inertia (p = 0.028) was measured in OVX mice compared to the control. A trend was seen where OVX bone displayed increased elastic modulus, ductility, storage modulus, and loss modulus, suggesting the ω-9 diet paradoxically increased both stiffness and viscosity. This implies beneficial alterations on the macro-structural, and micro-tissue level in OVX bone, potentially decreasing the fracture risk. Supporting this, no significant differences in ultimate, fracture, and yield stresses were measured. A diet high in ω-9 did not prevent microarchitectural deterioration, nevertheless, healthy tibial strength and resistance to fracture was maintained via mechanisms independent of bone structure/shape. Further investigation of ω-9 as a therapeutic in osteoporosis is warranted.
The influence of diet on the development of osteoporosis is significant and not fully understood. This study investigated the effect of diets of varying lipid profiles and ω-3, ω-6 and ω-9 composition on the structural and mechanical properties of bone. The hypothesis studied was that a diet high in saturated fat would induce osteoporosis and produce an overall increased detrimental bony response when compared with a diet high in unsaturated ω-6, or ω-9. Male C57BL/6J mice were fed either a control diet, 50:50 mix (saturated:unsaturated) high in ω-9 (HFD50:50), a diet high in saturated fat (HSF) or a polyunsaturated fat diet high in ω-6 (PUFA) over an 8-week duration. Tibiae were retrieved and evaluated using DMA, 3-point-bending, histomorphometry, and microCT. Mice fed a HSF diet displayed key features characteristic of osteoporosis. The loss tangent was significantly increased in the HFD50:50 diet group compared with control (p = 0.016) and PUFA-fed animals (p = 0.049). HFD50:50-fed mice presented with an increased viscous component, longer tibiae, increased loss modulus (p = 0.009), and ultimate stress, smaller microcracks (p < 0.001), and increased trabecular width (p = 0.002) compared with control animals. A diet high in ω-9 resulted in an overall superior bone response and further analysis of its role in bone health is warranted.
Amphiphilic phospholipid-iodinated polymer conjugates were designed and synthesized as new macromolecular probes for a highly radiopaque and biocompatible imaging technology. Bioconjugation of PEG 2000-phospholipids and iodinated polyesters by click chemistry created amphiphilic moieties with hydrophobic polyesters and hydrophilic PEG units, which allowed their self-assemblies into vesicles or spiked vesicles. More importantly, the conjugates exhibited high radiopacity and biocompatibility in in vitro X-ray and cell viability measurements. This new type of bioimaging contrast agent with a Mn value of 11 289 g mol-1 was found to have a significant X-ray signal at 3.13 mg mL-1 of iodine equivalent than baseline and no cytotoxicity after 48 hours incubation of with HEK and 3T3 cells at 20 μM (20 picomoles) concentration of conjugates per well. The potential of adopting the described macromolecular probes for bioimaging was demonstrated, which could further promote the development of a field-friendly and highly sensitive bioimaging contrast agent for point-of-care diagnostic applications.
Earlier, various attempts to develop graphene structures using chemical and nonchemical routes were reported. Being efficient, scalable, and repeatable, 3D printing of graphene-based polymer inks and aerogels seems attractive; however, the produced structures highly rely on a binder or an ice support to stay intact. The presence of a binder or graphene oxide hinders the translation of the excellent graphene properties to the 3D structure. In this communication, we report our efforts to synthesize a 3D-shaped 3D graphene (3D2G) with good quality, desirable shape, and structure control by combining 3D printing with the atmospheric pressure chemical vapor deposition (CVD) process. Direct ink writing has been used in this work as a 3D-printing technique to print nickel powder-PLGA slurry into various shapes. The latter has been employed as a catalyst for graphene growth via CVD. Porous 3D2G with high purity was obtained after etching out the nickel substrate. The conducted micro CT and 2D Raman study of pristine 3D2G revealed important features of this new material. The interconnected porous nature of the obtained 3D2G combined with its good electrical conductivity (about 17 S/cm) and promising electrochemical properties invites applications for energy storage electrodes, where fast electron transfer and intimate contact with the active material and with the electrolyte are critically important. By changing the printing design, one can manipulate the electrical, electrochemical, and mechanical properties, including the structural porosity, without any requirement for additional doping or chemical postprocessing. The obtained binder-free 3D2G showed a very good thermal stability, tested by thermo-gravimetric analysis in air up to 500 °C. This work brings together two advanced manufacturing approaches, CVD and 3D printing, thus enabling the synthesis of high-quality, binder-free 3D2G structures with a tailored design that appeared to be suitable for multiple applications.
Understanding the structural and mechanical properties of coral skeletons is important to assess their responses to natural and anthropogenic challenges and to predict the long-term viability of hermatypic corals in a changing ocean. Here, we describe the microstructure of the critically endangered staghorn coral (Acropora cervicornis) skeleton and its mechanical properties, spectral and fluidic behavior, including uniaxial compressive strength, resistance to plastic deformation, spectral vibrational response, and flow-field analysis. We evaluated skeletons of A. cervicornis retrieved from a nursery off Broward County, Florida, USA. Optical micrographs and X-ray computed topography revealed a complex system of canals and pores that allow rapid skeletal elongation while retaining sufficient strength to withstand currents, waves, and other physical forces. Compressive loading of the aragonite skeleton resulted in complex stress–strain deformation behavior; the unique pore arrangement resisted catastrophic cracks and prevented instantaneous failure. Vickers microhardness was 3.56 ± 0.31 GPa, which is typical for soft aragonite materials yet sufficient to withstand the hydraulic pressure of ocean waves. Impressions made by the diamond indenter had almost no cracks radiating from their corners, which again demonstrated the ability of the complex skeleton microstructure to suppress crack formation and growth (e.g., from the bites of grazers). Maps of the ν1 mode Raman peak of identation surfaces showed evidence of residual strain. However, the ν1 peak’s position barely changed (from 1083.6 cm−1 outside the impression to 1083.9 cm−1 in the center), indicating weak stress sensitivity. Flow-field analysis revealed small-scale, counter-rotating vortices formed in the skeleton’s wake, which can entrain food particles within range of polyp tentacles and facilitate transport of respiratory gases and wastes. Considered together, our results demonstrate that the perforate skeleton of A. cervicornis is well-adapted to withstand physical forces normally encountered in its shallow-water habitat, but may be susceptible to anthropogenic stressors that alter its architecture.
Coral reefs provide habitat for most oceanic life forms, however, they are declining worldwide due to pollution, increased ocean temperature, diseases and other factors. In this paper, structural and mechanical properties of endangered coral (Acropora cervicornis) skeletons cleaned by chemical bleaching and biological processes were studied. The structure of CaCO3 aragonite skeleton is porous and very complex and affects the deformation behaviour of coral skeletons. The average compressive strength was equal to 9.5 +/- 2.3 MPa and 14.5 +/- 6.4 MPa, while Vickers hardness was measured to be equal to 3.67 +/- 0.33 GPa and 3.65 +/- 0.24 GPa for the chemically bleached and biologically cleaned skeletons, respectively, thus showing similar values regardless of the cleaning techniques. The results are important for understanding the fundamental relationship between the coral skeleton's microstructure and mechanical behaviour.
Reduced weight bearing, and to a lesser extent radiation, during spaceflight have been shown as potential hazards to astronaut joint health. These hazards combined effect to the knee and hip joints are not well defined, particularly with low-dose exposure to radiation. In this study, we examined the individual and combined effects of varying low-dose radiation (≤1 Gy) and reduced weight bearing on the cartilage of the knee and hip joints. C57BL/6J mice (n = 80) were either tail suspended via hindlimb unloading (HLU) or remained full-weight bearing (ground). On day 6, each group was divided and irradiated with 0 Gy (sham), 0.1 Gy, 0.5 Gy or 1.0 Gy (n = 10/group), yielding eight groups: ground-sham; ground-0.1 Gy; ground-0.5 Gy; ground-1.0 Gy; HLU-sham; HLU-0.1 Gy; HLU-0.5 Gy; and HLU-1.0 Gy. On day 30, the hindlimbs, hip cartilage and serum were collected from the mice. Significant differences were identified statistically between treatment groups and the ground-sham control group, but no significant differences were observed between HLU and/or radiation groups. Contrast-enhanced micro-computed tomography (microCECT) demonstrated decrease in volume and thickness at the weight-bearing femoral-tibial cartilage-cartilage contact point in all treatment groups compared to ground-sham. Lower collagen was observed in all groups compared to ground-sham. Circulating serum cartilage oligomeric matrix protein (sCOMP), a biomarker for ongoing cartilage degradation, was increased in all of the irradiated groups compared to ground-sham, regardless of unloading. Mass spectrometry of the cartilage lining the femoral head and subsequent Ingenuity Pathway Analysis (IPA) identified a decrease in cartilage compositional proteins indicative of osteoarthritis. Our findings demonstrate that both individually and combined, HLU and exposure to spaceflight relevant radiation doses lead to cartilage degradation of the knee and hip with expression of an arthritic phenotype. Moreover, early administration of low-dose irradiation (0.1, 0.5 or 1.0 Gy) causes an active catabolic response in cartilage 24 days postirradiation. Further research is warranted with a focus on the prevention of cartilage degradation from long-term periods of reduced weight bearing and spaceflight-relevant low doses and qualities of radiation.
Degradation rate is an important property to evaluate bioabsorbable metallic material; however, values vary depending on the method of measurement. In this study, three different methods of measuring corrosion rate are compared. The degradable samples to analyze corrosion rates include pure magnesium (Mg), lab produced Mg–Zn–Ca alloy (47-7-2), Mg–Zn–Zr–RE (rare earth) alloys (60-13, 60-14), Mg–Zn–Ca–RE alloy (59B), and pure zinc (Zn). A eudiometer was used to measure hydrogen evolution from the reaction of degradable alloys in Hank’s Balanced Salt Solution (HBSS). Corrosion rates based on volume loss of tested alloys in 30 days were calculated using Micro-computed tomography (micro-CT). Final mass change due to corrosion and corrosion removal was measured with a scale. We observed that the corrosion rates indicated by hydrogen evolution were high initially, and slowed down sharply in the following measurements. The corrosion rates of tested alloys calculated by volume loss and mass loss from high to low are: 60–13 ≈ 60–14 ≈ 47–7–2 > 59B > Mg > Zn (p < 0.05). The results provide instruction to experimental methodology to measure corrosion rates of degradable alloys.
Magnesium (Mg)-based stents are extensively explored to alleviate atherosclerosis due to their biodegradability and relative hemocompatibility. To ensure the quality, safety and cost-efficacy of bioresorbable scaffolds and full utilization of the material tunability afforded by alloying, it is critical to access degradability and thrombosis potential of Mg-based alloys using improved in vitro models that mimic as closely as possible the in vivo microenvironment. In this study, we investigated biodegradation and initial thrombogenic behavior of Mg-based alloys at the interface between Mg alloys' surface and simulated physiological environment using a microfluidic system. The degradation properties of Mg-based alloys WE43, AZ31, ZWEK-L, and ZWEK-C were evaluated in complete culture medium and their thrombosis potentials in platelet rich plasma, respectively. The results show that 1) physiological shear stress increased the corrosion rate and decreased platelets adhesion rate as compared to static immersion; 2) secondary phases and impurities in material composition induced galvanic corrosion, resulting in higher corrosion resistance and platelet adhesion rate; 3) Mg-based alloys with higher corrosion rate showed higher platelets adhesion rate. We conclude that a microfluidic-based in vitro system allows evaluation of biodegradation behaviors and platelets responses of Mg-based alloys under specific shear stress, and degradability is related to platelets adhesion.
In recent years, magnesium alloys have emerged as possible biodegradable implant material. A fundamental understanding of the nature of magnesium corrosion and the ability to control this process in vivo is critical to advancing the case for clinical use of magnesium based biomaterials. The biodegradation of magnesium is fundamentally linked to studies of its corrosion, which is dependent on the interfacing dynamics between the material and its environment. Thus, it is required to confirm what variable differentiate the corrosion behavior between in vitro and in vivo before optimizing and standardizing of in vitro test. This study was conducted to understand the biodegradation behavior of commercial AZ31 and Mg-Zn-Ca alloys with plasma electrolyte oxidation (PEO) under various biological environments using in vivo and in vitro testing methods mimicking in vivo physiological environment. This study is focused on the effect of Zn element concentration and PEO coating for magnesium alloys, and the correlation between the in vivo and in vitro in terms of corrosion rate, types of corrosion and corrosion product formation.
The aim of this work was to study corrosion behavior of magnesium (Mg) alloys (MgZnCa plates and AZ31 stents) under varied fluid flow conditions representative of the vascular environment. Experiments revealed that fluid hydrodynamics, fluid flow velocity and shear stress play essential roles in the corrosion behavior of absorbable magnesium-based stent devices. Flow-induced shear stress (FISS) accelerates the overall corrosion (including localized, uniform, pitting and erosion corrosions) due to the increased mass transfer and mechanical force. FISS increased the average uniform corrosion rate, the localized corrosion coverage ratios and depths and the removal rate of corrosion products inside the corrosion pits. For MgZnCa plates, an increase of FISS results in an increased pitting factor but saturates at an FISS of ∼0.15 Pa. For AZ31 stents, the volume loss ratio (31%) at 0.056 Pa was nearly twice that (17%) at 0 Pa before and after corrosion. Flow direction has a significant impact on corrosion behavior as more severe pitting and erosion corrosion was observed on the back ends of the MgZnCa plates, and the corrosion product layer facing the flow direction peeled off from the AZ31 stent struts. This study demonstrates that flow-induced corrosion needs be understood so that Mg-based stents in vascular environments can be effectively designed.
The biodegradable ability of magnesium alloys is an attractive feature for tracheal stents since they can be absorbed by the body through gradual degradation after healing of the airway structure, which can reduce the risk of inflammation caused by long-term implantation and prevent the repetitive surgery for removal of existing stent. In this study, the effects of bicarbonate ion (HCO3−) and mucin in Gamble’s solution on the corrosion behavior of AZ31 magnesium alloy were investigated, using immersion and electrochemical tests to systematically identify the biodegradation kinetics of magnesium alloy under in vitro environment, mimicking the epithelial mucus surfaces in a trachea for development of biodegradable airway stents. Analysis of corrosion products after immersion test was performed using scanning electron microscopy (SEM), energy dispersive X-ray spectroscopy (EDX) and X-ray diffraction (XRD). Electrochemical impedance spectroscopy (EIS) was used to identify the effects of bicarbonate ions and mucin on the corrosion behavior of AZ31 magnesium alloys with the temporal change of corrosion resistance. The results show that the increase of the bicarbonate ions in Gamble’s solution accelerates the dissolution of AZ31 magnesium alloy, while the addition of mucin retards the corrosion. The experimental data in this work is intended to be used as foundational knowledge to predict the corrosion behavior of AZ31 magnesium alloy in the airway environment while providing degradation information for future in vivo studies.
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.