Effects of Amyloid Beta (Aß) Oligomers on Blood-Brain Barrier Using a 3D Microfluidic Vasculature-on-a-Chip Model.

The disruption of the blood-brain barrier (BBB) in Alzheimer's Disease (AD) is largely influenced by amyloid beta (Aß). 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 Aß1-42 oligomers on BBB dysfunction by treating them in the luminal. Our findings reveal a pronounced accumulation of Aß1-42 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 Aß1-42 oligomers (LC50 ~ 1 µM). This study underscores the utility of our membrane-free vascular chip in elucidating the dysfunction induced by Aß with respect to the BBB.

The Effect of Omega-9 on Bone Viscoelasticity and Strength in an Ovariectomized Diet-Fed Murine Model.

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.

Omega-9 Modifies Viscoelasticity and Augments Bone Strength and Architecture in a High-Fat Diet-Fed Murine Model.

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.

CVD Synthesis of 3D-Shaped 3D Graphene Using a 3D-Printed Nickel-PLGA Catalyst Precursor.

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.

Amphiphilic phospholipid-iodinated polymer conjugates for bioimaging.

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.

Knee and Hip Joint Cartilage Damage from Combined Spaceflight Hazards of Low-Dose Radiation Less than 1 Gy and Prolonged Hindlimb Unloading.

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.

Biodegradability and platelets adhesion assessment of magnesium-based alloys using a microfluidic system.

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.

Understanding corrosion behavior of Mg-Zn-Ca alloys from subcutaneous mouse model: effect of Zn element concentration and plasma electrolytic oxidation.

Mg-Zn-Ca alloys are considered as suitable biodegradable metallic implants because of their biocompatibility and proper physical properties. In this study, we investigated the effect of Zn concentration of Mg-xZn-0.3Ca (x=1, 3 and 5wt.%) alloys and surface modification by plasma electrolytic oxidation (PEO) on corrosion behavior in in vivo environment in terms of microstructure, corrosion rate, types of corrosion, and corrosion product formation. Microstructure analysis of alloys and morphological characterization of corrosion products were conducted using x-ray computed tomography (micro-CT) and scanning electron microscopy (SEM). Elemental composition and crystal structure of corrosion products were determined using x-ray diffraction (XRD) and electron dispersive x-ray spectroscopy (EDX). The results show that 1) as-cast Mg-xZn-0.3Ca alloys are composed of Mg matrix and a secondary phase of Ca2Mg6Zn3 formed along grain boundaries, 2) the corrosion rate of Mg-xZn-0.3Ca alloys increases with increasing concentration of Zn in the alloy, 3) corrosion rates of alloys treated by PEO sample are decreased in in vivo environment, and 4) the corrosion products of these alloys after in vivo tests are identified as brucite (Mg(OH)2), hydroxyapatite (Ca10(PO4)6(OH)2), and magnesite (MgCO3·3H2O).

Systematic understanding of corrosion behavior of plasma electrolytic oxidation treated AZ31 magnesium alloy using a mouse model of subcutaneous implant.

This study was conducted to identify the differences between corrosion rates, corrosion types, and corrosion products in different physiological environments for AZ31 magnesium alloy and plasma electrolytic oxidation (PEO) treated AZ31 magnesium alloy. In vitro and in vivo tests were performed in Hank's Balanced Salt Solution (HBSS) and mice for 12 weeks, respectively. The corrosion rates of both AZ31 magnesium alloy and PEO treated AZ31 magnesium alloy were calculated based on DC polarization curves, volume of hydrogen evolution, and the thickness of corrosion products formed on the surface. Micro X-ray computed tomography (Micro-CT), scanning electron microscopy (SEM), energy dispersive X-ray spectroscopy (EDX) and X-ray diffraction (XRD) were used to analyze morphological and chemical characterizations of corrosion products. The results show that there is more severe localized corrosion after in vitro test in HBSS; however, the thicknesses of corrosion products formed on the surface for AZ31 magnesium alloy and PEO treated AZ31 magnesium alloy in vivo were about 40% thicker than the thickness of corrosion products generated in vitro. The ratio of Ca and P (Ca/P) in the corrosion products also differed. The Ca deficient region and higher content of Al in corrosion product than AZ31 magnesium alloy were identified after in vivo test in contrast with the result of in vitro test.

Flow-induced corrosion behavior of absorbable magnesium-based stents.

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 ∼0.15Pa. For AZ31 stents, the volume loss ratio (31%) at 0.056Pa was nearly twice that (17%) at 0Pa 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.

Total-body irradiation produces late degenerative joint damage in rats.

PURPOSE: Premature musculoskeletal joint failure is a major source of morbidity among childhood cancer survivors. Radiation effects on synovial joint tissues of the skeleton are poorly understood. Our goal was to assess long-term changes in the knee joint from skeletally mature rats that received total-body irradiation while skeletal growth was ongoing. MATERIALS AND METHODS: 14 week-old rats were irradiated with 1, 3 or 7 Gy total-body doses of 18 MV X-rays. At 53 weeks of age, structural and compositional changes in knee joint tissues (articular cartilage, subchondral bone, and trabecular bone) were characterized using 7T MRI, nanocomputed tomography (nanoCT), microcomputed tomography (microCT), and histology. RESULTS: T2 relaxation times of the articular cartilage were lower after exposure to all doses. Likewise, calcifications were observed in the articular cartilage. Trabecular bone microarchitecture was compromised in the tibial metaphysis at 7 Gy. Mild to moderate cartilage erosion was scored in the 3 and 7 Gy rats. CONCLUSIONS: Late degenerative changes in articular cartilage and bone were observed after total-body irradiation in adult rats exposed prior to skeletal maturity. 7T MRI, microCT, nanoCT, and histology identified potential prognostic indicators of late radiation-induced joint damage.

Effect of Mucin and Bicarbonate Ion on Corrosion Behavior of AZ31 Magnesium Alloy for Airway Stents.

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.

In vitro degradation and cytotoxicity response of Mg-4% Zn-0.5% Zr (ZK40) alloy as a potential biodegradable material.

Mg-4 wt.% Zn-0.5 wt.% Zr (ZK40) alloy was studied as a candidate material for biodegradable metallic implants in terms of its biocorrosion resistance, mechanical properties and cytocompatibility. The corrosion characteristics of ZK40 alloy were assessed by potentiodynamic polarization and immersion testing in DMEM+10% FBS solution. Analysis of the degradation characteristics by potentiodynamic polarization measurements shows the corrosion rates of ZK40 alloy in as-cast and solution treatment (T4) condition were slightly higher than those of pure Mg or as-drawn AZ31. Determination of the corrosion rate by the weight loss technique reveals that the as-cast ZK40 resulted in slower degradation than other alloy specimens after 7 days of immersion but exhibited accelerated degradation after 14 and 21 days, respectively. T4-treated ZK40 exhibited stable degradation rates compared to as-cast ZK40 and close to those of pure Mg and AZ31 during immersion testing for 14 and 21 days. In order to examine the in vitro cytocompatibility of ZK40 alloy, live/dead cell viability assay and indirect MTT assay were performed using a murine osteoblast-like cell line (MC3T3). After 3 days of direct culture of MC3T3 on ZK40 alloys the live/dead assay indicated favorable cell viability and attachment. The degradation product of ZK40 also showed minimal cytotoxicity when assessed in indirect MTT assay. The mechanical properties of the as-cast and T4-treated ZK40 alloy were superior to those of pure Mg and comparable to as-drawn AZ31. Solution treatment did not significantly enhance the cytocompatibility and mechanical properties of ZK40 alloy. Overall, the ZK40 alloy exhibited favorable cytocompatibility, biocorrosion, and mechanical properties rendering it a potential candidate for degradable implant applications.

A surface-eroding poly(1,3-trimethylene carbonate) coating for fully biodegradable magnesium-based stent applications: toward better biofunction, biodegradation and biocompatibility.

Biodegradable magnesium-based materials have a high potential for cardiovascular stent applications; however, there exist concerns on corrosion control and biocompatibility. A surface-eroding coating of poly(1,3-trimethylene carbonate) (PTMC) on magnesium (Mg) alloy was studied, and its dynamic degradation behavior, electrochemical corrosion, hemocompatibility and histocompatibility were investigated. The PTMC coating effectively protected the corrosion of the Mg alloy in the dynamic degradation test. The corrosion current density of the PTMC-coated alloy reduced by three orders and one order of magnitude compared to bare and poly(ε-caprolactone) (PCL)-coated Mg alloy, respectively. Static and dynamic blood tests in vitro indicated that significantly fewer platelets were adherent and activated, and fewer erythrocytes attached on the PTMC-coated surface and showed less hemolysis than on the controls. The PTMC coating after 16 weeks' subcutaneous implantation in rats maintained ~55% of its original thickness and presented a homogeneously flat surface demonstrating surface erosion, in contrast to the PCL coated control, which exhibited non-uniform bulk erosion. The Mg alloy coated with PTMC showed less volume reduction and fewer corrosion products as compared to the controls after 52 weeks in vivo. Excessive inflammation, necrosis and hydrogen gas accumulation were not observed. The homogeneous surface erosion of the PTMC coating from exterior to interior (surface-eroding behavior) and its charge neutral degradation products contribute to its excellent protective performance. It is concluded that PTMC is a promising candidate for a surface-eroding coating applied to Mg-based implants.

Effect of biologically relevant ions on the corrosion products formed on alloy AZ31B: an improved understanding of magnesium corrosion.

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.