A Gallium-Doped Cement for the Treatment of Bone Cancers. the Effect of ZnO ↔ Ga2O3substitution of an Ionomeric Glass Series on the Rheological, Mechanical, PH and Ion-Eluting Properties of their Corresponding Glass Polyalkenoate Cements

The primary treatment for patients suffering from bone cancers is resection of the tumor followed by reconstruction of the damaged bone. Despite the administration of post-operative chemotherapy, tumor recurrence continues to present itself as a severe complication leading to re-operation. Attempts to incorporate chemotherapeutic drugs into bone cements elicits local toxic effects on healthy bone, which could compromise implant fixation. Alternatively, the local administration of gallium (Ga) may prove to be more effective. This report considers the development of a Ga ionomeric glass series (0.48SiO2-0.355ZnO-0.06CaO-0.08SrO-0.02P2O5-0.005Ta2O5, with 0.01-0.05 mol% substitution for ZnO). X-ray Diffraction (XRD) confirmed the amorphous glass structure and Energy Dispersive x-ray Fluorescence (EDXRF) verified the successful addition of Ga into the glass series at the expense of Zinc (Zn). A Ga-GPC series was then formulated by mixing the glass particles with aqueous poly(acrylic) acid (PAA) and trisodium citrate (TSC). Fourier transform infrared (FTIR) spectroscopy demonstrated no structural changes to the GPC matrix with the incorporation of Ga. Measurements of the rheological properties demonstrated an exponential increase in setting time with increasing Ga content. Furthermore, the addition of ≥ 3 mol% Ga demonstrated deleterious effects on the GPC\u27s mechanical properties and an analysis of pH confirmed that it decreased with increasing Ga content, suggesting a reduction in glass reactivity and PAA cross-linking. Finally, inductively coupled plasma - optical emission spectrometry (ICP-OES) demonstrated the controlled release of Ga across the GPC series, which will prove beneficial to future in vitro studies

The Impact of Gallium Content on Degradation, Bioactivity, and Antibacterial Potency of Zinc Borate Bioactive Glass

Zinc borate glasses with increasing gallium content (0, 2.5, 5, 10, and 15 Wt % Ga) were synthesized and their degradation, bioactivity in simulated body fluid (SBF), and antibacterial properties were investigated. ICP measurements showed that increased gallium content in the glass resulted in increased gallium ion release and decreased release of other ions. Degradability declined with the addition of gallium, indicating the formation of more symmetric BO3 units with three bridging oxygens and asymmetric BO3 units with two bridging oxygens in the glass network as the gallium content in the series increased. The formation of amorphous Ca-P on the glass surface after 24 h of incubation in SBF was confirmed by SEM, XRD, and FTIR analyses. Finally, antibacterial evaluation of the glasses using the agar disc-diffusion method demonstrated that the addition of gallium increased the antibacterial potency of the glasses against P. aeruginosa (Gram-negative) while decreasing it against S. epidermidis (Gram-positive); considering the ion release trends, this indicates that the gallium ion is responsible for the glasses\u27 antibacterial behavior against P. aeruginosa while the zinc ion controls the antibacterial activity against S. epidermidis. The statistical significance of the observed trends in the measurements were confirmed by applying the Kruskal-Wallis H Test. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 367–376, 2018

Modification of an erodibility category limit for the pocket erodometer

The pocket erodometer test (PET) is an inexpensive and expedient way to derive the erosion categories of soils. The test involves impinging a regulated jet of water at the end of an undisturbed soil sample and measuring the depth of scoured hole after 20 jet applications. The depth of the scoured hole provides an indication of the erosion category. PET and companion erosion function apparatus (EFA) tests were per-formed on 33 cohesive soil samples from 5 different sites on the island of Oahu, Hawaii. In the EFA test, water is run over a Shelby tube of soil placed at the bottom of a flume. The rate of scour is measured under different flow velocities. PET and EFA tests data were used to develop a plot of the PET erosion depth versus EFA erosion category which revealed that a correlation clearly exists between PET erosion depth and EFA erosion category value, the PET erosion depth that separates medium and high erodibility categories should be revised and the erodibility criteria based on soil classification is not very reliable for Hawaiian fine-grained soils

In Vitro Osteogenic Performance of Two Novel Strontium and Zinc-Containing Glass Polyalkenoate Cements

Glass polyalkenoate cements (GPCs) are under investigation as potential bone adhesives, as they may provide an alternative to polymethylmethacrylate-based cements. GPCs containing strontium (Sr) and zinc (Zn) in place of aluminum (Al) are of particular interest because these ions are known stimulators of osteoprogenitor differentiation. GPCs have been manufactured from a novel bioactive glass (SiO2:0.48, ZnO:0.36, CaO:0.12, SrO:0.04) in the past, but, while such materials have been assessed for their influence on viability, their influence on osteogenic function has not been investigated until now. For this study, two GPCs were formulated from the same glass precursor evaluated in previous studies. These GPCs were named GPC A and GPC B, and they differed in glass particle size, polyacrylic acid molecular weight, and their powder: liquid ratios. The effect of these two GPCs on osteogenic differentiation of primary rat osteoblasts were evaluated using three culture systems: culture with dissolution extracts, indirect contact with trans well-inserts and direct contact. Additionally, the degradation characteristics of GPCs were assessed, including their interfacial pH and surrounding pH. The experimental outcomes revealed that collagen deposition, alkaline phosphatase expression, and mineralization were largely dependent on GPC composition as well as the mode of interaction with cells. These markers were found to be significantly elevated in response to GPC A\u27s dissolution products. However, osteogenic differentiation was inhibited when osteoblasts were cultured indirectly and directly with GPCs, with, overall, GPC B significantly outperforming GPC A. These results suggest that GPC degradation products effect osteogenic differentiation in a dose-dependent manner

A Review of the Latest Insights into the Mechanism of Action of Strontium in Bone

Interest in strontium (Sr) has persisted over the last three decades due to its unique mechanism of action: it simultaneously promotes osteoblast function and inhibits osteoclast function. While this mechanism of action is strongly supported by in vitro studies and small animal trials, recent large-scale clinical trials have demonstrated that orally administered strontium ranelate (SrRan) may have no anabolic effect on bone formation in humans. Yet, there is a strong correlation between Sr accumulation in bone and reduced fracture risk in post-menopausal women, suggesting Sr acts via a purely physiochemical mechanism to enhance bone strength. Conversely, the local administration of Sr with the use of modified biomaterials has been shown to enhance bone growth, osseointegration and bone healing at the bone-implant interface, to a greater degree than Sr-free materials. This review summarizes current knowledge of the main cellular and physiochemical mechanisms that underly Sr\u27s effect in bone, which center around Sr\u27s similarity to calcium (Ca). We will also summarize the main controversies in Sr research which cast doubt on the \u27dual-acting mechanism\u27. Lastly, we will explore the effects of Sr-modified bone-implant materials both in vitro and in vivo, examining whether Sr may act via an alternate mechanism when administered locally

Bone Cement as a Local Chemotherapeutic Drug Delivery Carrier in Orthopedic Oncology: A Review

Metastatic bone lesions are common among patients with advanced cancers. While chemotherapy and radiotherapy may be prescribed immediately after diagnosis, the majority of severe metastatic bone lesions are treated by reconstructive surgery, which, in some cases, is followed by postoperative radiotherapy or chemotherapy. However, despite recent advancements in orthopedic surgery, patients undergoing reconstruction still have the risk of developing severe complications such as tumor recurrence and reconstruction failure. This has led to the introduction and evaluation of poly (methyl methacrylate) and inorganic bone cements as local carriers for chemotherapeutic drugs (usually, antineoplastic drugs (ANPDs)). The present work is a critical review of the literature on the potential use of these cements in orthopedic oncology. While several studies have demonstrated the benefits of providing high local drug concentrations while minimizing systemic side effects, only six studies have been conducted to assess the local toxic effect of these drug-loaded cements and they all reported negative effects on healthy bone structure. These findings do not close the door on chemotherapeutic bone cements; rather, they should assist in materials selection when designing future materials for the treatment of metastatic bone disease

Development of a Novel Bioactive Glass Suitable for Osteosarcoma-Related Bone Grafts

In this study, zinc borate-based glasses with increasing gallium content (0, 2.5, 5, 10, and 15 wt % Ga) were synthesized and their effect on the viability and proliferation of preosteoblasts and osteosarcoma cancer cells were investigated. Methyl thiazolyl tetrazolium (MTT) cell viability assays using glass degradation extracts revealed that the extracts from glasses with lower Ga contents could enhance the viability of preosteoblasts, while extracts from the glass composition with 15 wt % Ga caused statistically significant reduction of their viability. MTT cell viability assays using the extracts and osteosarcoma cells showed that only extracts from the glass composition with 5 wt % Ga (G3) did not cause a statistically significant increase in the viability of cancer cells for all degradation periods (1 day, 7 days, and 28 days). G3 was selected as the most suitable composition for the osteosarcoma-related graft operations as it could improve the viability of preosteoblasts without increasing the viability of cancer cells. The viability of preosteoblasts and osteosarcoma cells in contact with the glass powders were also investigated using MTT assays. The results showed that the G3 powders could enhance the viability of preosteoblasts while decreasing the viability of osteosarcoma cells. Finally, live/dead assays revealed that suppression of proliferation appeared to be the mechanism causing the observed reductions in the viability of osteosarcoma cells exposed to G3 powders. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 1186–1193, 2018

Metformin attenuates lipid accumulation in hepatocytes of blunt snout bream (Megalobrama amblycephala) via activation of AMP-activated protein kinase

Currently, there is a trend to use high-fat diets in intensive aquaculture that is accompanied with incidence of fatty liver when dietary lipid level surpasses an upper limit. So, it is necessary to develop appropriate strategies to reduce the risk of fatty liver in commercial fish farming. Studies in mammals have revealed a correlation between fatty liver and AMP-activated protein kinase (AMPK) activity, which has been recognized as a key modulator of lipid metabolism. Considering the frequent occurrence of fatty liver in blunt snout bream farming, an in-vitro study was designed to evaluate the efficiency of metformin, as a stimulator of AMPK, in activation of AMPK and its subsequent effects on lipid metabolism in primary hepatocytes. Fish hepatocytes were seeded at a density of 1 × 106 ml−1 in 6-well tissue culture plates and treated with three different media including: 1) Leibovitz's L-15 medium [L15] as control, 2) high-fat medium [L15 + 400 μM oleic acid], and 3) metformin medium [L15 + 400 μM oleic acid+200 μM metformin]. After 48 h of culture, the cells and supernatant were collected for analysis. The results showed significant (P

EvoBot: Towards a Robot-Chemostat for Culturing and Maintaining Microbial Fuel Cells (MFCs)

In this paper we present EvoBot, a RepRap open-source 3D-printer modified to operate like a robot for culturing and maintaining Microbial Fuel Cells (MFCs). EvoBot is a modular liquid handling robot that has been adapted to host MFCs in its experimental layer, gather data from the MFCs and react on the set thresholds based on a feedback loop. This type of robot-MFC interaction, based on the feedback loop mechanism, will enable us to study further the adaptability and stability of these systems. To date, EvoBot has automated the nurturing process of MFCs with the aim of controlling liquid delivery, which is akin to a chemostat. The chemostat is a well-known microbiology method for culturing bacterial cells under controlled conditions with continuous nutrient supply. EvoBot is perhaps the first pioneering attempt at functionalizing the 3D printing technology by combining it with the chemostat methods. In this paper, we will explore the experiments that EvoBot has carried out so far and how the platform has been optimised over the past two years