Efficacy of the Biomaterials 3 wt%-nanostrontium-hydroxyapatite-enhanced Calcium Phosphate Cement (nanoSr-CPC) and nanoSr-CPC-incorporated Simvastatin-loaded Poly(lactic-co-glycolic-acid) Microspheres in Osteogenesis Improvement

Aims The purpose of this multi-phase explorative in vivo animal/surgical and in vitro multi-test experimental study was to (1) create a 3 wt%-nanostrontium hydroxyapatite-enhanced calcium phosphate cement (Sr-HA/CPC) for increasing bone formation and (2) creating a simvastatin-loaded poly(lactic-co-glycolic acid) (SIM-loaded PLGA) microspheres plus CPC composite (SIM-loaded PLGA + nanostrontium-CPC). The third goal was the extensive assessment of multiple in vitro and in vivo characteristics of the above experimental explorative products in vitro and in vivo (animal and surgical studies). Methods and results pertaining to Sr-HA/CPC Physical and chemical properties of the prepared Sr-HA/CPC were evaluated. MTT assay and alkaline phosphatase activities, and radiological and histological examinations of Sr-HA/CPC, CPC and negative control were compared. X-ray diffraction (XRD) indicated that crystallinity of the prepared cement increased by increasing the powder-to-liquid ratio. Incorporation of Sr-HA into CPC increased MTT assay (biocompatibility) and ALP activity (P \u3c 0.05). Histomorphometry showed greater bone formation after 4 weeks, after implantation of Sr-HA/CPC in 10 rats compared to implantations of CPC or empty defects in the same rats (n = 30, ANOVA P \u3c 0.05). Methods and results pertaining to SIM-loaded PLGA microspheres + nanostrontium-CPC composite After SEM assessment, the produced composite of microspheres and enhanced CPC were implanted for 8 weeks in 10 rabbits, along with positive and negative controls, enhanced CPC, and enhanced CPC plus SIM (n = 50). In the control group, only a small amount of bone had been regenerated (localized at the boundary of the defect); whereas, other groups showed new bone formation within and around the materials. A significant difference was found in the osteogenesis induced by the groups sham control (16.96 ± 1.01), bone materials (32.28 ± 4.03), nanostrontium-CPC (24.84 ± 2.6), nanostrontium-CPC-simvastatin (40.12 ± 3.29), and SIM-loaded PLGA + nanostrontium-CPC (44.8 ± 6.45) (ANOVA P \u3c 0.001). All the pairwise comparisons were significant (Tukey P \u3c 0.01), except that of nanostrontium-CPC-simvastatin and SIM-loaded PLGA + nanostrontium-CPC. This confirmed the efficacy of the SIM-loaded PLGA + nanostrontium-CPC composite, and its superiority over all materials except SIM-containing nanostrontium-CPC

Melanoma Spheroids Grown Under Neural Crest Cell Conditions Are Highly Plastic Migratory/Invasive Tumor Cells Endowed with Immunomodulator Function

International audienceBACKGROUND: The aggressiveness of melanoma tumors is likely to rely on their well-recognized heterogeneity and plasticity. Melanoma comprises multi-subpopulations of cancer cells some of which may possess stem cell-like properties. Although useful, the sphere-formation assay to identify stem cell-like or tumor initiating cell subpopulations in melanoma has been challenged, and it is unclear if this model can predict a functional phenotype associated with aggressive tumor cells. METHODOLOGY/PRINCIPAL FINDINGS: We analyzed the molecular and functional phenotypes of melanoma spheroids formed in neural crest cell medium. Whether from metastatic or advanced primary tumors, spheroid cells expressed melanoma-associated markers. They displayed higher capacity to differentiate along mesenchymal lineages and enhanced expression of SOX2, NANOG, KLF4, and/or OCT4 transcription factors, but not enhanced self-renewal or tumorigenicity when compared to their adherent counterparts. Gene expression profiling attributed a neural crest cell signature to these spheroids and indicated that a migratory/invasive and immune-function modulating program could be associated with these cells. In vitro assays confirmed that spheroids display enhanced migratory/invasive capacities. In immune activation assays, spheroid cells elicited a poorer allogenic response from immune cells and inhibited mitogen-dependent T cells activation and proliferation more efficiently than their adherent counterparts. Our findings reveal a novel immune-modulator function of melanoma spheroids and suggest specific roles for spheroids in invasion and in evasion of antitumor immunity. CONCLUSION/SIGNIFICANCE: The association of a more plastic, invasive and evasive, thus a more aggressive tumor phenotype with melanoma spheroids reveals a previously unrecognized aspect of tumor cells expanded as spheroid cultures. While of limited efficiency for melanoma initiating cell identification, our melanoma spheroid model predicted aggressive phenotype and suggested that aggressiveness and heterogeneity of melanoma tumors can be supported by subpopulations other than cancer stem cells. Therefore, it could be constructive to investigate melanoma aggressiveness, relevant to patients and clinical transferability

Electrospun Poly Caprolactone-Carbon Nanotube Scaffold for Nerve Regeneration in Dental Tissue Engineering

Regeneration and engineering of functional new tissues containing the neural network have great importance. Progression of neural network into the dental tissue has a crucial role in dental tissue regeneration. In the present study polymer-ceramic blended scaffolds containing different weight percentages of carbon nanotube in poly caprolactone nanofiber matrix were fabricated. Morphological, mechanical and electrical properties of the prepared scaffolds have been characterized. Results showed that the sample containing 5 weight % of carbon nanotube had the smallest mean fiber diameter (50 - 300 nm) and the highest mechanical behavior. Also, its electrical conductivity was suitable to be used in nerve tissue scaffolds. The static culture of the Schwann cells on the prepared scaffolds indicated that increasing weight percentage of carbon nanotube into the polycaprolactone matrix up to the 5 wt. % enhanced cell viability

Repetitive Testing Strategies When the Testing Process Is Imperfect

This paper considers the problem of test design and implementation when testing is imperfect. Items that are classified as conforming may be nonconforming, resulting in a poor outgoing quality level. Items that are classified as nonconforming may be conforming, resulting in excessive scrapping of conforming items. The failed items are commonly retested to reduce the scrapping problem. Alternatively, the accepted items may be retested to improve outgoing quality. In this paper, we examine the question of whether it is better to repetitively test rejected items, or to repetitively test accepted items. We also examine the relationship between the two testing policies, testing equipment accuracy and capacity, incoming quality, and outgoing quality requirements.Computer/Electronic Industry, Semiconductor Manufacturing, Inspection, Optimal Testing Strategies

Liberating methodologies and Nakba studies: Palestinian history and memory from below as sites of lifelong learning

Historians too often construct frameworks and methodologies which obfuscate social, economic and political oppression. This article explores new historical methodologies that can represent oppressed and marginalised groups in Palestine. In particular the article focuses on the role of indigenous history and memory in critical learning and shaping individual and collective identity in Palestine. It further argues that Palestinian memories ‘from below’ since the Nakba have played a major positive role in the recovery from the traumatic catastrophe and the reconstruction of Palestinian identity. The article critiques the manipulation of collective memory by social, political and economic elites and top-down nationalist approaches. It argues that reconfigured popular memories can be liberating and empowering for embattled Palestinians. The article also calls for the establishment of an interdisciplinary subfield of Nakba Studies that would bring together historians, social memory and cultural theorists, postcolonial scholars and scholars of trauma studies with the aim of documenting and studying the embattled social memory of Palestine as a site of lifelong learning and empowerment