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      Production and Physicochemical Characterization of Cu-Doped Silicate Bioceramic Scaffolds

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          Abstract

          Development of ion-releasing implantable biomaterials is a valuable approach for advanced medical therapies. In the effort of tackling this challenge, we explored the feasibility of porous bioceramic scaffolds releasing copper ions, which are potentially able to elicit angiogenetic and antibacterial effects. First, small amounts of CuO were incorporated in the base silicate glass during melting and the obtained powders were further processed to fabricate glass–ceramic scaffolds by sponge replica method followed by sinter crystallization. As the release of copper ions from these foams in simulated body fluid (SBF) was very limited, a second processing strategy was developed. Silicate glass–ceramic scaffolds were coated with a layer of Cu-doped mesoporous glass, which exhibited favorable textural properties (ultrahigh specific surface area >200 m 2/g, mesopore size about 5 nm) for modulating the release of copper. All the produced scaffolds, containing biocompatible crystals of wollastonite (CaSiO 3), revealed high stability in a biological environment. Furthermore, the materials had adequate compressive strength (>10 MPa) for allowing safe manipulation during surgery. Overall, the results achieved in the present work suggest that these Cu-doped glass-derived scaffolds show promise for biomedical application and motivate further investigation of their suitability from a biological viewpoint.

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          Most cited references39

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          Copper-containing mesoporous bioactive glass scaffolds with multifunctional properties of angiogenesis capacity, osteostimulation and antibacterial activity.

          It is of great importance to develop multifunctional bioactive scaffolds, which combine angiogenesis capacity, osteostimulation, and antibacterial properties for regenerating lost bone tissues. In order to achieve this aim, we prepared copper (Cu)-containing mesoporous bioactive glass (Cu-MBG) scaffolds with interconnective large pores (several hundred micrometer) and well-ordered mesopore channels (around 5 nm). Both Cu-MBG scaffolds and their ionic extracts could stimulate hypoxia-inducible factor (HIF)-1α and vascular endothelial growth factor (VEGF) expression in human bone marrow stromal cells (hBMSCs). In addition, both Cu-MBG scaffolds and their ionic extracts significantly promoted the osteogenic differentiation of hBMSCs by improving their bone-related gene expression (alkaline phosphatase (ALP), osteopontin (OPN) and osteocalcin (OCN)). Furthermore, Cu-MBG scaffolds could maintain a sustained release of ibuprofen and significantly inhibited the viability of bacteria. This study indicates that the incorporation of Cu(2+) ions into MBG scaffolds significantly enhances hypoxia-like tissue reaction leading to the coupling of angiogenesis and osteogenesis. Cu(2+) ions play an important role to offer the multifunctional properties of MBG scaffold system. This study has demonstrated that it is possible to develop multifunctional scaffolds by combining enhanced angiogenesis potential, osteostimulation, and antibacterial properties for the treatment of large bone defects. Copyright © 2012 Elsevier Ltd. All rights reserved.
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            Gene-expression profiling of human osteoblasts following treatment with the ionic products of Bioglass 45S5 dissolution.

            The effect of the ionic products of Bioglass 45S5 dissolution on the gene-expression profile of human osteoblasts was investigated by cDNA microarray analysis of 1,176 genes. Treatment with the ionic products of Bioglass 45S5 dissolution increased the levels of 60 transcripts twofold or more and reduced the levels of five transcripts to one-half or less than in control. Markedly up-regulated genes included RCL, a c-myc responsive growth related gene, cell cycle regulators such as G1/S specific cyclin D1, and apoptosis regulators including calpain and defender against cell death (DAD1). Other significantly up-regulated genes included the cell surface receptors CD44 and integrin beta1, and various extracellular matrix regulators including metalloproteinases-2 and -4 and their inhibitors TIMP-1 and TIMP-2. The identification of differentially expressed genes by cDNA microarray analysis has offered new insights into the mode of action of bioactive glasses and has proven to be an effective tool in evaluating their osteoproductive properties. Copyright 2001 John Wiley & Sons, Inc.
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              Mechanism of antibacterial activity of copper nanoparticles.

              In a previous communication, we reported a new method of synthesis of stable metallic copper nanoparticles (Cu-NPs), which had high potency for bacterial cell filamentation and cell killing. The present study deals with the mechanism of filament formation and antibacterial roles of Cu-NPs in E. coli cells. Our results demonstrate that NP-mediated dissipation of cell membrane potential was the probable reason for the formation of cell filaments. On the other hand, Cu-NPs were found to cause multiple toxic effects such as generation of reactive oxygen species, lipid peroxidation, protein oxidation and DNA degradation in E. coli cells. In vitro interaction between plasmid pUC19 DNA and Cu-NPs showed that the degradation of DNA was highly inhibited in the presence of the divalent metal ion chelator EDTA, which indicated a positive role of Cu(2+) ions in the degradation process. Moreover, the fast destabilization, i.e. the reduction in size, of NPs in the presence of EDTA led us to propose that the nascent Cu ions liberated from the NP surface were responsible for higher reactivity of the Cu-NPs than the equivalent amount of its precursor CuCl2; the nascent ions were generated from the oxidation of metallic NPs when they were in the vicinity of agents, namely cells, biomolecules or medium components, to be reduced simultaneously.
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                Author and article information

                Journal
                Materials (Basel)
                Materials (Basel)
                materials
                Materials
                MDPI
                1996-1944
                24 August 2018
                September 2018
                : 11
                : 9
                : 1524
                Affiliations
                [1 ]Department of Applied Science and Technology, Politecnico di Torino, Corso Duca degli Abruzzi 24, 10129 Torino, Italy; chiara.vitale@ 123456polito.it
                [2 ]Lithoz CmbH, Mollardgasse 85a/2/64-69, 1060 Vienna, Austria; ipotestio@ 123456lithoz.com
                Author notes
                [* ]Correspondence: francesco.baino@ 123456polito.it ; Tel.: +39-011-090-4668
                Author information
                https://orcid.org/0000-0001-8860-0497
                https://orcid.org/0000-0001-7624-4579
                Article
                materials-11-01524
                10.3390/ma11091524
                6164809
                30149542
                9f571927-ba52-437f-961a-8d0d0c1492dc
                © 2018 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 07 August 2018
                : 21 August 2018
                Categories
                Article

                bioactive glass,glass–ceramic,scaffold,mesoporous,copper,angiogenesis,antibacterial,bioactivity,orbital implants

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