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      Applications of Metals for Bone Regeneration

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          Abstract

          The regeneration of bone tissue is the main purpose of most therapies in dental medicine. For bone regeneration, calcium phosphate (CaP)-based substitute materials based on natural (allo- and xenografts) and synthetic origins (alloplastic materials) are applied for guiding the regeneration processes. The optimal bone substitute has to act as a substrate for bone ingrowth into a defect, as well as resorb in the time frame needed for complete regeneration up to the condition of restitution ad integrum. In this context, the modes of action of CaP-based substitute materials have been frequently investigated, where it has been shown that such materials strongly influence regenerative processes such as osteoblast growth or differentiation and also osteoclastic resorption due to different physicochemical properties of the materials. However, the material characteristics needed for the required ratio between new bone tissue formation and material degradation has not been found, until now. The addition of different substances such as collagen or growth factors and also of different cell types has already been tested but did not allow for sufficient or prompt application. Moreover, metals or metal ions are used differently as a basis or as supplement for different materials in the field of bone regeneration. Moreover, it has already been shown that different metal ions are integral components of bone tissue, playing functional roles in the physiological cellular environment as well as in the course of bone healing. The present review focuses on frequently used metals as integral parts of materials designed for bone regeneration, with the aim to provide an overview of currently existing knowledge about the effects of metals in the field of bone regeneration.

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          Store-operated calcium channels.

          In electrically nonexcitable cells, Ca(2+) influx is essential for regulating a host of kinetically distinct processes involving exocytosis, enzyme control, gene regulation, cell growth and proliferation, and apoptosis. The major Ca(2+) entry pathway in these cells is the store-operated one, in which the emptying of intracellular Ca(2+) stores activates Ca(2+) influx (store-operated Ca(2+) entry, or capacitative Ca(2+) entry). Several biophysically distinct store-operated currents have been reported, but the best characterized is the Ca(2+) release-activated Ca(2+) current, I(CRAC). Although it was initially considered to function only in nonexcitable cells, growing evidence now points towards a central role for I(CRAC)-like currents in excitable cells too. In spite of intense research, the signal that relays the store Ca(2+) content to CRAC channels in the plasma membrane, as well as the molecular identity of the Ca(2+) sensor within the stores, remains elusive. Resolution of these issues would be greatly helped by the identification of the CRAC channel gene. In some systems, evidence suggests that store-operated channels might be related to TRP homologs, although no consensus has yet been reached. Better understood are mechanisms that inactivate store-operated entry and hence control the overall duration of Ca(2+) entry. Recent work has revealed a central role for mitochondria in the regulation of I(CRAC), and this is particularly prominent under physiological conditions. I(CRAC) therefore represents a dynamic interplay between endoplasmic reticulum, mitochondria, and plasma membrane. In this review, we describe the key electrophysiological features of I(CRAC) and other store-operated Ca(2+) currents and how they are regulated, and we consider recent advances that have shed insight into the molecular mechanisms involved in this ubiquitous and vital Ca(2+) entry pathway.
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            An Overview of Poly(lactic-co-glycolic) Acid (PLGA)-Based Biomaterials for Bone Tissue Engineering

            Poly(lactic-co-glycolic) acid (PLGA) has attracted considerable interest as a base material for biomedical applications due to its: (i) biocompatibility; (ii) tailored biodegradation rate (depending on the molecular weight and copolymer ratio); (iii) approval for clinical use in humans by the U.S. Food and Drug Administration (FDA); (iv) potential to modify surface properties to provide better interaction with biological materials; and (v) suitability for export to countries and cultures where implantation of animal-derived products is unpopular. This paper critically reviews the scientific challenge of manufacturing PLGA-based materials with suitable properties and shapes for specific biomedical applications, with special emphasis on bone tissue engineering. The analysis of the state of the art in the field reveals the presence of current innovative techniques for scaffolds and material manufacturing that are currently opening the way to prepare biomimetic PLGA substrates able to modulate cell interaction for improved substitution, restoration, or enhancement of bone tissue function.
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              Review on iron and its importance for human health

              It is well-known that deficiency or over exposure to various elements has noticeable effects on human health. The effect of an element is determined by several characteristics, including absorption, metabolism, and degree of interaction with physiological processes. Iron is an essential element for almost all living organisms as it participates in a wide variety of metabolic processes, including oxygen transport, deoxyribonucleic acid (DNA) synthesis, and electron transport. However, as iron can form free radicals, its concentration in body tissues must be tightly regulated because in excessive amounts, it can lead to tissue damage. Disorders of iron metabolism are among the most common diseases of humans and encompass a broad spectrum of diseases with diverse clinical manifestations, ranging from anemia to iron overload, and possibly to neurodegenerative diseases. In this review, we discuss the latest progress in studies of iron metabolism and bioavailability, and our current understanding of human iron requirement and consequences and causes of iron deficiency. Finally, we discuss strategies for prevention of iron deficiency.
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                Author and article information

                Journal
                Int J Mol Sci
                Int J Mol Sci
                ijms
                International Journal of Molecular Sciences
                MDPI
                1422-0067
                12 March 2018
                March 2018
                : 19
                : 3
                : 826
                Affiliations
                [1 ]Clinic of Small Animals, c/o Institute of Veterinary Anatomy, Histology and Embryology, Justus Liebig University of Giessen, D-35392 Giessen, Germany; Kristina.Glenske@ 123456vetmed.uni-giessen.de (K.G.); Nada.Milosevic-Oljaca@ 123456vetmed.uni-giessen.de (N.M.-O.)
                [2 ]Botiss Biomaterials, D-12109 Berlin, Germany; Phil.Donkiewicz@ 123456botiss.com (P.D.); alexander.koewitsch@ 123456botiss.com (A.K.); patrick.rider@ 123456botiss.com (P.R.); Sven.Rofall@ 123456botiss.com (S.R.)
                [3 ]Clinic for Trauma Surgery and Orthopedics, Elbe Kliniken Stade-Buxtehude, D-21682 Stade, Germany; Joerg.Franke@ 123456elbekliniken.de
                [4 ]Department of Oral and Maxillofacial Surgery, University Hospital Hamburg- Eppendorf, D-20246 Hamburg, Germany; ol.jung@ 123456uke.de (O.J.); r.smeets@ 123456uke.de (R.S.)
                [5 ]Justus Liebig University of Giessen, 35390 Giessen, Germany; reiner.schnettler@ 123456mac.com
                Author notes
                [* ]Correspondence: Sabine.Wenisch@ 123456vetmed.uni-giessen.de (S.W.); mike.barbeck@ 123456icloud.com (M.B.); Tel.: +49-641-9938111 (S.W.); +49-176-81022467 (M.B.)
                [†]

                Kristina Glenske and Phil Donkiewicz contributed equally to this work; Sabine Wenisch and Mike Barbeck contributed equally to this work.

                Author information
                https://orcid.org/0000-0002-3001-1347
                Article
                ijms-19-00826
                10.3390/ijms19030826
                5877687
                29534546
                046c3cc8-0d90-4297-a780-c1b432000060
                © 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
                : 05 February 2018
                : 11 March 2018
                Categories
                Review

                Molecular biology
                metals,dental regeneration,bioactivity,tissue regeneration,bone
                Molecular biology
                metals, dental regeneration, bioactivity, tissue regeneration, bone

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