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      Multifunctional zinc ion doped sol – gel derived mesoporous bioactive glass nanoparticles for biomedical applications

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          Abstract

          Mesoporous bioactive glasses have been widely investigated for applications in bone tissue regeneration and, more recently, in soft tissue repair and wound healing. In this study we produced mesoporous bioactive glass nanoparticles (MBGNs) based on the SiO 2–CaO system. With the intention of adding subsidiary biological function, MBGNs were doped with Zn 2+ ions. Zn-MBGNs with 8 mol% ZnO content were synthesized via microemulsion assisted sol-gel method. The synthesized particles were homogeneous in shape and size. They exhibited spherical shape, good dispersity, and a size of 130 ± 10 nm. The addition of zinc precursors did not affect the morphology of particles, while their specific surface area increased in comparison to MBGNs. The presence of Zn 2+ ions inhibited the formation of hydroxycarbonate apatite (HCAp) on the particles after immersion in simulated body fluid (SBF). No formation of HCAp crystals on the surface of Zn-MBGNs could be observed after 14 days of immersion. Interestingly, powders containing relatively high amount of zinc released Zn 2+ ions in low concentration (0.6–1.2 mg L −1) but in a sustained manner. This releasing feature enables Zn-MBGNs to avoid potentially toxic levels of Zn 2+ ions, indeed Zn-MBGNs were seen to improve the differentiation of osteoblast-like cells (MG-63). Additionally, Zn-MBGNs showed higher ability to adsorb proteins in comparison to MBGNs, which could indicate a favourable later attachment of cells. Due to their advantageous morphological and physiochemical properties, Zn-MBGNs show great potential as bioactive fillers or drug delivery systems in a variety of applications including bone regeneration and wound healing.

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          Highlights

          • Zn doped mesoporous bioactive glass nanoparticles synthesized via microemulsion - sol-gel method.

          • Synthesized particles were homogeneous in shape and size.

          • Particles released Zn 2+ ions in low concentration and in sustained manner.

          • Zn-MBGNs improved differentiation of osteoblast-like cells (MG-63).

          • Zn-MBGNs show potential for hard and soft tissue engineering.

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          Most cited references41

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          Mesoporous Silica Nanoparticles: A Comprehensive Review on Synthesis and Recent Advances

          Recent advancements in drug delivery technologies utilizing a variety of carriers have resulted in a path-breaking revolution in the approach towards diagnosis and therapy alike in the current times. Need for materials with high thermal, chemical and mechanical properties have led to the development of mesoporous silica nanoparticles (MSNs). These ordered porous materials have garnered immense attention as drug carriers owing to their distinctive features over the others. They can be synthesized using a relatively simple process, thus making it cost effective. Moreover, by controlling the parameters during the synthesis; the morphology, pore size and volume and particle size can be transformed accordingly. Over the last few years, a rapid increase in research on MSNs as drug carriers for the treatment of various diseases has been observed indicating its potential benefits in drug delivery. Their widespread application for the loading of small molecules as well as macromolecules such as proteins, siRNA and so forth, has made it a versatile carrier. In the recent times, researchers have sorted to several modifications in the framework of MSNs to explore its potential in drug resistant chemotherapy, antimicrobial therapy. In this review, we have discussed the synthesis of these multitalented nanoparticles and the factors influencing the size and morphology of this wonder carrier. The second part of this review emphasizes on the applications and the advances made in the MSNs to broaden the spectrum of its use especially in the field of biomedicine. We have also touched upon the lacunae in the thorough understanding of its interaction with a biological system which poses a major hurdle in the passage of this carrier to the clinical level. In the final part of this review, we have discussed some of the major patents filed in the field of MSNs for therapeutic purpose.
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            Zinc in wound healing: theoretical, experimental, and clinical aspects.

            Zinc is an essential trace element in the human body and its importance in health and disease is appreciated. It serves as a cofactor in numerous transcription factors and enzyme systems including zinc-dependent matrix metalloproteinases that augment autodebridement and keratinocyte migration during wound repair. Zinc confers resistance to epithelial apoptosis through cytoprotection against reactive oxygen species and bacterial toxins possibly through antioxidant activity of the cysteine-rich metallothioneins. Zinc deficiency of hereditary or dietary cause can lead to pathological changes and delayed wound healing. Oral zinc supplementation may be beneficial in treating zinc-deficient leg ulcer patients, but its therapeutic place in surgical patients needs further clarification. Topical administration of zinc appears to be superior to oral therapy due to its action in reducing superinfections and necrotic material via enhanced local defense systems and collagenolytic activity, and the sustained release of zinc ions that stimulates epithelialization of wounds in normozincemic individuals. Zinc oxide in paste bandages (Unna boot) protects and soothes inflamed peri-ulcer skin. Zinc is transported through the skin from these formulations, although the systemic effects seem insignificant. We present here the first comprehensive account of zinc in wound management in relation to current concepts of wound bed preparation and the wound-healing cascade. This review article suggests that topical zinc therapy is underappreciated even though clinical evidence emphasizes its importance in autodebridement, anti-infective action, and promotion of epithelialization.
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              Understanding and controlling the bone-implant interface.

              D Puleo (1999)
              A goal of current implantology research is to design devices that induce controlled, guided, and rapid healing. In addition to acceleration of normal wound healing phenomena, endosseous implants should result in formation of a characteristic interfacial layer and bone matrix with adequate biomechanical properties. To achieve these goals, however, a better understanding of events at the interface and of the effects biomaterials have on bone and bone cells is needed. Such knowledge is essential for developing strategies to optimally control osseointegration. This paper reviews current knowledge of the bone-biomaterial interface and methods being investigated for controlling it. Morphological studies have revealed the heterogeneity of the bone-implant interface. One feature often reported, regardless of implant material, is an afibrillar interfacial zone, comparable to cement lines and laminae limitantes at natural bone interfaces. These electron-dense interfacial layers are rich in noncollagenous proteins, such as osteopontin and bone sialoprotein. Several approaches, involving alteration of surface physicochemical, morphological, and/or biochemical properties, are being investigated in an effort to obtain a desirable bone-implant interface. Of particular interest are biochemical methods of surface modification, which immobilize molecules on biomaterials for the purpose of inducing specific cell and tissue responses or, in other words, to control the tissue-implant interface with biomolecules delivered directly to the interface. Although still in its infancy, early studies indicate the value of this methodology for controlling cell and matrix events at the bone-implant interface.
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                Author and article information

                Contributors
                Journal
                Bioact Mater
                Bioact Mater
                Bioactive Materials
                KeAi Publishing
                2452-199X
                27 October 2019
                December 2019
                27 October 2019
                : 4
                : 312-321
                Affiliations
                [a ]Dept. of Biomaterials, FunGlass - Centre for Functional and Surface Functionalized Glass, Alexander Dubček University of Trenčín, Slovakia
                [b ]Central Laboratories, FunGlass - Centre for Functional and Surface Functionalized Glass, Alexander Dubček University of Trenčín, Slovakia
                [c ]Institute of Biomaterials, Department of Materials Science and Engineering, University of Erlangen, Nuremberg, Germany
                Author notes
                []Corresponding author. aldo.boccaccini@ 123456fau.de
                Article
                S2452-199X(19)30048-9
                10.1016/j.bioactmat.2019.10.002
                6833310
                31709314
                194757e4-9c22-4123-a6eb-9d539a25a49a
                .

                This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

                History
                : 15 June 2019
                : 19 September 2019
                : 7 October 2019
                Categories
                Article

                bioactive particles,sol-gel synthesis,zinc,bioactivity,ion release,bioactive glass

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