Elsevier

Journal of Non-Crystalline Solids

Volume 455, 1 January 2017, Pages 90-97
Journal of Non-Crystalline Solids

Novel ion-doped mesoporous glasses for bone tissue engineering: Study of their structural characteristics influenced by the presence of phosphorous oxide

https://doi.org/10.1016/j.jnoncrysol.2016.10.031Get rights and content

Abstract

Ion-doped binary SiO2-CaO and ternary SiO2-CaO-P2O5 mesoporous bioactive glasses were synthesized and characterized to evaluate the influence of P2O5 in the glass network structure. Strontium, copper and cobalt oxides in a proportion of 0.8 mol% were selected as dopants because the osteogenic and angiogenic properties reported for these elements. Although the four glass compositions investigated presented analogous textural properties, TEM analysis revealed that the structure of those containing P2O5 exhibited an increased ordered mesoporosity. Furthermore, 29Si NMR revealed that the incorporation of P2O5 increased the network connectivity and that this compound captured the Sr2 +, Cu2 + and Co2 + ions preventing them to behave as modifiers of the silica network. In addition, 31P NMR results revealed that the nature of the cation directly influences the characteristics of the phosphate clusters. In this study, we have proven that phosphorous oxide entraps doping-metallic ions, granting these glasses with a greater mesopores order.

Introduction

Bioactive glasses (BGs) are known to have an outstanding capability to stimulate bone regeneration [1] by their bone-bonding properties. Two processing methods are mainly used to prepare these glasses: the traditional melt-quenching process and the sol-gel technique. One of the main advantages of sol-gel glasses is their high bioactive behavior due to the rapid dissolution of this material originated from their fine porous structure and the important quantity of silanol groups present in their surface, which could act as nucleation sites for the formation of an apatite layer when in contact with simulated body fluid (SBF) [2], [3], [4]. Furthermore, in 2004 [5] a new generation of bioactive glasses, namely mesoporous bioactive glasses (MBGs), was introduced. MBGs are characterized by presenting tailored (ordered) porosity at the nanometer scale, which is created by combination of supramolecular chemistry of surfactants and sol-gel chemistry and opened new application fields to these materials, such as drug delivery. Research on the application of MBGs in tissue engineering and drug delivery has been accelerated in recent years as emphasized in recent reviews [6], [7], [8]. These materials, whose composition is mostly based on the SiO2-CaO-P2O5 system, have a highly ordered mesoporous structure, which induces an accelerated bioactive behavior and the capacity of confining drug molecules to be released in a controlled manner [6]. It has also been reported that the addition of phosphorous is not necessary to obtain silicate MBGs of high bioactivity [9]. However, P2O5 plays a significant role on the local structure of the MBGs network. In this sense, it has been reported that most of the phosphorous atoms are incorporated as orthophosphates within the silica network, thus resulting in the formation of small clusters with Ca2 + cations [10] that highly determines the bioactive behavior of these glasses.

During the last decade, metallic ions such as boron, copper, lithium, gallium, silver, strontium, cerium, cobalt and zinc, among others, have emerged as potential therapeutic agents with the ability to enhance bone formation by their stimulating effects on osteogenesis and angiogenesis [11], [12]. In recent studies, new compositions of mesoporous materials including the addition of therapeutic ions have been suggested in order to increase the materials' functionality and biological activity, particularly for applications in large-size bone defects, which are a significant clinical challenge [8]. A main property of some of the commonly used therapeutic ions such as boron, zinc, cerium and gallium, is that they are known to be osteogenic. Other functional properties such as angiogenesis and antibacterial activity can also be assigned to some therapeutic ions [8], [11], [12].

Notably, copper, strontium and cobalt ions have attracted particular interest as they have been reported to confer osteogenesis, angiogenesis and antibacterial properties to MBGs [8]. Cu2 + ions are known to stimulate the proliferation of endothelial cells, enhance cell activity and proliferation of osteoblastic cells, improve micro-vessel formation as well as to promote wound healing and to have antibacterial effects [8], [12], [13]. Furthermore, copper ions are not affected during scaffolds processing which involves high temperatures [14]. Sr2 + ions have been shown to promote osteoblast activity and to inhibit osteoclast differentiation, as well as to maintain excellent acellular bioactivity of the glasses [8], [12]. Furthermore, it has been observed that the release of Sr2 + ions also stimulates significantly ALP activity [8], [12]. Nevertheless, the doping amount within the glass must be carefully controlled as a high content of Sr will influence the glass network formation and decrease the degree of order of the mesoporous structure [8]. Co2 + ions are described in the literature as having angiogenic capacity determined by inducing a hypoxic cascade (including HIF-1α stabilization and VEGF secretion from hBMSCs) [15]. Generally, Co2 + ions are added to the composition in order to develop hypoxia-mimicking (low oxygen pressure environment) materials [8], [12], [15], [16]. It has been reported that by mimicking hypoxic condition, Co2 + ions could induce the coupling of osteogenesis and angiogenesis [15]. Nonetheless, it has also been reported that Co2 + ions lead easier to potential cytotoxicity compared to Cu2 + ions [8], an important aspect to be considered when doping the material with this ion. However, the role that even small amounts of these dopants can play on the mesoporous structure of MBG remains unclear.

In the present study, we attempt to demonstrate that the presence of phosphorous oxide in the composition allows capturing selected ionic dopants in the network, namely Sr and Co, thus conferring the material porosity of greater order. The incorporation of SrO and CuO in MBGs in an independent way has been previously reported in literature [8]. In the present investigation, both dopants were incorporated simultaneously with the aim of achieving a synergy role of both compounds for future biological assays. Results of structural characterization to elucidate the influence of the ion content on the developed MBGs are presented. Based on previous work performed on ion-doped glasses [17], [18], [19], [20], the range of substituent's concentration was chosen so that they did not inhibit or decrease the bioactivity of the MBGs. Moreover, the amounts of the leached ions (Cu2 +, Sr2 +, Co2 +) were chosen to be below the toxic level in blood plasma [8], [11], [12], [20].

Section snippets

Preparation of ion-doped mesoporous glasses

Ion-doped mesoporous glasses in the systems 78SiO2 20CaO 1.2P2O5 0.8Xion oxide and 79.2SiO2 20CaO 0.8Xion oxide (in mol%) were synthesized, keeping the total amount of ion constant. The glasses were doped on the one hand with a mixture of strontium and copper ions, on the other hand with cobalt ions. The MBGs were prepared by the evaporation-induced self-assembly method (EISA) [20], [21] and using Pluronic® F127 as structure-directing agent. Pluronic® F127 was dissolved overnight in 85 mL EtOH

Results and discussion

The developed samples SrCu/P2O5 and Co/P2O5 were heat treated at 700 °C. In order to confirm the amorphous state of the samples, XRD analyses were conducted. Results are shown in Fig. 1.

No diffraction peaks are observed from the XRD spectra (Fig. 1) of samples SrCu/P2O5 and Co/P2O5 indicating the amorphous state. A broad reflection in the range between 2θ = 20 and 35° is clearly noticed for both samples suggesting that no crystalline phase is developed within the sample. Similar curves were

Conclusions

Mesoporous bioactive glasses doped with Sr2 +/Cu2 + or Co2 + have been synthesized. In order to evaluate the role of P2O5 in the mesoporous structure, two series with and without P2O5 were prepared. The incorporation of a small amount (0.8 mol%) of Sr2 +/Cu2 + or Co2 + ions was shown to lead to defective mesoporous structures, as evidenced by TEM. However, when 1.2 mol% of P2O5 is present, the MBGs exhibited a highly ordered mesoporous structure. This fact is due to the capability of P2O5 to form

Acknowledgments

This study was supported by research grants from the Ministerio de Economía y Competitividad (projects MAT2013-43299-R and MAT2015-64831-R), European Research Council (ERC-2015-AdG). Advanced Grant Verdi-694160, Agening Network of Excellence (CSO2010-11384-E), Instituto de Salud Carlos III (PI15/00978), and EU-ITN project GlaCERCo (GA 264526). The authors thank the staff of the ICTS National Center for Electron Microscopy, UCM, Madrid (Spain) for the assistance in the scanning and transmission

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