Synthesis and characterization of Barium–Iron containing magnetic bioactive glasses: The effect of magnetic component on structure and in vitro bioactivity

Highlights

• Synthesis of CaO-P₂O₅-SiO₂-BaO-Fe₂O₃ bioactive glasses.

• All the tested samples showed the growth of nonstoichiometric HAp on their surface after 14 days of immersion in SBF.

• pH has shown a significant increase as the soaking duration increases.

• Narrow distribution of bioactive glass particle sizes.

Abstract

CaO-P₂O₅-SiO₂-BaO-Fe₂O₃ magnetic bioactive glasses were prepared via an optimized sol–gel method. This study is focused on investigating effects of magnetic content addition on the bioactive glass properties. To this aim, we evaluate the physical, rheological, and biocompatibility properties of synthesized magnetic bioactive glass. The morphology and composition of these glasses were studied using X-ray Diffraction (XRD), Scanning Electron Microscopy (SEM), and Transmission Electron Microscopy (TEM). The particle size was also determined using Laser Particle Size Analyzer (LPSA). The thermal measurements were carried out using Differential Thermal Analysis (DTA). For assessing the in-vitro bioactive character of synthesized glasses, the ability for apatite formation on their surface upon immersion in simulated body fluid (SBF) was checked using SEM, EDX and pH measurements. Furthermore, the Ca, Si, Ba and Fe ions in SBF were monitored using Inductively Coupled Plasma-Atomic Emission Spectrometry (ICP-AES). The results showed that the addition of Ba and Fe in the glass composition affect formation of apatite layer onto the glass surfaces. Morphologies of the apatite layers were also different in which the bioactivity decreased with increasing Fe concentration, but the increase of Ba concentration led to an increase in bioactivity. However all of the synthesized glasses are still highly bioactive. Finally, this research demonstrates that the synthesized magnetic bioactive glasses are nontoxic and biocompatible and they can be used as thermoseeds for cancer hyperthermia studies.

Introduction

Since the discovery of Bioglass by Hench in the late 1960s [1], a variety of bioactive glasses have been developed for clinical applications because they are not only biocompatible, but also bioactive, i.e., they are osteoconductive, osteoinductive, angiogenic and antibacterial [[2], [3], [4]]. It has been long known that when a bioactive glass is implanted in human body, an hydroxyl carbonate apatite layer may form on its surface, which chemically bonds with living bone [[5], [6], [7], [8], [9], [10], [11]]. Moreover, several studies have shown that some bioglass compositions are also capable of bonding to soft tissues [12].

Despite its attractive properties, bioactive glasses lack the desirable magnetic properties, displayed by only a few crystalline phases. To combine bioactivity, solubility and magnetic properties in the same material is a rather difficult problem. However, glass-ceramics may be the solution. Glass-ceramics are polycrystalline materials produced by the controlled crystallization of glasses [13]. Since their accidental discovery by Stookey in the early 1950’s [14], glass-ceramics gained scientific importance and have been used in several commercial applications. The conventional way to synthesize a glass–ceramic is the melt-quenching technique, followed by a single or double-stage heat treatment, providing the nucleation and growth of specific crystalline phases. The phase(s) present, crystallized fraction percentage, nano- or micro structure, and therefore the material’s properties, can be tailored to specific purposes [15].

Crystallization of bioactive glasses does not necessarily transform them into inert materials, even when full crystallization is reached [16]. Recently, development of bioactive glass-ceramics exhibiting magnetic properties has received much attention as “thermoseeds” for hyperthermia treatment of cancer, especially deep-seated bone tumors. Generally, these deep-regional tumors are effectively heated and destroyed at temperatures around 42–45 °C, without the damage of normal tissue [17]. When glass-ceramic particles containing a magnetic phase are implanted around tumors and then subjected to alternating magnetic fields of high frequency, these materials produce sufficient heat by hysteresis and eddy current losses. Such magnetic heat generation depends upon various factors: the magnetic properties of the material, the amount of magnetic phase, the strength and frequency of the applied alternating magnetic field, the microstructure and particle size of the ferromagnetic bioactive glass-ceramic [[18], [19], [20], [21]].

The conventional way to synthesis glass–ceramics is the melt-quenching and subsequent heat treatment technique, but in recent years, other synthesis methods like sol–gel and solid-state reaction have been examined [20,22]. In 1983, Luderer et al. [23] were the first authors to mention a ferromagnetic glass-ceramic as thermoseeds for cancer hyperthermia. Their glass-ceramic contained lithium ferrite (LiFe₅O₈) and hematite (Fe₂O₃) crystals. This glass-ceramic was not bioactive. The heat generation of these materials was not high enough to kill the malignant carcinoma in rats [23]. Therefore, it became clear that ferromagnetic thermoseeds having higher heat generating power were required.

The magnetic properties of ferromagnetic glass-ceramics are usually investigated using Vibrating Sample Magnetometer (VSM) or Superconducting Quantum Interference Device (SQUID) magnetometer at room temperature. The magnetic hysteresis loops of glass-ceramic samples are normally measured using two different external magnetic fields: one very intensive (≥10 kOe), and the other one much lower (500 Oe). The intense magnetic field is sufficient for the evaluation of saturation magnetization. Low-field measurements had been chosen for being more appropriate for a clinical laboratory [18]. Also, in ferromagnetic glass-ceramic samples, magnetic heat generation or calorimetric measurements are commonly performed using a magnetic induction furnace operating generally at a magnetic field of 500 Oe and a frequency of ∼400 kHz [18,24].

Leenakul et al. [17] prepared ferromagnetic bioactive glass-ceramics from the BaFe₁₂O₁₉(BF)–SiO₂–CaO–Na₂O–P₂O₅ (45S5) system using the incorporation method [17]. From structural characterization, two major phases, sodium calcium silicate (Na₂Ca₂Si₃O₉) and barium iron oxide (BaFe₁₂O₁₉) were identified in all of the sintered samples containing BF [17]. In order to evaluate the potential of these glass-ceramics for hyperthermia treatment of cancer, magnetic hysteresis loops of the samples were obtained. It was found that the saturation magnetization increases with an increase in the BF content because of its dependence on the magnetic phase concentration. On the other hand, since the BF crystallite has a multi-domain structure, the coercivity of the glass-ceramics decreases with higher amounts of BF present in the samples. Moreover, it is clearly shown that, for an applied field of ±10 kOe, the area of the hysteresis loop increases with the content of barium ferrite from 5 wt.% to 40 wt.% [17]. In vitro bioactivity investigation in SBF for 14 days confirmed that all of the glass ceramics possess good bioactivity with the formation of a bone-like apatite phase. Also, it was found that the bioactivity increased with an increase in BF contents [17]. Hence, the addition of BF into bioglass 45S5 can improve both the magnetic properties and bioactivity of the glass materials [17].

Generally, ferromagnetic bioactive glass-ceramics have dual properties: they generate heat under (externally applied) alternating magnetic fields and have the capability to bond with the living tissues by forming a biologically active hydroxyapatite layer. Thus, these materials cannot only be used for hyperthermia treatment of cancer, but also as a substitute for a cancerous-damaged bone [18,25]. Due to the bioactivity and magnetic properties, various kinds of ferromagnetic bioactive glass-ceramics have been investigated.

In this study we synthesize a new Barium–Iron containing magnetic bioactive glasses with sol-gel method and we report the effect of magnetic components on structural properties and in vitro bioactivity of bioactive glasses. The obtained glasses were evaluated by XRD, FTIR, SEM, EDX, DTA, TEM and LPSA analyses. Furthermore, we carried out in vitro biomineralization and biocompatibility studies in SBF at 37 °C and in direct contact with L929 fibroblast cells, respectively. The changes in SBF composition during soaking time was studied using ICP-AES, therefore the reacted solution was saved for ICP-AES analysis of Ca, P, Si, Fe and Ba to measure ionic concentration in the SBF solution. We also monitored the pH changes in SBF during soaking time. The physicochemical properties of the formed phases on the surface of the magnetic bioactive glass was investigated using XRD, SEM and EDX analyses.