Correlating the Effect of Composition and Textural Properties on Bioactivity for Pristine and Copper-Doped Binary Mesoporous Bioactive Glass Nanoparticles.

Multifunctional substitutes for bone tissue engineering have gained significant interest in recent years in the aim to address the clinical challenge of treating large bone defects resulting from surgical procedures. Sol-gel mesoporous bioactive glass nanoparticles (MBGNs) have emerged as a promising solution due to their high reactivity and versatility. The effect of calcium content on MBGNs textural properties is well known. However, the relationship between their composition, textural properties, and reactivity has not yet been thoroughly discussed in existing studies, leading to divergent conclusions. In this study, pristine and copper-doped binary MGBNs were synthesized by a modified Stöber method, using a cationic surfactant as pore-templating agent. An opposite evolution between calcium content (12-26 wt%) and specific surface area (909-208 m2/g) was evidenced, while copper introduction (8.8 wt%) did not strongly affect the textural properties. In vitro bioactivity assessments conducted in simulated body fluid (SBF) revealed that the kinetics of hydroxyapatite (HAp) crystallization are mainly influenced by the specific surface area, while the composition primarily controls the quantity of calcium phosphate produced. The MBGNs exhibited a good bioactivity within 3 h, while Cu-MBGNs showed HAp crystallization after 48 h, along with a controlled copper release (up to 84 ppm at a concentration of 1 mg/mL). This comprehensive understanding of the interplay between composition, textural properties, and bioactivity, offers insights for the design of tailored MBGNs for bone tissue regeneration with additional biological and antibacterial effects.

Magnetic bioactive glass nano-heterostructures: a deeper insight into magnetic hyperthermia properties in the scope of bone cancer treatment.

Primary bone cancers commonly involve surgery to remove the malignant tumor, complemented with a postoperative treatment to prevent cancer resurgence. Studies on magnetic hyperthermia, used as a single treatment or in synergy with chemo- or radiotherapy, have shown remarkable success in the past few decades. Multifunctional biomaterials with bone healing ability coupled with hyperthermia property could thus be of great interest to repair critical bone defects resulting from tumor resection. For this purpose, we designed superparamagnetic and bioactive nanoparticles (NPs) based on iron oxide cores (γ-Fe2O3) encapsulated in a bioactive glass (SiO2-CaO) shell. Nanometric heterostructures (122 ± 12 nm) were obtained through a two-step process: co-precipitation of 16 nm sized iron oxide NPs, followed by the growth of a bioactive glass shell via a modified Stöber method. Their bioactivity was confirmed by hydroxyapatite growth in simulated body fluid, and cytotoxicity assays showed they induced no significant death of human mesenchymal stem cells after 7 days. Calorimetric measurements were carried out under a wide range of alternating magnetic field amplitudes and frequencies, considering clinically relevant parameters, and some were made in viscous medium (agar) to mimic the implantation conditions. The experimental specific loss power was predictable with respect to the Linear Response Theory, and showed a maximal value of 767 ± 77 W gFe-1 (769 kHz, 23.9 kA m-1 in water). An interesting value of 166 ± 24 W gFe-1 was obtained under clinically relevant conditions (157 kHz, 23.9 kA m-1) for the heterostructures immobilized in agar. The good biocompatibility, bioactivity and heating ability suggest that these γ-Fe2O3@SiO2-CaO NPs are a promising biomaterial to be used as it is or included in a scaffold to heal bone defects resulting from bone tumor resection.

Elaboration of Superparamagnetic and Bioactive Multicore-Shell Nanoparticles (γ-Fe2O3@SiO2-CaO): A Promising Material for Bone Cancer Treatment.

The past few decades have seen the development of new bone cancer therapies, triggered by the discovery of new biomaterials. When the tumoral area is small and accessible, the common clinical treatment implies the tumor mass removal followed by bone reconstruction or consolidation with a bioceramic or a metallic scaffold. Even though the treatment also involves chemotherapy or radiotherapy, resurgence of cancer cells remains possible. We have thus designed a new kind of heterostructured nanobiomaterial, composed of SiO2-CaO bioactive glass as the shell and superparamagnetic γ-Fe2O3 iron oxide as the core in order to combine the benefits of bone repair thanks to the glass bioactivity and cancer cell destruction through magnetic hyperthermia. These multifunctional core-shell nanoparticles (NPs) have been obtained using a two-stage procedure, involving the coprecipitation of 11 nm sized iron oxide NPs followed by their encapsulation inside a bioactive glass shell by sol-gel chemistry. The as-produced spherical multicore-shell NPs show a narrow size distribution of 73 ± 7 nm. Magnetothermal loss measurements by calorimetry under an alternating magnetic field and in vitro bioactivity assessment performed in simulated body fluid showed that these heterostructures exhibit a good heating capacity and a fast mineralization process (hydroxyapatite forming ability). In addition, their in vitro cytocompatibility, evaluated in the presence of human mesenchymal stem cells during 3 and 7 days, has been demonstrated. These first findings suggest that γ-Fe2O3@SiO2-CaO heterostructures are a promising biomaterial to fill bone defects resulting from bone tumor resection, as they have the ability to both repair bone tissue and act as thermoseeds for cancer therapy.

Unravelling the Impact of Calcium Content on the Bioactivity of Sol-Gel-Derived Bioactive Glass Nanoparticles.

Sol-gel-derived bioactive glass nanoparticles (BGNs) are fascinating materials for bone regeneration. In the literature, it can be found that their specific surface area and their calcium content (Ca/Si ratio) are the two key parameters impacting strongly the particles' bioactivity. Nevertheless, in most studies, in vitro bioactivity tests are performed on a series of materials where both the composition and the specific surface area are varied. It is thus difficult to unravel the effect of each parameter independently. In this study, spherical and monodispersed BGNs with different Ca/Si ratios and a similar specific surface area have been synthesized by a modified Stöber method in order to specify the impact of the calcium content only. The mineralization studies performed in simulated body fluid showed that the bioactivity increases with the amount of calcium incorporated in the glass matrix. However, this effect is not significant in the composition interval studied (7-15% mol of CaO). Such a result proves that the effective Ca/Si ratio is not the major parameter that affects the bioactivity of sol-gel binary BGs. In vitro biocompatibility assessment during 3 and 7 days using human mesenchymal stem cells in contact with the sample showing the fastest mineralization proved its noncytotoxicity. Hence, biomedical applications can be intended for this sample.

Deeper Insights into a Bioactive Glass Nanoparticle Synthesis Protocol To Control Its Morphology, Dispersibility, and Composition.

The aim of this study was to investigate the effect of three synthesis parameters on the morphology and composition of nanosized binary bioactive glass particles (nBGPs) obtained through a modified Stöber process. Syntheses were conducted by varying only one parameter at a time while keeping the other parameters constant. As already mentioned in the literature, the ammonium hydroxide volume conditioned the size of the nanoparticles. Nonagglomerated monodispersed spherical particles with a diameter between 70 and 452 nm were produced. The quantity of calcium nitrate and the moment it was introduced in the sol had a tremendous impact on the quantity of calcium inserted and on the particle morphology and aggregation state. High Ca-content particles were obtained when the calcium precursor addition time was 1 h or less after the beginning of the sol-gel reaction but at the cost of a strong aggregation. A better control on the morphology, polydispersity and dispersibility of the nBGPs was achieved when the Ca(NO3)2 addition time was increased up to 6 h. However, a significant decrease of the quantity of Ca2+ inserted was also noticed. Using an intermediate (3 h) addition time, the quantity of calcium nitrate has been optimized to maximize the insertion of Ca2+ ions inside the silica particles. Finally, an optimum initial Ca/Si atomic ratio of 2, maximizing Ca insertion while limiting the salt quantity used, was found. It led to the synthesis of particles with a molar composition of 0.9SiO2-0.1CaO without any side effect on the particle stability and morphological characteristics.

Cu-doping of calcium phosphate bioceramics: From mechanism to the control of cytotoxicity.

In this study, the Cu-doping mechanism of Biphasic Calcium Phosphate (BCP) was thoroughly investigated, as was its ionic release behavior, in order to elucidate cytotoxicity features of these bioceramics. BCP are composed of hydroxyapatite (Ca10(PO4)6(OH)2) and ß-TCP (Ca3(PO4)2). The two phases present two different doping mechanisms. Incorporation into the ß-TCP structure is achieved at around 700 °C thanks to a substitution mechanism leading to the Cu-doped Ca3-xCux(PO4)2 compound. Incorporation into the HAp structure is achieved thanks to an interstitial mechanism that is limited to a Cu-poor HAp phase for temperatures below 1100 °C (Ca10Cux(PO4)6(OH)2-2xO2x with x < 0.1). Above 1100 °C, the same interstitial mechanism leads to the formation of a Cu-rich HAp mixed-valence phase (Ca10Cu2+xCu+y(PO4)6(OH)2-2x-yO2x+y with x + y ∼ 0.5). The formation of both high-temperature Cu-doped α-TCP and Cu3(PO4)2 phases above 1100 °C induces a transformation into the Cu-rich HAp phase on cooling. The linear OCuO oxocuprate entity was confirmed by EXAFS spectroscopy, and the mixed Cu+/Cu2+ valence was evidenced by XPS analyses. Ionic releases (Cu+/Cu2+, Ca2+, PO42- and OH-) in water and in simulated body media were investigated on as-synthesized ceramics to establish a pretreatment before biological applications. Finally the cytotoxicity of pretreated disks was evaluated, and results confirm that Cu-doped BCP samples are promising bioceramics for bone substitutes and/or prosthesis coatings. STATEMENT OF SIGNIFICANCE: Biphasic Calcium Phosphates (BCP) are bioceramics composed of hydroxyapatite (HAp, Ca10(PO4)6(OH)2) and beta-Tricalium Phosphate (ß-TCP, Ca3(PO4)2). Because their chemical and mineral composition closely resembles that of the mineral component of bone, they are potentially interesting candidates for bone repair surgery. Doping can advantageously be used to improve their biological behaviors; however, it is important to describe the doping mechanism of BCP thoroughly in order to fully appraise the benefit of the doping process. The present paper scrutinizes in detail the incorporation of copper cation in order to correctly interpret the behavior of the Cu-doped bioceramic in biological fluid. The understanding of the copper doping mechanism, related to doping mechanism of others 3d-metal cations, makes it possible to explain the rates and kinetic of release of the dopant in biological medium. Finally, the knowledge of the behavior of the copper doped ceramic in biological environment allowed the tuning of its cytotoxicity properties. The present study resulted on pre-treated ceramic disks which have been evaluated as promising biocompatible ceramic for bone substitute and/or prosthesis coating: good adherence of bone marrow cells with good cell viability.

Bioactive Glass Nanoparticles: From Synthesis to Materials Design for Biomedical Applications.

Thanks to their high biocompatibility and bioactivity, bioactive glasses are very promising materials for soft and hard tissue repair and engineering. Because bioactivity and specific surface area intrinsically linked, the last decade has seen a focus on the development of highly porous and/or nano-sized materials. This review emphasizes the synthesis of bioactive glass nanoparticles and materials design strategies. The first part comprehensively covers mainly soft chemistry processes, which aim to obtain dispersible and monodispersed nanoparticles. The second part discusses the use of bioactive glass nanoparticles for medical applications, highlighting the design of materials. Mesoporous nanoparticles for drug delivery, injectable systems and scaffolds consisting of bioactive glass nanoparticles dispersed in a polymer, implant coatings and particle dispersions will be presented.