Tailoring of bioactive glass and glass-ceramics properties for in vitro and in vivo response optimization: a review.

Bioactive glasses are inorganic biocompatible materials that can find applications in many biomedical fields. The main application is bone and dental tissue engineering. However, some applications in contact with soft tissues are emerging. It is well known that both bulk (such as composition) and surface properties (such as morphology and wettability) of an implanted material influence the response of cells in contact with the implant. This review aims to elucidate and compare the main strategies that are employed to modulate cell behavior in contact with bioactive glasses. The first part of this review is focused on the doping of bioactive glasses with ions and drugs, which can be incorporated into the bioceramic to impart several therapeutic properties, such as osteogenic, proangiogenic, or/and antibacterial ones. The second part of this review is devoted to the chemical functionalization of bioactive glasses using drugs, extra-cellular matrix proteins, vitamins, and polyphenols. In the third and final part, the physical modifications of the surfaces of bioactive glasses are reviewed. Both top-down (removing materials from the surface, for example using laser treatment and etching strategies) and bottom-up (depositing materials on the surface, for example through the deposition of coatings) strategies are discussed.

Human T-Cell Responses to Metallic Ion-Doped Bioactive Glasses.

Biomaterials are extensively used as replacements for damaged tissue with bioactive glasses standing out as bone substitutes for their intrinsic osteogenic properties. However, biomaterial implantation has the following risks: the development of implant-associated infections and adverse immune responses. Thus, incorporating metallic ions with known antimicrobial properties can prevent infection, but should also modulate the immune response. Therefore, we selected silver, copper and tellurium as doping for bioactive glasses and evaluated the immunophenotype and cytokine profile of human T-cells cultured on top of these discs. Results showed that silver significantly decreased cell viability, copper increased the T helper (Th)-1 cell percentage while decreasing that of Th17, while tellurium did not affect either cell viability or immune response, as evaluated via multiparametric flow cytometry. Multiplex cytokines assay showed that IL-5 levels were decreased in the copper-doped discs, compared with its undoped control, while IL-10 tended to be lower in the doped glass, compared with the control (plastic) while undoped condition showed lower expression of IL-13 and increased MCP-1 and MIP-1ß secretion. Overall, we hypothesized that the Th1/Th17 shift, and specific cytokine expression indicated that T-cells might cross-activate other cell types, potentially macrophages and eosinophils, in response to the scaffolds.

The unexplored role of alkali and alkaline earth elements (ALAEs) on the structure, processing, and biological effects of bioactive glasses.

Bioactive glass has been employed in several medical applications since its inception in 1969. The compositions of these materials have been investigated extensively with emphasis on glass network formers, therapeutic transition metals, and glass network modifiers. Through these experiments, several commercial and experimental compositions have been developed with varying chemical durability, induced physiological responses, and hydroxyapatite forming abilities. In many of these studies, the concentrations of each alkali and alkaline earth element have been altered to monitor changes in structure and biological response. This review aims to discuss the impact of each alkali and alkaline earth element on the structure, processing, and biological effects of bioactive glass. We explore critical questions regarding these elements from both a glass science and biological perspective. Should elements with little biological impact be included? Are alkali free bioactive glasses more promising for greater biological responses? Does this mixed alkali effect show increased degradation rates and should it be employed for optimized dissolution? Each of these questions along with others are evaluated comprehensively and discussed in the final section where guidance for compositional design is provided.

Development of Super-Paramagnetic Iron Oxide Nanoparticle-Coated Melt Electrowritten Scaffolds for Biomedical Applications.

Polycaprolactone (PCL) is usually the material chosen for melt electrowriting (MEW) due to its biocompatibility, mechanical strength, and melt processability. This work first investigates the effect of different processing parameters to obtain optimum PCL-MEW scaffolds. Secondly, to increase PCL`s hydrophilicity and cell affinity, and to enable coating with superparamagnetic iron oxide nanoparticles (SPIONs) and silica-coated-SPIONs (Si-SPIONs), the scaffolds are modified with alkaline surface treatment. Finally, SPIONs and Si-SPIONs are successfully coated on MEW scaffolds. Results show that reproducible scaffolds are fabricated. Additionally, the alkaline treatment does not change the three-dimensional morphology of scaffolds while reducing fiber diameter. Furthermore, SEM images and ATR-FTIR results confirmed that SPIONs and Si-SPIONs-were coated on scaffolds. A cytocompatibility assay showed a non-toxic effect on MG-63 osteoblast-like cells in all scaffolds. Additionally, higher MC3T3-E1 pre-osteoblastic cell adhesion efficiency and proliferation are achieved for the alkaline-treated scaffolds and SPIONs/Si-SPIONs-coated scaffolds. All samples demonstrated the ability to generate heat, useful for hyperthermia-treatment, when subjected to an alternating magnetic field. Overall, the findings suggest that the strategy of coating PCL-MEW scaffolds with SPIONs/Si-SPIONs has the potential to improve scaffold performance for biomedical applications, especially for producing magnetically responsive MEW scaffolds.

3D bioprinting of multifunctional alginate dialdehyde (ADA)-gelatin (GEL) (ADA-GEL) hydrogels incorporating ferulic acid.

The present work explores the 3D extrusion printing of ferulic acid (FA)-containing alginate dialdehyde (ADA)-gelatin (GEL) scaffolds with a wide spectrum of biophysical and pharmacological properties. The tailored addition of FA (≤0.2 %) increases the crosslinking between FA and GEL in the presence of calcium chloride (CaCl2) and microbial transglutaminase, as confirmed using trinitrobenzenesulfonic acid (TNBS) assay. In agreement with an increase in crosslinking density, a higher viscosity of ADA-GEL with FA incorporation was achieved, leading to better printability. Importantly, FA release, enzymatic degradation and swelling were progressively reduced with an increase in FA loading to ADA-GEL, over 28 days. Similar positive impact on antibacterial properties with S. epidermidis strains as well as antioxidant properties were recorded. Intriguingly, FA incorporated ADA-GEL supported murine pre-osteoblast proliferation with reduced osteosarcoma cell proliferation over 7 days in culture, implicating potential anticancer property. Most importantly, FA-incorporated and cell-encapsulated ADA-GEL can be extrusion printed to shape fidelity-compliant multilayer scaffolds, which also support pre-osteoblast cells over 7 days in culture. Taken together, the present study has confirmed the significant potential of 3D bioprinting of ADA-GEL-FA ink to obtain structurally stable scaffolds with a broad spectrum of biophysical and therapeutically significant properties, for bone tissue engineering applications.

Tannic-acid-mediated synthesis and characterization of magnetite-gold nanoplatforms for photothermal therapy.

Aim: The design of new hybrid nanoplatforms (HNPs) through the innovative and eco-friendly use of tannic acid (TA) for the synthesis and stabilization of the nanoplatforms. Materials & methods: The size, morphology, composition and magnetic and plasmonic properties of HNPs were investigated together with their ability to generate heat under laser irradiation and the hemotoxicity to explore their potential use for biomedical applications. Results & conclusion: The use of TA allowed the synthesis of the HNPs by adopting a simple and green method. The HNPs preserved the peculiar properties of both magnetic and plasmonic nanoparticles and did not show any hemotoxic effect.

The aim of this research was to prepare new nanoparticles (called nanoplatforms) made from two parts: a magnetic core and the addition of gold particles. These particles can be used for cancer treatment because, when stimulated by light, they are able to release heat, which can kill cancer cells. In particular, in this work, we investigated the preparation of these particles using green methods, without the use of toxic reagents. The obtained nanoparticles were studied to investigate their size, shape, composition, magnetic properties, ability to generate heat and possible toxic effect toward blood cells. The results show that these particles can be produced with green methods, release heat and are not toxic.

UV-Cured Bio-Based Acrylated Soybean Oil Scaffold Reinforced with Bioactive Glasses.

In this study, a bio-based acrylate resin derived from soybean oil was used in combination with a reactive diluent, isobornyl acrylate, to synthetize a composite scaffold reinforced with bioactive glass particles. The formulation contained acrylated epoxidized soybean oil (AESO), isobornyl acrylate (IBOA), a photo-initiator (Irgacure 819) and a bioactive glass particle. The resin showed high reactivity towards radical photopolymerisation, and the presence of the bioactive glass did not significantly affect the photocuring process. The 3D-printed samples showed different properties from the mould-polymerised samples. The glass transition temperature Tg showed an increase of 3D samples with increasing bioactive glass content, attributed to the layer-by-layer curing process that resulted in improved interaction between the bioactive glass and the polymer matrix. Scanning electron microscope analysis revealed an optimal distribution on bioactive glass within the samples. Compression tests indicated that the 3D-printed sample exhibited higher modulus compared to mould-synthetized samples, proving the enhanced mechanical behaviour of 3D-printed scaffolds. The cytocompatibility and biocompatibility of the samples were evaluated using human bone marrow mesenchymal stem cells (bMSCs). The metabolic activity and attachment of cells on the samples' surfaces were analysed, and the results demonstrated higher metabolic activity and increased cell attachment on the surfaces containing higher bioactive glass content. The viability of the cells was further confirmed through live/dead staining and reseeding experiments. Overall, this study presents a novel approach for fabricating bioactive glass reinforced scaffolds using 3D printing technology, offering potential applications in tissue engineering.

Physical, Mechanical, and Biological Properties of PMMA-Based Composite Bone Cement Containing Silver-Doped Bioactive and Antibacterial Glass Particles with Different Particles Sizes.

In the present work, antibacterial composite bone cement was designed by introducing a bioactive and antibacterial glass into a commercial formulation. The effect of glass particles' addition on the curing parameters of the polymeric matrix was evaluated; moreover, the influence of the glass particle size on the glass dispersion, compressive and bending strength, bioactivity, and antibacterial effect was estimated. The results evidence a delay in the polymerization kinetics of the composite cement, which nevertheless complies with the requirements of the ISO standard. Morphological characterization provides evidence of good dispersion of the glass in the polymeric matrix and its exposition on the cement surface. The different glass grain sizes do not affect the composites' bioactivity and compressive strength, while a slight reduction in bending strength was observed for samples containing glass powders with greater dimensions. The size of the glass particles also appears to have an effect on the antibacterial properties, since the composites containing larger glass particles do not produce an inhibition halo towards the S. aureus strain. The obtained results demonstrate that, by carefully tailoring the glass amount and size, a multifunctional device for artificial joint fixing, temporary prostheses, or spinal surgery can be obtained.

Poly(ε-caprolactone)/bioactive glass composite electrospun fibers for tissue engineering applications.

In this work, composite electrospun fibers containing innovative bioactive glass nanoparticles were produced and characterized. Poly(ε-caprolactone), benign solvents, and sol-gel B- and Cu-doped bioactive glass powders were used to fabricate fibrous scaffolds. The retention of bioactive glass nanoparticles in the polymer matrix, the electrospinnability of this novel solution and the obtained electrospun composites were extensively characterized. As a result, composite electrospun fibers characterized by biocompatibility, bioactivity, and exhibiting overall properties adequate for both hard and soft tissue engineering applications, have been produced. The addition of these bioactive glass nanoparticles was, indeed, able to impart bioactive properties to the fibers. Cell culture studies show promising results, demonstrating proliferation and growth of cells on the composite fibers. Wettability, degradation rate, and mechanical performance were also tested and are in line with previous results.

Iron Oxide-Au Magneto-Plasmonic Heterostructures: Advances in Their Eco-Friendly Synthesis.

In recent years, nanotechnologies have attracted considerable interest, especially in the biomedical field. Among the most investigated particles, magnetic based on iron oxides and Au nanoparticles gained huge interest for their magnetic and plasmonic properties, respectively. These nanoparticles are usually produced starting from processes and reagents that can be the cause of potential human health and environmental concerns. For this reason, there is a need to develop simple, green, low-cost, and non-toxic synthesis methods and reagents. This review aims at providing an overview of the most recently developed processes to produce iron oxide magnetic nanoparticles, Au nanoparticles, and their magneto-plasmonic heterostructures using eco-friendly approaches, focusing the attention on the microorganisms and plant-assisted syntheses and showing the first results of the development of magneto-plasmonic heterostructures.