Mechanical properties of bioactive glasses, ceramics, glass-ceramics and composites: State-of-the-art review and future challenges.

The repair and restoration of bone defects in orthopaedic and dental surgery remains a major challenge despite advances in surgical procedures and post-operative treatments. Bioactive glasses, ceramics, glass-ceramics and composites show considerable potential for such applications as they can promote bone tissue regeneration. This paper presents an overview of the mechanical properties of various bioactive materials, which have the potential for bone regeneration. It also identifies current strategies for improving the mechanical properties of these novel materials, as these are rarely ideal as direct replacements for human bone. For this reason bioactive organic-inorganic composites and hybrids that have tailorable mechanical properties are of particular interest. The inorganic component (bioactive glass, ceramic or glass-ceramic) can provide both strength and bioactivity, while the organic component can add structural reinforcement, toughness and processability. Another topic presented in this paper includes 3D porous scaffolds that act as a template for cell attachment, proliferation and bone growth. Mechanical limitations of existing glass and ceramic scaffolds are discussed, along with the relevant challenges and strategies for further improvement. Advantages and disadvantages of different bioactive materials are critically examined. This paper is focused on optimization of biomaterials properties, in particular mechanical properties and bioactivity.

Glass-ceramics for cancer treatment: So close, or yet so far?

After years of research on the ability of glass-ceramics in bone regeneration, this family of biomaterials has shown revolutionary potentials in a couple of emerging applications such as cancer treatment. Although glass-ceramics have not yet reached their actual potential in cancer therapy, the relevant research activity is significantly growing in this field. It has been projected that this idea and the advent of magnetic bioactive glass-ceramics and mesoporous bioactive glasses could result in major future developments in the field of cancer. Undoubtedly, this strategy needs further developments to better answer the critical questions essential for clinical usage. This review aims to address the existing research developments on glass-ceramics for cancer treatment, starting with the current status and moving to future advances. STATEMENT OF SIGNIFICANCE: Although glass-ceramics have not yet reached their potential in cancer therapy, research activity is significantly growing. It has been speculated that this idea and the advent of modern glass-ceramics could result in significant future advances. Undoubtedly, this strategy needs further investigations and many critical questions have to be answered before it can be successfully applied for cancer treatment. This paper reviews the current state-of-the-art, starting with current products and moving onto recent developments in this field. According to our knowledge, there is a lack of a systematic review on the importance and developments of magnetic bioactive glass-ceramics and mesoporous bioactive glasses for cancer treatment, and it is expected that this review will be of interest to those working in this area.

In vitro biocompatibility of a ferrimagnetic glass-ceramic for hyperthermia application.

Ferrimagnetic glass-ceramics containing magnetite crystals were developed for hyperthermia applications of solid neoplastic tissue. The present work is focused on in vitro evaluation of the biocompatibility of these materials, before and after soaking in a simulated body fluid (SBF). X-ray diffraction, scanning electron microscopy, atomic absorption spectrophotometry, X-ray photoelectron spectrometry and pH measurements were employed in glass-ceramic characterisation. The free-radical mediated reactivity of the glass-ceramic was evaluated by Electron Paramagnetic Resonance (EPR) spin trapping. Cell adhesion and proliferation tests were carried out by using 3T3 murine fibroblasts. Cytotoxicity was performed by qualitative evaluation of human bone osteosarcoma cells U2OS cell line. The results show that almost two times more 3T3 cells proliferated on the samples pre-treated in SBF, compared with the untreated specimens. Moreover a decrease of confluence was observed at 48 and 72h for U2OS cells exposed to the untreated glass-ceramic, while the powder suspensions of glass-ceramic pre-treated in SBF did not influence the cell morphology up to 72h of exposition. The untreated glass-ceramic exhibited Fenton-like reactivity, as well as reactivity towards formate molecule. After pre-treatment with SBF the reactivity towards formate was completely suppressed. The concentration of iron released into the SBF solution was below 0.1ppm at 37°C, during one month of soaking. The different in vitro behaviour of the samples before and after SBF treatment has been correlated to the bioactive glass-ceramic surface modifications as detected by morphological, structural and compositional analyses.

Development of multisubstituted hydroxyapatite nanopowders as biomedical materials for bone tissue engineering applications.

Ionic substitutions have been proposed as a tool to control the functional behavior of synthetic hydroxyapatite (HA), particularly for Bone Tissue Engineering applications. The effect of simultaneous substitution of different levels of carbonate (CO3 ) and silicon (Si) ions in the HA lattice was investigated. Furthermore, human bone marrow-derived mesenchymal stem cells (hMSCs) were cultured on multi-substituted HA (SiCHA) to determine if biomimetic chemical compositions were osteoconductive. Of the four different compositions investigates, SiCHA-1 (0.58 wt % Si) and SiCHA-2 (0.45 wt % Si) showed missing bands for CO3 and Si using FTIR analysis, indicating competition for occupation of the phosphate site in the HA lattice; 500°C was considered the most favorable calcination temperature as: (i) the powders produced possessed a similar amount of CO3 (2-8 wt %) and Si (<1.0 wt %) as present in native bone; and (ii) there was a minimal loss of CO3 and Si from the HA structure to the surroundings during calcination. Higher Si content in SiCHA-1 led to lower cell viability and at most hindered proliferation, but no toxicity effect occurred. While, lower Si content in SiCHA-2 showed the highest ALP/DNA ratio after 21 days culture with hMSCs, indicating that the powder may stimulate osteogenic behavior to a greater extent than other powders. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 1775-1785, 2017.

Composite bone cements loaded with a bioactive and ferrimagnetic glass-ceramic. Part I: Morphological, mechanical and calorimetric characterization.

Hyperthermia is a technique for destroying cancer cells which involves the exposition of body's tissue to a controlled heat, normally between 41℃ and 46℃. It has been reported that ferro- or ferrimagnetic materials can heat locally, if they are placed (after being implanted) under an alternating magnetic field, damaging only tumoral cells and not the healthy ones. The power loss produced by the magnetic materials can be dissipated in the form of heat. This phenomenon has to be regulated in order to obtain a controlled temperature inside the tissues. The material that was produced and characterized in this work is composed of two phases: a polymethylmethacrylate (PMMA) matrix in which a ferrimagnetic biocompatible/bioactive glass ceramic is dispersed. This composite material is intended to be applied as bone filler for the hyperthermic treatment of bone tumors. The ferrimagnetic bioactive glass-ceramic belongs to the system SiO2-Na2O-CaO-P2O5-FeO-Fe2O3 and contains magnetite (FeO*Fe2O3) inside an amorphous bioactive residual phase. The composite material possesses structural, magnetic and bioactivity properties. The structural ones are conferred by PMMA which acts as filler for the bone defect or its damaged area. Bioactivity is conferred by the composition of the residual amorphous phase of the glass-ceramic and magnetic properties are conferred by magnetite crystals embedded in the bioactive glass-ceramic. The characterization involved the following tests: morphological and chemical characterization (scanning electron microscopy-energy dispersion spectrometry-micro computed tomography analysis), calorimetric tests and mechanical test (compression and flexural four point test). In vitro assessment of biological behavior will be the object of the part II of this work.

Resorbable glass-ceramic phosphate-based scaffolds for bone tissue engineering: synthesis, properties, and in vitro effects on human marrow stromal cells.

Highly porous bioresorbable glass-ceramic scaffolds were prepared via sponge replication method by using an open-cell polyurethane foam as a template and phosphate-based glass powders. The glass, belonging to the P2O5-SiO2-CaO-MgO-Na2O-K2O system, was synthesized by a melting-quenching route, ground, and sieved to obtain powders with a grain size of less than 30 µm. A slurry containing glass powders, polyvinyl alcohol, and water was prepared to coat the polymeric template. The removal of the polymer and the sintering of the glass powders were performed by a thermal treatment, in order to obtain an inorganic replica of the template structure. The structure and properties of the scaffold were investigated from structural, morphological, and mechanical viewpoints by means of X-ray diffraction, scanning electron microscopy, density measurements, image analysis, and compressive tests. The scaffolds exhibited a trabecular architecture that closely mimics the structure of a natural spongy bone. The solubility of the porous structures was assessed by soaking the samples in acellular simulated body fluid (SBF) and Tris-HCl for different time frames and then by assessing the scaffold weight loss. As far as the test in SBF is concerned, the nucleation of hydroxyapatite on the scaffold trabeculae demonstrates the bioactivity of the material. Biological tests were carried out using human bone marrow stromal cells to test the osteoconductivity of the material. The cells adhered to the scaffold struts and were metabolically active; it was found that cell differentiation over proliferation occurred. Therefore, the produced scaffolds, being biocompatible, bioactive, resorbable, and structurally similar to a spongy bone, can be proposed as interesting candidates for bone grafting.

Foam-like scaffolds for bone tissue engineering based on a novel couple of silicate-phosphate specular glasses: synthesis and properties.

Glass-ceramic scaffolds mimicking the structure of cancellous bone were produced via sponge replication technique by using a polyurethane foam as template and glass powder below 30 lm as inorganic phase. Specifically, a SiO2-based glass of complex composition and its corresponding P2O5-based "specular" glass were used as materials for scaffolding. The polymeric sponge was thermally removed and the glass powders were sintered to obtain a replica of the template structure. The scaffolds were investigated and compared from a structural, morphological and mechanical viewpoint by assessing their crystalline phases, volumetric shrinkage, pores content and interconnection, mechanical strength. In addition, the scaffolds were soaked in acellular simulated body fluid to investigate their in vitro behaviour. The produced scaffolds have a great potential for bone reconstructive surgery because their features, such as shape, strength, bioactivity and bioresorption, can be easily tailored according to the end use.

In vitro biocompatibility of 45S5 Bioglass-derived glass-ceramic scaffolds coated with poly(3-hydroxybutyrate).

The aim of this work was to study the in vitro biocompatibility of glass-ceramic scaffolds based on 45S5 Bioglass, using a human osteosarcoma cell line (HOS-TE85). The highly porous scaffolds were produced by the foam replication technique. Two different types of scaffolds with different porosities were analysed. They were coated with a biodegradable polymer, poly(3-hydroxybutyrate) (P(3HB)). The scaffold bioactivity was evaluated by soaking in a simulated body fluid (SBF) for different durations. Compression strength tests were performed before and after immersion in SBF. These experiments showed that the scaffolds are highly bioactive, as after a few days of immersion in SBF a hydroxyapatite-like layer was formed on the scaffold's surface. It was also observed that P(3HB)-coated samples exhibited higher values of compression strength than uncoated samples. Biocompatibility assessment was carried out by qualitative evaluation of cell morphology after different culture periods, using scanning electron microscopy, while cell proliferation was determined by using the AlamarBlue assay. Alkaline phosphatase (ALP) and osteocalcin (OC) assays were used as quantitative in vitro indicators of osteoblast function. Two different types of medium were used for ALP and OC tests: normal supplemented medium and osteogenic medium. HOS cells were seeded and cultured onto the scaffolds for up to 2 weeks. The AlamarBlue assay showed that cells were able to proliferate and grow on the scaffold surface. After 7 days in culture, the P(3HB)-coated samples had a higher number of cells on their surfaces than the uncoated samples. Regarding ALP- and OC-specific activity, no significant differences were found between samples with different pore sizes. All scaffolds containing osteogenic medium seemed to have a slightly higher level of ALP and OC concentration. These experiments confirmed that Bioglass/P(3HB) scaffolds have potential as osteoconductive tissue engineering substrates for maintenance and normal functioning of bone tissue.

Matrix-assisted pulsed laser evaporation of poly(D,L-lactide) for biomedical applications: effect of near infrared radiation.

The deposition of thin films of poly(D,L-lactide) (PDLLA) by using the matrix-assisted pulsed laser evaporation (MAPLE) technique is investigated. PDLLA is a highly biocompatible and biodegradable polymer, with wide applicability in the biomedical field. The laser wavelength used in the MAPLE process is optimized to obtain a good-quality deposition. The structure of the polymer film is analyzed by Fourier transform infrared spectroscopy (FTIR). It is found that the chemical structure of PDLLA undergoes little or no damage during deposition with near-infrared laser radiation (1064 nm). It is thus confirmed that at this wavelength, the MAPLE technique can be applied for fragile biopolymer molecules, which are easily damaged by other laser radiations (UV radiation). This method allows future development of tailored polymer coatings for biomedical applications.