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Historically the function of biomaterials was to replace diseased or damaged tissues. First generation biomaterials were selected to be as bio-inert as possible and thereby minimize formation of scar tissue at the interface with host tissues. Bioactive glasseswere discovered in 1969 and provided for the first time an alternative; strong, stable interfacial bonding of an implant with host tissues. In the 1980’s it was discovered that bioactive glasses could be used in particulae form to stimulate osteogenesiswhich thereby led to the concept of regeneration of tissues. This article summarizes the four eras of development of bioactive glasses that have led from concept of bioactivity to widespread clinical and commercial use, with emphasis on the first composition, 45S5 Bioglassr. The four eras are; A) Era of Discovery, B) Era of Clinical Application, C) Era of Tissue Regeneration, and D) Era of Innovation. Key scientific and technological questions answered for the first three eras are presented. Questions still to be answered for the fourth era are included to stimulate innovation in the field.

A new method of calcination for the sol-gel derived bioactive glass sample has been developed to produce superior textural and bioactive properties. Based on this method, mesoporous 67.4 SiO 2 -25 Na 2 O-5 CaO- 2.6 P 2 O 5 (mol.%) bioactive glasses (MBGs) have been synthesized through acid assisted sol-gel technique followed by evaporation induced self-assembly (EISA) process, commonly used for obtaining bioactive glasses. Moreover, the use of microwave irradiation has been compared with that of conventional heat treatment for a particular quaternary composition,which has allowed the homogeneous spatial distribution of heat and to obtain smaller, uniform pore sizes with high surface area. The distinctions between the two methods of calcination have been observed in the structural, morphology and textural characteristics. The superior textural characteristics have allowed the rapid dissolution of MBGs followed by development of nanocrystalline hydroxycarbonate apatite (HCA) layer. In vitro bioactive analyses on both MBGs have revealed a rapid formation HCA layer with distinct behavior on the biomineralization process. The difference in the behavior of biomineralization process is attributed to the kinetics of supersaturation of the biological medium.

In the last few years, optimal fixation of orthopaedic implants evolved to preserve host bone and enhance tissue integration by surface modifications, including the use of coatings with bioactive ceramics. In this work, we fabricated a novel bone-like porous bioactive glass-ceramic coating on curved alumina substrates; good joining between the two components was possible due to the interposition of a glass-derived dense interlayer. The mechanical properties of the porous glass-ceramic, which mimics the 3-D pore architecture of cancellous bone, are adequate for load-bearing applications (compressive strength of 19 MPa and fracture energy around 6.5×10 −4 J mm −3 , with a total porosity of 62 vol.%). In vitro bioactive behaviour was investigated by testing the samples in simulated body fluid and by evaluating the apatite formation on the surface and pore struts of the trabecular coating, which is a key precondition for in vivo osteointegration. The concepts disclosed in the present study could find interesting application in the context of orthopaedic implants, with particular reference to full-ceramic acetabular cups for hip joint prosthesis.

Phosphate glasses are novel amorphous biomaterials due to their fully resorbable characteristics, with controllable degradation profiles. In this study, phosphate glasses containing titanium and/or iron were identified to exhibit sufficiently matched thermal properties (glass transition temperature, thermal expansion coefficient and viscosity) which enabled successful co-extrusion of glass billets to form a core/clad preform. The cladding composition for the core/clad preforms were also reversed. Fe clad and Ti clad fibres were successfully drawn with an average diameter of between 30~50 μm. The average cladding annular thickness was estimated to be less than 2 μm. Annealed core/clad fibres were degraded in PBS for a period of 27 days. The strength of the Fe clad fibres appeared to increase from 303 ± 73 MPa to 386 ± 45 MPa after nearly 2 weeks in the dissolution medium (phosphate buffered solution) before decreasing by day 27. The strength of the Ti clad fibres revealed an increase from 236 ± 53 MPa to 295 ± 61 MPa when compared at week 3. The tensile modulus measured for both core/clad fibres ranged between 51 GPa to 60 GPa. During the dissolution study, Fe clad fibres showed a peeling mechanism compared to the Ti clad fibres.

Objectives. The aim was to introduce a new methodology to characterize toothpaste containing bioactive glass and to evaluate the effect of release of fluoride ions, by cleaving monofluorophosphate (MFP), on the mineral forming ability of Sensodyne Repair & Protect (SRP). which contains NovaMinTM (bioactive glass, 45S5 composition). Methods. SRP, NovaMin particles, and placebo paste (PLA) which did not contain NovaMin, were immersed into a remineralization media (RS), which mimics the ionic strength of human saliva, for 3 days with different concentrations of alkaline phosphatase (ALP): 0, 25 and 75 U.L −1 . Ion concentration profiles and pH were monitored by ICPOES and F− ion selective electrode. Remaining solids were collected by freeze-drying and their surfaces analysed. Results. Hydroxyapatite (HA) formed on the surface of BG alone (after 1 h) and in toothpaste (after 2 h), whereas PLA did not induce any precipitation. ALP cleaved MFP at different rates depending on the enzyme concentration. Increasing the concentration of ALP from 0 and 75 U.L −1 reduced the time of HA formation from 2 h to 24 h. However, the presence of fluoride induced the precipitation of fluorapatite. No evidence of fluorite (CaF2) was observed. The apatite formation ability of toothpaste can be assessed using the presented method.

Zinc is a vital and beneficial trace element found in the human body. Though found in small proportions, zinc performs a variety of functions in relation to the immune system, cell division, fertility and the body growth and maintenance. In particular, zinc is proven to be a necessary element for the formation, mineralization, development and maintenance of healthy bones. Considering this attractive attributes of zinc, recent research has widely focused on using zinc along with silicate-based bioactive glasses for bone tissue engineering applications. This paper reviews relevant literature discussing the significance of zinc in the human body, along with its ability to enhance antibacterial effects, bioactivity and distinct physical, structural and mechanical properties of bioactive glasses. In this context, even if the present analysis is not meant to be exhaustive and only representative studies are discussed, literature results confirm that it is essential to understand the properties of zinc-containing bioactive glasses with respect to their in vitro biological behavior, possible cytotoxic effects and degradation characteristics to be able to effectively apply these glasses in bone regeneration strategies. Topics attracting increasing research efforts in this field are elaborated in detail in this review, including a summary of the structural, physical, biological and mechanical properties of zinc-containing bioactive glasses. This paper also presents an overview of the various applications in which zinc-containing bioactive glasses are considered for use as bone tissue scaffolds, bone filling granules, bioactive coatings and bone cements, and advances and remaining challenges are highlighted.

Intrinsically radiopaque (imageable) microspheres for transarterial embolization (TAE) are required to enable real-time intraprocedural feedback and definition of spatial distribution patterns of embolic materials in target tissues. This pilot study evaluates acute and sub-chronic safety and efficacy of imageable zinc-silicate (Zn-Si) glass microspheres in a swine renal artery embolization (RAE) model. Eight swine were divided into two cohorts. Clinical determinants of embolization effectiveness, including imageability, deliverability and temporal/ spatial distribution of microspheres in target tissues were assessed. Subsequently, cohort I and II were used to evaluate the acute and subchronic host response against the Zn-Si microspheres versus a clinical control. The developed microspheres provide for direct intraprocedural feedback using standard diagnostic imaging techniques. Fluoroscopy correlated with ex-vivo high-resolution radiography, CT and micro-CT, demonstrating high imageability, excellent spatial distribution and packing of the Zn- Si microspheres. At follow-up, infarction of the embolized kidneys was noted without any major adverse tissue reaction. Mild recanalization was observed microscopically for both experimental and control microspheres. Zn-Si microspheres permit the definition of spatial distribution in a target tissue, consequently permitting the optimization, personalization and improvement of TAE techniques.

The 45S5 Bioglassr and its sintered bioactive glass-ceramic (BGC) have been widely investigated as bone implants, mainly for its ability to bond to hard tissues. However, high temperature treatment is not enough to improve its poor mechanical properties, but compromise its biologically relevant performances. The innovative BGC compositions based on the thermally treated 45S5 Bioglassr were developed by decreasing the P2O5 quantity and adding B2O3 (0-6%) into the Na2O–2CaO–3SiO2- based bioactive glasses (BG). The thermally treated BGCs were fully characterized from the microstructural and mechanical points of view and compared to each other. Their bioactivity and bio-dissolutionwere established by means of in vitro soaking tests. The new B2O3-added 45S5 BG analogues, named NCS-xB, can be transformed to crystalline phase (Na2Ca2Si3O9)-based BGCs of high compactness and bioactivity at a relatively low temperature heat treatment (≤ 900ºC), since their bioactivity is preserved. Our experimental results suggest that the new 45S5 BGC analogues with optimized composition exhibit improved micro- structural and mechanical properties, and are beneficial for making specific products such as porous scaffolds or composites for bone defect repair.

Ion release of Mg- and Zn-substituted Bioglass 45S5 (46.1 SiO2-2.6 P2O5-26.9 CaO-24.3Na2O; mol%; with 0, 25, 50, 75 or 100% of calcium replaced bymagnesium/zinc) was investigated at pH 7.4 (Tris buffer) and pH 4 (acetic acid/sodium acetate buffer) in static and dynamic dissolution experiments. Despite Mg2+ and Zn2+ having the same charge and comparable ionic radii, they influenced the dissolution behaviour in very different ways. In Tris, Mgsubstituted glasses showed similar ion release as 45S5, while Zn-substituted glasses showed negligible ion release. At low pH, however, release behaviour was similar, with all glasses releasing large percentages of ions within a few minutes. Precipitation of crystalline phases also varied, as Mg- and Zn-substitution inhibited apatite formation, and Zn-substitution resulted in formation of zinc phosphate phases at low pH. These results are relevant for glasses used in aluminium-free glass ionomer bone cements, as they show that Zn/Mg-substituted glasses release ions similarly fast as glasses containing no Zn/Mg, suggesting that these ions are no prerequisite for ionomer glasses. Zn-substituted glasses may potentially be used as controlled-release materials, which release antibacterial zinc ions when needed only, i.e. at low pH conditions (e.g. bacterial infection), but not at normal physiological pH conditions.

Addition of CaF2 to a silicate bioactive glass favours formation of fluorapatite, which is less soluble in acidic environment than hydroxyapatite. However, excess CaF2 in the glass is problematic, owing to the formation of crystalline calcium fluoride rather than fluorapatite on immersion. In this paper we investigate chloride as an alternative to fluoride in bioactive silicate glasses and in particular their bioactivity for the first time. Meltderived bioactive glasses based on SiO2-P2O5-CaO-CaCl2 with varying CaCl2 contents were synthesised and characterised by DSC. Chemical analysis of the chloride content was performed by using an ion selective electrode. Glass density was determined using Helium Pycnometry. The glass bioactivity was investigated in Tris buffer. Ion release measurements were carried out by using ICP-OES. The chemical analysis results indicated that the majority of the chloride is retained in the Q2 type silicate glasses during synthesis. Tg and glass density reduced with increasing CaCl2 content. Apatite-like phase formation was confirmed by FITR, XRD and 31P MAS-NMR. The results of the in vitro studies demonstrated that the chloride containing bioactive glasses are highly degradable and form apatite-like phase within three hours in Tris buffer and, therefore, are certainly suitable for use in remineralising toothpastes. The dissolution rate of the glass was found to increase with CaCl2 content. Faster dissolving bioactive glasses may be attractive for more resorbable bone grafts and scaffolds.

In this work, sintered pellets of a silica-based bioactive glass were dip-coated with a biocompatible natural-derived polymer in order to investigate the influence of the organic coating on the glass bioactivity. After the sintering process optimization, uncoated and coated pellets have been characterized by means of scanning electron microscopy with energy dispersive spectroscopy (SEM, EDS), X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FT-IR) and pH measurements, after the immersion in a simulated body fluid (SBF). An increased apatite forming ability and a better control of the pH during soaking of the samples in SBF were observed in the presence of the biopolymer. This result opens a new insight on the simple fabrication of highly bioactive hybrid inorganic-organic materials for medical applications.

To prevent the high frequency of wound infections, anti-bacterial agents can be loaded onto composites. In the present study, the antibiotic tetracycline hydrochloride (TC)was incorporated, for the first time, in collagen type I membranes coated with nano-sized SiO2-CaOP2O5 bioactive glass (n-BG) obtained by a sol-gel chemical route. Collagen membranes coated with n-BG were immersed in simulated body fluid (SBF) containing 0.25, 0.75 or 1.25 mg mL−1 of TC for 48 h at 37∘C following a coprecipitation method. The antibiotic was released in distilledwater at 37∘C for up to 72 h. The antibacterial activity of the composites was evaluated in vitro by the inhibition zone test and plate count method. Two different Staphylococcus aureus strains, S. aureus ATCC29213 and S. aureus ATCC25923, were exposed to the biomaterials. The results showed that the incorporation but not the release of TC was dependent on the initial concentration of TC in SBF. The biomaterials inhibited S. aureus growth, although the efficacy was similar for all the concentrations. The results allow us to conclude that the new composite could have potential in the prevention of wound infections.

In this communication, hollow bioactive glass (BG) nanofibers were fabricated via a single-nozzle electrospinning method. The morphology of the prepared hollow BG nanofibers was observed by SEM and TEM, and the results showed that BG nanofibers had a continuous hollow interior. The hollow BG nanofibers were incubated in simulated body fluid (SBF) to investigate their apatitemineralization ability, and the result showed that after incubation for 6 h a flower-like apatite was observed on the surface of hollowBGnanofibers, and the Fourier transform infrared (FTIR) result further confirmed the formation of apatite. The results suggested that hollow BG nanofibers could be used for drug delivery and bone regeneration applications due to their unique hollow structure and bioactivity.

In the last decade, the development of third generation bioceramics for Bone Tissue Regeneration has experienced significant progress with the emergence of a new generation of nanostructured materials named mesoporous bioactive glasses (MBG). This new generation of materials, also known as “templated glasses”, presents chemical compositions similar to those of conventional bioactive sol–gel glasses and the added value of an ordered mesopore arrangement. This article shows an indepth comparative study of the ordered porous structures of MBGs compared to conventional glasses (melt and solgel) andhowthese properties influence the bioactivity process. Moreover, the possibility to tailor the textural and structural properties of these nanostructured materials by an exhaustive control of the different synthesis parameters is also discussed. A brief overview regarding the possibility of using these materials as controlled drug delivery systems and as starting materials for the fabrication of 3D scaffolds for bone tissue regeneration is also given.

Owing to their controlled solubility, phosphate invert glasses are of interest for use as temporary implant materials or tissue engineering scaffolds for controlled ion release.MgO-CaO-SrO-TiO2-P2O5 invert glasses were prepared and their dissolution behavior and cell response were examined.MgO addition to the phosphate invert glass system improved glass formation, owing to the relatively large field strength of Mg2+ ions. In osteoblastlike MC3T3-E1 cell culture tests, cell numbers on the invert glasses were significantly larger compared with the control, possibly caused by the release of Mg2+ ions promoting enhanced cell adhesion and proliferation. Alkaline phosphatase (ALP) activity varied with glass composition, with higher strontium for calcium substitution (33 to 100%) showing highest ALP activity. This effect may be caused by the release of strontium ions from the glasses.

The purpose of this project was to investigate the angiogenic mechanism of bioactive borate glass for soft tissue repair in a ‘hairless’ SKH1 mouse model. Subcutaneous microvascular responses to bioactive glass microfibers (45S5, 13-93B3, and 13-93B3Cu) and bioactive glass beads (13-93, 13-93B3, and 13-93B3Cu) were assessed via: noninvasive imaging of skin microvasculature; histomorphometry of microvascular densities; and quantitative PCR measurements of mRNA expression of VEGF and FGF-2 cytokines. Live imaging via dorsal skin windows showed the formation at twoweeks of a halo-like structure infused with microvessels surrounding implanted boratebased 13-93B3 and 13-93B3Cu glass beads, a response not observed with silicate-based 13-93 glass beads. Quantitative histomorphometry of tissues implanted with plugs of 45S5, 13-93B3, and 13-93B3Cu glass microfibers revealed microvascular densities that were 1.6-, 2.3-, and 2.7-times higher, respectively, than the sham control valueswhereas 13-93, 13-93B3, and 13-93B3Cu glass beads caused the microvascular density to increase 1.3-, 1.6-, and 2.5-fold, respectively, relative to sham controls. Quantitative PCR measurements indicate a marginally significant increased expression of VEGF mRNA in tissues with 13-93B3Cu glass beads, an outcome that supported the hypothesis that copper-doped borate glass could promote VEGF expression followed by angiogenesis for enhanced wound healing.

The structural effects of yttrium (Y) and cerium (Ce) are investigated when substituted for sodium (Na) in a 0.52SiO2–0.24SrO–(0.24−x)Na2O–xMO (where x = 0.08; MO = Y2O3 and CeO2) glass series. Network connectivity (NC) was calculated assuming both Y and Ce can act as a network modifier (NC = 2.2) or as a network former (NC up to 2.9). Thermal analysis showed an increase in glass transition temperature (Tg) with increasing Y and Ce content, Y causing the greater increase from the control (Con) at 493∘C to 8 mol% Y (HY) at 660∘C. Vickers hardness (HV) was not significantly different between glasses. 29Si Magic Angle Spinning-Nuclear Magnetic Resonance (MAS-NMR) did not show peak shift with addition of Y, however Ce produced peak broadening and a negative shift in ppm. The addition of 4 mol% Ce in the YCe and LCe glasses shifted the peak from Con at −81.3 ppm to −82.8 ppm and −82.7 ppm respectively; while the HCe glass produced a much broader peak and a shift to −84.8 ppm. High resolution X-ray Photoelectron Spectroscopy for the O 1s spectral line showed the ratio of bridging (BO) to non-bridging oxygens (NBO), BO:NBO,was altered,where Con had a ratio of 0.7, HY decreased to 0.4 and HCe to 0.5.