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Mesoporous silica particles (MCM-41) decorated with Ag nanoparticles were prepared by the template ion exchange (TIE) method. The properties of the synthesized material were investigated by several techniques, including the nitrogen sorption measurements, X-ray diffraction (XRD), scanning electron microscopy (SEM), transmission electron microscopy (TEM) and Fourier Transform Infrared Spectroscopy (FTIR). Moreover, the degradability of the particles was tested in simulated body fluid (SBF) in order to evaluate the degradation rate of the material. The silica particles were loaded with different Ag concentrations but no structural changes were observed in the ordered mesoporosity. Already after 1 day of immersion in SBF most of the silver particles were released and partial degradation of the silica particles was observed. Ibuprofen was loaded into the Ag containing MCM-41 particles in order to evaluate their drug up-take/release capability. Silver and silicon ion release was quantified with inductively coupled plasma optical emission spectroscopy (ICP-OES). The novel silver doped MCM-41 particles were used as a functional coating on bioactive glass (BG) based scaffolds intended for bone tissue engineering application.

Bioactive glasses and related bioactive glass-ceramics have been used for over three decades in biomedical applications such as bulk, particulate, or coatings materials. More recently, highly porous bioactive glass-ceramic scaffolds for bone-tissue engineering have also been developed from selected compositions of bioactive glasses. Current bioactive glass-ceramic scaffolds are characterized by an open porous network, high bioactivity, and mechanical properties similar to those of trabecular bone. This article reviews the latest achievements in the development of porous bioactive glass-ceramics intended for bone-tissue engineering applications, highlighting the fabrication technologies and scaffold properties. Improvements in the mechanical properties of bioactive glass-ceramic scaffolds exhibiting high bioactivity have been achieved by different approaches in the last 10 years. Relevant long-term in vivo studies are required to confirm the suitability of such bioactive glass-ceramic scaffolds in clinical applications.

Bioactive glass (BG) based scaffolds (45S5 BG composition) were developed by the replica technique using natural marine sponges as sacrificial templates. The resulting scaffolds were characterized by superior mechanical properties (compression strength up to 4 MPa) compared to conventional BG scaffolds prepared using polyurethane (PU) packaging foam as a template. This result was ascribed to a reduction of the total scaffold porosity without affecting the pore interconnectivity (>99%). It was demonstrated that the reduction of total porosity did not affect the bioactivity of the BG-based scaffolds, tested by immersion of scaffolds in simulated body fluid (SBF). After 1 day of immersion in SBF, a homogeneous CaP deposit on the surface of the scaffolds was formed, which evolved over time into carbonate hydroxyapatite (HCA). Moreover, the enhanced mechanical properties of these scaffolds were constant over time in SBF; after an initial reduction of the maximum compressive strength upon 7 days of immersion in SBF (to 1.2 ± 0.2 MPa), the strength values remained almost constant and higher than those of BG-based scaffolds prepared using PU foam (

Hydroxyapatite (HA) filled poly(methyl methacrylate)/poly(hydroxyethyl methacrylate) (PMMA/PHEMA) blends were prepared by reactive suspension method: HA was synthesized by co-precipitation process directly within a HEMA solution and the so-obtained suspension was polymerized in the presence of PMMA. HA particles were obtained in form of nanorods with a length of 50–200 nm and a diameter of 10–30 nm. A significant increase in glass transition temperature was observed in the nanocomposites with respect to the unfilled polymer blends. Dynamic-mechanical thermal analysis showed a significant increase in the storage modulus in the nanocomposites measured in the rubbery region. This increase was unpredicted by Mooney’s predictive equation and was attributed to the presence of cross-linking points due to the in situ generated HA particles. An increase in the elastic modulus was also observed at room temperature in compression and three-point bending tests. The presence of HA in the polymer blends resulte...

Mesoporous silica particles of type MCM-41 (Mobile Composition of Matter No. 41), exhibiting highly ordered mesoporosity (pores with diameter between 2 and 50 nm) and surface roughness, are developed and used as a functional coating on bioactive glass-based scaffolds for bone tissue engineering. The degradability and the mesostructure stability of these novel MCM-41 particles were evaluated. The particles are immersed in simulated body fluid (SBF) for up to 28 days at 37 °C, and the variation of the ordered porosity, surface characteristics, and chemical composition of the particles are assessed by SEM-EDX, HRTEM, FTIR, ICP-OES, and pH measurements. The results indicate that the MCM-41 particles are affected by immersion in SBF only during the first few days; however, the surface and the mesopore structure of the particles do not change further with increasing time in SBF. The pore channel diameter increased slightly, confirming the stability of the developed material. The release of dissolved Si-species, which reached a maximum of 260 mg SiO per gram of material, could play a key role in gene activation of osteoblast cells and in inducing new bone matrix formation.

A comparative characterisation of Bioglass based scaffolds for bone tissue engineering applications developed via a replication technique of natural marine sponges as sacrificial template is presented, focusing on their architecture and mechanical properties. The use of these sponges presents several advantages, including the possibility of attaining higher mechanical properties than those scaffolds made by foam replica method (up to 4 MPa) due to a decrease in porosity (68-76%) without affecting the pore interconnectivity (higher than 99%). The obtained pore structure possesses not only pores with a diameter in the range 150-500 mm, necessary to induce bone ingrowth, but also pores in the range of 0-200 mm, which are requested for complete integration of the scaffold and for neovascularisation. In this way, it is possible to combine the main properties that a three-dimensional scaffold should have for bone regeneration: interconnected and high porosity, adequate mechanical properties and bioactivity.

Ion-doped binary SiO2-CaO and ternary SiO2-CaO-P2O5 mesoporous bioactive glasses were synthesised and characterised to evaluate the influence of P2O5 in the glass network structure. Strontium, copper and cobalt oxides in a proportion of 0.8 mol% were selected as dopants because the osteogenic and angiogenic properties reported for these elements. Although the four glass compositions investigated presented analogous textural properties, TEM analysis revealed that the structure of those containing P2O5 exhibited an increased ordered mesoporosity. Furthermore, 29Si NMR revealed that the incorporation of P2O5 increased the network connectivity and that this compound captured the Sr2+, Cu2+ and Co2+ ions preventing them to behave as modifiers of the silica network. In addition, 31P NMR results revealed that the nature of the cation directly influences the characteristics of the phosphate clusters. In this study, we have proven that phosphorous oxide entraps doping-metallic ions, granting these glasses with a greater mesopores order., Comment: 16 pages, 9 figures

The use of bioactive glass (BG) particles as a filler for the development of composite electrospun fibers has already been widely reported and investigated. The novelty of the present research work is represented by the use of benign solvents (like acetic acid and formic acid) for electrospinning of composite fibers containing BG particles, by using a blend of PCL and chitosan. In this work, different BG particle sizes were investigated, namely nanosized and micron-sized. A preliminary investigation about the possible alteration of BG particles in the electrospinning solvents was performed using SEM analysis. The obtained composite fibers were investigated in terms of morphological, chemical and mechanical properties. An in vitro mineralization assay in simulated body fluid (SBF) was performed to investigate the capability of the composite electrospun fibers to induce the formation of hydroxycarbonate apatite (HCA)., Graphical abstract Image 1, Highlights • Use of benign solvents for electrospinning of composite PCL/chitosan fibers containing nano and micronsized BG particles. • Successfully dispersion of BG nano and micronsized particles in electrospun PCL/chitosan nanofibrous mats. • Deposition of hydroxycarbonate apatite after immersion in SBF solution confirmed for both composites fibers.

© 2016 by the authors.Monodispersed spherical Ag-doped bioactive glass nanoparticles (Ag-BGNs) were synthesized by a modified Stöber method combined with surface modification. The surface modification was carried out at 25, 60, and 80 °C, respectively, to investigate the influence of processing temperature on particle properties. Energy-dispersive X-ray spectroscopy (EDS) results indicated that higher temperatures facilitate the incorporation of Ag. Hydroxyapatite (HA) formation on Ag-BGNs was detected upon immersion of the particles in simulated body fluid for 7 days, which indicated that Ag-BGNs maintained high bioactivity after surface modification. The conducted antibacterial assay confirmed that Ag-BGNs had an antibacterial effect on E. coli. The above results thereby suggest that surface modification is an effective way to incorporate Ag into BGNs and that the modified BGNs can remain monodispersed as well as exhibit bioactivity and antibacterial capability for biomedical applications.

Large bone defects are challenging to heal, and often require an osteoconductive and stable support to help the repair of damaged tissue. Bioglass-based scaffolds are particularly promising for this purpose due to their ability to stimulate bone regeneration. However, processing technologies adopted so far do not allow for the synthesis of scaffolds with suitable mechanical properties. Also, conventional sintering processes result in glass de-vitrification, which generates concerns about bioactivity. In this work, we studied the bioactivity and the mechanical properties of Bioglass® based scaffolds, produced via a powder technology inspired process. The scaffolds showed compressive strengths in the range of 5–40 MPa, i.e. in the upper range of values reported so far for these materials, had tunable porosity, in the range between 55 and 77%, and pore sizes that are optimal for bone tissue regeneration (100–500 μm). We immersed the scaffolds in simulated body fluid (SBF) for 28 d and analyzed the evolution of the scaffold mechanical properties and microstructure. Even if, after sintering, partial de-vitrification occurred, immersion in SBF caused ion release and the formation of a Ca-P coating within 2 d, which reached a thickness of 10–15 μm after 28 d. This coating contained both hydroxyapatite and an amorphous background, indicating microstructural amorphization of the base material. Scaffolds retained a good compressive strength and structural integrity also after 28 d of immersion (6 MPa compressive strength). The decrease in mechanical properties was mainly related to the increase in porosity, caused by its dissolution, rather than to the amorphization process and the formation of a Ca-P coating. These results suggest that Bioglass® based scaffolds produced via powder metallurgy-inspired technique are excellent candidates for bone regeneration applications., Conference of the Association for Machine Translation in the Americas (AMTA), October 22-26, 2014, Vancouver, BC, Canada

Following on from the introduction and discussions centred on porous silica drug delivery systems (DDS) in Chapter 4 , this next chapter introduces and highlights the benefits of a related but compositionally extended family of biomaterials—mesoporous bioactive glasses. Rather than just containing silica, these materials include other ions which may have beneficial effects for the properties of the DDS in question or may even have therapeutic effects in their own right. General synthetic considerations for these inorganic systems will be introduced as will the effects the inclusion of non-silica-based ions into the mesoporous glass network has on both the physical properties and microstructure of the product glasses. The drug releasing properties of these systems will also be discussed as will the availability of different product morphologies to assist in achieving the desired in vitro therapeutic response.

This paper addresses the computation of the effective diffusivity in new bioactive glass (BG) based tissue engineering scaffolds. High diffusivities facilitate the supply of oxygen and nutrients to grown tissue as well as the rapid disposal of toxic waste products. The present study addresses required novel types of bone tissue engineering BG scaffolds that are derived from natural marine sponges. Using the foam replication method, the scaffold geometry is defined by the porous structure of Spongia Agaricina and Spongia Lamella. These sponges present the advantage of attaining scaffolds with higher mechanical properties (2–4 MPa) due to a decrease in porosity (68–76 %). The effective diffusivities of these structures are compared with that of conventional scaffolds based on polyurethane (PU) foam templates, characterised by high porosity (>90 %) and lower mechanical properties (>0.05 MPa). Both the spatial and directional variations of diffusivity are investigated. Furthermore, the effect of scaffold decomposition due to immersion in simulated body fluid (SBF) on the diffusivity is addressed. Scaffolds based on natural marine sponges are characterised by lower oxygen diffusivity due to their lower porosity compared with the PU replica foams, which should enable the best oxygen supply to newly formed bone according the numerical results. The oxygen diffusivity of these new BG scaffolds increases over time as a consequence of the degradation in SBF.

The electrospinning technique is a versatile method for the production of fibrous scaffolds able to resemble the morphology of the native extra cellular matrix. In the present paper, electrospinning is used to fabricate novel SiO2 particles (type MCM-41) containing poly(epsilon-caprolactone) (PCL) fibers. The main aims of the present work are both the optimization of the particle synthesis and the fabrication of composite fibers, obtained using benign solvents, suitable as drug delivery systems and scaffolds for soft tissue engineering applications. The optimized synthesis and characterization of calcium-containing MCM-41 particles are reported. Homogeneous bead-free composite electrospun mats were obtained by using acetic acid and formic acid as solvents; neat PCL electrospun mats were used as control. Initially, an optimization of the electrospinning environmental parameters, like relative humidity, was performed. The obtained composite nanofibers were characterized from the morphological, chemical and mechanical points of view, the acellular bioactivity of the composite nanofibers was also investigated. Positive results were obtained in terms of mesoporous particle incorporation in the fibers and no significant differences in terms of average fiber diameter were detected between the neat and composite electrospun fibers. Even if the Ca-containing MCM-41 particles are bioactive, this property is not preserved in the composite fibers. In fact, during the bioactivity assessment, the particles were released confirming the potential application of the composite fibers as a drug delivery system. Preliminary in vitro tests with bone marrow stromal cells were performed to investigate cell adhesion on the fabricated composite mats, the positive obtained results confirmed the suitability of the composite fibers as scaffolds for soft tissue engineering.

Novel silica-based bioactive glasses were successfully prepared by the sol-gel method. The optimized glass composition for fabrication of the scaffolds was (in mol.%) 60% SiO2 – 30% CaO - 5% Na2O - 5% P2O5 (60S30C5N5P). This composition was confirmed to develop a thick hydroxycarbonate apatite (HCA) layer in Simulated Body Fluid (SBF) after 7 days, as revealed by Fourier Transform Infrared Spectroscopy (FTIR), indicating the bioactive character of the scaffolds. The mesoporous nature of the glass structure allows the load of tetracycline and a sustained release of the drug in PBS during 7 days was measured.

Bioactive glasses (BGs) are being increasingly considered for biomedical applications in bone and soft tissue replacement approaches thanks to their ability to form strong bonding with tissues. However, due to their high reactivity once in contact with water-based solutions BGs rapidly exchange ions with the surrounding environment leading in most cases to an undesired increase of the pH under static in vitro conditions (due to alkaline ion “burst release”), making difficult or even impossible to perform cell culture studies. Several pre-conditioning treatments have been therefore proposed in laboratories worldwide to limit this problem. This paper presents an overview of the different strategies that have been put forward to pre-treat BG samples to tackle the pH raise issue in order to enable cell biology studies. The paper also discusses the relevant criteria that determine the selection of the optimal pre-treatment depending on the BG composition and morphology (e.g. particles, scaffolds). Statement of Significance Bioactive glasses (BGs), since their discovery in 1971 by L.L Hench, have been widely used for bone replacement and repair, and, more recently, they are becoming highly attractive for bone and soft tissue engineering applications. BGs have in fact the ability to form a strong bond with both hard and soft tissues once in contact with biological fluid. The enhanced interaction of BGs with the biological environment is based on their significant surface bioreactivity. This surface effect of BGs is, on the other hand, problematic for cell biology studies by standard (static) cell culture methods: an excessive bioreactivity leads in most cases to a rapid and dramatic increase of the pH of the surrounding medium, which results in cell death and makes cell culture tests on BG samples impossible. The BG research community has been aware of this for many years and numerous pre-treatments have been proposed by different groups worldwide to limit this problem. For the first time, we have reviewed in this paper the variety of surface preconditioning treatments that have been put forward over the years, we provide a summary of such pre-treatments used in laboratory practice, discussing and offering criteria that can be used for the determination of the optimal pre-treatment depending on BG composition and morphology of the sample tested (bulk, particulate, scaffolds). The information and discussion provided in this review should support best research practice when testing bioactive glasses in cell culture.