Elena Boccardi

Synthesis of Monodispersed Ag-Doped Bioactive Glass Nanoparticles via Surface Modification

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.

Uniform Surface Modification of 3D Bioglass(®)-Based Scaffolds with Mesoporous Silica Particles (MCM-41) for Enhancing Drug Delivery Capability.

The design and characterization of a new family of multifunctional scaffolds based on bioactive glass (BG) of 45S5 composition for bone tissue engineering and drug delivery applications are presented. These BG-based scaffolds are developed via a replication method of polyurethane packaging foam. In order to increase the therapeutic functionality, the scaffolds were coated with mesoporous silica particles (MCM-41), which act as an in situ drug delivery system. These sub-micron spheres are characterized by large surface area and pore volume with a narrow pore diameter distribution. The solution used for the synthesis of the silica mesoporous particles was designed to obtain a high-ordered mesoporous structure and spherical shape – both are key factors for achieving the desired controlled drug release. The MCM-41 particles were synthesized directly inside the BG-based scaffolds, and the drug-release capability of this combined system was evaluated. Moreover, the effect of MCM-41 particle coating on the bioactivity of the BG-based scaffolds was assessed. The results indicate that it is possible to obtain a multifunctional scaffold system characterized by high and interconnected porosity, high bioactivity, and sustained drug delivery capability.

Characterisation of Bioglass based foams developed via replication of natural marine sponges

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 μm, necessary to induce bone ingrowth, but also pores in the range of 0–200 μm, 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.

Incorporation of bioactive glass nanoparticles in electrospun PCL/chitosan fibers by using benign solvents

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).

Study of the mechanical stability and bioactivity of Bioglass(®) based glass-ceramic scaffolds produced via powder metallurgy-inspired technology.

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.

Development of Novel Mesoporous Silica-Based Bioactive Glass Scaffolds with Drug Delivery Capabilities

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.

Incorporation of Calcium Containing Mesoporous (MCM-41-Type) Particles in Electrospun PCL Fibers by Using Benign Solvents

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.

Biodegradabiliy of spherical mesoporous silica particles (MCM-41) in simulated body fluid (SBF)

Abstract 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 SiO2 per gram of material, could play a key role in gene activation of osteoblast cells and in inducing new bone matrix formation.

Bioactive nanocomposites for dental application obtained by reactive suspension method

Abstract 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 resulted in an important decrease in the water sorption values. The bioactivity of the nanocomposites was verified by the precipitation of HA layer on the surface after soaking in simulated body fluid. Graphical abstract

Mesoporous Bioactive Glass-Based Controlled Release Systems

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.