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Title: Mesoporous bioactive glass and alginate composite scaffolds for tissue engineering
Author: Fan, J. P.
ISNI:       0000 0004 5358 8338
Awarding Body: University College London (University of London)
Current Institution: University College London (University of London)
Date of Award: 2014
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Sol-gel derived, silica-based bioactive glasses of a ternary system (SiO₂ – CaO – P₂O₅) has the potential to promote hard and soft tissue regeneration. Compared to melt-derived glasses, glasses synthesised from the sol-gel process has the advantage of low processing temperatures, high specific surface areas (SSA) and tailorable porous nanostructures. Using scaffolds as a strategy for tissue engineering, the application of sol-gel derived bioactive glasses in combination with alginate polymers as scaffold composite materials has great potential and therefore requires further study. This thesis investigates the synthesis of bioactive glasses via the sol-gel (acidic) route and the multi-step (alkali) route, through the sol → drying → sintering stages. Sol-gel route nanoparticles derived were heterogeneous in shape, while the multi-step route produced spherical (30 – 90 nm diameter) nanoparticles. Increases in calcium content of the sol led to an increase in pore size and a decrease in SSA. Three dehydration methods: oven, vacuum and freeze drying were devised to control the morphology of nanoparticles. Freeze dried nanoparticles were found to have a rough surface texture, with an aligned ordered porous nanostructure. This led to faster apatite formation when compared to oven dried nanoparticles immersed in simulated body fluid (SBF). A novel internal ionic diffusion cross-linking method of alginate was developed, utilising the glass nanoparticles as nanocarriers, for the synthesis of alginate-bioactive glass composite scaffolds. Strontium chloride (SrCl₂) and copper chloride (CuCl₂), which provided therapeutic ions, were impregnated into the nanocarriers, and were compared to calcium chloride (CaCl₂), as the control. Impregnation efficiency was in the order of CuCl₂ > SrCl₂ ≈ CaCl₂, attributed to Cu²⁺ having the smallest ionic radii and its interaction with silinol groups on the nanocarrier surfaces. Scaffold gelation time was correlated to the type of cross-linking salt, its loading concentration and glass to alginate (G/A) ratio. It was observed that SrCl₂ loaded nanocarriers (BGSr) were most efficient in cross-linking when compared to CuCl₂ and CaCl₂ loaded nanocarriers (BGCu and BGCa respectively), due to Sr²⁺ having a greater affinity towards alginate. Results showed that nanocarriers with the highest SSA possessed the highest impregnation efficiency; however nanocarriers with the largest pore diameter and volume led to the fastest scaffold gelation time. BGCa and BGSr scaffolds showed significant improvements in maintaining stiffness (Young’s modulus) and shear resistance (maximum shear stress) after incubation in aqueous solutions for up to 28 days, which were in contrast to the deterioration in mechanical properties of conventional CaCl₂ cross-linked scaffolds. Calcium ions were detected in the range above 260 ppm in BGCa nanocarrier supernatant, suggesting the gradual release of ions from the nanocarriers, internally diffusing into the scaffold matrix, leading to continuous cross-linking over time. Meanwhile, in vitro biological studies showed fast apatite formation on BGCa cross-linked scaffolds in SBF, with the scaffolds capable of supporting the attachment, growth and proliferation of human osteoblast cells, thus indicating their high bioactivity. Control over glass nanoparticle morphology was achieved and through specific ionic impregnation, the successful synthesis of alginate-bioactive glass composite scaffolds was demonstrated, producing bioactive scaffolds with improved mechanical properties.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available