Tailoring the nanostructure of sol-gel derived bioactive glasses and investigating their interactions with proteins

Sol-gel derived bioactive glasses with the 70S30C composition (70 mol% SiO2 and 30 mol% CaO) have high potential as materials for bone regeneration and devices for sustained drug delivery. They bond to bone and have a unique tailorable nanoporosity, which affects protein adsorption and cellular response. The first aim of this thesis is to fully characterise the evolution of the nanoporous structure of sol-gel derived bioactive glass for the first time, to fully understand its nanostructure evolution and control. Nanoparticles that were produced early in the sol-gel process, agglomerated into larger particles during gelation and during thermal stabilisation. Calcium was found to not enter the silica network until the material was heated to 400 °C. This has implications for the homogeneity of the calcium distribution in sol-gel derived bioactive glasses. Region separation was found within sol-gel derived bioactive glass monoliths produced by the standard procedure. The calcium concentration and nanoporosity were found to be higher near the edge of the monoliths. This is believed to be caused by calcium accumulation on the outer surface of the monoliths during the drying stage of the sol-gel process. The homogeneity of monoliths was successfully improved by using Teflon moulds. To provide further control of the nanostructure of 70S30C, a method for increasing the nanopore diameter from 12 nm to 30 nm was devised by adding specific amount of trimethylethoxysilane (TMES) during the sol-gel process. A series of amounts of TMES were added at different time points during the sol-gel process. Solid state nuclear magnetic resonance (NMR) and electron microscopy were used to explore the mechanisms behind the changes in nanostructure. Protein adsorption to sol-gel glass was investigated using in situ studies by monitoring the adsorption of fluorescent-labelled proteins onto various types of solgel derived bioactive glasses under confocal microscope with fibrinogen as model protein. Fibrinogen molecules were found to penetrate into inner nanopores of TheraGlass® (a commercial glass with 17 nm nanopores) whereas no penetration was found into sol-gel derived silica (with 3 nm nanopores). Protein interactions were further studied by conducting bioactivity tests with SBF supplemented with 10% serum. Apatite deposition was found inhibited by the interference of serum proteins

On Degrees of Freedom of Projection Estimators with Applications to Multivariate Nonparametric Regression

In this paper, we consider the nonparametric regression problem with multivariate predictors. We provide a characterization of the degrees of freedom and divergence for estimators of the unknown regression function, which are obtained as outputs of linearly constrained quadratic optimization procedures, namely, minimizers of the least squares criterion with linear constraints and/or quadratic penalties. As special cases of our results, we derive explicit expressions for the degrees of freedom in many nonparametric regression problems, e.g., bounded isotonic regression, multivariate (penalized) convex regression, and additive total variation regularization. Our theory also yields, as special cases, known results on the degrees of freedom of many well-studied estimators in the statistics literature, such as ridge regression, Lasso and generalized Lasso. Our results can be readily used to choose the tuning parameter(s) involved in the estimation procedure by minimizing the Stein's unbiased risk estimate. As a by-product of our analysis we derive an interesting connection between bounded isotonic regression and isotonic regression on a general partially ordered set, which is of independent interest.Comment: 72 pages, 7 figures, Journal of the American Statistical Association (Theory and Methods), 201