Tillotson, MJ; (2014) The influence of titanium dioxide surface chemistry on osteogenic stem cell selection. Doctoral thesis , UCL (University College London).

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Abstract

Micro structured, high surface energy titanium (Ti) has been shown to be an effective substrate for osseointegration of an implant with surrounding bone tissue. The aim of this project is to test the hypothesis that the enhanced osteogenic differentiation and function of multipotent stromal cells (MSCs) in response to modified Ti surfaces is caused by a selection event within the population. The first cell type capable of producing new bone on an implant after placement are the MSCs which circulate in the bloodstream and are recruited to the site of tissue damage. The reservoirs of these cells are heterogeneous in nature, consisting of a mixture of cells with varying differentiation abilities. In order to utilise these cells and to reduce the chance of unwanted events during regenerative therapies, the selection of a subset of cells that is truly multipotent is required. The behaviour of the cells is altered by the modifications to the Ti surfaces and this underpins the differences seen in clinical performance. Stem cells from various tissues have been used to seed modified Ti surfaces in order to analyse these changes in cell behaviour. Combined with subsequent expansion, selected cells could be used for regenerative or bone engineering applications. The outer atoms of Ti form a stable, passive surface oxide layer that serves as a substrate for the formation of an osseous bond between tissue and fixture. Initial interactions occur between adhesion proteins on bone cell surfaces and the metal oxide layer. I discuss the contribution of van der Waals forces on molecular chemistry at the TiO2 [110] surface. The nano-roughened, hydrophilic surface of Ti has been attributed to improved biocompatibility. Spectroscopic and computational techniques demonstrate that the UV induced hydrophilic conversion of Ti occurs through surface hydroxyl group reorganisation. This enhances the adsorption effect of peptide adhesion domains. Thus, altered chemical interactions between simple molecules and the crystal surface determines the differential cellular osteogenic response to rough, hydrophilic Ti surfaces, through the increased expression of extra cellular matrix (ECM) adhesion components.

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