Khan, M.R.; (2012) The differential modulation of receptor tyrosine kinase Axl in human mesenchymal stromal cell responses to modified titanium surfaces. Doctoral thesis , UCL (University College London).

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Abstract

Osseointegration is the process of de novo bone regeneration on the surface of an endosseous titanium (Ti) implant in vivo. This neo formation of bone underlies the physical integration of a Ti implant in bone at a level sufficient to restore loss of function; for example, of mastication due to absent teeth. The outer atoms of a bulk of Ti metal form a stable and passive surface oxide layer that serves as a substrate for the amalgamation of tissue reparative components, which entail the formation of an osseous bond between tissue and fixture. This interaction was empirically demonstrated to be highly affected by the characteristics of the surface an implant in experimental studies querying the varied effects of additive or subtractive physical modifications, as well as altered chemical compositions, of Ti implant surfaces on osseointegration. Subsequent clinical and experimental practices have demonstrated that rough surfaced implants perform comparatively ‘better’ than their smooth surfaced counterparts by promoting bone growth on the fixture. Moreover, a particular surface modification that yields high surface energy combined with a widely tested micron scaled topographical roughness (modSLA) has been shown to further promote the timely enhancement of osseointegration compared to its hydrophobic rough counterpart (SLA). The biological mechanisms underlying this apparent enhancement of osseointegration by modified Ti implant surfaces are still subject to intense study due to the materials’ implications in bone related tissue engineering applications. Amongst the several views being opined is a proposition mainly arising from in vitro experimentation, which suggests modified Ti implant surfaces possess an ‘intrinsic’ osteoinductive potential that affects uncommitted reparative cells by inducing a temporal and magnitudinal enhancement in cellular differentiation and function; in turn, implying the early formation of functional osteoblasts and bone tissue matrix in an in vivo scenario. The observations of differential cellular behavior include the apparent modulation by the modified surfaces, of a cell surface receptor tyrosine kinase Axl in human osteoblasts. The proposed role of the receptor in negatively regulating osteogenic mineralisation in uncommitted pericytic cells suggests an association with the altered response of cells to these substrates. The aim of this project was to examine and test the hypothesised differential modulation of Axl in the responses of human marrow derived mesenchymal stromal cells to modified Ti implant substrates.

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