Effects of Titanium Surface Modification on Inflammation and Osseous Healing in Diabetes

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Thesis (PhD Doctorate)
Doctor of Philosophy (PhD)
School of Dentistry&Oral Hlth
Griffith Health
Successful osseous healing is achieved by highly organised and controlled biological processes. Inflammation is an initial and integral part of these biological processes, influencing the fate of overall healing outcomes. Indeed, it has been well established that the skeletal and immune systems closely interact and influence each other in order to regulate bone homeostasis, both in healthy and diseased conditions. Compromised wound healing is one of the major clinical complications of diabetes, often leading to high morbidity and mortality. Pathophysiological changes, such as chronic hyperglycaemia and a resultant pro-inflammatory microenvironment, are considered to be the main aetiological factors in diabetes, contributing to a compromised immune system and poor wound healing potential. Macrophages play a pivotal role in both the initiation and resolution of inflammation by expressing an array of functional phenotypes (e.g. M1 and M2) in response to diverse local microenvironmental chemical cues. A timely transition of inflammatory status from ‘proinflammatory (M1)’ to ‘anti-inflammatory/pro-healing (M2)’, is believed to be a crucial biological step in order to achieve successful wound healing, and there is increasing evidence supporting the notion that macrophages are responsible for this ‘switch’ of microenvironment. This important cellular phenomenon of M1 and M2 phenotypic transition is disrupted in diabetes due to various systemic and local factors, however the underlying cellular mechanisms are yet to be fully elucidated. Recently, numerous in vitro and in vivo studies have investigated the influence of different biomaterial surface characteristics on the resultant immune responses, demonstrating that the expression of macrophage phenotypes can be modulated by surface topography, chemistry and hydrophilicity, thus resulting in enhanced osseous healing. However, there is insufficient evidence in the current literature to support whether such biomaterial enhanc