Characterizing TiO2 as an Anti-Inflammatory Biomaterial

描述（由申请人提供）：钛已成功用于 几十年的牙科和骨科植入物，但确切的机制， 成功的骨整合尚未确定。我们将调查 假设钛的生物相容性涉及相互作用 在金属植入物上的二氧化钛表面层和反应性二氧化钛之间 在模型系统中的炎症反应的氧介质， 复杂程度。不同形式的表面氧化物可存在于钛上， 以及确定的表面氧化物和抗炎之间的关系 答案将被确定。我们最近证明，过氧亚硝酸盐， 高反应性化合物和炎症介质在体内产生的 反应的自由基一氧化氮和超氧化物，是显着的 被氧化钛降解此外，似乎有一个强大的 过氧亚硝基阴离子的降解能力与体内极限之间的相关性 生物相容性具体目标1将检查钛和其他材料的能力， 氧化物以抑制活性氧物质和过氧亚硝酸盐的反应性。 在具体目标2中，明确定义和表征的氧化钛薄膜 和其他金属氧化物表面将制造在石英，不锈钢， 和热固性有机硅基材以及受刺激的 具有这些表面的多形核白细胞和巨噬细胞将 研究以确定这些制造的表面是否可以抑制响应 炎性细胞。在具体目标3中，体内实验将与 这种能力与正常和关节炎大鼠的炎症反应有关 模型所提出的实验将比较二氧化钛的能力， 与其它材料相比，抑制炎性活性氧， 确定这种特性是否可以赋予其他表面。我们将 确定化学品的结果之间是否存在相关性 在确定的晶体和化学组成的表面上的反应动力学 在特定目标1中，以及在特定目标1中对这些表面的体外细胞反应。 特异性目标2，特异性目标3中的长期体内反应。如果 正相关性得到证明，我们将建立抗氧化剂， 生物材料的特性作为体内生物相容性的预测因子。我们 长期目标是将这一知识扩展到开发新的生物相容性 比钛具有上级机械和材料性能的材料。

DESCRIPTION (provided by applicant): Titanium has been successfully used for decades in dental and orthopedic implants, but the exact mechanism of successful osseointegration has not been determined. We will investigate the hypothesis that the biocompatibility of titanium involves an interaction between the surface layer of titanium dioxide on the metal implant and reactive oxygen mediators of the inflammatory response in model systems with varying degrees of complexity. Different forms of surface oxide can exist on titanium, and the relationship between defined surface oxides and anti-inflammatory response will be determined. We recently demonstrated that peroxynitrite, a highly reactive compound and inflammatory mediator produced in vivo by the reaction of the free radicals nitric oxide and superoxide, is significantly degraded by titanium oxides. Furthermore, there appears to be a strong correlation between the ability to degrade peroxynitrite and ultimate in vivo biocompatibility. Specific Aim 1 will examine the ability of titanium and other oxides to inhibit the reactivity of reactive oxygen species and peroxynitrite. In Specific Aim 2, well-defined and characterized thin films of titanium oxide and other metal oxide surfaces will be fabricated on quartz, stainless steel and thermoset silicone substrates and the interaction of stimulated polymorphonuclear leukocytes and macrophages with these surfaces will be investigated to determine if these fabricated surfaces can inhibit the response of inflammatory cells. In Specific Aim 3, in vivo experiments will correlate this ability with the inflammatory response in both normal and arthritic rat models. The proposed experiments will compare the ability of titanium oxide to inhibit inflammatory reactive oxygen species compared with other materials and determine whether this property can be conferred onto other surfaces. We will determine if there is a correlation between the results of the chemical reaction kinetics on surfaces of defined crystalline and chemical composition in Specific Aim 1, and the in vitro cellular responses to these surfaces in Specific Aim 2, with the longer-term in vivo responses in Specific Aim 3. If a positive correlation is demonstrated, we will have established that antioxidant properties of biomaterials as a predictor of in vivo biocompatibility. Our long-term goal is to extend this knowledge to develop new biocompatible materials with superior mechanical and material properties than titanium.