Characterizing TiO2 as an Anti-Inflammatory Biomaterial

描述(申请人提供)：钛已成功用于 牙科和整形外科植入物，但其确切的机制 成功的骨整合还没有确定。我们将调查 钛的生物相容性涉及相互作用的假说 表面二氧化钛对金属植入物和反应性的影响 模型系统中炎症反应的氧介质 复杂程度。不同形式的表面氧化物可以存在于钛上， 以及确定的表面氧化物与抗炎的关系 回应将会被确定。我们最近证明了过氧亚硝酸盐，一种 体内产生的高活性化合物和炎症介质 自由基一氧化氮和超氧化物的反应，是显著的 被钛氧化物降解。此外，似乎有一个强大的 体内降解过氧亚硝酸根能力与体内终末浓度的相关性 生物兼容性。具体目标1将检查钛和其他 抑制活性氧物种和过氧亚硝酸根反应性的氧化物。 在具体目标2中，明确定义和表征的二氧化钛薄膜 和其他金属氧化物表面将被制造在石英，不锈钢 与热固性有机硅基材的相互作用和受刺激 有这些表面的中性粒细胞和巨噬细胞 调查以确定这些制成的表面是否可以抑制反应 炎性细胞。在特定的目标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 模特们。拟议中的实验将比较二氧化钛对 与其他材料相比，抑制炎性活性氧物种和 确定是否可以将此属性授予其他曲面。我们会 确定化学物质的结果之间是否存在相关性 确定晶体和化学组成表面上的反应动力学 在特定的目标1中，以及在体外对这些表面的细胞反应 特定目标2，在特定目标3中有较长期的体内反应。 呈正相关，我们就会建立起抗氧化剂 生物材料的特性作为体内生物相容性的预测因子。我们的 长期目标是扩展这一知识以开发新的生物相容性 具有比钛更优越的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.