Characterizing TiO2 as an Anti-Inflammatory Biomaterial

表征 TiO2 作为抗炎生物材料的特性

• 批准号: 6797853
• 负责人: JOHN A FRANGOS
• 金额: $ 42.65万
• 依托单位: LA JOLLA BIOENGINEERING INSTITUTE
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-09-01 至 2006-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6797853
• 关键词: X ray crystallography; aluminum oxide; biomaterial compatibility; biomaterial development /preparation; biomaterial evaluation; biomaterial interface interaction; biotechnology; chemical reaction; electrochemistry; free radical oxygen; human tissue; inflammation; laboratory rat; macrophage; medical implant science; metal oxide; molecular film; neutrophil; osteoarthritis; peroxynitrites; scanning electron microscopy; skeletal prosthesis; surface coating; titanium; transmission electron microscopy; zirconium

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.

描述（由申请人提供）： 钛已成功用于 牙科和骨科植入物的研究已有数十年历史，但其确切机制 骨整合是否成功尚未确定。我们将调查 钛的生物相容性涉及相互作用的假设 金属植入物上的二氧化钛表面层和活性物质之间 模型系统中炎症反应的氧介质具有不同的 复杂程度。钛上可以存在不同形式的表面氧化物， 以及确定的表面氧化物和抗炎之间的关系 将确定响应。我们最近证明了过氧亚硝酸盐 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，显着 被氧化钛降解。此外，似乎还有很强的 体内降解过亚硝酸盐的能力与最终浓度之间的相关性 生物相容性。具体目标 1 将检查钛和其他材料的能力 氧化物抑制活性氧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在石英、不锈钢上制造 和热固性有机硅基材以及受激相互作用 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 的炎症细胞。在具体目标 3 中，体内实验将关联 这种能力与正常和关节炎大鼠的炎症反应有关 模型。拟议的实验将比较二氧化钛的能力 与其他材料相比，抑制炎症活性氧 确定是否可以将此属性赋予其他表面。我们将 确定化学结果之间是否存在相关性 特定晶体和化学成分表面的反应动力学 具体目标 1 中，以及体外细胞对这些表面的反应 具体目标 2，以及具体目标 3 中的长期体内反应。 证明了正相关性，我们将确定抗氧化剂 生物材料的特性作为体内生物相容性的预测因子。我们的 长期目标是扩展这些知识以开发新的生物相容性 具有比钛优越的机械和材料性能的材料。