Anti-Inflamatory Coatings for Biomaterials

描述(由申请人提供)：长期的炎症反应 植入物是不能融入的主要原因之一。 组织。几乎所有植入物共同的两个炎症来源是 异物反应和植入物的相对运动 周围的组织。基于文献和我们研究中的证据 团队，炎症反应是由活性氧物种介导的 由巨噬细胞、白细胞和周围结缔组织产生。 根据我们的发现，很明显二氧化钛和类似的 陶瓷，即使作为聚合物生物材料的表面涂层，也具有 分解已被确认为 炎症反应的中介物。该计划的目标是开发 我们的催化抗氧化剂陶瓷技术在工业中的应用 生物材料和医疗器械行业。该计划由加州大学圣迭戈分校领导，包括 与十个学术和工业合作伙伴合作的五个项目。项目1将 探讨金属氧化物在催化反应中的基本作用机理 活性氧物种的分解。通过了解基本反应 二氧化钛催化剂催化作用的动力学研究 效率可能会被发现。项目2将制作和表征 其他四个项目的材料。该项目涉及来自 劳伦斯·利弗莫尔国家实验室、德雷塞尔大学和加州大学圣地亚哥分校。 项目3将测试体内炎症反应和异物反应 活体动物模型；标准大鼠模型和仓鼠窗口模型。这个项目 为其他项目提供核心服务，但也调查 生物材料炎症反应的基本机制。项目4 将决定陶瓷的催化抗氧化剂技术是否能够 减轻种植体-组织拉伤引起的炎症。它还将调查 应激性炎症的基本机制。项目5是界面 与医疗器械行业合作。四个行业合作伙伴已被选中 开发将该技术应用于四种不同的生物材料需求：生物传感器 植入式葡萄糖传感器(GlySens)和可生物降解聚合物的膜 用于减少异物的组织工程(高级组织科学) 反应；具有抗炎性能的伤口敷料材料(3M)；以及。 改善软组织整合的牙科材料(诺贝尔生物护理)。由 第一年，我们将阐明二氧化钛的催化作用机理。 建立了陶瓷包衣工艺，表征了其抗炎性能 在仓鼠模型中的反应，并制备和测试牙科涂层。我们的 总体目标是为我们的工业提供原则证明 合作伙伴，这将鼓励他们参与更具体的产品 发展战略计划第二阶段(6-10年)的发展。

DESCRIPTION (provided by the applicant): The prolonged inflammatory response to an implant is one of the primary causes for the failure to integrate into tissue. The two sources of inflammation common to almost all implants are the foreign body response and the relative movement of the implant with the surrounding tissue. Based on evidence in the literature and from our research team, the inflammatory response is mediated by the reactive oxygen species generated by macrophages, leukocytes, and the surrounding connective tissue. Based on our findings, it is evident that titanium dioxide and similar ceramics, even when present as surface coatings of polymeric biomaterials, have the ability to breakdown reactive oxygen species that have been identified as mediators of the inflammatory response. The goal of this Program is to develop applications for our catalytic antioxidant ceramic technology in the biomaterials and medical device industry. This Program, led by UCSD, consists of five projects with ten academic and industrial partners. Project 1 will investigate the basic mechanisms of action of metal oxides in the catalytic breakdown of reactive oxygen species. By understanding the fundamental reaction kinetics of the catalytic action of titanium dioxide, catalysts of greater efficiency may be discovered. Project 2 will fabricate and characterize materials for the other four projects. This project involves partners from Lawrence Livermore National Labs, Drexel Univ., and UCSD. Project 3 will test the in vivo inflammatory and foreign body response in two in vivo models; a standard rat model and the hamster window model. This project provides a core service to the other projects, but also investigates fundamental mechanisms of the inflammatory response to biomaterials. Project 4 will determine if the catalytic antioxidant ceramic technology is able to mitigate implant-tissue strain-induced inflammation. It will also investigate basic mechanisms of strain-induced inflammation. Project 5 is the interface with the medical device industry. Four Industrial Partners have been chosen to develop to apply the technology to four different biomaterial needs: Biosensor membranes for inplantable glucose sensors (GlySens) and biodegradable polymers for tissue engineering (Advanced Tissue Sciences) with reduced foreign body response; wound dressing material with anti-inflammatory properties (3M); and. dental materials with improved soft tissue integration (Nobel BioCare). By the first year, we will have elucidated the catalytic mechanisms of action of TiO,, established the ceramic coating technologies, characterized the inflammation response in the hamster model, and fabricated and tested dental coatings. Our overall objective is to provide the proof-of-principle to our industrial partners, which will encourage them to participate in more specific product development in the second phase (years 6-10) of the BRP.