Stimulation of tooth repair and regeneration by interaction with dental meterials

描述(由申请人提供)：本申请的总体目标是为应聘者提供在牙科材料研究方面具有广泛背景的高级研究员的经验，该技术用于研究由于牙科疾病造成的伤害或侮辱以及它们随后与牙科材料的相互作用而导致的活的牙科组织、牙髓和牙本质的再生。再生医学的进步正在为修复牙科的新纪元铺平道路，这次培训将使候选人成为这一领域的关键参与者。这一经验，包括具体的研究项目，支持了NIDCR的目标，即鼓励对口腔面部组织的修复和再生进行研究，确定常用牙科材料的安全性，并提供足够和训练有素的研究队伍。为了实现总体目标，候选人在发起人、该领域的专家托尼·史密斯博士(英国伯明翰大学)的建议下，设计了一系列实验。使用和不使用生物活性玻璃添加剂的牙本质粘合剂和玻璃离子修复剂将作为测试材料。这项高级奖学金申请的研究计划有三个具体目标。第一个目标是用系统地更高强度(较低pH)的酸来处理人牙本质，这代表了目前的自提取牙科粘合剂以及自酸蚀粘合剂和传统玻璃离子粘结剂的商业版本的不同，并识别和定量释放的生物活性分子，如生长因子。第二个目的是利用细胞培养和基因表达来检测不同材料从牙本质中释放的生物活性分子的活性，以了解它们刺激牙本质再生的能力。第三个目标是使用伯明翰大学开发的牙齿切片器官培养模型来研究暴露在特定牙科材料下的牙本质细胞死亡的程度和愈合过程；并确定是否可以通过在自酸蚀粘合剂和玻璃离子中加入钙磷释放材料来促进愈合过程，这是一种二氧化硅基生物活性玻璃，目前申请人正在研究用于牙科粘合剂和修复剂。公共卫生相关性：这项工作与公共卫生相关，因为它调查牙齿组织对用于修复牙齿以及修复和再生的材料做出反应的方式。这项工作还试图通过释放牙齿修复或再生过程所需的自身分子来识别可能有助于修复过程的牙科材料。

DESCRIPTION (provided by applicant): The overall goal of this application is to provide the candidate, a senior investigator with an extensive background in dental materials research, with experience in the techniques used to study the regeneration of living dental tissues, pulp and dentin, as a result of injury or insult from dental disease and their subsequent interactions with dental materials. Advances in regenerative medicine are paving the way for a new era in restorative dentistry and this training will position the candidate to be a key player in contributing to this field. This experience, including the specific research project, are in support of the goals of the NIDCR which is to encourage research on the repair and regeneration of orofacial tissues, to determine the safety of commonly used dental materials, and to provide an adequate and well-trained research workforce. To accomplish the overall goal, a series of experiments have been designed by the candidate, with the advice of the sponsor, Dr. Tony Smith (U. Birmingham), an expert in this field. Dentin adhesives and glass ionomer restoratives, with and without a bioactive glass additive, will serve as the test materials. The research plan for this senior fellowship application has three specific aims. The first aim is to treat human dentin with acid of systematically greater strength (lower pH), representing differences in current "selfetching" dental adhesives, as well as commercial versions of self-etching adhesives and conventional glass ionomer, and to identify and quantitate the bioactive molecules, such as growth factors, that are released. The second aim is to use cell culture and gene expression to examine the viability of the bioactive molecules released from dentin by the various materials in terms of their ability to stimulate dentin regeneration. The third aim is to use the tooth slice organ culture model developed at the University of Birmingham to study the extent of cell death and the healing process of dentin exposed to specific dental materials; and to determine if the healing process can be enhanced by incorporating into the self-etching adhesive and glass ionomer a calcium and phosphate releasing material, a silica-based bioactive glass, that is currently being studied by the applicant for use in dental adhesives and restoratives. Public Health Relevance: This work is relevant to public health in that it investigates the manner in which tooth tissues respond to materials used to restore teeth and repair and regenerate themselves. This work also seeks to identify dental materials that may aid in the healing process by releasing the tooth's own molecules needed for the repair or regeneration process.