A New Normothermic Solution for Protecting Avulsed Teeth Prior to Re-implantation

描述(由申请人提供)：在过去的10年里，保护撕脱的牙齿的科学进展甚微。虽然商业解决方案是可用的，但大多数只是由pH平衡的盐溶液组成。在过去的两年里，几篇同行评议的引文比较了SAVE-A-Tooth、其他食盐配方、椰汁和牛奶作为候选方案在种植之前保持撕脱牙齿的有效性。在其中一些情况下，脱脂牛奶和汉克平衡盐溶液(HBSS)对维持关键牙周膜成纤维细胞(PDLF)的活力具有最大的能力。针对缺乏科学合理的牙齿专用保持剂的问题，该项目建议开发ToothGuardTM-一种新的常温(20至37℃)保持剂，旨在基于对激活的细胞特定应激通路的控制，在体外保持期维持PDLF 当他们被从他们自己的颅面环境中移走时，他们会被PDLF发现。ToothGuard将是第一个以完全脱水(粉末)和液体形式设计的夹持剂。该试剂的配方将通过控制细胞和分子细胞应激通路来保护在常温(室温)下体外保持的PDLF，以响应与拔牙相关的应激反应。其具体目标如下：(1)确定在PDLF中激活的细胞应激途径，当它们存在于被撕脱的牙齿中时，它们将在原位经历；(2)通过改善应激通路的反应，识别将维持PDLF的抑制剂，并在它们受到撕脱样应力状态时分别在PDLF上测试这些药物；以及(3)构建两个ToothGuard原型，并比较它们与Save-A-Tooth、HBSS和MEM的各自有效性。第二阶段将致力于优化ToothGuard，开发用于治疗炎症性/非炎症性牙根替代吸收的TGpak，开发一种用于撕脱牙齿的独特传输设备，并与一家制药/牙科供应公司以及波士顿地区的一家学术机构合作，在体内测试ToothGuard和TGpak。这一第一阶段项目的总体结果将是开发出第一种温度不敏感的室温试剂，用于在体外维持撕脱牙齿，这种试剂基于PDLF中独特的细胞应力途径，当它们受到撕脱牙齿所经历的条件时，这些细胞应激通路被激活。 公共卫生相关性：CPSI Biotech打算开发一种独特的解决方案，旨在在种植前保护撕脱(被剔除的)牙齿。该项目的创新之处在于，这款产品(ToothGuard)将是有史以来第一个基于关键细胞(牙周膜成纤维细胞)激活的个体应激通路而设计的产品，当关键细胞(牙周韧带成纤维细胞)从其自然的颅面环境中移除时，这些细胞被激活。储存在ToothGuard中的牙齿与储存在另一种解决方案中的牙齿相比，成功重新种植的机会更高，如保存一颗牙齿和牛奶。

DESCRIPTION (provided by applicant): The science of protecting avulsed teeth has progressed little in the past 10 years. While commercial solutions are available, most simply consist of a pH balanced salt solution. Several peer-reviewed citations in the last two years have compared the efficacy of Save-A-Tooth, other salt formulations, coconut water and milk as candidates for maintaining avulsed teeth until such time that they can be implanted. In some of these cases skim milk and Hank's Balanced Salt Solution (HBSS) have the greatest capacity to maintain the viability of the critical periodontal ligament fibroblasts (PDLF). In response to the lack of a scientifically sound, tooth-specific, holding medium this project proposes to develop ToothGuardTM - a new normothermic (20 to 37oC) medium designed to maintain the PDLF during the ex vivo holding interval based on the control of cell specific stress pathways activated by PDLF when they are removed from their native craniofacial environment. ToothGuard will be the first holding reagent designed both in a fully dehydrated (powder) and liquid format. The reagent will be formulated to protect PDLF during ex vivo holding at normothermic temperatures (room temperature) through the control of the cellular and molecular cell stress pathways activated in response to the stresses associated with tooth avulsion. The Specific Aims are as follows: (1) Identify the cell stress pathways activated in PDLF under conditions that they would experience in situ when present in an avulsed tooth; (2) Identify inhibitors that will maintain PDLF by ameliorating the stress pathway response and test these agents individually on PDLF when they are subjected to avulsion-like stress regimes; and (3) Formulate two ToothGuard prototypes and compare them for their respective effectiveness against Save-A-Tooth, HBSS and MEM. Phase 2 will be dedicated to optimizing ToothGuard, developing TGpak for treating inflammatory/non-inflammatory root replacement resorption, developing a unique transport device for the avulsed tooth and teaming with a pharmaceutical/dental supply company as well as a Boston area academic institution to test ToothGuard and TGpak in vivo. The sum consequence of this Phase 1 project will be the first thermally insensitive, room temperature, reagent developed to maintain avulsed teeth ex vivo based on the unique, cell stress pathways activated in PDLF when they are subjected to conditions experienced in an avulsed tooth. PUBLIC HEALTH RELEVANCE: CPSI Biotech intends to develop a unique solution designed to protect avulsed (knocked out) teeth prior to implantation. The innovation of this project is tha this product (ToothGuard) will be the first ever designed based on the individual stress pathways that are activated by the key cells (periodontal ligament fibroblasts) when they are removed from their native craniofacial environment. Teeth stored in ToothGuard will have a higher chance of successful re-implantation compared to teeth stored in alternative solutions such as Save-A-Tooth and milk.