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，保护脱落牙齿的科学进展甚微。虽然有商业解决方案，但大多数只是由pH平衡的盐溶液组成。在过去的两年里，几篇经过同行评议的引文比较了Save-A-Tooth、其他盐配方、椰子水和牛奶作为维持撕脱牙齿直到可以植入的候选产品的功效。在某些情况下，脱脂牛奶和汉克平衡盐溶液（HBSS）对维持关键牙周韧带成纤维细胞（ppdf）的活力有最大的作用。由于缺乏科学合理的牙齿特异性保持介质，本项目提出开发一种新的恒温（20至37℃）培养基，旨在通过控制激活的细胞特异性应激途径，在离体保持间隔期间维持PDLF

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.