Riboflavin and riboflavin-derivatives as collagen cross-linker agents for improved longevity of dental restorations

蛀牙是一项重大的公共卫生挑战，给医疗保健系统带来了巨大的负担。为了美观地替换丢失的牙齿组织和龋齿缺陷，粘合剂放置的牙齿着色修复是当今最常见的干预措施。然而，它们的寿命是有限的，因为牙齿结构和修复材料之间的结合容易降解。通过额外的交联加强粘结牙齿区域中的牙本质胶原网络是预防或延迟这种降解的合理机制。因此，该项目旨在帮助了解外部应用的佐剂胶原交联剂和牙齿结构之间的基本相互作用机制，特别是在临床挑战性条件下潜在增强的抗降解性。该项目分为三个阶段，首先将筛选人体中发现的天然材料，如维生素B2（核黄素，RB）和RB衍生物，沿着在环境条件下实现最佳功能的参数。从物理、化学、力学、生物学和毒理学等多个方面综合分析了交联剂与牙齿结构的基本作用机理，并对胶原交联程度进行了量化。最后，将在不同的模拟和越来越积极的临床条件下开发和评估临床适用的治疗方案。该项目将结合联合收割机多学科的调查方法，在宏观到纳米尺度，并提供以前不可用的见解与交联处理相关的过程。这些包括扫描电子显微镜（SEM）和扫描近场显微镜（SNOM），使用量子级联激光的高分辨率红外成像光谱，准静态和动态力学分析，酶谱，SDS-PAGE，生物相容性和细胞毒性。

Tooth decay is a major public health challenge that places an enormous burden on the healthcare system. In order to aesthetically replace lost tooth tissue and carious defects, adhesive placed tooth-colored restorations are the most common interventions today. However, their lifespan is limited because the bond between tooth structure and restorative material is prone to degradation. Strengthening the dentinal collagen network in the bonded tooth area through additional cross-linking is a plausible mechanism to prevent or delay this degradation. The project aim therefore to contribute to the understanding of the fundamental interaction mechanisms between externally applied adjuvant collagen cross-linkers and tooth structure, in particular with regard to potentially enhanced resistance to degradation under clinically challenging conditions. Divided into three phases, the project will first screen natural materials found in the human body, such as vitamin B2 (riboflavin, RB) and RB derivatives, along with parameters for optimal functionality under environmental conditions. From a complex perspective, that includes physical, chemical, mechanical, biological and toxicological aspects, the basic interaction mechanisms of the cross-linking agents and the tooth structure will be analyzed, and the degree of collagen cross-linking quantified. Finally, a clinically applicable treatment protocol will be developed and evaluated under different simulated and increasingly aggressive clinical conditions. The project will combine multidisciplinary investigation methods at macroscopic to nanoscopic scale and provide previously unavailable insights into the processes associated with cross-linking treatment. These include scanning electron microscopy (SEM) and scanning near-field microscopy (SNOM), high-resolution infrared imaging spectroscopy using a quantum cascade laser, quasi-static and dynamic mechanical analysis, zymography, SDS-PAGE, biocompatibility and cytotoxicity.