Blending Dentin to Dentin: Biometric Hydrogels for Dentin Tissue Engineering

项目摘要 龋齿是大多数工业化国家的主要健康问题，其中大多数儿童，年轻人和老年人， 成年人一生中至少经历过一次这种疾病。在最近的一项研究（2019年）中， 在全球公共卫生的疾病中，未经治疗的龋齿是最普遍和最重要的， 口腔疾病，影响全球超过30亿人，对生活质量有很大的不利影响， 对个人、家庭和社会都有很高的成本。此外，龋病在人群中的分布是不均匀的 社会经济梯度很大。虽然龋齿基本上是一种可预防的疾病， 在过去40年中，流行率几乎没有下降。 虽然尚未发现预防和管理龋齿的明确方法，但修复生物材料 并且技术仍然是修复龋齿影响的牙齿的唯一现有资源。主 修复牙科学的目标是通过用合成材料替代牙齿来修复受损的结构 旨在重建牙齿的美学和功能。目前的恢复性程序完全依赖于 甲基丙烯酸树脂与纳米结构有机物之间的有效微机械相互作用 牙本质的大分子（主要是胶原蛋白），牙齿的最大基质，需要在牙科中进行实质性修复， 康复计划。正如几位牙科材料科学家所引用的那样， 部分脱矿质牙本质是一种按需组织工程。 尽管如此，创造耐用的树脂基填充物仍然是粘接牙科的一个重大挑战。NIDCR 2009-2013年关于牙齿彩色树脂漂白剂的战略计划报告说， 仅用了5.7年。更换这些设备的主要原因是 树脂-牙本质结合界面的酶降解，最终促进复发性龋齿。 在美国，更换有缺陷的树脂填充物的估计成本约为每年50亿美元 一个人该提案的总体目标是使用改性天然生物材料来解决这一问题。本研究 将通过脱矿物质的细胞外基质（ECM）的功能化来开发杂化水凝胶。 用丙烯酰胺处理牙本质，以生产不易发生水解的树脂牙科粘合剂 降解此外，该提案将开创一种真正仿生内源性的牙科粘合剂， 因此，不仅具有修复龋齿损伤的能力，而且能够更好地再生牙本质 比目前的甲基丙烯酸酯牙科粘合剂。 该计划将为研究生和专业学生提供良好的培训机会，从而提供 为下一代临床医生提供科学支持。虽然这项技术主要用于 先进的牙本质生物工程和康复，有可能将我们的发现转化为其他生物医学 ECM衍生物水凝胶的使用是介导原位组织再生的关键。

Project Summary Dental caries is a major health concern in most industrialized countries, in which most children, young and older adults have experienced the disease at least once in their lifetime. In recent study (2019) on the impact of oral diseases on global public health, untreated caries figures as the most prevalent and consequential amongst all oral conditions, affecting more than 3 billion people worldwide, with strong detrimental effect on quality of life and high costs for individuals, families, and society. Moreover, caries disease is unequally distributed in populations with a significant socioeconomic gradient. Although dental caries is essentially a preventable condition, its prevalence has barely diminished over the last 40 years. While a definitive approach to prevent and manage dental caries has yet to be found, restorative biomaterials and techniques remain as the only existing resources for rehabilitation of the caries-affected tooth. The primary goal of restorative dentistry is to repair tooth damaged structures by replacing them with synthetic materials aiming at the re-establishment of tooth aesthetics and function. Current restorative procedures fully depend on effective micromechanical interactions between resin methacrylates and nanostructured organic macromolecules of dentin (mainly collagen), the bulkiest substrate of tooth demanding substantial repair in dental rehabilitation schemes. As quoted by several dental material scientists, infiltration of resin methacrylates within partially demineralized dentin is a type of on-demand tissue engineering. Nonetheless, creating durable resin-based fillings is still a significant challenge in adhesive dentistry. The NIDCR 2009-2013 strategic plan on tooth-colored resin restorations reported that the average replacement time of these restorations is only 5.7 years. The major reason for replacement of such restorations has been attributed to enzymatic degradation of the resin-dentin bonded interface, which ultimately facilitates recurrent caries. Estimated costs to replace defective resin fillings are in the order of about five billion dollars per year in the US alone. The overall goal of this proposal is to use modified natural biomaterials to address this matter. This study will develop hybrid hydrogels by means the functionalization of extracellular matrix (ECM) of demineralized dentin with acrylamides to produce resin dental adhesives that are less vulnerable to undergo hydrolytic degradation. In addition, this proposal will pioneer a dental adhesive that is truly biomimetic for endogenous dentin and, as such, will have the capacity not only repair dental caries lesions, but to regenerate dentin better than current methacrylate dental adhesives. This program will offer excellent training opportunities for graduate and professional students, thus providing scientific support to the next generation of clinicians. Furthermore, while this technology intends primarily advance dentin bioengineering and rehabilitation, there is a potential to translate our findings to other biomedical applications where the use of ECM-derivative hydrogels is key to mediate in-situ tissue regeneration.