Remineralization carious lesions in dentin using the PILP-approach

使用 PILP 方法再矿化牙本质龋损

• 批准号: 9980847
• 负责人: Stefan Friedrich Habelitz
• 金额: $ 24.23万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-08-01 至 2022-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9980847
• 关键词: Acids; Adult; Affect; Age; American; Apatites; Aspartic Acid; Chemicals; Child; Clinical; Collagen; Collagen Fibril; Data; Dental; Dental Care; Dental Enamel; Dental Philosophy; Dental Pulp; Dental caries; Dentin; Dentistry; Digestion; Disease; Effectiveness; Elements; Endodontics; Excision; Exposure to; Fluorides; Formulation; Human; In Vitro; Lead; Left; Lesion; Life; Liquid substance; Literature; Mastication; Mechanics; Methods; Minerals; Natural regeneration; Normal tissue morphology; Papain; Philosophy; Polymers; Prevention; Procedures; Process; Proteins; Psychological reinforcement; Recovery of Function; Reporting; Specimen; Speed; Stress; Structure; System; Techniques; Testing; Time; Tissues; Tooth Loss; Tooth structure; Translations; Weight-Bearing state; base; bone; demineralization; dental infection; functional restoration; mechanical properties; microCT; mineralization; minimally invasive; nanoindentation; novel; osteopontin; preservation; regenerative; remineralization; repaired; restoration; restorative treatment; seal; standard of care; tissue repair

Project Summary/Abstract The last decade has seen a shift in the philosophy of dental care towards prevention and minimal-invasive restorative approaches, promoting tissue repair by remineralization as a key element of dental treatments. Remineralization of enamel, which is 95% mineral, is an accepted phenomenon with established mechanisms relying mainly on fluoride release. Those mechanisms, however, do not apply to dentin, as they do not produce intrafibrillar mineral as demonstrated in our preliminary studies. Dentin is a collagenous tissue, similar to bone, and requires apatite mineral to form inside collagen fibrils (intrafibrillar) for mechanical reinforcement. We have shown that the “Polymer-Induced Liquid Precursor” (PILP) approach is suitable and effective to reintroduce mineral into collagen in vitro restoring the mechanical properties of the tissue, which is critical for its function. PILP-treatments performed on demineralized specimens recovered their mechanical properties at 50 to 100% of normal tissue value when evaluated by nanoindentation and 4-point bending tests, respectively. We have identified two proteins, osteopontin (OPN-10) and phosvitin (PV) in addition to synthetic poly-aspartic acid (pAsp), among a larger set of possible systems, reported in the literature, that reintroduce oriented apatite crystallites in the interstices of collagen-I fibrils in dentin matrices. Based on this concept, we propose to develop PILP-releasing materials and procedures that can be applied to dentin caries and be integrated with a restorative treatment facilitating long-term collagen remineralization leading to a restoration of tissue function, ultimately extending the life-time of the tooth and thus reducing the incidents of pulp exposure and endodontic treatment or tooth loss due to caries. The proposed reparative procedures will interfere with the current standard of care for caries management in dentistry that stresses excessive tissue removal. Instead this approach will promote repair, regeneration and conservation of the natural tissue. Dentin's function is primarily mechanical as it supports the stiff enamel in the mastication process. That function is lost when bacterial acid dissolves and removes apatite from collagen fibrils. PILP-mineralization is thus far the only known method to restore this function in vitro in artificial lesions. We consider this approach a regenerative approach as it rebuilds a weight-bearing tissue which would otherwise not contribute to the mastication process. Here we propose to test the standard PILP-mineralization method as well as novel cement formulations that are comprised of PILP-components for their potential to repair natural caries lesions in vitro as a further step towards translation of the PILP-mineralization concept into a clinical setting.

项目总结/摘要 在过去的十年里，牙科护理理念发生了转变，转向预防和微创治疗。 修复方法，通过矿化促进组织修复，作为牙科治疗的关键要素。 釉质的再矿化是一种公认的现象，其95%是矿物， 主要依靠氟化物的释放。然而，这些机制不适用于牙本质，因为它们不产生 我们的初步研究表明，纤维内的矿物。牙本质是一种胶原组织，类似于骨骼， 并且需要磷灰石矿物质在胶原纤维内部形成（纤维内）用于机械增强。我们有 表明"聚合物诱导的液体前体"（PILP）方法是合适和有效的重新引入 矿物质转化为胶原蛋白在体外恢复组织的机械性能，这是其功能的关键。 在脱矿物质试样上进行的PILP处理使其机械性能恢复了50%至100% 正常组织值时，分别通过纳米压痕和4点弯曲试验进行评估。我们有 除了合成的聚天冬氨酸外，还鉴定了两种蛋白质，骨桥蛋白（OPN-10）和骨桥蛋白（PV （pAsp），在文献中报道的较大的一组可能的系统中，重新引入定向磷灰石 牙本质基质中胶原-I原纤维间隙中的微晶。基于这一概念，我们建议 开发可应用于牙本质龋的PILP释放材料和程序，并与 促进长期胶原蛋白再矿化的恢复性治疗导致组织功能的恢复， 最终延长牙齿的寿命，从而减少牙髓暴露和牙髓炎的发生， 治疗或牙齿脱落由于龋齿。 建议的修复程序将干扰目前的标准护理龋齿管理， 强调过度组织去除的牙科学。相反，这种方法将促进修复，再生和 自然组织的保存。牙本质的功能主要是机械性的，因为它支持牙釉质的坚硬。 咀嚼过程当细菌酸溶解并从胶原蛋白中去除磷灰石时， 纤维PILP矿化是迄今为止唯一已知的在体外人工损伤中恢复这种功能的方法。 我们认为这种方法是一种再生方法，因为它重建了一个承重组织， 否则对咀嚼过程没有贡献。在这里，我们建议测试标准的PILP矿化 本发明涉及一种方法以及由PILP组分组成的新型水泥制剂， 在体外修复自然龋损，作为将PILP矿化概念转化为 临床环境。