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.

项目摘要/摘要 在过去的十年里，牙科保健的理念已经转向预防和微创。 修复方法，通过再矿化促进组织修复，将其作为牙科治疗的一个关键要素。 牙釉质中95%是矿物质，牙釉质的再矿化是一种公认的现象，有既定的机制 主要依靠氟化物的释放。然而，这些机制不适用于牙本质，因为它们不会产生 在我们的初步研究中证明了纤维内矿物。牙本质是一种胶原组织，类似于骨， 并且需要磷灰石矿物在胶原纤维(纤维内)内形成以用于机械增强。我们有 结果表明，“聚合物诱导液体前驱体”(PILP)法是一种合适且有效的再引入方法 矿物质在体外转化为胶原蛋白，恢复组织的机械性能，这对其功能至关重要。 对脱矿样品进行PILP处理后，其力学性能恢复到50%至100% 分别通过纳米压痕和四点弯曲试验评估正常组织价值。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)和磷高磷蛋白(PV) (PAsp)，在文献中报道的一组更大的可能的系统中，重新引入定向磷灰石 牙本质基质中I型胶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齿的PILP释放材料和程序，并与 促进长期胶原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，从而减少牙髓外露和牙髓损伤的发生 治疗或因龋齿而掉牙。 拟议的修复程序将干扰#年龋齿管理的现行护理标准。 强调过度去除组织的牙科。相反，这种方法将促进修复、再生和 保护自然组织。牙本质的功能主要是机械的，因为它支持牙本质中的坚硬牙釉质 咀嚼过程。当细菌酸溶解并从胶原中去除磷灰石时，这种功能就会丧失 纤维。到目前为止，PILP矿化是唯一已知的在人工损伤的体外恢复这一功能的方法。 我们认为这种方法是一种再生方法，因为它重建了承重组织， 否则不会对咀嚼过程做出贡献。在这里，我们建议测试标准的PILP矿化 方法以及由PILP组分组成的新型水泥配方 体外修复天然龋损作为将PILP矿化概念转化为 一种临床环境。