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仿生牙齿修复:牙釉蛋白衍生肽可实现人牙釉质的体外再矿化。

Biomimetic Tooth Repair: Amelogenin-Derived Peptide Enables in Vitro Remineralization of Human Enamel.

作者信息

Dogan Sami, Fong Hanson, Yucesoy Deniz T, Cousin Timothee, Gresswell Carolyn, Dag Sefa, Huang Greg, Sarikaya Mehmet

出版信息

ACS Biomater Sci Eng. 2018 May 14;4(5):1788-1796. doi: 10.1021/acsbiomaterials.7b00959. Epub 2018 Mar 21.

Abstract

White spot lesions (WSL) and incipient caries on enamel surfaces are the earliest clinical outcomes for demineralization and caries. If left untreated, the caries can progress and may cause complex restorative procedures or even tooth extraction which destroys soft and hard tissue architecture as a consequence of connective tissue and bone loss. Current clinical practices are insufficient in treating dental caries. A long-standing practical challenge associated with demineralization related to dental diseases is incorporating a functional mineral microlayer which is fully integrated into the molecular structure of the tooth in repairing damaged enamel. This study demonstrates that small peptide domains derived from native protein amelogenin can be utilized to construct a mineral layer on damaged human enamel in vitro. Six groups were prepared to carry out remineralization on artificially created lesions on enamel: (1) no treatment, (2) Ca and PO only, (3) 1100 ppm fluoride (F), (4) 20 000 ppm F, (5) 1100 ppm F and peptide, and (6) peptide alone. While the 1100 ppm F sample (indicative of common F content of toothpaste for homecare) did not deliver F to the thinly deposited mineral layer, high F test sample (indicative of clinical varnish treatment) formed mainly CaF nanoparticles on the surface. Fluoride, however, was deposited in the presence of the peptide, which also formed a thin mineral layer which was partially crystallized as fluorapatite. Among the test groups, only the peptide-alone sample resulted in remineralization of fairly thick (10 μm) dense mineralized layer containing HAp mineral, resembling the structure of the healthy enamel. The newly formed mineralized layer exhibited integration with the underlying enamel as evident by cross-sectional imaging. The peptide-guided remineralization approach sets the foundation for future development of biomimetic products and treatments for dental health care.

摘要

牙釉质表面的白斑病变(WSL)和早期龋是脱矿和龋齿的最早临床症状。如果不进行治疗,龋齿会继续发展,可能需要进行复杂的修复手术,甚至拔牙,最终会导致结缔组织和骨质流失,破坏软硬组织结构。目前的临床治疗方法在治疗龋齿方面存在不足。与牙齿疾病相关的脱矿问题长期以来面临的一个实际挑战是,如何形成一个能完全融入牙齿分子结构的功能性矿物微层,以修复受损的牙釉质。本研究表明,源自天然蛋白质釉原蛋白的小肽结构域可用于在体外受损的人牙釉质上构建矿物层。本研究设置了六组实验,对人工制造的牙釉质病变进行再矿化处理:(1)不治疗;(2)仅使用钙和磷;(3)1100 ppm氟化物(F);(4)20000 ppm F;(5)1100 ppm F和肽;(6)仅使用肽。虽然1100 ppm F的样本(代表家庭护理牙膏的常见F含量)没有向薄沉积矿物层输送F,但高F测试样本(代表临床清漆治疗)在表面主要形成了CaF纳米颗粒。然而,在肽存在的情况下氟化物会沉积下来,同时也会形成一层薄的矿物层,该矿物层部分结晶为氟磷灰石。在测试组中,只有仅使用肽的样本使相当厚(10μm)的含有羟基磷灰石(HAp)矿物的致密矿化层实现了再矿化,类似于健康牙釉质的结构。通过横截面成像可以明显看出,新形成的矿化层与下层牙釉质融合在一起。肽引导的再矿化方法为未来牙科保健仿生产品和治疗方法的开发奠定了基础。

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