Dataset Information

Enhancing Collagen Mineralization with Amelogenin Peptide: Towards the Restoration of Dentin.

ABSTRACT: Mammalian teeth primarily consist of two distinct calcified tissues, enamel and dentin, that are intricately integrated by a complex and critical structure, the dentin-enamel junction (DEJ). Loss of enamel exposes the underlying dentin, increasing the risk of several irreversible dental diseases. This paper highlights the significance of utilizing the functional domains of a major enamel matrix protein, amelogenin, intrinsic to tooth enamel and the DEJ interface, to rationally design smaller bioinspired peptides for regeneration of tooth microstructures. Using this strategy, we designed a synthetic peptide, P26, that demonstrates a remarkable dual mineralization potential to restore incipient enamel decay and mineralization defects localized in peripheral dentin below the DEJ. As a proof of principle, we demonstrate that interaction between P26 and collagen prompts peptide self-assembly, followed by mineralization of collagen fibrils in vitro. P26-mediated nucleation of hydroxyapatite (HAP) crystals on demineralized dentin in situ significantly facilitates the recovery of mineral density and effectively restores the biomechanical properties of dentin to near-native levels, suggesting that P26-based therapy has promising applications for treating diverse mineralized tissue defects in the tooth.

SUBMITTER: Mukherjee K

PROVIDER: S-EPMC7725229 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature

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Enhancing Collagen Mineralization with Amelogenin Peptide: Towards the Restoration of Dentin.

Mukherjee Kaushik K Visakan Gayathri G Phark Jin-Ho JH Moradian-Oldak Janet J

ACS biomaterials science & engineering 20200221 4

Mammalian teeth primarily consist of two distinct calcified tissues, enamel and dentin, that are intricately integrated by a complex and critical structure, the dentin-enamel junction (DEJ). Loss of enamel exposes the underlying dentin, increasing the risk of several irreversible dental diseases. This paper highlights the significance of utilizing the functional domains of a major enamel matrix protein, amelogenin, intrinsic to tooth enamel and the DEJ interface, to rationally design smaller bio ...[more]

PMID: 33313393

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Project description:Exposure of dentin tubules due to loss of protective enamel (crown) and cementum (root) tissues as a result of erosion, mechanical wear, gingival recession, etc. has been the leading causes of dentin hypersensitivity. Despite being a widespread ailment, no permanent solution exists to address this oral condition. Current treatments are designed to alleviate the pain by either using desensitizers or blocking dentin tubules by deposition of minerals or solid precipitates, which often have short-lived effects. Reproducing an integrated mineral layer that occludes exposed dentin with concomitant peritubular mineralization is essential to reestablish the structural and mechanical integrity of the tooth with long-term durability. Here, we describe a biomimetic treatment that promotes dentin repair using a mineralization-directing peptide, sADP5, derived from amelogenin. The occlusion was achieved through a layer-by-layer peptide-guided remineralization process that forms an infiltrating mineral layer on dentin. The structure, composition, and nanomechanical properties of the remineralized dentin were analyzed by cross-sectional scanning electron microscopy imaging, energy dispersive X-ray spectroscopy, and nanomechanical testing. The elemental analysis provided calcium and phosphate compositions that are similar to those in hydroxyapatite. The measured average hardness and reduced elastic modulus values for the mineral layer were significantly higher than those of the demineralized and sound human dentin. The structural integration of the new mineral and underlying dentin was confirmed by thermal aging demonstrating no physical separation. These results suggest that a structurally robust and mechanically durable interface is formed between the interpenetrating mineral layer and underlying dentin that can withstand long-term mechanical and thermal stresses naturally experienced in the oral environment. The peptide-guided remineralization procedure described herein could provide a foundation for the development of highly effective oral care products leading to novel biomimetic treatments for a wide range of demineralization-related ailments and, in particular, offers a potent long-term solution for dentin hypersensitivity.

Project description:Dentin Sialoprotein (DSP) and phosphophoryn (PP) are two most dominant non-collagenous proteins in dentin, which are the cleavage products of the DSPP (dentin sialophosphoprotein) precursor protein. The absence of the DSPP gene in DSPP knock-out (KO) mice results in characteristics that are consistent with dentinogenesis imperfecta type III in humans. Symptoms include thin dentin, bigger pulp chamber with frequent pulp exposure as well as abnormal epithelial-mesenchymal interactions, and the appearance of chondrocyte-like cells in dental pulp. To better understand how DSPP influences tooth development and dentin formation, we used a bacterial artificial chromosome transgene construct (BAC-DSPP) that contained the complete DSPP gene and promoter to generate BAC-DSPP transgenic mice directly in a mouse DSPP KO background. Two BAC-DSPP transgenic mouse strains were generated and characterized. DSPP mRNA expression in BAC-DSPP Strain A incisors was similar to that from wild-type (wt) mice. DSPP mRNA expression in BAC-DSPP Strain B animals was only 10% that of wt mice. PP protein content in Strain A incisors was 25% of that found in wt mice, which was sufficient to completely rescue the DSPP KO defect in mineral density, since microCT dentin mineral density analysis in 21-day postnatal animal molars showed essentially identical mineral density in both strain A and wt mice. Strain B mouse incisors, with 5% PP expression, only partially rescued the DSPP KO defect in mineral density, as microCT scans of 21-day postnatal animal molars indicated a reduced dentin mineral density compared to wt mice, though the mineral density was still increased over that of DSPP KO. Furthermore, our findings showed that DSPP dosage in Strain A was sufficient to rescue the DSPP KO defect in terms of epithelial-mesenchymal interactions, odontoblast lineage maintenance, along with normal dentin thickness and normal mineral density while DSPP gene dosage in Strain B only partially rescued the aforementioned DSPP KO defect.

Dataset Information

Enhancing Collagen Mineralization with Amelogenin Peptide: Towards the Restoration of Dentin.

Publications

Enhancing Collagen Mineralization with Amelogenin Peptide: Towards the Restoration of Dentin.

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