Treatment of early caries lesions using biomimetic self-assembling peptides--a clinical safety trial

Abstract

Objective: We previously reported that a rationally designed biomimetic self-assembling peptide, P₁₁-4, nucleated hydroxyapatite de novo and was apparently capable of in situ enamel regeneration following infiltration into caries-like lesions. Our present aim was to determine the safety and potential clinical efficacy of a single application of P₁₁-4 on early enamel lesions.

Materials and methods: Fifteen healthy adults with Class V 'white spot' lesions received a single application of P₁₁-4. Adverse events and lesion appearances were recorded over 180 days.

Results: Patients treated with P₁₁-4 experienced a total of 11 adverse events during the study, of which two were possibly related to the protocol. Efficacy evaluation suggested that treatment with P₁₁-4 significantly decreased lesion size (p = 0.02) after 30 days and shifted the apparent progression of the lesions from 'arrested/progressing' to 'remineralising' (p <0.001). A highly significant improvement in the global impression of change was recorded at day 30 compared with baseline (p <0.001).

Conclusions: The results suggest that treatment of early caries lesions with P₁₁-4 is safe, and that a single application is associated with significant enamel regeneration, presumably by promoting mineral deposition within the subsurface tissue.

Figure 1. Diagrammatic illustration of structure of hydroxyapatite, originally described by Kay et al., and modified here from Elliott

Figure 1. Diagram illustrating nucleation and crystal growth

Figure 2. Schematic showing underlying hypothesis for treatment of early caries using P₁₁−4 self assembling peptides.

(1) Early caries appears as a 'white spot' on the enamel surface (^*), this is due to the underlying porosity in the tissue (2). Aqueous P₁₁−4 in its monomeric form applied to the lesion surface (3) will penetrate in to the pores due to its low viscosity (4). Self-assembly is triggered by the conditions (pH <7.4, presence of salts) within the lesion forming fibres (5) which can nucleate hydroxyapatite mineral (6). This restores both the enamel mineral and the natural appearance (7) of the original lesion

Figure 3. Examples of clinical appearance of two Class V caries lesions (arrows) in different subjects included in the study.

Images selected to show the range of response to a single application of P₁₁−4 with time. (a, d) Lesion appearance at baseline (D0); (b, e) and (c, f) appearance of same lesion at D30 and D180 respectively

Figure 4. Schematic showing underlying hypothesis for treatment of early caries using P₁₁−4 self assembling peptides.

(1) Early caries appears as a 'white spot' on the enamel surface (^*), this is due to the underlying porosity in the tissue (2). Aqueous P₁₁−4 in its monomeric form applied to the lesion surface (3) will penetrate in to the pores due to its low viscosity (4). Self-assembly is triggered by the conditions (pH <7.4, presence of salts) within the lesion forming fibres (5) which can nucleate hydroxyapatite mineral (6). This restores both the enamel mineral and the natural appearance (7) of the original lesion

Figure 5. Effect of a single application of P₁₁−4 on colour, size and progression of the treated caries lesion compared to baseline (D0) as judged by blinded assessors using a visual analogue scale from −100 to +100.

Histograms show change in lesion colour (red); change in lesion size (yellow) and change in lesion progression (blue). Lesion colour: positive values indicate an improvement in lesion colour (ie less white). Lesion size: positive values indicate a lesion that is increasing in size; negative values a decrease in lesion size. Lesion progression: positive values indicate a lesion that is judged to be progressing, negative values indicate a lesion that is judged to be remineralising. Significance when compared with baseline indicated by ^*(p ≤0.05); ^**(p ≤0.001)