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

P A Brunton, R P W Davies, J L Burke, A Smith, A Aggeli, S J Brookes, J Kirkham, P A Brunton, R P W Davies, J L Burke, A Smith, A Aggeli, S J Brookes, J Kirkham

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.

Conflict of interest statement

Conflict of interest declaration: J. Kirkham and A. Aggeli are named inventors on the underlying patent on self-assembling peptides. The University of Leeds holds an equity stake in credentis.

Figures

Figure 1. Diagrammatic illustration of structure of…
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…
Figure 1. Diagram illustrating nucleation and crystal growth
Figure 2. Schematic showing underlying hypothesis for…
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…
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…
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…
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)

References

    1. Kirkham J, Firth A, Vernals D et al.. Self-assembling peptide scaffolds promote enamel remineralization. J Dent Res 2007; 86: 426–430.
    1. Aggeli A, Bell M, Boden N et al.. Responsive gels formed by the spontaneous self-assembly of peptides into polymeric beta-sheet tapes. Nature 1997; 386: 259–262.
    1. Aggeli A, Bell M, Boden N et al.. Engineering of peptide beta-sheet nanotapes. J Mater Chem 1997; 7: 1135–1145.
    1. Aggeli A, Bell M, Carrick L M et al.. pH as a trigger of peptide beta-sheet self-assembly and reversible switching between nematic and isotropic phases. J Am Chem Soc 2003; 125: 9619–9628.
    1. Aggeli A, Fytas G, Vlassopoulos D et al.. Structure and dynamics of self-assembling beta-sheet peptide tapes by dynamic light scattering. Biomacromolecules 2001; 2: 378–388.
    1. Aggeli A, Nyrkova I A, Bell M et al.. Hierarchical self-assembly of chiral rod-like molecules as a model for peptide beta -sheet tapes, ribbons, fibrils, and fibres. Proc Natl Acad Sci U S A 2001; 98: 11857–11862.
    1. Firth A, Aggeli A, Burke J L, Yang X, Kirkham J. Biomimetic self-assembling peptides as injectable scaffolds for hard tissue engineering. Nanomedicine (Lond) 2006; 1: 189–199.
    1. Kitasako Y, Hiraishi N, Nakajima M et al.. In vitro surface analysis of active and arrested dentinal caries using a pH-imaging microscope. Oper Dent 2002; 27: 354–359.
    1. Burke J L. In situ engineering of skeletal tissues using self-assembled biomimetic scaffolds [PhD]. Leeds: The University of Leeds, 2011.
    1. Felton S. Self assembling -sheet peptide networks as smart scaffolds for tissue engineering [PhD Thesis]. Leeds: University of Leeds, 2005.
    1. Kirkham J, Brookes S J, Shore R C et al.. Physico-chemical properties of crystal surfaces in matrix- mineral interactions during mammalian biomineralisation. Curr Opin Colloid In 2002; 7: 124–132.
    1. Wen H B, Moradian-Oldak J, Leung W, Bringas P Jr., Fincham A G. Microstructures of an amelogenin gel matrix. J Struct Biol 1999; 126: 42–51.
    1. Simmer J P, Fincham A G. Molecular mechanisms of dental enamel formation. Crit Rev Oral Biol M 1995; 6: 84–108.
    1. Kim J W, Seymen F, Lin B P et al.. ENAM mutations in autosomal-dominant amelogenesis imperfecta. J Dent Res 2005; 84: 278–282.
    1. Wright J T, Hart P S, Aldred M J et al.. Relationship of phenotype and genotype in X-linked amelogenesis imperfecta. Connect Tissue Res 2003; 44: 72–78.
    1. Robinson C, Kirkham J, Brookes S J, Shore R C. Chemistry of mature enamel. In Robinson C, Kirkham J, Shore R C (eds) Dental enamel formation to destruction. pp 167–191. Boca Raton: CRC Press, 1995.
    1. Robinson C, Shore R C, Brookes S J et al.. The chemistry of enamel caries. Crit Rev Oral Biol M 2000; 11: 481–495.
    1. Johnson A R. The early carious lesion of enamel. J Oral Pathol 1975; 4: 128–157.
    1. Fan PL, Seluk L W, O'Brien W J. Penetrativity of sealants: I. J Dent Res 1975; 54: 262–264.
    1. Robinson C, Brookes S J, Kirkham J, Wood S R, Shore R C. In vitro studies of the penetration of adhesive resins into artificial caries-like lesions. Caries Res 2001; 35: 136–141.
    1. Paris S, Meyer-Lueckel H. Inhibition of caries progression by resin infiltration in situ. Caries Res 2010; 44: 47–54.
    1. Paris S, Hopfenmuller W, Meyer-Lueckel H. Resin infiltration of caries lesions: an efficacy randomized trial. J Dent Res 2010; 89: 823–826.
    1. Vieira A P, Lawrence H P, Limeback H, Sampaio F C, Grynpas M. A visual analogue scale for measuring dental fluorosis severity. J Am Dent Assoc 2005; 136: 895–901.
    1. Shore R C, Kirkham J, Brookes S J, Wood S R, Robinson C. Distribution of exogenous proteins in caries lesions in relation to the pattern of demineralisation. Caries Res 2000; 34: 188–193.
    1. Kay MI, Young R A, Posner A S. Crystal structure of hydroxyapatite. Nature 1964; 204: 1050–1052.
    1. Elliott J C. Structure and chemistry of the apatites and other calcium orthophosphates. Amsterdam: Elsevier, 1994.

Source: PubMed

Sponsors en medewerkers

Medische omstandigheden

Geneesmiddelinterventies

3
Abonneren