Targeted enamel remineralization with mineral-loaded starch particles

Abstract

Background: Noninvasive caries treatments work topically, which may limit efficacy. The authors hypothesized that an alternative approach using mineral-loaded particles designed to target the subsurface of noncavitated caries lesions could be advantageous. This study shows in vitro proof-of-concept.

Methods: Mineral-loaded cationic starch (MLCS) particles were prepared, containing calcium, phosphate, and fluoride to provide fluoride-plus (FP) and fluoride-free (FF) alternatives. Particles were characterized for mineral loading and release. MLCS-FP and -FF treatments vs 1,000 ppm fluoride and deionized water controls were evaluated on natural smooth-surface caries lesions (n = 15 per group) after a 20-day protocol with immersion in artificial saliva with amylase and acid challenge. Treatment efficacy was assessed by microcomputed tomography, labeled fluorescence imaging, and blinded qualitative visual assessment.

Results: In aqueous suspension and absent amylase, particles showed sustained mineral ion release. The tomographic evaluation found significant (multivariable regression analysis, P < .05) restoration of lesion mineral density by MLCS-FP and MLCS-FF (42.9% and 38.6%, respectively) vs fluoride and negative controls (7.4% and -18%, respectively), particularly for the lesion subsurface (13.8% [13.0%], 15.9% [9.4%], -2.2% [7.3%], and -1.8% [4.0%] relative hydroxyapatite density for 0.25 through 0.45 μm lesion depth for FP, FF, fluoride, and deionized water, respectively). Visually reduced white opacity (Fisher exact test, P = .038, MLCS-FF vs fluoride) and labeled fluorescence (analysis of variance, P < .05 for MLCS-FF [75.4%], MLCS-FP [75.7%], fluoride [64.1%] vs negative control [-0.2%]) were observed.

Conclusions: These foundational studies show the potential of mineral-loaded starch particles to remineralize enamel as a new approach to treating early caries by subsurface targeted mineral delivery. The in vitro study results indicated that targeted particles improved treatment efficacy, with the data supporting the superiority of MLCS-FP and FF formulations over control conditions for subsurface remineralization and visual esthetic.

Keywords: Caries; esthetics; nanotechnology; noncavitated carious lesions; noninvasive treatment; remineralization; targeted delivery.

Figure 1

A. The concept of a surface treatment paradigm is illustrated with a diagram of the cross-section of a noncavitated caries lesion, with higher mineral treatment concentrations limited to the lesion surface. B. The subsurface targeted treatment paradigm concept is illustrated with guided mineral delivery using targeted particles, which shift the axis of treatment. Ca²⁺: Calcium cation. F⁻: Fluoride ion. PO₄³⁻: Phosphate ion.

Figure 2

Release profiles from fluoride-free (FF) and fluoride-plus (FP) mineral-loaded cationic starch (MLCS) particles into deionized water at 37 °C and released mineral (lighter shading) compared with total mineral loading (darker shading) for phosphorus release (A) and loading (B), calcium release (C) and loading (D), and fluoride release (E) and loading (F), respectively.

Figure 3

Analysis of natural lesions. A. Changes in mineral density after treatment as measured by microcomputed tomography. Statistically significant (P < .05) differences are denoted by the alpha symbol (α) for comparisons to negative control alone or an asterisk (*) for comparisons to both fluoride and negative controls. B. Example of microcomputed tomographic histograms for depth segments before (red) and after (blue) treatment with fluoride-plus mineral-loaded cationic starch particles.

Figure 4

A. Quantitation of reduction in LumiCare Caries Detection Rinse (Greenmark Biomedical Inc) fluorescence pixels after treatment, as measured with machine-learning-based fluorescence analysis algorithm. The negative control was deionized water. B. Examples of LumiCare Caries Detection Rinse fluorescence before and after treatment, showing cases with complete and partial reduction in LumiCare fluorescence.

Figure 5

A. Blinded qualitative assessment of white-spot lesion esthetic change after treatment. The negative control was deionized water. B. Example of improved lesion appearance for tooth after treatment with fluoride-plus particles, with corresponding LumiCare Caries Detection Rinse (Greenmark Biomedicial Inc) fluorescence images. The varnish-coated half of the tooth region (untreated control) has been demarcated.