Dentin biomodification: strategies, renewable resources and clinical applications

Abstract

Objectives: The biomodification of dentin is a biomimetic approach, mediated by bioactive agents, to enhance and reinforce the dentin by locally altering the biochemistry and biomechanical properties. This review provides an overview of key dentin matrix components, targeting effects of biomodification strategies, the chemistry of renewable natural sources, and current research on their potential clinical applications.

Methods: The PubMed database and collected literature were used as a resource for peer-reviewed articles to highlight the topics of dentin hierarchical structure, biomodification agents, and laboratorial investigations of their clinical applications. In addition, new data is presented on laboratorial methods for the standardization of proanthocyanidin-rich preparations as a renewable source of plant-derived biomodification agents.

Results: Biomodification agents can be categorized as physical methods and chemical agents. Synthetic and naturally occurring chemical strategies present distinctive mechanism of interaction with the tissue. Initially thought to be driven only by inter- or intra-molecular collagen induced non-enzymatic cross-linking, multiple interactions with other dentin components are fundamental for the long-term biomechanics and biostability of the tissue. Oligomeric proanthocyanidins show promising bioactivity, and their chemical complexity requires systematic evaluation of the active compounds to produce a fully standardized intervention material from renewable resource, prior to their detailed clinical evaluation.

Significance: Understanding the hierarchical structure of dentin and the targeting effect of the bioactive compounds will establish their use in both dentin-biomaterials interface and caries management.

Keywords: Biomaterials; Carbodiimide; Collagen cross-linking; Dental caries; Dentin; Proanthocyanidins; Resin–dentin interfaces; Surface biomodification.

Figure 1

Distribution and hierarchical structure of dentin extracellular matrix components relevant to dentin biomodification. (A) Tooth structure. EN: enamel, D: dentin, PD: predentin, P: pulp. (B) Proteoglycans and endogenous proteases distribution in coronal dentin. Endogenous proteases include MMPs and cysteine-cathepsins with greater presence of both enzymes in deep dentin areas and predentin and the dentin enamel junction [31, 134, 135]. Proteoglycans are also identified in deep dentin, especially predentin region [136]. (C) Dentinal tubule cross-section view at higher magnification representing collagen fibrils, proteoglycans and endogenous proteases. ITD: intertubular dentin; T: dentin tubule. Proteoglycans are bound to collagen and immunolocalized throughout and highly concentrated at the peritubular dentin [136, 137]. Cathepsin B was localized in the odontoblasts and dentinal tubules, especially in peritubular dentin [31]. MMP-2, -9 and -3 are localized along collagen fibrils, mainly at intertubular dentin [28, 138], but no MMPs were identified inside the tubules [134]. (D) Collagen fibril interactions with non-collagenous proteins in dentin organic matrix. The protein core present in proteoglycans binds to collagen and forms aggregates of microfibrils by holding the collagen network together [137]. (E) Enzymatic collagen cross-links provide tensile properties and stability to the collagen fibrils.

Figure 2

(A) Composition of the monomeric building block of proanthocyanidins. (B) Schematic representation of the permutation of catechin monomers in PACs with various degrees of polymerization.

Figure 3

Structures of common procyanidins. The color coding distinguishes the two most abundant monomers, catechin(C) and epicatechin (EC).

Figure 4

Comparison of the structures of procyanidin B1 and B7 in 2D structure drawings and a 3D-model. The difference in their inter-flavanol linkages leads to an important change in the overall geometry. While the overlay of their 2D structures can demonstrates the effect when arranging the molecules as shown here, a comparison of 3D models is required to assess the actual differences in molecular shape. C- Cathechin; EC -Epicatechin

Figure 5

Diol-Phased HPLC UV 280 nm trace of procyanidins of cacao.

Figure 6

HPLC Profiles of Fractions (UV 280 nm): (A) Grape seed extract sub-fractions and (B) Cocoa seed extract sub-fractions.