Reviewing the Prospects for Dentin Regeneration
The regrowth of teeth - and the components of teeth, such as dental pulp, dentin, and enamel, that do not naturally exhibit sufficient regenerative capacity to address damage - has been a goal for researchers for some years now. Inroads have been made, but the research community is still some years from being able to sufficiently control the regrowth of entire teeth to produce more than technology demonstrations. Meanwhile, perhaps more meaningful advances have been made towards provoking the regeneration of damaged teeth in situ, finding ways to program cells in and around teeth into more regenerative modes of behavior.
Dentin is a complex mineralized tissue primarily composed of hydroxyapatite crystals, collagen fibers, and a fluid-filled tubular structure that extends from the pulp to the dentino-enamel or dentino-cementum junctions. Dentin is formed by highly specialized cells called odontoblasts, which secrete an extracellular matrix comprising collagen fibers and non-collagen proteins that serve as a scaffold for subsequent mineralization. Odontoblasts deposit dentin throughout the life of a tooth, albeit at a slower rate after early dentinogenesis, contributing to the thickening of dentin and potentially aiding in response of the tooth to external insults.
As a consequence of dentinal injury or decay, tertiary dentinogenesis of two different natures occur to protect and maintain dental pulp integrity. When secretory activities of quiescent odontoblasts are re-activated, reactionary dentin that is structurally and functionally similar to physiologic dentin is formed. On the other hand, newly differentiated odontoblast-like cells form pathologic reparative dentin, which is often less organized and more akin to bone-like tissue rather than dentin at the histological level. Likewise, physiologic dentin regeneration and pathologic dentin repair are two distinct processes aimed at restoring dentin functionality following damage, and re-establish a protective barrier for the pulp, alleviate sensitivity, and prevent further loss.
Physiologic dentin regeneration, in particular, seeks to recreate dentin that closely mimics its original, healthy state. This includes the reconstruction of dentinal tubules that integrate seamlessly with remaining dentin, the restoration of dentin-pulp complex, and the engagement of cellular and molecular pathways that govern dentinogenesis. The unique structure and function of true dentin, characterized by its distinctive tubular architecture housing odontoblasts and nerve endings, not only confers mechanical resilience to the tooth but plays a crucial role in the tooth's immune and sensitivity responses. A number of biological molecules that can direct the odontoblastic differentiation of dental pulp cells have been studied, most of which are part of key signaling pathways regulating dentinogenesis during tooth development. These include TGF-β, BMP, and Wnt/β-catenin signaling known to orchestrate the complex processes of cell differentiation, matrix deposition, and mineralization. The use of bioactive molecules in dentin regeneration has emerged as a promising approach, leveraging the biological cues to promote natural tissue regeneration.