Dentin Mechanobiology: Bridging the Gap between Architecture and Function

Abstract

It is remarkable how teeth maintain their healthy condition under exceptionally high levels of mechanical loading. This suggests the presence of inherent mechanical adaptation mechanisms within their structure to counter constant stress. Dentin, situated between enamel and pulp, plays a crucial role in mechanically supporting tooth function. Its intermediate stiffness and viscoelastic properties, attributed to its mineralized, nanofibrous extracellular matrix, provide flexibility, strength, and rigidity, enabling it to withstand mechanical loading without fracturing. Moreover, dentin's unique architectural features, such as odontoblast processes within dentinal tubules and spatial compartmentalization between odontoblasts in dentin and sensory neurons in pulp, contribute to a distinctive sensory perception of external stimuli while acting as a defensive barrier for the dentin-pulp complex. Since dentin's architecture governs its functions in nociception and repair in response to mechanical stimuli, understanding dentin mechanobiology is crucial for developing treatments for pain management in dentin-associated diseases and dentin-pulp regeneration. This review discusses how dentin's physical features regulate mechano-sensing, focusing on mechano-sensitive ion channels. Additionally, we explore advanced in vitro platforms that mimic dentin's physical features, providing deeper insights into fundamental mechanobiological phenomena and laying the groundwork for effective mechano-therapeutic strategies for dentinal diseases.

Keywords: dentin; dentin-mimicking in vitro platforms; mechanobiology; mechanosensing; mechanotransduction; viscoelastic properties.

Figure 2

Advanced dentin-mimicking in vitro models. (A) The design of the microfluidic chip, comprising four reservoirs, two chambers, and hundreds of microchannels connecting them. (B) The morphologies of odontoblasts within the chip. An optical microscope image (left) and an immunofluorescence image (right) demonstrate that odontoblasts extend their processes along the microchannels (green: Aquaporin 4, blue: nucleus). (C) The fabrication process of a nanofibrous tubular 3D platform that integrates micropatterned microstructures into biomimetic 3D fibrous scaffolds. This innovative approach combines nanofabrication, micropatterning, and computer-assisted laser ablation to create a biomimetic nanofibrous tubular 3D matrix. (D) A cross-section view of DPSCs cultured on the matrix. (a–c) fluorescence images presenting cross-section views (red: F-actin, blue: nucleus, green: micropattern). (d) scanning electron microscope (SEM) images and (e) fluorescence images of a DPSC cultured on a microisland, showcasing highly polarized morphologies on the tubular matrix. (f) SEM images of the morphology of odontoblast in vivo (pseudo-colored in red). References [89,93] provide further details, with permission from ACS Publications and Wiley Publishing Group, respectively.

Figure 1

Schematic of mechano-sensing/transduction/transmission in dentin. Odontoblasts adopt a cylindrical shape and exhibit structural polarity, forming the outermost cell layer of the dental pulp tissue, which is advantageous for their role as sensory transducers. The nerve endings of dental primary afferents extend into dentinal tubules, establishing a distinct sensory mechanism for the tooth. (A) Diagram depicting the hierarchical structure of dentin’s extracellular matrix, including dentinal tubules, and mineralized nanofibrous networks. (B) Odontoblast bodies align at the periphery of the dental pulp and establish physical contact with nearby odontoblasts, forming an intercellular odontoblast-odontoblast network. (C) Odontoblasts sense mechanical stimuli through mechano-sensitive ion channels, such as PIEZO and TRP channels, within their processes located in dentinal tubules. (D) Upon mechano-sensing, mechanically activated odontoblasts transmit sensory signals to adjacent odontoblasts and sensory neurons, initiating mechano-transduction and related downstream signaling pathways and eventually regulating the functional behaviors of odontoblasts in response to mechanical stimuli accordingly. (E) Odontoblasts convert external mechanical stimuli into biological signals and generate electrophysiological responses for sensory signaling transmission to adjacent TG neurons, facilitating mechano-sensing as well as nociception.