A multi-scale, discrete-cell simulation of organogenesis: Application to the effects of strain stimulus on collective cell behavior during ameloblast migration.

A multi-scale strategy is presented for simulating organogenesis that uses a single cell response function to define the behavior of individual cells in an organ-scale simulation of a large cell population. The response function summarizes detailed information about the behavior of individual cells in a sufficiently economical way that the organ-scale model can be commensurate with the entire organ. The first application demonstrates the effects of strain stimulus on the migration of ameloblasts during enamel formation. Ameloblasts are an attractive study case because mineralization preserves a complete record of their migratory paths. The response function in this case specifies the motions of cells responding to strain stimuli that propagate through the population. The strain stimuli are related to the curvature of the surface from which the ameloblasts migrate (the dentin-enamel junction or DEJ). A single unknown rate parameter is calibrated by an independent datum from the human tooth. With no remaining adjustable parameters, the theory correctly predicts aspects of the fracture-resistant, wavy microstructure of enamel in the human molar, including wavelength variations and the rate of wave amplitude damping. At a critical value of curvature of the DEJ, a transition in the ordering of cells occurs, from invariant order over the whole population to self-assembly of the population into groups or gangs. The prediction of an ordering transition and the predicted critical curvature are consistent with gnarled enamel in the cusps of the human molar. The calibration of the model using human data also predicts waves in the mouse incisor and an ordering transition at the chimpanzee cingulum. Widespread compressive strain is predicted late in the migration for both the human molar and mouse incisor, providing a possible signal for the termination of amelogenesis.

The effect of partial damage to the enamel-related periodontium combined with root resection on eruption of the rat incisor eruption.

Previous work has indicated that the enamel-related periodontium (ERP) has a role in the eruptive process of the rat lower incisor. By combining partial damage of this tissue with resection of the odontogenic organ, we examined the effect of the damage on subsequent incisor eruption. The connective tissue of the enamel-related periodontium was regenerated in less than 2 weeks, showing morphology close to normal. The injured part of the enamel organ was neither regenerated nor repaired, and a cement-like tissue, continuous with the true acellular cement, was formed on the denuded enamel. Before tooth exfoliation, the operated teeth erupted at a slower rate compared with root-resected and sham-operated incisors, probably because of the absence of a substantial part of the enamel organ due to surgical damage. As with the coronal dental follicle and the enamel organ in rat molars, the enamel-related periodontium and the enamel organ of rat incisors may have some control on their eruptive process.

The effects of local trauma to the enamel-related periodontal tissues in the eruption of the rat incisor.

The periodontal tissues related to enamel (PTE) of the rat incisor comprise a connective tissue derived from the dental follicle and the enamel organ with its successive stages of development. Localized damage to these tissues in rat lower incisors was done surgically in three ways: with an endodontic file introduced into the labial periodontal space through either (i) its basal or (ii) its incisal extremities, or (iii) by the partial removal of the mandibular lower border, at the level of the molar teeth, together with the introduction of an endodontic file into the incisal part of that space. The lesions in the molar region of the PTE produced first a variable period of retarded eruption, and, depending upon their extent or degree were followed by a cessation of the eruptive movement and, in the majority of the operated teeth, a recovery of the normal eruption rate before the end of the experiment (17 weeks after surgery). Access to the PTE through the basal portion of the socket was erratic, but when the tissues were damaged produced similar effects. Effects on eruption of lesions produced through the alveolar crest were minimal or even absent. Localized injury to the periodontal ligament of either lower or upper incisors did not produce similar effects on tooth eruption. The dental follicle and the enamel organ of teeth of limited growth when their crown is completed are similar to the PTE in the molar region of continuously growing rodent incisors. In teeth of limited growth these tissues play an essential part in the intraosseous stage of eruption. The results here suggest that the PTE may also have a role in the supraosseous stage of eruption, which is continuous in teeth such as rat incisors due to the presence of a continuously functioning odontogenic organ.

Continued apexogenesis of immature permanent incisors following trauma.

Two cases of trauma to immature teeth are described which differed significantly in their initial severity. However, both subsequently presented with continued apical root formation. In the two cases a histological examination after tooth removal confirmed continued apical development of the traumatised immature teeth distant to their respective coronal portions. These cases highlight the resilience of the root sheath of Hertwig to trauma.

Response of the rat incisor dental tissues to penetration of the labial alveolar bone in preparation of a surgical window.

The orderly formation of rod and interrod enamel containing precisely-oriented hydroxyapatite crystallites requires a high degree of cellular cooperation. This work examines the susceptibility and response of the rat incisor enamel organ and enamel to mechanically-induced trauma. Such trauma is induced by drilling through the labial alveolar bone of the rat incisor in preparation of a surgical window for a micro-injection technique (McKee and Warshawsky, 1984). The drilling ruptures the enamel organ and removes the underlying enamel. Various experiments indicate that the enamel lesion is a result of aspiration by the rotating bur. The histology of the enamel lesion is described. Several morphological changes which may indicate attempted repair are noted as the lesion moves incisally with time due to the eruption of the tooth. It is concluded that the rat incisor enamel organ is an extremely sensitive cellular system, that if sufficiently disturbed is not capable of restablishing the cellular relations necessary to produce a new enamel layer.

Traumatic injuries to enamel formation in rat incisors.

Twenty-three fullgrown white male rats were fitted with an inclined plane on the mandibular incisors with consequent raising of the bite by 2.5 mm. After an observation period of between 1 and 30 d the animals were killed. In all cases traumatic injuries to the enamel organs were seen. The defects were mainly of four different types. Type 1 occurred in the early maturation zone of the enamel as a local defect with dedifferentiated ameloblasts. Vascular injury was moderate and deformation of the dentin was seen. After 30 d there was still a local defect of the enamel organ. Type 2 occurred apically to the maturation zone and caused a two-layered ameloblastoma resembling a sandwich. Hemorrhages were commmon in the surrounding connective tissue, with accompanying appearance of phospholipids in the tissue. After 30 d some restitution of the enamel formation was seen. Type 3 was necrosis was seen in the surrounding tissue. After 30 d a new ameloblastoma had developed in some areas. These three types appeared separately or combined. Type 4 occurred as a folding of newly formed apical dentin in areas without differentiated ameloblastoma and was seen in all of the experimental animals.