Endodontic regeneration: hard shell, soft core

Abstract

A loss of organs or the destruction of tissue leaves wounds to which organisms and living things react differently. Their response depends on the extent of damage, the functional impairment and the biological potential of the organism. Some can completely regenerate lost body parts or tissues, whereas others react by forming scars in the sense of a tissue repair. Overall, the regenerative capacities of the human body are limited and only a few tissues are fully restored when injured. Dental tissues may suffer severe damage due to various influences such as caries or trauma; however, dental care aims at preserving unharmed structures and, thus, the functionality of the teeth. The dentin-pulp complex, a vital compound tissue that is enclosed by enamel, holds many important functions and is particularly worth protecting. It reacts physiologically to deleterious impacts with an interplay of regenerative and reparative processes to ensure its functionality and facilitate healing. While there were initially no biological treatment options available for the irreversible destruction of dentin or pulp, many promising approaches for endodontic regeneration based on the principles of tissue engineering have been developed in recent years. This review describes the regenerative and reparative processes of the dentin-pulp complex as well as the morphological criteria of possible healing results. Furthermore, it summarizes the current knowledge on tissue engineering of dentin and pulp, and potential future developments in this thriving field.

Keywords: Dentin; Pulp; Regeneration; Regenerative medicine; Tissue engineering.

Fig. 1

Masson trichrome staining of a healthy molar. a Dentine (white asterisk) and pulp (black asterisk) form a closely interconnected tissue complex. b Physiologically, dentin has a uniform structure of slightly curved tubules and odontoblasts are located at the interface of pulp and dentin. The pulp core consists of a structured and inflammation-free connective tissue with vascular and nerve components. c The primary odontoblasts are of columnar shape and polarized with nuclei located at their basal end (white asterisk). They are arranged in a palisade-like formation and extend their processes into the dentin tubules. Dashed boxes mark the view of the subsequent image. Scale bars: 600 µm (a), 200 µm (b), 50 µm (c)

Fig. 2

Injured or lost tissue can heal by tissue regeneration or tissue repair. While regeneration restores the tissue to its original state, repair largely creates replacement tissue that substantially differs anatomically or functionally from the original

Fig. 3

A comparative presentation of the relationship between regenerative medicine (RM) and tissue engineering (TE). Although RM is a broader and more general field than TE, one does not fully encompass the other. Both aim to restore the function of lost or destroyed tissue and can be seen as one research unit: tissue engineering and regenerative medicine (TERM). In the field of TE, a distinction is made between in vitro and in vivo concepts. While functional organs or tissues are constructed and implanted in the first, functionalization takes place in the body in the second approach. For this purpose, cells can be transplanted (cell transplantation), or a suitable scaffold can be used to attract cells from local sources (cell homing)

Fig. 4

Regeneration and repair processes in dentin. a Mechanical preparation, dental materials or caries represent an irritation to odontoblasts that leads to intratubular deposition of minerals as well as reactionary dentin formation (indicated by ‡). Dentine areas demineralized by caries (indicated by *) can be remineralized to a certain extent. b Severe stimuli lead to the loss of odontoblasts. The odontoblast-like replacement cells secrete unstructured repair dentin (indicated by #). c A tissue engineering approach to dentin regeneration is based on the idea that cells of the pulp migrate into a scaffold (green), form hard tissue (indicated by §) and, thus, seal the dentin wound. In contrast to reactionary or reparative dentinogenesis, there is no narrowing of the pulp cavity

Fig. 5

Regenerative endodontic treatment approaches. a Revitalization is the process of inducing apical bleeding by which cells are brought into the root canal. b In the idea of in situ tissue engineering cells are expanded ex vivo and transplanted into the root canal with a scaffold. c Cell homing, on the other hand, is a primarily cell-free approach that makes use of locally available cell sources. A custom-made scaffold with biomolecules is placed in the canal and cells migrate from the periapical tissues. d This concept is also applicable if there is residual pulp tissue in the root canal, which in this case serves as cell source and is, thus, expanded