Biomimetic microenvironments for regenerative endodontics

Abstract

Regenerative endodontics has been proposed to replace damaged and underdeveloped tooth structures with normal pulp-dentin tissue by providing a natural extracellular matrix (ECM) mimicking environment; stem cells, signaling molecules, and scaffolds. In addition, clinical success of the regenerative endodontic treatments can be evidenced by absence of signs and symptoms; no bony pathology, a disinfected pulp, and the maturation of root dentin in length and thickness. In spite of the various approaches of regenerative endodontics, there are several major challenges that remain to be improved: a) the endodontic root canal is a strong harbor of the endodontic bacterial biofilm and the fundamental etiologic factors of recurrent endodontic diseases, (b) tooth discolorations are caused by antibiotics and filling materials, (c) cervical root fractures are caused by endodontic medicaments, (d) pulp tissue is not vascularized nor innervated, and (e) the dentin matrix is not developed with adequate root thickness and length. Generally, current clinical protocols and recent studies have shown a limited success of the pulp-dentin tissue regeneration. Throughout the various approaches, the construction of biomimetic microenvironments of pulp-dentin tissue is a key concept of the tissue engineering based regenerative endodontics. The biomimetic microenvironments are composed of a synthetic nano-scaled polymeric fiber structure that mimics native pulp ECM and functions as a scaffold of the pulp-dentin tissue complex. They will provide a framework of the pulp ECM, can deliver selective bioactive molecules, and may recruit pluripotent stem cells from the vicinity of the pulp apex. The polymeric nanofibers are produced by methods of self-assembly, electrospinning, and phase separation. In order to be applied to biomedical use, the polymeric nanofibers require biocompatibility, stability, and biodegradability. Therefore, this review focuses on the development and application of the biomimetic microenvironments of pulp-dentin tissue among the current regenerative endodontics.

Keywords: Biomimetic microenvironments; Extracellular matrix; Pulp-dentin tissue; Regenerative endodontics; Revascularization; Tissue engineering.

Fig. 1

Anatomy of tooth; (a) a healthy immature tooth with the distinct open root apex surrounded by dental papilla. b a healthy mature tooth with a closed root apex

Fig. 2

Engineered nano-scale scaffold for the regenerative endodontics treatment for an infected tooth; after removal of infected pulp-dentin tissue; the root canal is irrigated with NaOCl and EDTA. Engineered nano-scale scaffold containing a mixture of antibiotics, growth factors, and/or stem cells is applied to the root canal

Fig. 3

Regenerated pulp-dentin tissue with closed root apex; regenerated pulp-dentin tissue with closed root apex is observed after the regenerative endodontic treatment using an engineered nano-scale scaffold. Removed coronal structure is restored with adhesive materials with base sealing materials. Plus (+) signs indicate the area of dentin formation

Fig. 4

General scheme of the design for the biomimetic approach; (a). Synthesis of peptide amphiphiles (PAs), (b). Self-assembly of PAs, (c). Encapsulation of antibiotics, (d). Formation of the nanomatrix gel, Modified with permission from Kaushik et al. [119]