Tissue-engineering-based Strategies for Regenerative Endodontics

Abstract

Stemming from in vitro and in vivo pre-clinical and human models, tissue-engineering-based strategies continue to demonstrate great potential for the regeneration of the pulp-dentin complex, particularly in necrotic, immature permanent teeth. Nanofibrous scaffolds, which closely resemble the native extracellular matrix, have been successfully synthesized by various techniques, including but not limited to electrospinning. A common goal in scaffold synthesis has been the notion of promoting cell guidance through the careful design and use of a collection of biochemical and physical cues capable of governing and stimulating specific events at the cellular and tissue levels. The latest advances in processing technologies allow for the fabrication of scaffolds where selected bioactive molecules can be delivered locally, thus increasing the possibilities for clinical success. Though electrospun scaffolds have not yet been tested in vivo in either human or animal pulpless models in immature permanent teeth, recent studies have highlighted their regenerative potential both from an in vitro and in vivo ( i.e., subcutaneous model) standpoint. Possible applications for these bioactive scaffolds continue to evolve, with significant prospects related to the regeneration of both dentin and pulp tissue and, more recently, to root canal disinfection. Nonetheless, no single implantable scaffold can consistently guide the coordinated growth and development of the multiple tissue types involved in the functional regeneration of the pulp-dentin complex. The purpose of this review is to provide a comprehensive perspective on the latest discoveries related to the use of scaffolds and/or stem cells in regenerative endodontics. The authors focused this review on bioactive nanofibrous scaffolds, injectable scaffolds and stem cells, and pre-clinical findings using stem-cell-based strategies. These topics are discussed in detail in an attempt to provide future direction and to shed light on their potential translation to clinical settings.

Human ex vivo dentin-pulp complex preservation in a full crown model

“…5,23 The heterogeneous nature of dental pulp niches, within the central pulp stroma and in perivascular regions, implicates local tissue signals for self-renewal, proliferation, differentiation, mobilization, and homing of cells. 20,24,25 So, the tooth itself as a preservation system ensures unique features that none of the 2D and 3D in vitro models guarantees.…”

Stem Cell Transplantation for Pulpal Regeneration: A Systematic Review

“…3,23 The efficacy of pulpal tissue regeneration has been predominantly assessed using qualitative histological approaches, with only few studies applying quantitative evaluations (defining and quantifying the amount of the experimentally regenerated tissues). A challenge to the quantitative assessment of a successful pulpdentin complex regeneration remains-the definition of the primary regenerative outcomes; whether neural, vascular, soft, or hard tissue/dentinal regeneration.…”

“…26 Even minute differences in the scaffold geometry, pore size, elasticity, mechanical properties, chemical composition, and degradation rate can greatly influence the cells regenerative behavior in vivo. 23,27 In the analyzed studies, the scaffold/carrier selection was closely related to the design of the experimental defect, with mineralized b-TCP used for capping of pulp defects, while those studies with partial to complete pulpal removal/amputation used cell pellets in the absence of a scaffold or applied cells on different collagen carriers to conform to the respective pulp chamber form. Again, these scaffolds have not been sufficiently and comparatively validated a priori while potentially affecting the transplanted cells' attributes, including cell proliferation rate and differentiation.…”

Future prospects in endodontic regeneration - A review article

“…They should have an inductive ability with added growth factors and morphogens for a more rapid cell attachment, proliferation, migration, and differentiation into a specific tissue. [2,[20][21][22] The choice of a scaffold is critical in tissue regeneration. Most scaffolds are organic in nature and used to provide surfaces on which cells may adhere, grow, and organize.…”