Functionalized scaffolds to control dental pulp stem cell fate

Abstract

Emerging understanding about interactions between stem cells, scaffolds, and morphogenic factors has accelerated translational research in the field of dental pulp tissue engineering. Dental pulp stem cells constitute a subpopulation of cells endowed with self-renewal and multipotency. Dental pulp stem cells seeded in biodegradable scaffolds and exposed to dentin-derived morphogenic factors give rise to a pulplike tissue capable of generating new dentin. Notably, dentin-derived proteins are sufficient to induce dental pulp stem cell differentiation into odontoblasts. Ongoing work is focused on developing ways of mobilizing dentin-derived proteins and disinfecting the root canal of necrotic teeth without compromising the morphogenic potential of these signaling molecules. On the other hand, dentin by itself does not appear to be capable of inducing endothelial differentiation of dental pulp stem cells despite the well-known presence of angiogenic factors in dentin. This is particularly relevant in the context of dental pulp tissue engineering in full root canals in which access to blood supply is limited to the apical foramina. To address this challenge, scientists are looking at ways to use the scaffold as a controlled-release device for angiogenic factors. The aim of this article was to present and discuss current strategies to functionalize injectable scaffolds and customize them for dental pulp tissue engineering. The long-term goal of this work is to develop stem cell-based therapies that enable the engineering of functional dental pulps capable of generating new tubular dentin in humans.

Keywords: Angiogenesis; dental pulp stem cells; dentin; morphogenic signals; pulp biology; regenerative endodontics; tissue engineering.

Figure 1

Schematic representation of a strategy for dental pulp tissue engineering that is based on the use of a functionalized injectable scaffold and transplantation of dental pulp stem cells.

Figure 2

Characterization of VEGF-containing alginate microspheres. (A) Alginate microspheres loaded with VEGF. (B,C) Graphs depicting release kinetics of VEFG from alginate microspheres (500 or 1,000 ng/ml VEGF) dispersed in a self-assembling hydrogel (Puramatrix™) and PBS. Supernatant was collected and VEGF₁₆₅ concentration was determined by ELISA, and shown either at indicated time periods (B) or cumulative over the duration of the experiment (C).