Novel Strategy for the Modulation of Pulpal Inflammation

Objectives: A sustained inflammatory environment leads to irreversible damage of the dental pulp tissue (DP). Traditionally, severely inflamed DP is removed and replaced with inert materials via root canal therapy (RCT). However, devitalized teeth are brittle, and may be more susceptible to structural failure. Therefore, it is desirable to preserve the vital pulp. Unfortunately, effective treatments to promote pulp regeneration are still limited in adults. The transition from the inflammatory to the regenerative phase is perhaps the most important step to facilitate healing. Thus, we develop an approach by culturing mesenchymal stem cells (MSC) in self-assembling multidomain peptides hydrogel (MDP). After decellularization, this material (DM-MDP) can modulate inflammatory reactions and create a microenvironment more favorable for regeneration, which is likely to be more effective than a single factor in therapeutic development. To develop a novel and therapeutic material that utilizes multiple bioactive factors that can be tailored to carry anti-inflammatory and regenerative properties to treat DP damage.


Methods: We cultured MSCs from human exfoliated deciduous tooth pulp (SHED) in MDPs-based 3D tissue construct under normal or hypoxia condition followed by decellularization to deposit DM-MDPs (DM-MDP^NORMAL and DM-MDP^H2O2). J774 macrophages were treated with lipopolysaccharides (LPS) alone or co-incubated with DM-MDP^NORMAL or DM-MDP^H2O2. We utilized qPCR to analyze the expression pattern of a range of genes involved in pro-inflammation, anti-inflammation, and macrophages-2 (M2) polarization.
Results: In controlled culture conditions, MSCs cultured within MDPs produce bioactive factors that are sequestered within the nanofibrillar environment. The DMs captured within MDPs (DM-MDPs) have the ability to decrease inflammation and enhanced expression of common M2 macrophages signature genes in vitro.
Conclusions: Collectively, our data support the use of MDP scaffolds as repositories to capture the MSC-derived factors that impact the progress of inflammation while favoring regeneration. The use of such bioactive scaffolds, can therefore overcome the many shortcomings of cell-based therapy.