Title: 1717 - Novel Strategy for the Modulation of Pulpal Inflammation
Yinshen Wee (Presenter)
University of Utah
John Colombo, University of Utah
Rena D'Souza, University of Utah
Objectives: A sustained inflammatory environment eventually leads to necrosis of the dental pulp tissue. Unfortunately, effective treatments to promote pulp regeneration are still limited. Developing more effective therapeutic interventions for dental pulp regeneration requires an understanding of the capacity of pulp tissue for repair and timely resolution of sustained inflammation. 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 single factor in therapeutic development. This novel and therapeutic material that utilizes multiple bioactive factors that can be tailored to carry anti-inflammatory and regenerative properties may have great potential for translational treatments and cures for dental pulp 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-MDPNORMAL and DM-MDPH2O2). J774 macrophages were treated with lipopolysaccharides (LPS) alone or co-incubated with DM-MDPNORMAL or DM-MDPH2O2 . 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.
This abstract is based on research that was funded entirely or partially by an outside source:
The submitter must disclose the names of the organizations with which any author have a relationship, the nature of the relationship, and the clinical or research area involved. The following is submitted: None