Project Summary/Abstract
Caries is a near-ubiquitous infectious oral disease with an enormous direct and indirect impact on human health
care, well-being, workforce, and the economy. The quality and longevity of dental restorative interventions
depend largely on the integrity and biomechanical properties of dentin, the tooth’s bulk soft tissue that largely
consists of type I collagen and mineral. Formation and sustainability of the widely used resin-based restorations
rely on micro-mechanical adhesion to the collagenous dentin structures. Our interdisciplinary research team has
produced extensive evidence for the utility of oligomeric proanthocyanidins as novel bioactive materials sources
from plants. This body of data supports the feasibility of a biomimetic strategy that enhances the performance of
adhesive-based restorations. Insights gained from the underlying pre-clinical studies led to the recognition of
modular oligomeric plant phenols (MOPPs) as the common structural motif of compounds that interact with
structural proteins such as collagen. Supported by separate exploratory phytochemical and biomechanical
studies as well as considering structural characteristics, this project seeks to explore two biologically
understudied classes yet chemically diverse of MOPPs, stilbenoids from vascular plants and phloroglucinols
from ferns, as potentially promising additional leads. The core hypothesis is that medium-oligomeric stilbenoids
and phloroglucinols have analogous yet distinctly different structural characteristics that make these MOPPs
suitable for dentin biomodulation and orthogonal tools for biological/biomechanical studies. The overarching goal
is to extend the dentistry toolbox with previously un(der)explored structural classes of chemically diverse
biomodulators with modular build patterns.
Approaching the overall hypothesis at the dentistry-pharmacy interface, the two Aims reflect the phytoanalytical
and biomaterial angles of an interactive approach: (Aim 1) Source, purify, and characterize new modular
oligomeric plant phenols (MOPPs); (Aim 2) Establish and compare mechanisms of interactions of MOPPs with
human teeth constituents (enamel, dentin and pulp cells). Employing innovative purification and advanced
structural characterization methodologies for the complex MOPPs and performing their parallel state-of-the-art
biomechanical evaluation, the project has significant ability to harness the structural complexity and define the
utility and modular natural biomodulation agents. The potential to introduce natural modularity of MOPPs for
tailored biomodulatory therapeutics and enhance their clinical applicability are innovative aspects of the project.
The studies will build a solid phytochemical and biological foundation for the potential oral biomedical
applications of stilbenoids and phloroglucinols as underexplored bioactive agents. The ultimate project outcome
is the establishment of new classes of MOPPs as tissue biomodulators for future preclinical development.