Title: 1422 - Bio-Instructive Polymeric Restorations for Stem Cell Therapies in Regenerative Dentistry
Kyle Vining (Presenter)
Jacob Scherba, Harvard University
Alaina Bever, Harvard University
Morgan Alexander, School of Pharmacy, University of Nottingham
Adam Celiz, Imperial College London
David Mooney, Harvard University
Objectives: Regenerative dentistry aims to biologically repair dental tissue, but existing polymeric restorative materials do not directly participate in cell-mediated repair and regeneration. Bio-instructive restorations could aid the translation of regenerative therapies if they can support the native regenerative functions of dental pulp stem cells (DPSCs). Here we identify novel synthetic polymeric materials that provide a supportive niche for DPSCs to differentiate to odontoblasts, as well as demonstrate potential clinical utility in a relevant animal model.
Methods: High-throughput screening of polymer libraries is performed with microarrays formed from 119 distinct commercially-available monomers to rapidly test and identify lead materials that support DPSC adhesion. Based on these findings, we employ thiol-ene chemistry to generate monolithic materials by rapid light-curing and to minimize residual monomer in vitro, measured by oscillatory rheology and Fourier-transform infrared spectroscopy, respectively.
Results: The materials exhibit stiffness and tensile strength similar to existing dental materials, measured by axial tension and compression, as well as atomic force microscopy. Several triacrylate polymers support DPSC adhesion and proliferation in vitro. Blocking antibody experiments are used to show that DPSCs require integrin beta-1 signaling to remain adhered to triacrylate materials. Quantitative PCR measurements show that collagen-1 expression is correlated with DPSC adhesion. Conversely, materials composed of a trimethacrylate, which is structurally-related to the lead polymers, and BisGMA, which is a monomer standard in dental materials, do not support stem cell adhesion, downregulate collagen-1 expression, and dysregulate Ras and Wnt signaling pathways. Triacrylate materials support DPSCs’ upregulation of osteogenic and odontogenic markers following long-term culture with inductive conditions. Furthermore, thiol-ene polymerized triacrylates are used as permanent filling materials at the dentin-pulp interface in direct contact with irreversibly injured pulp tissue.
Conclusions: These novel triacrylate-based biomaterials may enable novel regenerative dental therapies in the clinic by both restoring teeth and providing a supportive niche for DPSCs.
This abstract is based on research that was funded entirely or partially by an outside source:
NIH/NIDCR - 5R01DE013033 (DM) and K08DE025292 (KV); European Commission under FP7 agreement number 629320 (AC); Royal Society of Chemistry Emerging Technologies Prize (AC and KV), Anne Marcus Wedner Graduate Research and Henry M. Thornton/SCADA Fellowships (KV), Harvard-Amgen Scholars Program (AB), and Harvard PRISE Fellowship (JS)
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