Novel Hydrogel Systems for Dentin Regeneration

Advances in stem cell biology, tissue engineering and nanotechnology make it feasible to develop alternative, biomimetic treatment strategies to regenerate the tooth's soft and mineralized matrices. The availability of stem cell lines isolated from adult and exfoliated deciduous human teeth (DPSC and SHED, respectively) now make it possible to create functional bioengineered scaffolds for dentin regeneration. New generations of scaffold materials that are either natural or synthetic allow for a three-dimensional environment that mimics extracellular matrix and are further conducive for cell differentiation and matrix formation. Objective: To describe our ongoing research on the optimization of conditions for differentiation of two dental stem cell lines (SHED and DPSC), in hydrogels of either PEGylated fibrin or peptide-based nanostructured matrices with the overarching goal of regeneration of the dentin-pulp complex. Methods: The differentiation potential of both dental stem cell lines under different culture conditions was explored. Cells were seeded into fibrin and peptide hydrogels with different designs. Cell shape, spreading and proliferation were assessed and gene expression profiles analyzed by real-time PCR along with ECM formation and mineralization. Results: Both types of hydrogels offer great potential as matrices for cell growth, differentiation and tissue formation. Conclusions: Peptide-based hydrogels allow for more flexibility concerning their design and the incorporation of growth and differentiation factors. SHED cells seem more adept for soft tissue formation similar to dental pulp, whereas DPSC show a high potential for the generation of mineralized matrices. Hydrogel systems could easily be injected into small defects and provide carrier systems for either autologous or allogenic dental stem cells to induce regeneration of the dentin-pulp complex in situ. (Support R01-DE013368 to RDS, a grant from NSF to JDH and KMG.