Regeneration of Dentin‐Pulp Complex Using Biophysical Cues

Abstract

Successful pulpodentin regeneration should include both dentin and pulp tissues in order to fully restore the biological and mechanical functions of the diseased tooth. To date, a rational scaffolding design to regenerate a complete tooth-like dentin-pulp complex has not been achieved. In this study, we aimed to use biophysical cues (scaffolding stiffness) to control dental pulp stem cell (DPSC) fate and regenerate a complete pulpodentin complex. We developed a facile method of integrating the nanofibrous gelatin matrices with two different rigidities into a single scaffold. Our results indicate that DPSCs differentiated into odontoblasts and formed mineralized tissue on high-stiffness structures, whereas pulp-like tissue was regenerated on low-stiffness structures. A complete pulpodentin complex similar to natural pulpodentin was successfully regenerated after subcutaneous implantation of the DPSC/scaffold in nude mice for 4 weeks. A quantitative analysis indicated that the regenerated dentin density was more than 58% of natural human dentin. Histological staining showed a significant amount of ECM formation in the newly formed pulpodentin complex, and a number of blood vessels were observed in the pulp tissue. Taken together, modulation of the scaffolding stiffness is a successful approach to regenerating a complete tooth-like pulpodentin complex. Supported by- NIH/NIDCR 1R03DE22838-01A1