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
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