Bidirectional Differentiation of Human-Derived Stem Cells Induced by Biomimetic Calcium Silicate-Reinforced Gelatin Methacrylate Bioink for Odontogenic Regeneration

<jats:p>Tooth loss or damage is a common problem affecting millions of people worldwide, and it results in significant impacts on one’s quality of life. Dental regeneration with the support of stem cell-containing scaffolds has emerged as an alternative treatment strategy for such cases. With this concept in mind, we developed various concentrations of calcium silicate (CS) in a gelatin methacryloyl (GelMa) matrix and fabricated human dental pulp stem cells (hDPSCs)-laden scaffolds via the use of a bioprinting technology in order to determine their feasibility in promoting odontogenesis. The X-ray diffraction and Fourier transform-infrared spectroscopy showed that the incorporation of CS increased the number of covalent bonds in the GelMa hydrogels. In addition, rheological analyses were conducted for the different concentrations of hydrogels to evaluate their sol–gel transition temperature. It was shown that incorporation of CS improved the printability and printing quality of the scaffolds. The printed CS-containing scaffolds were able to release silicate (Si) ions, which subsequently significantly enhanced the activation of signaling-related markers such as ERK and significantly improved the expression of odontogenic-related markers such as alkaline phosphatase (ALP), dentin matrix protein-1 (DMP-1), and osteocalcin (OC). The calcium deposition assays were also significantly enhanced in the CS-containing scaffold. Our results demonstrated that CS/GelMa scaffolds were not only enhanced in terms of their physicochemical behaviors but the odontogenesis of the hDPSCs was also promoted as compared to GelMa scaffolds. These results demonstrated that CS/GelMa scaffolds can serve as cell-laden materials for future clinical applications and use in dentin regeneration.</jats:p>