Understanding the multi-functionality and tissue-specificity of decellularized dental pulp matrix hydrogels for endodontic regeneration.

Dental pulp is the only soft tissue in the tooth which plays a crucial role in maintaining intrinsic multi-functional behaviors of the dentin-pulp complex. Nevertheless, the restoration of fully functional pulps after pulpitis or pulp necrosis, termed endodontic regeneration, remained a major challenge for decades. Therefore, a bioactive and in-situ injectable biomaterial is highly desired for tissue-engineered pulp regeneration. Herein, a decellularized matrix hydrogel derived from porcine dental pulps (pDDPM-G) was prepared and characterized through systematic comparison against the porcine decellularized nerve matrix hydrogel (pDNM-G). The pDDPM-G not only exhibited superior capabilities in facilitating multi-directional differentiation of dental pulp stem cells (DPSCs) during 3D culture, but also promoted regeneration of pulp-like tissues after DPSCs encapsulation and transplantation. Further comparative proteomic and transcriptome analyses revealed the differential compositions and potential mechanisms that endow the pDDPM-G with highly tissue-specific properties. Finally, it was realized that the abundant tenascin C (TNC) in pDDPM served as key factor responsible for the activation of Notch signaling cascades and promoted DPSCs odontoblastic differentiation. Overall, it is believed that pDDPM-G is a sort of multi-functional and tissue-specific hydrogel-based material that holds great promise in endodontic regeneration and clinical translation. STATEMENT OF SIGNIFICANCE: Functional hydrogel-based biomaterials are highly desirable for endodontic regeneration treatments. Decellularized extracellular matrix (dECM) preserves most extracellular matrix components of its native tissue, exhibiting unique advantages in promoting tissue regeneration and functional restoration. In this study, we prepared a porcine dental pulp-derived dECM hydrogel (pDDPM-G), which exhibited superior performance in promoting odontogenesis, angiogenesis, and neurogenesis of the regenerating pulp-like tissue, further showed its tissue-specificity compared to the peripheral nerve-derived dECM hydrogel. In-depth proteomic and transcriptomic analyses revealed that the activation of tenascin C-Notch axis played an important role in facilitating odontogenic regeneration. This biomaterial-based study validated the great potential of the dental pulp-specific pDDPM-G for clinical applications, and provides a springboard for research strategies in ECM-related regenerative medicine.

Size Dependence of Particulate Calcium Phosphate Fillers in Dental Resin Composites.

Resin composites that consist of polymeric resins and functional fillers are commonly used as restorative materials for dental caries. Various types of calcium phosphates (CaPs) are studied as remineralizing fillers in the formulation of dental resin composites, which are generally inhibitory to demineralization of teeth, but the performance of resin composites has not yet been investigated comprehensively with respect to the size of CaP particles. In this study, the same tricalcium phosphate (TCP) particles within two different size ranges, the as-received TCP particles (TCP) and those resulted from grinding (TCP-G), were tested to determine the size dependence of CaP fillers in dental resin composites. The buffering capability, mechanical properties, ion release, antibacterial performance, and remineralization effect of TCP/TCP-G-containing composites were experimentally characterized and compared against two other commercial dental materials. The integration of micrometer-sized TCP particles resulted in a similar buffering effect and Ca2+/PO4 3- release behaviors compared to the resin composite containing much smaller TCP-G particles. The flexural strength of the TCP-G resin composite was lower than that of the TCP composite after immersion in water for 30 days. However, the TCP-G composite facilitated crystal deposition toward better gap-closing performance at the dentin-composite interface. This study explored detailed insights about the size effect of CaP fillers, which is useful for the development of functional dental resin composites and their clinical translation.