Affiliation:
1. State Key Laboratory of Oral Diseases National Clinical Research Center for Oral Diseases National Engineering Laboratory for Oral Regenerative Medicine Engineering Research Center of Oral Translational Medicine Ministry of Education West China Hospital of Stomatology Sichuan University Chengdu 610041 P. R. China
2. State Key Laboratory of Oral Diseases National Clinical Research Center for Oral Diseases National Engineering Laboratory for Oral Regenerative Medicine Engineering Research Center of Oral Translational Medicine Ministry of Education Department of Oral and Maxillofacial Surgery West China Hospital of Stomatology Sichuan University Chengdu 610041 P. R. China
Abstract
AbstractSuccessful dental pulp regeneration is closely associated with rapid revascularization and angiogenesis, processes driven by the Jagged1(JAG1)/Notch signaling pathway. However, soluble Notch ligands have proven ineffective in activating this pathway. To overcome this limitation, a Notch signaling hydrogel is developed by indirectly immobilizing JAG1, aimed at precisely directing the regeneration of vascularized pulp tissue. This hydrogel displays favorable mechanical properties and biocompatibility. Cultivating dental pulp stem cells (DPSCs) and endothelial cells (ECs) on this hydrogel significantly upregulate Notch target genes and key proangiogenic markers expression. Three‐dimensional (3D) culture assays demonstrate Notch signaling hydrogels improve effectiveness by facilitating encapsulated cell differentiation, enhancing their paracrine functions, and promoting capillary lumen formation. Furthermore, it effectively communicates with the Wnt signaling pathway, creating an odontoinductive microenvironment for pulp‐dentin complex formation. In vivo studies show that short‐term transplantation of the Notch signaling hydrogel accelerates angiogenesis, stabilizes capillary‐like structures, and improves cell survival. Long‐term transplantation further confirms its capability to promote the formation of pulp‐like tissues rich in blood vessels and peripheral nerve‐like structures. In conclusion, this study introduces a feasible and effective hydrogel tailored to specifically regulate the JAG1/Notch signaling pathway, showing potential in advancing regenerative strategies for dental pulp tissue.
Funder
National Basic Research Program of China
National Natural Science Foundation of China
West China Hospital, Sichuan University
Sichuan Province Science and Technology Support Program