3D-bioprinted hydrogels with instructive niches for dental pulp regeneration

Infections to dental pulp commonly result in pulpitis and pulp necrosis, and surgical removal of the infected tissues is the only therapeutic approach. Dental pulp injury remains a challenging medical issue due to the limited regenerative capability of dental pulp. In this work, a dental pulp guidance construct (DPGC) with the instructive niche was bioprinted to mimic native teeth for dentin and neovascular-like structure reconstruction. GelMA-Dextran aqueous emulsion was used as an ink for in situ printing of porous DPGC to induce predominant nuclear localization of Yes-associated protein (YAP) in the encapsulated dental pulp stem cells (DPSCs) and enhance their stemness properties. Furthermore, the DPSCs encapsulated in DPGC with microporous structures exhibited enhanced viability, migration, and spreading. Meanwhile, we found that DPGC could promote capillary tube formation and induce neurogenesis. In a mouse subcutaneous implant model, the DPGC consisted of porous structures, such as odontoblasts and newly formed vascular structures, that mimic dental pulp characteristics. This study demonstrated a new strategy to design DPGC with instructive niche for dental pulp regeneration, presenting a potential treatment alternative to root canal therapy.