The sufficient imitation of tissue structures and components represents an effective and promising approach for tissue engineering and regenerative medicine applications.
Dental pulp disease is one of the most common oral diseases, although functional pulp regeneration remains challenging. Herein, we propose a strategy that employs
hydrogel microspheres incorporated with decellularized dental pulp matrix-derived bioactive factors to simulate a pulp-specific three-dimensional (3D) microenvironment. The dental pulp microenvironment-specific
microspheres constructed by this regenerative strategy exhibited favorable plasticity, biocompatibility, and
biological performances. Human dental pulp stem cells (hDPSCs) cultured on the constructed
microspheres exhibited enhanced pulp-formation ability in vitro. Furthermore, the hDPSCs-microcarriers achieved the regeneration of pulp-like tissue and new dentin in a semi-orthotopic model in vivo. Mechanistically, the decellularized pulp matrix-derived bioactive factors mediated the multi-directional differentiation of hDPSCs to regenerate the pulp tissue by eliciting the secretion of crucial bioactive cues. Our findings demonstrated that a 3D dental pulp-specific microenvironment facilitated by
hydrogel microspheres and dental pulp-specific bioactive factors regenerated the pulp-dentin complex and could be served as a promising treatment option for
dental pulp disease. STATEMENT OF SIGNIFICANCE:
Injectable bioscaffolds are increasingly used for
regenerative endodontic treatment. Despite their success related to their ability to load stem cells, bioactive factors, and injectability, conventional bulk bioscaffolds have drawbacks such as ischemic
necrosis in the central region. Various studies have shown that ischemic
necrosis in the central region can be corrected by
injectable hydrogel microspheres. Unfortunately, pristine
microspheres or
microspheres without dental pulp-specific bioactive factor would oftentimes fail to regulate stem cells fates in dental pulp multi-directional differentiation. Our present study reported the biofabrication of dental pulp-derived decellularized matrix functionalized
gelatin microspheres, which contained dental pulp-specific bioactive factors and have the potential application in endodontic regeneration.