Bioinspired Microgel Assembly of Liver‐Derived Decellularized Extracellular Matrix Enhances Dentin‐Pulp Regeneration via Stemness Awakening

Gradual loss of cellular potency during in vitro expansion is a primary challenge in the clinical translation of stem cell therapies. This decline in regenerative potential significantly compromises regenerative endodontic therapy (RET)—an emerging strategy for reconstructing dentin‐pulp complex. Hence, we develop an injectable microgel scaffold composed of porcine liver‐derived decellularized extracellular matrix (dECM) and gelatin methacryloyl (GelMA). This system, which is designated as a high‐concentration dECM/GelMA assembled microgel scaffold (HdG‐AMS), integrates the bioactivity of dECM with the structural stability of GelMA to reconstitute a native‐like stem cell niche. The HdG‐AMS creates a robust biomimetic niche that effectively restores dental pulp stem cell (DPSC) stemness while simultaneously activating the odontogenic and angiogenic pathways. Through RNA sequencing, we mechanistically identify that the HdG‐AMS counteracts cellular senescence by upregulating FOXM1—a pivotal activator of the Wnt/ β ‐catenin signaling pathway. Functional validation in two animal models demonstrate effective dentin‐bridge formation in direct pulp capping therapy and the regeneration of vascularized dentin‐pulp complex upon subcutaneous transplantation. Collectively, the HdG‐AMS functions as a bioinspired signaling niche that awakens DPSC stemness and orchestrates dentin formation and vascularization via FOXM1/Wnt/ β ‐catenin axis, thus offering a translational scaffold for next‐generation RET.