Bioinspired Microgel Assembly of Liver-Derived Decellularized Extracellular Matrix Enhances Dentin-Pulp Regeneration...

Area of Science:

• Biomaterials Science
• Stem Cell Biology
• Regenerative Medicine

Background:

• Stem cell potency loss during expansion hinders clinical translation.
• Regenerative endodontic therapy (RET) for dentin-pulp complex reconstruction faces challenges due to compromised stem cell potential.

Purpose of the Study:

• To develop an injectable microgel scaffold that restores stemness and regenerative capacity of dental pulp stem cells (DPSC).
• To investigate the mechanism by which the scaffold promotes dentin formation and vascularization for RET.

Main Methods:

• Fabrication of a high-concentration decellularized extracellular matrix (dECM) and gelatin methacryloyl (GelMA) assembled microgel scaffold (HdG-AMS).
• Assessment of DPSC stemness, odontogenic, and angiogenic potential in vitro.
• RNA sequencing to identify molecular pathways involved in scaffold-mediated stemness restoration.
• In vivo functional validation using direct pulp capping and subcutaneous transplantation models.

Main Results:

• HdG-AMS effectively restored DPSC stemness and activated odontogenic and angiogenic pathways.
• Mechanistic studies revealed HdG-AMS upregulates FOXM1, activating the Wnt/β-catenin signaling pathway to counteract cellular senescence.
• In vivo studies demonstrated significant dentin-bridge formation and regeneration of vascularized dentin-pulp complex.

Conclusions:

• HdG-AMS serves as a bioinspired signaling niche that revitalizes DPSC stemness.
• The scaffold orchestrates dentin formation and vascularization via the FOXM1/Wnt/β-catenin axis.
• HdG-AMS presents a promising translational scaffold for next-generation RET.