Extracellular matrix in dental pulp and dentin regeneration: from compositional and mechanical cues to scaffold-based translational strategies

Conventional pulpitis treatment sacrifices the pulp-dentin complex structure and function, precluding physiologic repair. Regenerative endodontic procedures integrate stem cells, scaffolds, and growth factors to restore this complex, where the extracellular matrix (ECM) serves as a dynamic microenvironment coordinating biochemical and mechanical signals to regulate cell behavior. Clinical translation of ECM-based strategies remains constrained by a fragmented understanding of its dual reparative/degradative roles and how matrix physical properties govern cell fate. This review systematically summarizes ECM composition and its applications in tissue regeneration, delineates the regulatory networks governing ECM homeostasis. Building on this foundation, it further delineates the structural and functional evolution of pulpal ECM during pulpitis progression, examines how specific matrix constituents and mechanotransduction influence diverse pulp cell populations, compares the regenerative efficacy and translational potential of ECM-derived scaffolds from various sources with an objective assessment of their translational challenges, while summarizing key signaling networks underlying ECM-guided pulp regeneration. By bridging pathological changes, mechanobiological regulation, and scaffold strategies, this review positions the ECM as a central hub for pulp-dentin regeneration, identifies key knowledge gaps, and proposes future directions for engineering smart, mechanically optimized, and immunomodulatory ECM-based biomaterials, providing theoretical support and practical guidance to accelerate clinical translation of regenerative endodontics.