Self-setting calcium polyphosphate coacervate composite for pulp capping treatment

Capping materials are critical for vital pulp therapy in endodontic treatment, whereas the currently available ones remain inadequate in meeting the multiple requirements of the complex tissue defects. Herein, we report an injectable and self-setting calcium polyphosphate coacervate composite (polyP-Ca-CS) that exploits an acid neutralization mechanism based on the coacervate and chitosan, engineered for direct pulp capping. The material leverages polyP-Ca coacervate (formed through liquid-liquid phase separation) as an injectable matrix and chitosan that initiates setting via acid neutralization, enhances mechanical strength, and confers antibacterial properties. polyP-Ca-CS sets into a rigid solid under both aqueous and anhydrous conditions without significant exothermic reaction or volume change-features that are critical for clinical reliability. Mechanistic investigations reveal that neutralization of the coacervate's intrinsic acidity drives the setting, thereby advancing fundamental understanding of setting mechanisms in polyphosphate-based materials. In vitro, polyP-Ca-CS significantly boosts ATP production, mitochondrial function, cell migration, metabolic activity and odontogenic differentiation of dental pulp stem cells (DPSCs). In a rabbit pulp exposure model, it effectively induces reparative dentin formation and preserves pulp vitality, performing comparably to commercial bioceramics. This work presents a bioenergetic-active biomaterial that meets the complex requirements of vital pulp therapy and offers a promising alternative for regenerative endodontics. STATEMENT OF SIGNIFICANCE: This work presents an application of a polyphosphate-based coacervate system in vital pulp therapy, opening an avenue for bioactive dental biomaterials. Besides, it elucidates that setting of the calcium polyphosphate coacervate is driven by acid neutralization, advancing fundamental insights into inorganic coacervate chemistry. The prepared calcium polyphosphate coacervate composite not only meets stringent physical requirements but also activates cellular energy metabolism. Additionally, this work also demonstrates that chitosan-a normal biopolymer-can serve as an setting initiator for inorganic coacervate systems, while simultaneously enhancing mechanical integrity and conferring antibacterial activity.