Cucurbit[ n ]uril-Programmed Chlorogenic Acid Release for Collagen Mineralization and Pulp–Dentin Repair in Near-Pulp Bonding

Abstract Long-term failure of resin–dentin bonding arises from persistent hydration and enzymatic degradation of exposed collagen in the deep hybrid layer, whereas diffusion of bioactive components through dentinal tubules toward the pulp may cause pulpal irritation. An ideal pretreatment should therefore promote collagen remineralization and interfacial stabilization while reducing pulp-adjacent cellular irritation and supporting pulp–dentin repair. Herein, supramolecular complexes of chlorogenic acid (CGA) and cucurbit[n]uril (Q[n], n = 6, 7, and 8), denoted CGA@Q[n], were constructed to regulate CGA loading, release, and interfacial exposure. CGA@Q[6] showed limited loading, release, and mineralization capacity. CGA@Q[7] exhibited faster early release and achieved complete collagen mineralization within 24 h, whereas CGA@Q[8] showed the highest encapsulation efficiency, sustained CGA supply, complete mineralization at 36 h, and a continuous, dense, integrated intrafibrillar mineral phase. Molecular dynamics simulations indicated that CGA released from Q[8] reanchored to collagen and recruited Ca2+, promoting mineral formation within confined intrafibrillar spaces. These advantages extended to three-dimensional collagen networks and demineralized dentin, yielding higher HAp content, enhanced mineral–collagen integration, tubule occlusion, mechanical recovery, and MMP-9 inhibition. As a bonding pretreatment, CGA@Q[8] reduced nanoleakage, endogenous gelatinolytic activity, and aging-induced bond-strength loss. It also improved cytocompatibility relative to free CGA and promoted mineralization and odontogenic differentiation of human dental pulp stem cells (hDPSCs). In vivo, CGA@Q[8] promoted dentin remineralization, maintained near-pulp interfacial stability, alleviated pulpal irritation, and enhanced odontogenic repair. Together, these findings identify CGA@Q[8] as the most effective formulation and show that homologue selection can tune CGA exposure kinetics for coordinated dentin interface repair.