OBJECTIVES: To investigate the effects of the sixth generation of poly(amidoamine) (G6-PAMAM)-based extrafibrillar demineralization on bonding durability of deciduous dentin and explore the possible mechanisms. METHODS: The cytotoxicity and inhibitory effects on recombinant human matrix metalloproteinases-9 (rhMMP-9) of G6-PAMAM were investigated. The chelation demineralization capacity of G6-PAMAM with molecular weight >
40 kDa was quantitatively analyzed. Atomic force microscopy-infrared spectroscopy (AFM-IR) was used to verify selective extrafibrillar demineralization of dentin conditioned by G6-PAMAM. After dentin surfaces were conditioned with G6-PAMAM or phosphoric acid (H RESULTS: In addition to being nontoxic, 20 µg/mL G6-PAMAM showed inhibitory effects on rhMMP-9 and calcium-chelating capability. AFM-IR confirmed that G6-PAMAM conditioning can achieve selective demineralization of dentin extrafibrillar minerals. Deciduous dentin treated with 20 µg/mL G6-PAMAM for 60 s produced μTBS equivalent to H CONCLUSION: The G6-PAMAM-based extrafibrillar demineralization strategy under dry-bonding technique could enhance bonding durability of deciduous dentin by retaining intrafibrillar minerals, decreasing interfacial nanoleakage, and preventing endogenous protease-initiated collagen degradation. CLINICAL RELEVANCE: The G6-PAMAM-based extrafibrillar demineralization strategy has the potential to improve the stability of the resin-dentin bonding interface and prolong the longevity of resin restorations in deciduous teeth.