Bio-NR1@ZIF8 Ameliorate Pulpitis Via Alleviating RSAD2-Mediated Mitochondrial Dysfunction

Introduction and aims We aimed to construct a Notoginsenoside R1 (NR1)-sustained release biomembrane to attenuate early-stage pulpitis and further investigating its underlying mechanisms of action. Methods A layer-by-layer self-assembled biomembrane based on a bamboo cellulose matrix was engineered for the sustained delivery of NR1. The functional efficacy of the biomembrane was validated in vitro via co-culture with human dental pulp stem cells (hDPSCs), while its in vivo therapeutic performance was confirmed using a rat pulpitis model. Furthermore, the underlying therapeutic mechanisms of the material were systematically elucidated through high-throughput sequencing combined with rescue experiments. Results Bio-NR1@ZIF8 exhibited favourable handling, drug-loading capacity, sustained release and biocompatibility. It recruited hDPSCs and promoted anti-inflammatory and differentiation responses by improving mitochondrial function. In vivo, Bio-NR1@ZIF8 reduced inflammatory cytokine levels to 18% of control levels and increased angiogenic capacity approximately 6.5-fold. Rescue experiments indicated that RSAD2 regulates mitochondrial function in the inflammatory microenvironment and contributes to the therapeutic effects of Bio-NR1@ZIF8. Conclusion Bio-NR1@ZIF8 effectively alleviates pulpal inflammation by ameliorating mitochondrial function. Clinical relevance These findings effectively link the functional research of hDPSCs to clinical application, thereby providing a viable strategy for vital pulp therapy.