Synergistic effect of ROS-generating polydopamine on drug-induced bone tissue regeneration

A PHD (prolyl hydroxylase) inhibitor, 1,4-dihydrophenonthrolin-4-one-3-carboxylic acid (1,4-DPCA), is a drug that can artificially promote tissue regeneration by enhancing metabolic activity through the upregulation of hypoxia inducible factor 1 subunit alpha (Hif-1α) under normoxic conditions. This study presents a novel design methodology for a drug delivery system to maximize the regenerative effect of 1,4-DPCA. Specifically, by encapsulating 1,4-DPCA in polydopamine (PDA) that generates reactive oxygen species (ROS), the combined effects of Hif-1α upregulation and the induction of cellular antioxidant defense mechanisms by localized ROS can significantly enhance tissue regeneration. The study confirmed that each material (PDA and 1,4-DPCA) triggers a positive synergistic effect on the regenerative mechanisms. As a result, the use of a PDA drug delivery system loaded with 1,4-DPCA showed approximately six times greater bone regeneration compared to the control (no treatment) in a mouse calvarial defect model. The combination of PDA NPs and 1,4-DPCA leads to a synergistic effect that enhances bone tissue regeneration in vivo .