Abstract

Regenerating periodontal bone tissues in the aggravated inflammatory periodontal microenvironment under diabetic conditions is a great challenge. Here, a polydopamine-mediated graphene oxide (PGO) and hydroxyapatite nanoparticle (PHA)-incorporated conductive alginate/gelatin (AG) scaffold is developed to accelerate periodontal bone regeneration by modulating the diabetic inflammatory microenvironment. PHA confers the scaffold with osteoinductivity and PGO provides a conductive pathway for the scaffold. The conductive scaffold promotes bone regeneration by transferring endogenous electrical signals to cells and activating Ca 2+ channels. Moreover, the scaffold with polydopamine-mediated nanomaterials has a reactive oxygen species (ROS)-scavenging ability and anti-inflammatory activity. It also exhibits an immunomodulatory ability that suppresses M1 macrophage polarization and activates M2 macrophages to secrete osteogenesis-related cytokines by mediating glycolytic and RhoA/ROCK pathways in macrophages. The scaffold induces excellent bone regeneration in periodontal bone defects of diabetic rats because of the synergistic effects of good conductive, ROS-scavenging, anti-inflammatory, and immunomodulatory abilities. This study provides fundamental insights into the synergistical effects of conductivity, osteoinductivity, and immunomodulatory abilities on bone regeneration and offers a novel strategy to design immunomodulatory biomaterials for treatment of immune-related diseases and tissue regeneration.