Polydopamine-mediated graphene oxide and nanohydroxyapatite-incorporated conductive scaffold with an immunomodulatory ability accelerates periodontal bone regeneration in diabetes

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 Ca2+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.