机构地区:[1]State Key Laboratory of Oral Diseases,National Clinical Research Center for Oral Diseases,Department of Orthodontics,West China Hospital of Stomatology,Sichuan University,Chengdu,Sichuan,610041,China [2]Key Lab of Advanced Technologies of Materials,Ministry of Education,School of Materials Science and Engineering,Southwest Jiaotong University,Chengdu,Sichuan,610031,China [3]State Key Laboratory of Oral Diseases,National Clinical Research Center for Oral Diseases,Department of Oral Implantology,West China Hospital of Stomatology,Sichuan University,Chengdu,Sichuan,610041,China [4]Lab for Aging Research and National Clinical Research Center for Geriatrics,West China Hospital,Sichuan University,Chengdu,Sichuan,610041,China
出 处:《Bioactive Materials》2022年第12期213-227,共15页生物活性材料(英文)
基 金:grants from Sichuan Key Research and Development Program of China(22ZDYF2034);National Natural Science Foundation of China(grant no.82072071,82072073);Key-Area Research and Development Program of Guang Dong Province(2019B010941002);Shenzhen Funds of the Central Government to Guide Local Scientific and Technological Development(2021SZVUP123);Sichuan Science and Technology Program(2020YFS0170);Fundamental Research Funds for the Central Universities(2682020ZT79);Guangdong Basic and Applied Basic Research Foundation(2021B1515120019);Research and Develop Program,West China Hospital of Stomatology Sichuan University(RD-03-202012,RD-03-202101).
摘 要: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.
关 键 词:POLYDOPAMINE Graphene oxide Conductive scaffold ROS-Scavenging Macrophage polarization
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