Synthetic high-density lipoprotein(sHDL):a bioinspired nanotherapeutics for managing periapical bone inflammation  

作　　者：Renan Dal-Fabbro Minzhi Yu Ling Mei Hajime Sasaki Anna Schwendeman Marco C.Bottino 

机构地区：[1]Department of Cariology,Restorative Sciences,and Endodontics,School of Dentistry,University of Michigan,Ann Arbor,MI,USA [2]Department of Pharmaceutical Sciences,College of Pharmacy and Biointerfaces Institute,University of Michigan,Ann Arbor,MI,USA [3]Department of Biomedical Engineering,College of Engineering,University of Michigan,Ann Arbor,MI,USA

出　　处：《International Journal of Oral Science》2024年第3期460-470,共11页国际口腔科学杂志（英文版）

基　　金：the National Institutes of Health(NIH–National Institute of Dental and Craniofacial Research,grant R01DE031476)。

摘　　要：Apical periodontitis(AP)is a dental-driven condition caused by pathogens and their toxins infecting the inner portion of the tooth(i.e.,dental pulp tissue),resulting in inflammation and apical bone resorption affecting 50%of the worldwide population,with more than 15 million root canals performed annually in the United States.Current treatment involves cleaning and decontaminating the infected tissue with chemo-mechanical approaches and materials introduced years ago,such as calcium hydroxide,zinc oxide–eugenol,or even formalin products.Here,we present,for the first time,a nanotherapeutics based on using synthetic highdensity lipoprotein(sHDL)as an innovative and safe strategy to manage dental bone inflammation.sHDL application in concentrations ranging from 25μg to 100μg/mL decreases nuclear factor Kappa B(NF-κB)activation promoted by an inflammatory stimulus(lipopolysaccharide,LPS).Moreover,sHDL at 500μg/mL concentration markedly decreases in vitro osteoclastogenesis(P<0.001),and inhibits IL-1α(P=0.027),TNF-α(P=0.004),and IL-6(P<0.001)production in an inflammatory state.Notably,sHDL strongly dampens the Toll-Like Receptor signaling pathway facing LPS stimulation,mainly by downregulating at least 3-fold the pro-inflammatory genes,such as Il1b,Il1a,Il6,Ptgs2,and Tnf.In vivo,the lipoprotein nanoparticle applied after NaOCl reduced bone resorption volume to(1.3±0.05)mm^(3) and attenuated the inflammatory reaction after treatment to(1090±184)cells compared to non-treated animals that had(2.9±0.6)mm^(3)(P=0.0123)and(2443±931)cells(P=0.004),thus highlighting its promising clinical potential as an alternative therapeutic for managing dental bone inflammation.

关 键 词：INFLAMMATION LIPOPROTEIN markedly 

分 类 号：R781.42[医药卫生—口腔医学]