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

Autor: Dal-Fabbro R; Department of Cariology, Restorative Sciences, and Endodontics, School of Dentistry, University of Michigan, Ann Arbor, MI, USA., Yu M; Department of Pharmaceutical Sciences, College of Pharmacy and Biointerfaces Institute, University of Michigan, Ann Arbor, MI, USA., Mei L; Department of Pharmaceutical Sciences, College of Pharmacy and Biointerfaces Institute, University of Michigan, Ann Arbor, MI, USA., Sasaki H; Department of Cariology, Restorative Sciences, and Endodontics, School of Dentistry, University of Michigan, Ann Arbor, MI, USA., Schwendeman A; Department of Pharmaceutical Sciences, College of Pharmacy and Biointerfaces Institute, University of Michigan, Ann Arbor, MI, USA., Bottino MC; Department of Cariology, Restorative Sciences, and Endodontics, School of Dentistry, University of Michigan, Ann Arbor, MI, USA. mbottino@umich.edu.; Department of Biomedical Engineering, College of Engineering, University of Michigan, Ann Arbor, MI, USA. mbottino@umich.edu.
Jazyk: angličtina
Zdroj: International journal of oral science [Int J Oral Sci] 2024 Jul 02; Vol. 16 (1), pp. 50. Date of Electronic Publication: 2024 Jul 02.
DOI: 10.1038/s41368-024-00316-w
Abstrakt: 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 high-density lipoprotein (sHDL) as an innovative and safe strategy to manage dental bone inflammation. sHDL application in concentrations ranging from 25 µg to 100 µg/mL decreases nuclear factor Kappa B (NF-κB) activation promoted by an inflammatory stimulus (lipopolysaccharide, LPS). Moreover, sHDL at 500 µg/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 (1 090 ± 184) cells compared to non-treated animals that had (2.9 ± 0.6) mm 3 (P = 0.012 3) and (2 443 ± 931) cells (P = 0.004), thus highlighting its promising clinical potential as an alternative therapeutic for managing dental bone inflammation.
(© 2024. The Author(s).)
Databáze: MEDLINE
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