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Current treatment involves cleaning and decontaminating the infected tissue with chemo-mechanical approaches and materials introduced years ago, such as calcium hydroxide, zinc oxide\u2013eugenol, 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\u2009\u00b5g to 100\u2009\u00b5g\/mL decreases nuclear factor Kappa B (NF-\u03baB) activation promoted by an inflammatory stimulus (lipopolysaccharide, LPS). Moreover, sHDL at 500\u2009\u00b5g\/mL concentration markedly decreases in vitro osteoclastogenesis (\n                    <jats:italic>P<\/jats:italic>\n                    \u2009&lt;\u20090.001), and inhibits IL-1\u03b1 (\n                    <jats:italic>P<\/jats:italic>\n                    \u2009=\u20090.027), TNF-\u03b1 (\n                    <jats:italic>P<\/jats:italic>\n                    \u2009=\u20090.004), and IL-6 (\n                    <jats:italic>P<\/jats:italic>\n                    \u2009&lt;\u20090.001) 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\n                    <jats:italic>Il1b<\/jats:italic>\n                    ,\n                    <jats:italic>Il1a<\/jats:italic>\n                    ,\n                    <jats:italic>Il6<\/jats:italic>\n                    ,\n                    <jats:italic>Ptgs2<\/jats:italic>\n                    , and\n                    <jats:italic>Tnf<\/jats:italic>\n                    . In vivo, the lipoprotein nanoparticle applied after NaOCl reduced bone resorption volume to (1.3 \u00b1 0.05) mm\n                    <jats:sup>3<\/jats:sup>\n                    and attenuated the inflammatory reaction after treatment to (1 090 \u00b1 184) cells compared to non-treated animals that had (2.9 \u00b1 0.6) mm\n                    <jats:sup>3<\/jats:sup>\n                    (\n                    <jats:italic>P<\/jats:italic>\n                    \u2009=\u20090.012 3) and (2 443 \u00b1 931) cells (\n                    <jats:italic>P<\/jats:italic>\n                    \u2009=\u20090.004), thus highlighting its promising clinical potential as an alternative therapeutic for managing dental bone inflammation.\n                  <\/jats:p>","DOI":"10.1038\/s41368-024-00316-w","type":"journal-article","created":{"date-parts":[[2024,7,2]],"date-time":"2024-07-02T03:02:34Z","timestamp":1719889354000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Synthetic high-density lipoprotein (sHDL): a bioinspired nanotherapeutics for managing periapical bone inflammation"],"prefix":"10.1038","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4125-8441","authenticated-orcid":false,"given":"Renan","family":"Dal-Fabbro","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Minzhi","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ling","family":"Mei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hajime","family":"Sasaki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Schwendeman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco C.","family":"Bottino","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,7,2]]},"reference":[{"key":"316_CR1","doi-asserted-by":"publisher","first-page":"428","DOI":"10.1038\/nature07201","volume":"454","author":"R Medzhitov","year":"2008","unstructured":"Medzhitov, R. 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