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

IF 10.8 1区 医学 Q1 DENTISTRY, ORAL SURGERY & MEDICINE
Renan Dal-Fabbro, Minzhi Yu, Ling Mei, Hajime Sasaki, Anna Schwendeman, Marco C. Bottino
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引用次数: 0

Abstract

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) mm3 and attenuated the inflammatory reaction after treatment to (1 090 ± 184) cells compared to non-treated animals that had (2.9 ± 0.6) mm3 (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.

Abstract Image

合成高密度脂蛋白(sHDL):一种用于控制根尖周骨炎的生物启发纳米疗法
牙根尖牙周炎(AP)是一种由病原体及其毒素感染牙齿内部(即牙髓组织)引起的牙科疾病,会导致炎症和牙根尖骨吸收,影响全球50%的人口,美国每年进行的根管治疗超过1500万例。目前的治疗方法包括使用多年前引入的化学机械方法和材料(如氢氧化钙、氧化锌-丁香酚,甚至福尔马林产品)清洁和净化受感染的组织。在这里,我们首次提出了一种基于合成高密度脂蛋白(sHDL)的纳米疗法,作为一种创新而安全的策略来控制牙槽骨炎症。sHDL 的应用浓度从 25 微克到 100 微克/毫升不等,可降低炎症刺激(脂多糖,LPS)引起的核因子卡巴 B(NF-κB)活化。此外,浓度为 500 µg/mL 的 sHDL 能显著降低体外破骨细胞生成(P < 0.001),并抑制炎症状态下 IL-1α (P = 0.027)、TNF-α (P = 0.004) 和 IL-6 (P < 0.001) 的产生。值得注意的是,sHDL 能强烈抑制 LPS 刺激下的 Toll-Like 受体信号通路,主要是通过下调至少 3 倍的促炎基因,如 Il1b、Il1a、Il6、Ptgs2 和 Tnf。在体内,与未处理动物的(2.9 ± 0.6)立方毫米(P = 0.012 3)和(2 443 ± 931)个细胞(P = 0.004)相比,NaOCl 处理后使用的脂蛋白纳米粒子可将骨吸收体积减少到(1.3 ± 0.05)立方毫米,并将处理后的炎症反应减弱到(1 090 ± 184)个细胞,从而凸显了其作为牙科骨炎替代疗法的巨大临床潜力。
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来源期刊
International Journal of Oral Science
International Journal of Oral Science DENTISTRY, ORAL SURGERY & MEDICINE-
CiteScore
31.80
自引率
1.30%
发文量
53
审稿时长
>12 weeks
期刊介绍: The International Journal of Oral Science covers various aspects of oral science and interdisciplinary fields, encompassing basic, applied, and clinical research. Topics include, but are not limited to: Oral microbiology Oral and maxillofacial oncology Cariology Oral inflammation and infection Dental stem cells and regenerative medicine Craniofacial surgery Dental material Oral biomechanics Oral, dental, and maxillofacial genetic and developmental diseases Craniofacial bone research Craniofacial-related biomaterials Temporomandibular joint disorder and osteoarthritis The journal publishes peer-reviewed Articles presenting new research results and Review Articles offering concise summaries of specific areas in oral science.
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