Saleh M H A, Roh A, Martin K, Mianecki M, Tariq Sheikh A, Singh P, Akorede K, Saunders M N, Shea L D, Decker A, Decker J T
Department of Periodontics and Oral Medicine, School of Dentistry, University of Michigan, Ann Arbor, MI, USA.
Department of Cariology, Restorative Sciences, and Endodontics, School of Dentistry, University of Michigan, Ann Arbor, MI, USA.
J Dent Res. 2025 Jul;104(8):862-869. doi: 10.1177/00220345251319256. Epub 2025 Mar 12.
Periodontal and peri-implant diseases are a significant public health problem worldwide, resulting in the destruction of the supporting bone. These bone defects can cause esthetic problems, increased relapse rate, and eventually tooth loss. The etiology of periodontal disease involves an influx of innate immune cells (neutrophils and monocytes) and upregulation of local inflammatory cytokines in the gingiva. Biodegradable polymeric nanoparticles are an inexpensive, safe, and effective means of preventing innate immune activation by bacterial biofilms. We therefore hypothesize that this technology is a potential means of managing periodontal disease. Polylactic acid (PLA) particles were fabricated using an oil-in-water emulsion and used as a therapy in ligature-induced periodontitis and peri-implantitis. Mice were treated daily with nanoparticles or saline control through intravenous injection for 5 or 7 d. Bone loss and quality were characterized using micro-computed tomography and histology, and immune cell infiltrate was characterized by flow cytometry and enzyme-linked immunosorbent assay. PLA particle therapy prevented bone loss in both periodontitis and peri-implantitis. Particle treatment was associated with decreased osteoclast activation. Flow cytometry showed particles were mainly taken up by macrophages and limited inflammatory monocyte recruitment to the ligature site. In vitro evaluation of particle therapy demonstrated the inhibition of toll-like receptor activation during particle treatment. These results extended to monocytes that had been presensitized by titania nanoparticles. Taken together, the results of these experiments demonstrated that cargo-less PLA particle therapy may be a safe, cost-effective therapy to manage inflammatory bone loss in periodontal disease.
牙周病和种植体周围疾病是全球范围内一个重大的公共卫生问题，会导致支持骨组织遭到破坏。这些骨缺损会引发美观问题、增加复发率，并最终导致牙齿脱落。牙周病的病因涉及固有免疫细胞（中性粒细胞和单核细胞）的涌入以及牙龈中局部炎性细胞因子的上调。可生物降解的聚合物纳米颗粒是一种廉价、安全且有效的手段，可防止细菌生物膜激活固有免疫。因此，我们推测这项技术是治疗牙周病的一种潜在手段。聚乳酸（PLA）颗粒通过水包油乳液法制备，并用于结扎诱导的牙周炎和种植体周围炎的治疗。通过静脉注射，每天用纳米颗粒或生理盐水对照处理小鼠，持续5天或7天。使用微型计算机断层扫描和组织学对骨丢失和骨质进行表征，通过流式细胞术和酶联免疫吸附测定对免疫细胞浸润进行表征。PLA颗粒疗法可预防牙周炎和种植体周围炎中的骨丢失。颗粒治疗与破骨细胞活化减少相关。流式细胞术显示颗粒主要被巨噬细胞摄取，并且炎症单核细胞向结扎部位的募集有限。颗粒疗法的体外评估表明在颗粒治疗期间Toll样受体激活受到抑制。这些结果扩展到已被二氧化钛纳米颗粒预致敏的单核细胞。综上所述，这些实验结果表明，无载药的PLA颗粒疗法可能是一种安全、经济有效的治疗方法，用于管理牙周病中的炎性骨丢失。
