Abstract
The regeneration of lost periodontal apparatus in periodontitis treatment remains a clinical challenge due to the limited regenerative capacity of cementum, periodontal ligament and alveolar bone in periodontitis condition. For periodontal tissue regeneration, it is essential to regulate the inflammatory response and the subsequent differentiation of periodontal cells under the condition due to the infectious nature of the disease. In this study, it was noted that 45 nm gold nanoparticles (AuNPs) could exhibit significant anti-inflammatory effect and improve the periodontal inflammatory microenvironment via regulating inflammatory and regenerative cytokine production and modulating macrophage polarization, subsequently affect the differentiation of human periodontal ligament cells (hPDLCs). With the addition of direct effects of AuNPs on hPDLCs, the periodontal tissue differentiation capacity of hPDLCs in LPS-activated inflammatory macrophage-hPDLCs coculture system was significantly enhanced by the interaction between AuNPs-conditioned macrophage and AuNPs-stimulated hPDLCs. The potential therapeutic application of AuNPs in periodontal tissue regeneration and periodontitis treatment was investigated using both rat fenestration and ligature-induced periodontitis models. It was found that the treatment of 45 AuNPs showed significantly increased newly-formed periodontal attachment, bone and cementum in periodontal defect and less tissue destruction in the progression of periodontitis. This study demonstrated that 45 nm AuNPs could not only directly modulate hPDLCs, but also regulate the early inflammatory response of periodontal tissues via the regulation of macrophage phenotypes, therefore, generate a microenvironment with constraint inflammatory cytokine levels and reparative cytokines such as bone morphogenetic protein-2 (BMP-2), leading to PDLC differentiation, periodontal tissue regeneration and the prevention of periodontitis progression.
Highlights
Periodontitis, a bacterially induced chronic inflammatory disease, usually progressively destroys the supporting structures of teeth, including the alveolar bone, cementum, periodontal ligament and gingiva, subsequently leading to the looseness and loss of teeth [1,2]
The RAW 264.7 cells were obtained from American Type Culture Collection (ATCC, Manassas, USA). human periodontal ligament cells (hPDLCs), the primary cells isolated from human periodontal ligament tissue, were purchased from ScienCell Research Laboratories (Catalog #2630, Carlsbad, USA)
Since macrophages play crucial roles in the pathological mechanism of periodontitis, these findings provides a new strategy to investigate the potential of biomaterials in periodontal regeneration and periodontitis treatment, that is to take the activity of macrophages into consideration during the process of tissue regeneration
Summary
Periodontitis, a bacterially induced chronic inflammatory disease, usually progressively destroys the supporting structures of teeth, including the alveolar bone, cementum, periodontal ligament and gingiva, subsequently leading to the looseness and loss of teeth [1,2]. Periodontitis is considered as the main cause of tooth loss in adults, and is reported to be interrelated with systemic health by increasing the risk of many diseases such as atherosclerosis, adverse pregnancy outcomes, rheumatoid arthritis, aspiration pneumonia and cancer [1,3]. A unique structure in periodontal tissues, is a thin layer of mineralized tissue covering the root surface of teeth that serves as the interface for periodontal ligament anchorage to the teeth and supports the binding between teeth and bone [7,8].
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