Nanochemistry of gold: from surface engineering to dental healthcare applications.

Advancements in nanochemistry have led to the development of engineered gold nanostructures (GNSs) with remarkable potential for a variety of dental healthcare applications. These innovative nanomaterials offer unique properties and functionalities that can significantly improve dental diagnostics, treatment, and overall oral healthcare applications. This review provides an overview of the latest advancements in the design, synthesis, and application of GNSs for dental healthcare applications. Engineered GNSs have emerged as versatile tools, demonstrating immense potential across different aspects of dentistry, including enhanced imaging and diagnosis, prevention, bioactive coatings, and targeted treatment of oral diseases. Key highlights encompass the precise control over GNSs' size, crystal structure, shape, and surface functionalization, enabling their integration into sensing, imaging diagnostics, drug delivery systems, and regenerative therapies. GNSs, with their exceptional biocompatibility and antimicrobial properties, have demonstrated efficacy in combating dental caries, periodontitis, peri-implantitis, and oral mucosal diseases. Additionally, they show great promise in the development of advanced sensing techniques for early diagnosis, such as nanobiosensor technology, while their role in targeted drug delivery, photothermal therapy, and immunomodulatory approaches has opened new avenues for oral cancer therapy. Challenges including long-term toxicity, biosafety, immune recognition, and personalized treatment are under rigorous investigation. As research at the intersection of nanotechnology and dentistry continues to thrive, this review highlights the transformative potential of engineered GNSs in revolutionizing dental healthcare, offering accurate, personalized, and minimally invasive solutions to address the oral health challenges of the modern era.

Knockdown of Bach1 protects periodontal bone regeneration from inflammatory damage.

Periodontal bone regeneration is a major challenge in the treatment of periodontitis. However, the regenerative vitality of periodontal ligament cells (PDLCs) declines in the environment of periodontitis and accompanying oxidative stress. This study aimed to investigate the functional mechanisms of Bach1, a transcriptional suppressor involved in oxidative stress response, and its regulation of PDLC osteogenesis under inflammatory conditions. We observed a significant elevation in Bach1 expression in periodontal tissues with periodontitis and PDLCs under inflammatory conditions. Knockdown of Bach1 alleviated the inflammation-induced oxidative stress level and partly offset the inhibitory effect of inflammatory conditions on osteogenesis, as well as the expression of osteogenic genes BMP6, OPG and RUNX2. Similarly, knockdown of Bach1 protects PDLCs from inflammatory damage to periodontal bone regeneration in vivo. Furthermore, we found that Bach1 could bind to the histone methyltransferase EZH2, and the binding increased under inflammatory conditions. Bach1 enhanced the ability of EZH2 to catalyse H3K27me3 on the promoter region of RUNX2 and BMP6, thus repressing the expression of osteoblastic genes. In conclusion, our study revealed that knockdown of Bach1 effectively rescued the osteogenesis and oxidative stress of PDLCs with inflammation. Bach1 could be a promising target for enhancing periodontal tissue regeneration under periodontitis conditions.

Correlation between serum α-Klotho levels and different stages of periodontitis.

BACKGROUND: Periodontitis is an inflammatory disease characterized by inflammation and progressive destruction of periodontal tissues including alveolar bone. α-klotho protein is a multifunctional protein related to age-related diseases, inflammatory diseases, and bone metabolism-related diseases. However, large-sample epidemiological research evidence on the correlation between α-Klotho and the aggravation of periodontitis stages is still lacking. METHODS: Cross-sectional study data of participants aged between 40 and 79 years in the National Health and Nutrition Examination Survey 2013‒2014 were selected and analyzed. The stages of periodontitis of the participants were determined according to the 2018 World Workshop Classification of Periodontal and Peri-implant Diseases. The serum α-Klotho levels in people with periodontitis in different stages were evaluated. Then the correlation between serum α-Klotho levels and different stages of periodontitis was analyzed by multiple linear regression (stepwise regression method). RESULTS: A total of 2378 participants were included in the study. The serum α-Klotho levels in people with stage I/II, III and IV periodontitis were 896.16 ± 304.84, 871.08 ± 266.42 and 840.52 ± 286.24 pg/mL, respectively. The levels of α-Klotho in people with stage IV periodontitis were significantly lower than those in people with stage I/II and III periodontitis. Linear regression analysis results showed that compared to stage I/II periodontitis, serum α-Klotho levels were significantly negatively correlated with stage III (B ± SE = -37.28 ± 16.00, 95% CI: -68.66 ~ -25.91, P = 0.020) and stage IV (B ± SE = -69.37 ± 16.11, 95% CI: -100.97 ~ -37.77, P < 0.001) periodontitis. CONCLUSION: The serum α-Klotho levels were negatively correlated with the severity of periodontitis. With the aggravation of periodontitis stages, the serum α-Klotho levels gradually decreased.

Three-dimensional positional relationship between impacted mandibular third molars and the mandibular canal.

OBJECTIVE: To observe the three-dimensional positional relationship between impacted mandibular third molars (IMTMs) and mandibular canal close contacts using cone beam computed tomography (CBCT). METHODS: A total of 101 patients with IMTMs were selected who met the diagnostic criteria for 142 teeth (no bone wall imaging area between IMTMs and the mandibular canal, a high-density bone cortical imaging area only, or a ≦1 mm bone imaging area). The parameters of the rotating CBCT anode were set as follows: 110 kV, 40-50 mA; the focal point and exposure field were set as 0.3 mmh and a high-resolution zoom, respectively; the exposure time and image layer thickness were set as 5.4 s and 0.25 mm. Three-dimensional reconstruction was performed, and the position of the mandibular canal through the IMTM area was observed continuously from the coronal, horizontal and sagittal planes. RESULTS: We found that the mandibular canal was interrupted below the third molar (TM) in 85 cases, accounting for 59.86% of all cases. The mandibular canal was located below the buccal and lingual curvatures in 33 and 19 cases, respectively, accounting for 23.23% and 19%. In addition, a small number of mandibular canals were also located on the buccal side of the mandibular molars (2.82%). We also found one case of direct insertion of the mandibular third molar (MTM) into the mandibular canal. In addition, the mandibular canal passed through the IMTM region with 125 close contacts at the roots (88.03%); 14 mandibular canals were in contact with all teeth and 3 were in contact with the crown. CONCLUSION: The use of CBCT can provide a dynamic and comprehensive understanding of the three-dimensional positional relationship of the mandibular alveolar nerve canal passing through the IMTM area, providing a high clinical reference value when extracting IMTMs and reducing the risk of injury to the inferior alveolar nerve.

Neural epidermal growth factor-like 1 protein (Nell-1) alleviates periodontal tissue destruction in periodontitis by regulating the ratio of M2/M1 macrophage phenotypes.

BACKGROUND: Periodontitis is a common oral disease with high prevalence worldwide. Neural epidermal growth factor-like 1 protein (Nell-1) has recently been reported to have anti-inflammation effects and may be a drug candidate for osteoarthritis. However, its immunotherapeutic effects in periodontitis remain unknown. Therefore, this study aimed to investigate the effects of Nell-1 on periodontitis in terms of macrophage polarization and analyze its possible underlying mechanism. METHODS: A rat ligation-induced experimental periodontitis model was established and locally injected with Nell-1 (n = 6/group). Periodontal tissue destruction and macrophage polarization in vivo were analyzed using micro-CT, histology analysis, and western blot. Enzyme-linked immunosorbent assay was used to evaluate serum inflammatory cytokines. Then, the RAW 264.7 macrophage cells were treated with lipopolysaccharide (LPS), Nell-1, and the c-Jun N-terminal kinases (JNK) inhibitor (SP600125). RT-PCR, western blot, and flow cytometry were performed to further analyze the effect of Nell-1 on macrophage polarization and the underlying mechanism in vitro. RESULTS: Local treatment with Nell-1 significantly alleviated the destruction of alveolar bone and fibers in periodontitis, and upregulated the ratio of M2/M1 macrophages in periodontal tissues (P < 0.05). In vitro, Nell-1 at the concentrations of 200 and 500 ng/mL could significantly inhibit the expression of M1-related inflammatory factors in LPS-stimulated macrophages, and increase the expression of M2-related markers, regulating the macrophage phenotype switch into M2 (P < 0.05). The mRNA of JNK and relative protein level of phospho-JNK/JNK were also upregulated by Nell-1 (P < 0.05). Additionally, the JNK inhibitor (SP600125) could reverse the effect of Nell-1 on macrophage polarization (P < 0.05). CONCLUSIONS: Nell-1 could modulate the ratio of M2/M1 macrophages possibly through the JNK/MAPK signaling pathway, subsequently attenuating the inflammation and destruction of periodontal tissues caused by periodontitis.

Nel-like Molecule Type 1 Combined with Gold Nanoparticles Modulates Macrophage Polarization, Osteoclastogenesis, and Oral Microbiota in Periodontitis.

The disruption of host-microbe homeostasis and uncontrolled inflammatory response have been considered as vital causes for developing periodontitis, subsequently leading to an imbalance between the bone and immune system and the collapse of bone homeostasis. Consequently, strategies to modulate the immune response and bone metabolization have become a promising approach to prevent and treat periodontitis. In this study, we investigated the cooperative effects of Nel-like molecule type 1 (Nell-1) and gold nanoparticles (AuNPs) on macrophage polarization, osteoclast differentiation, and the corresponding functions in an experimental model of periodontitis in rats. Nell-1-combined AuNPs in in vitro studies were found to reduce the production of inflammatory factors (TNF-α, p < 0.0001; IL-6, p = 0.0012), modulate the ratio of M2/M1 macrophages by inducing macrophage polarization into the M2 phenotype, and inhibit cell fusion, maturation, and activity of osteoclasts. Furthermore, the local application of Nell-1-combined AuNPs in in vivo studies resulted in alleviation of damages to the periodontal and bone tissues, modulation of macrophage polarization and the activity of osteoclasts, and alteration of the periodontal microbiota, in which the relative abundance of the probiotic Bifidobacterium increased (p < 0.05). These findings reveal that Nell-1-combined AuNPs could be a promising drug candidate for the prevention and treatment of periodontitis. However, Nell-1-combined AuNPs did not show organ toxicity or impair the integrity of intestinal epithelium but alter the gut microbiota, leading to the dysbiosis of gut microbiota. The adverse impact of changes in gut microbiota needs to be further investigated. Nonetheless, this study provides a novel perspective and direction for the biological safety assessment of biomaterials in oral clinical applications.

Gold nanoparticles modulate the crosstalk between macrophages and periodontal ligament cells for periodontitis treatment.

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.

Human oral microbiota and its modulation for oral health.

The oral microbiome is an important part of the human microbiome. The oral cavity contains several significantly different niches with distinct microbial communities. A wide range of microorganisms inhabit the human oral cavity, including bacteria, fungi, viruses, archaea and protozoa. These microorganisms form a complex ecological community that influences oral and systemic health. The most prevalent oral diseases, dental caries and periodontal diseases, are microbiota-associated diseases. Moreover, increasing evidences have supported that many systemic diseases are associated with disturbances in the oral ecosystem, such as diabetes, cardiovascular diseases and tumors. The current control of dental plaque-related diseases is nonspecific and is centered on the removal of plaque by mechanical means. Due to this realization about the oral microbiome, several new methods based on the modulation of the microbiome that aim at maintaining and reestablishing a healthy oral ecosystem have been developed.