Dioscin Alleviates Periodontitis by Inhibiting NLRP3 Inflammasome Activation via Regulation of K+ Homeostasis and Mitochondrial Function.

Gingival inflammation and alveolar bone loss are characteristic manifestations of periodontitis. Interleukin (IL)-1ß, the maturation of which is mainly regulated by NOD-like receptor protein (NLRP) 3 inflammasome, not only amplifies the inflammatory response but also triggers osteoclastogenesis, thereby accelerating the progression of periodontitis. Dioscin, a natural steroid saponin, has been shown to inhibit NLRP3 inflammasome. Nevertheless, research on the effectiveness of Dioscin for the management of periodontitis remains scarce. In this study, Dioscin was found to dramatically reduce the integral components of NLRP3 inflammasome, ultimately limiting IL-1ß secretion. Notably, the inhibitory impact of Dioscin on NLRP3 inflammasome might be exerted by curbing the generation of mitochondrial (mt) reactive oxygen species (ROS) and oxidized (ox) mtDNA, which were mediated by inhibition of K+ efflux. Furthermore, Dioscin effectively alleviated periodontitis in mice. Overall, the results established that Dioscin could alleviate periodontitis by inhibiting NLRP3 inflammasome via modulation of the K+ efflux-mtROS-ox-mtDNA pathway, holding the potential to treat periodontitis and other NLRP3-driven inflammatory diseases.

Cell Responses to Calcium- and Protein-Conditioned Titanium: An In Vitro Study.

Dental implants have become the leading choice for patients who lose teeth; however, dental implantation is challenged by peri-implant infections. Here, calcium-doped titanium was fabricated by the combinational use of thermal evaporation and electron beam evaporation in a vacuum; then, the material was immersed in a calcium-free phosphate-buffered saline solution containing human plasma fibrinogen and incubated at 37 °C for 1 h, creating calcium- and protein-conditioned titanium. The titanium contained 12.8 ± 1.8 at.% of calcium, which made the material more hydrophilic. Calcium release by the material during protein conditioning was able to change the conformation of the adsorbed fibrinogen, which acted against the colonization of peri-implantitis-associated pathogens (Streptococcus mutans, UA 159, and Porphyromonas gingivalis, ATCC 33277), while supporting the adhesion and growth of human gingival fibroblasts (hGFs). The present study confirms that the combination of calcium-doping and fibrinogen-conditioning is a promising pathway to meeting the clinical demand for suppressing peri-implantitis.

Remodeling immune microenvironment in periodontitis using resveratrol liposomes as an antibiotic-free therapeutic strategy.

BACKGROUND: Periodontitis is a complicated inflammatory disease that damages the tooth-supporting tissues, with limited pharmacotherapy available. Macrophage-targeting therapy is promising for inflammatory diseases. Resveratrol (RSV), a nonflavonoid polyphenol, is known for its anti-inflammatory and immunomodulatory effects. However, its medical application is limited by its poor stability and water-solubility, as well as its low bioavailability. RESULT: A therapeutic resveratrol-loaded liposomal system (Lipo-RSV) was developed to treat periodontitis. The physical properties of Lipo-RSV and its ability to regulate macrophages were investigated. The results showed that Lipo-RSV had good biocompatibility and could re-educate the inflammatory macrophages from M1- to M2-like phenotype through activating p-STAT3 and downregulating p-STAT1. Besides, the Lipo-RSV could scavenge ROS and inhibit the NF-κB signal and inflammasomes, thereby reducing the pro-inflammatory cytokines IL-1ß, IL-6, and TNF-α. CONCLUSION: These results revealed that Lipo-RSV could be a potential therapeutic system for the antibiotic-free treatment for periodontal diseases.

A biopolymer hydrogel electrostatically reinforced by amino-functionalized bioactive glass for accelerated bone regeneration.

Composite hydrogels incorporating natural polymers and bioactive glass (BG) are promising materials for bone regeneration. However, their applications are compromised by the poor interfacial compatibility between organic and inorganic phases. In this study, we developed an electrostatically reinforced hydrogel (CAG) with improved interfacial compatibility by introducing amino-functionalized 45S5 BG to the alginate/gellan gum (AG) matrix. BAG composed of AG and unmodified BG (10 to 100 µm in size) was prepared as a control. Compared with BAG, CAG had a more uniform porous structure with a pore size of 200 µm and optimal compressive strength of 66 kPa. Furthermore, CAG promoted the M2 phenotype transition of macrophages and up-regulated the osteogenic gene expression of stem cells. The new bone formation in vivo was also accelerated due to the enhanced biomineralization of CAG. Overall, this work suggests CAG with improved interfacial compatibility is an ideal material for bone regeneration application.

Melatonin prevents peri­implantitis via suppression of TLR4/NF-κB.

Peri­implantitis, which is characterized by peri­implant mucositis and alveolar bone resorption, significantly shortens the service life of dental implants. Melatonin is well-known for its anti-inflammatory and osteoprotective activities. Nevertheless, the effects and mechanisms of melatonin to prevent peri­implantitis remain unknown. In this study, the lipopolysaccharide-induced peri­implantitis model was established after the titanium implants were osseointegrated, and the rats received daily administrations of melatonin. The gingival fibroblasts and osteoclasts/osteoblasts were also co-cultured to simulate the inflammatory environment in vitro. We found that prophylactic administration of melatonin decreased proinflammatory cytokine levels and osteoclast numbers, attenuated alveolar bone resorption, and reduced the incidence of peri­implantitis in vivo. Furthermore, melatonin suppressed osteoclastic formation and function in the inflammatory co-culture environment, while melatonin promoted osteoblastic differentiation and function in the in vitro model. Mechanistically, melatonin reduced TLR4 protein levels, and inhibited activation of NF-κB to downregulate the levels of TNF, IL-1ß, and IL-6. These data showed that melatonin was a potent agent to prevent peri­implantitis through inhibiting TLR4/NF-κB signaling. Our findings provide a novel strategy to prevent peri­implantitis, and expand the applications of melatonin. STATEMENT OF SIGNIFICANCE: Dental implants have become the first choice for restoring partial and full edentulism, but its service life is seriously affected by peri­implantitis. Exploration of novel and effective approaches to prevent peri­implantitis is an important and urgent need. In the present study, we have reported for the first time that prophylactic administration of melatonin delayed the occurrence and reduced the incidence of peri­implantitis by decreasing proinflammatory cytokine levels, inhibiting osteoclastogenesis, and promoting osteogenesis. The study is expected to have an important significance on the prevention of peri­implantitis.

Graphene-Reinforced Titanium Enhances Soft Tissue Seal.

The integrity of soft tissue seal is essential for preventing peri-implant infection, mainly induced by established bacterial biofilms around dental implants. Nowadays, graphene is well-known for its potential in biocompatibility and antisepsis. Herein, a new titanium biomaterial containing graphene (Ti-0.125G) was synthesized using the spark plasma sintering (SPS) technique. After material characteristics detection, the subsequent responses of human gingival fibroblasts (HGFs) and multiple oral pathogens (including Streptococci mutans, Fusobacterium nucleatum, and Porphyromonas gingivalis) to the graphene-reinforced sample were assessed, respectively. Also, the dynamic change of the bacterial multispecies volume in biofilms was evaluated using absolute quantification PCR combined with Illumina high-throughput sequencing. Ti-0.125G, in addition to its particularly pronounced inhibitory effect on Porphyromonas gingivalis at 96 h, was broadly effective against multiple pathogens rather than just one strain. The reinforced material's selective responses were also evaluated by a co-culture model involving HGFs and multiple strains. The results disclosed that the graphene-reinforced samples were highly effective in keeping a balance between the favorable fibroblast responses and the suppressive microbial growth, which could account for the optimal soft tissue seal in the oral cavity. Furthermore, the underlying mechanism regarding new material's bactericidal property in the current study has been elucidated as the electron transfer, which disturbed the bacterial respiratory chain and resulted in a decrease of microbial viability. According to the Kyoto Encyclopedia of Genes and Genomes (KEGG) database, the PICRUSt tool was conducted for the prediction of microbial metabolism functions. Consequently, it is inferred that Ti-0.125G has promising potentials for application in implant dentistry, especially in enhancing the integrity of soft tissue and improving its resistance against bacterial infections around oral implants.

Novel application of bergapten and quercetin with anti-bacterial, osteogenesis-potentiating, and anti-inflammation tri-effects.

The bacteria-mediated inflammatory conditions adversely affect the osseointegration process of endosseous implants, which can even lead to implant malfunction or failure. Local drug delivery has been designed to exert anti-inflammatory and antibacterial activities, but whether this strategy has an effect on the compromised osseointegration under inflammation has rarely been studied. The present study focused on the osteoinductive efficacy of two known phytoestrogens [bergapten (BP) and quercetin (QE)] on implant sites under multiple bacteria-infected conditions in situ. Furthermore, the gene expression profiles of rat bone mesenchymal stem cells (rBMSCs) treated with BP and QE in the presence of Porphyromonas gingivalis-derived lipopolysaccharide were identified. The results showed that both drugs, especially QE, had significant potentiating effects on promoting osteogenic differentiation of rBMSCs, resisting multiple pathogens, and reducing inflammatory activity. Meanwhile, RNA sequencing analysis highlighted the enriched gene ontology terms and the differentially expressed genes (Vps25, Il1r2, Csf3, Efemp1, and Ccl20) that might play essential roles in regulating the above tri-effects, which provided the basis for the drug delivery system to be used as a novel therapeutic strategy for integrating peri-implant health. Overall, our study confirmed that QE appeared to outperform BP in osteogenesis and bacterial killing but not in anti-inflammation. Moreover, both drugs possess favorable tri-effects and can serve as the pivotal agents for the drug delivery system to boost osseointegration at inflammatory implant sites.

Accuracy of dynamic navigation in implant surgery: A systematic review and meta-analysis.

OBJECTIVE: To assess the accuracy of dynamic computer-assisted implant surgery. MATERIALS AND METHODS: An electronic search up to March 2020 was conducted using PubMed, Embase, and the Cochrane Central Register of Controlled Trial to identify studies using dynamic navigation in implant surgery, and additional manual search was performed as well. Clinical trials and model studies were selected. The primary outcome was accuracy. A single-arm meta-analysis of continuous data was conducted. Meta-regression was utilized for comparison on study design, guidance method, jaw, and systems. RESULTS: Ten studies, four randomized controlled trials (RCT) and six prospective studies, met the inclusion criteria. A total of 1,298 drillings and implants were evaluated. The meta-analysis of the accuracy (five clinical trials and five model studies) revealed average global platform deviation, global apex deviation, and angular deviation were 1.02 mm, 95% CI (0.83, 1.21), 1.33 mm, 95% CI (0.98, 1.67), and 3.59°, 95% CI (2.09, 5.09). Meta-regression shown no difference between model studies and clinical trials (p = .295, 0.336, 0.185), drilling holes and implant (p = .36, 0.279, 0.695), maxilla and mandible (p = .875, 0.632, 0.281), and five different systems (p = .762, 0.342, 0.336). CONCLUSION: Accuracy of dynamic computer-aided implant surgery reaches a clinically acceptable range and has potential in clinical usage, but more patient-centered outcomes and socio-economic benefits should be reported.