Ying Xue

This pilot in vitro study explored the tensile retention of lithium disilicate and monolithic zirconia crowns cemented onto zirconia one-piece implants using two resin cements and two cementation protocols. In addition, the relationship between micro-computed tomography (micro-CT)-derived cement layer characteristics and retention was explored for lithium disilicate crowns. Thirty-two implant–crown assemblies were prepared using 16 lithium disilicate and 16 zirconia crowns. Specimens were cemented with either an adhesive resin cement (Panavia V5) or a self-adhesive resin cement (SpeedCem Plus) using two protocols: conventional apical-half cementation (AH) and an abutment-assisted apical-half protocol (A-AH). Cement thickness and porosity for lithium disilicate crowns were obtained from a previously published micro-CT analysis of the same specimens; no micro-CT measurements were available for the zirconia specimens. Tensile pull-out testing was performed using a universal testing machine. The primary outcome was the maximum recorded force at the first observed mechanical failure, irrespective of the mode of that failure, so that all 32 specimens contributed a value. Failure occurred by crown debonding in 27 specimens, by crown fracture in 4 and by implant fracture in 1. For the primary outcome, the maximum recorded force was lower for lithium disilicate than for zirconia crowns (medians 347.20 versus 596.05 N; exact Mann–Whitney p = 0.017) and lower with the A-AH than with the AH protocol (medians 304.24 versus 614.38 N; p < 0.001), whereas the difference between the two resin cements was not statistically significant (medians 438.88 versus 550.83 N; p = 0.210). The highest observed mean maximum load was recorded for zirconia crowns cemented with Panavia V5 using the AH protocol (729.9 ± 237.7 N), whereas the lowest observed mean maximum load was recorded for lithium disilicate crowns cemented with Panavia V5 using the A-AH protocol (219.7 ± 105.1 N). In a secondary, cause-specific exploratory analysis restricted to crown debonding (27 events, 5 specimens censored at fracture), Cox proportional hazards regression on the applied-force scale gave hazard ratios of 3.75 (95% CI 1.40–10.01) for lithium disilicate versus zirconia, 6.47 (2.39–17.53) for A-AH versus AH and 1.82 (0.76–4.39) for Panavia V5 versus SpeedCem Plus. For lithium disilicate crowns, exploratory factorial ANOVA indicated that cementation protocol was associated with differences in cement thickness (p = 0.035), while cement type was associated with differences in porosity (p < 0.001). All 16 lithium disilicate cement thickness observations lay between 253.29 and 254.96 µm, a total span of 1.67 µm. Within that extremely restricted range, a univariable exploratory Cox model expressed per 0.1 µm gave a hazard ratio for debonding of 1.24 (95% CI 1.03–1.48; p = 0.024); this is an unadjusted association across a range that is itself associated with cementation protocol, and it does not demonstrate a clinically meaningful or independent effect of cement thickness. No association was detected for total porosity (0.959 per percentage point, 0.717–1.283); that interval is wide and indicates absence of evidence rather than evidence of no association. Within the limitations of this pilot in vitro study—four specimens per subgroup, wide confidence intervals and no adjustment for multiplicity—the findings suggest that crown material and cementation protocol may be associated with retention patterns. They are exploratory and hypothesis-generating and require confirmation in larger, independently powered studies.

Objectives: An infectious trigger can initiate a systemic inflammatory response, which in turn activates immune cells and causes the release of various mediators. Local mediators, such as resolvin D1 (RvD1), actively interact with immune cells to promote the resolution of inflammation. This study aimed to determine the impact of RvD1 on the inflammatory response mediated by monocytes in response to LPS. Methods: To investigate the mechanism by which RvD1 affects the monocyte-mediated inflammatory response to LPS, human THP-1 monocytic cells were treated with LPS, RvD1, or vehicle for 24 h. Inflammatory cytokines, interleukin-1β (IL-1β) and tumor necrosis factor (TNF-α), were measured using enzyme-linked immunosorbent assay (ELISA). RNA sequencing (RNA-seq) was used to identify differentially expressed genes (DEGs). The NF-κB and MAPK p38 signaling pathways were validated using real-time quantitative PCR (RT-qPCR) and Western blotting (WB). Results: RvD1 diminished the levels of IL-1β and TNF-α in LPS-induced inflammation. RvD1 significantly enhanced the mRNA expression of CREB, NRF2, and BCL-2. In addition, RvD1 significantly decreased the mRNA expression of CASP3. RvD1 regulated the inflammatory process in human monocytic THP-1 cells via the NF-κB p65 (MyD88, p65) and p38 MAPK signaling pathways (p38, BCL-2) and further suppressed the expression of apoptotic factors (PI3K, caspase-3). Conclusions: RvD1 has been shown to exert pro-resolving effects by regulating the anti-apoptotic gene BCL-2 and activating the NF-κB p65 and MAPK p38 signaling pathways.

Medication-related osteonecrosis of the jaw (MRONJ) is a severe complication associated with antiresorptive therapy, characterized by compromised bone and soft tissue integrity. However, the underlying tissue-level mechanisms remain poorly understood. To uncover cell functions and spatial organization surrounding ONJ lesions, imaging mass cytometry is used to profile lesions at single-cell resolution across epithelial, stromal, and vascular regions. Widespread immune infiltration is observed, with regulatory T cells, M2-like macrophages, exhausted T cells, and natural killer cells shifting from dispersed to clustered spatial patterns, indicating altered immune organization. Epithelial regions show reduced epithelial marker expression and disrupted architecture despite elevated proliferation-related markers, while fibroblasts and endothelial cells display signs of activation. Functional profiling reveals concurrent proliferative, apoptotic, and stress-associated signatures across multiple cell populations. This comprehensive spatial and functional atlas provides insights into the pathophysiology of MRONJ and may inform future therapeutic strategies aimed at restoring tissue homeostasis and promoting effective healing.

Objective: To evaluate the influence of two cementation protocols on lithium disilicate crowns cemented to zirconia one-piece implants by analyzing cement thickness, porosity, and excess cement using micro-computed tomography (micro-CT). Materials and methods: Sixteen Computer-Aided Design (CAD)/Computer-Aided Manufacturing (CAM)-fabricated lithium disilicate crowns were cemented onto zirconia one-piece implants (WhiteSKY, Bredent) using two resin-based cements: an adhesive resin cement (ARC) and a self-adhesive resin cement (SARC) based on multifunctional phosphoric methacrylates. Each cement was applied with either a conventional apical-half (AH) or an abutment-assisted apical-half protocol (A-AH), creating four groups (n = 4). Samples were scanned with micro-CT for volumetric analysis of the cement. Data were analyzed using Analysis of Variance (ANOVA) with Dunnett’s post hoc test (α = 0.05). Results: The ARC showed lower porosity and more uniform cement layers than the SARC. The A-AH technique significantly reduced excess cement in both cements, particularly with the self-adhesive resin type. All groups exceeded the 50 µm digital cement space, with the self-adhesive A-AH group showing the highest thickness. Conical abutment geometry contributed to localized cement accumulations. Conclusions: Both the cement type and the application protocol appeared to influence the characteristics of the cement interface. In this study, the ARC tended to produce a more uniform and less porous cement layer, whereas the abutment-assisted protocol was associated with reduced amounts of excess cement. These findings suggest that modifications to the cementation protocol may help to optimize outcomes for zirconia one-piece implant restorations, particularly when using self-adhesive resin systems.

Objectives: Periodontitis is a multifactorial inflammatory disease initiated by pathogenic bacteria, such as Porphyromonas gingivalis. Resolvin D1 (RvD1) plays a pivotal role in inflammation resolution. This study aimed to identify the mechanism of the regulatory effects of RvD1 on the inflammatory response of human periodontal ligament cells (hPDLCs). Methods: To investigate the mechanism of RvD1’s impact on the hPDLCs, RNA-sequencing (RNA-seq) was used and differentially expressed genes (DEGs) were identified. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed to assess the signaling pathways in which NF-κB and MAPK were determined to play a significant role. Alterations in NF-κB and MAPK pathways were verified by immunofluorescence (IF), quantitative real-time PCR (qRT-PCR), and Western blotting (WB). The expression of RvD1 and lipoxin A4/formyl peptide receptor 2 (ALX/FPR2) was assessed by IF and WB. Inflammatory cytokine interleukin (IL) 6 and IL-1β release was measured by ELISA. Results: GO and KEGG analyses indicated that RvD1 regulates the inflammatory process in PDLCs primarily via TLR4-MyD88-mediated NF-κB and MAPK signaling. RvD1 suppressed lipopolysaccharide (LPS)-induced TLR4 and MyD88 expression, inhibited phosphorylation of NF-κB p65 and its inhibitor IKBKB, and attenuated phosphorylation of p38 MAPK, ERK, and JNK. ALX/FPR2 was expressed on hPDLCs and was further upregulated upon treatment with RvD1. RvD1 significantly down-regulated the IL-6 and IL-1β levels in LPS-stimulated hPDLCs. Conclusions: RvD1 regulates the inflammatory response of LPS-stimulated hPDLCs by the TLR4-MyD88-MAPK and TLR4-MyD88-NF-κB signaling pathways, suggesting the potential role of RvD1 in restoring periodontal tissue homeostasis by regulating PDLC response to inflammatory and infectious stimuli.

Background/Objectives: Constant inflammation can be a detrimental response in bone regeneration. To regulate of the inflammatory response and synchronically promote rapid tissue regeneration is a vital clinical challenge. The urinary bladder matrix (UBM) and small intestinal submucosa (SIS) composite are commonly used extracellular matrix (ECM) materials. We designed a novel drug-loaded membrane by integrating the biological matrix (BM) composed of UBM and SIS composites with Resolvin D1 (RvD1), an endogenous pro-resolving lipid mediator, using the lyophilization process. This membrane is referred to as BRL, an acronym for BM-RvD1-Lyophilization. Methods: In this study, the physicochemical properties of the membranes were characterized. Fluorescence staining and the CCK8 assay kit were utilized to assess biocompatibility. To evaluate the inflammatory resolution properties and osteogenic ability of osteoblasts, real-time quantitative PCR and ELISA were conducted. Results: BRL exhibited a more pronounced three-dimensional pore structure, demonstrating excellent physicochemical properties and enabling the slow release of RvD1. This approach improved the viability of MG63 osteoblast-like cells, reduced LPS-induced inflammation, and upregulated osteogenesis-related genes significantly. Conclusions: By integrating inflammation control capabilities into tissue regeneration materials, BRL effectively regulates the tissue regeneration microenvironment, thereby enhancing regeneration efficiency and positioning itself as an exceptional candidate for future tissue regeneration membranes.

Objective: To evaluate the drug release, cytocompatibility with periodontal ligament cells (PDLCs), and therapeutic efficacy of GelMA hydrogel loaded with resolvin D1 (RvD1) in treating rat periodontal inflammation and alveolar bone damage. Methods: An RvD1 complexed with GelMA was prepared, and its release kinetics and compatibility with PDLCs were assessed. Rats with induced periodontitis were treated weekly with topical applications of vehicle, GelMA, RvD1, or RvD1 complexed with GelMA for four weeks. Periodontal inflammation and tissue regeneration were evaluated using quantitative PCR (qPCR) and histochemical staining, while alveolar bone repair and regeneration were analyzed through micro-CT. Results: The RvD1 complexed with GelMA effectively released RvD1 and enhanced the proliferation and viability of PDLCs. Compared to RvD1 alone, treatment with RvD1 complexed with GelMA significantly reduced inflammatory cell infiltration, TNF-α and RANKL expression, and osteoclast formation in periodontal tissues. Additionally, it promoted the expression of specific anti-inflammatory and regenerative markers. Micro-CT analysis confirmed significant new bone formation in the RvD1 complexed with GelMA-treated group. Conclusions: RvD1 complexed with GelMA provides sustained drug release and biocompatibility, effectively resolves periodontal inflammation, and promotes tissue regeneration in periodontitis.

Lymphatics are involved in the resolution of inflammation and wound healing, but their role in the oral wound healing process after tooth extraction has never been investigated. We therefore sought to evaluate the healing process following the extraction of maxillary molars in two transgenic mouse models: K14‐VEGFR3‐Ig mice, which lack initial mucosal lymphatic vessels, and K14‐VEGFC mice, which have hyperplastic mucosal lymphatics. Maxillary molars were extracted from both transgenic mouse types and their corresponding wild‐type (WT) controls. Mucosal and alveolar bone healing were evaluated. A delayed epithelialization and bone regeneration were observed in K14‐VEGFR3‐Ig mice compared with their WT littermates. The hampered wound closure was accompanied by decreased levels of epidermal growth factor (EGF) and persistent inflammation, characterized by infiltrates of immune cells and elevated levels of pro‐inflammatory markers in the wounds. Hyperplastic mucosal lymphatics did not enhance the healing process after tooth extraction in K14‐VEGFC mice. The findings indicate that initial mucosal lymphatics play a major role in the initial phase of the oral wound healing process.