Clinical feasibility evaluation of a digital workflow of prosthetically oriented onlay bone grafting for horizontal alveolar augmentation: a prospective pilot study.

BACKGROUND: Onlay bone grafting is considered highly reliable for reconstructing severe horizontal bone defects. A critical problem is how to achieve precise position of the bone block to control alveolar ridge dimensions. This research aims to establish a digital workflow for prosthetically oriented onlay bone grafting and evaluate its accuracy and efficiency. METHODS: This prospective pilot study investigated eight patients who required implant restoration in the esthetic area with horizontal alveolar bone defects. The workflow includes preoperative virtual planning, design and manufacture of patient-specific templates, bone grafting surgery, and implant insertion. Primary outcomes were graft accuracy, defined by root mean square estimate (RMSE) values between preoperatively designed and actual implanted outer contours of bone blocks. Secondary outcomes were bone graft and implant success rates. Besides, the surgeons used the visual analog scale (VAS) to rate the intuitiveness, ease of understanding, and helpfulness of the workflow. RESULTS: No bone grafts or implants failed in any of the eight patients, resulting in a 100% success rate. The RMSE values between the preoperative design and the implanted outer contour of bone blocks were 0.41 ± 0.15 mm. The digital approach showed advantages in intuitiveness (9.3 ± 0.5), understanding (9.0 ± 0.5), and helpfulness (8.4 ± 1.1) according to surgeons' VAS scores. CONCLUSIONS: A digital workflow provided encouraging results, in terms of accuracy and efficacy, for horizontal bone augmentation. TRIAL REGISTRATION: This study was registered in the National Clinical Trials Registry in 16/02/2023 under the identification number ChiCTR2300068361.

Evaluating the efficiency of three methods to clean and disinfect screw- and cement-retained prostheses.

STATEMENT OF PROBLEM: Screw- and cement-retained prostheses (SCRPs) may be contaminated during fabrication in a dental laboratory, leading to mechanical and biological complications related to the implant treatment. Studies that explored methods to efficiently and conveniently clean and disinfect SCRPs are sparse. PURPOSE: The purpose of this clinical study was to compare the efficiency of 3 methods to remove contaminants and microorganisms present on the surface of an SCRP. MATERIAL AND METHODS: Forty-eight 1-unit SCRPs fabricated in a dental laboratory were randomly divided into 3 groups: wiping, soaking, or ultrasonic cleaning. The presence of contaminants was determined by scanning electron microscopy, and microbial cells were cultured before and after treatment. Bacterial colony-forming units (CFUs) on the surface of the SCRPs and contamination density at the implant-abutment interface and emergence profile area were assessed. Statistical tests including ANCOVA were used to compare the efficiency of different methods before and after treatment (α=.05). RESULTS: Significant differences in contamination density were noted during the treatment at the implant-abutment interface and at the emergence profile area in the 3 groups (P<.05), but no significant differences were observed in the number of CFUs (P>.05). There were significant differences among the 3 methods for cleaning efficiency both at the implant-abutment interface (P=.023) and the emergence profile area (P=.038). At the implant-abutment interface, the contamination density after treatment was lower in the ultrasonic cleaning group than that in the soaking group (P=.007), whereas at the emergence profile area, the contamination density after treatment was lower in the ultrasonic cleaning group than that in the wiping group (P=.019) and the soaking group (P=.048). CONCLUSIONS: All 3 treatment methods reduced contaminants on the SCRP surface, but ultrasonic cleaning yielded the most favorable results. However, none of the methods provided additional disinfection for SCRPs previously disinfected by ozone and UV in a dental laboratory.

Pharmacokinetics of ceftiofur sodium in cats following a single intravenous and subcutaneous injection.

Ceftiofur, a third-generation cephalosporin antibiotic, is being extensively used by pet doctors in China. In the current study, the detection method was developed for ceftiofur and its metabolites, desfuroylceftiofur (DCE) and desfuroylceftiofur conjugates (DCEC), in feline plasma. Then, the pharmacokinetics studies were performed following one single intravenous and subcutaneous injection of ceftiofur sodium in cats both at 5 mg/kg body weight (BW) (calculated as pure ceftiofur). Ceftiofur, DCE, and DCEC were extracted from plasma samples, then derivatized and further quantified by high-performance liquid chromatography. The concentrations versus time data were subjected to noncompartmental analysis to obtain the pharmacokinetics parameters. The terminal half-life (t1/2λz ) was calculated as 11.29 ± 1.09 and 10.69 ± 1.31 hr following intravenous and subcutaneous injections, respectively. After intravenous treatment, the total body clearance (Cl) and volume of distribution at steady-state (VSS ) were determined as 14.14 ± 1.09 ml hr-1  kg-1 and 241.71 ± 22.40 ml/kg, respectively. After subcutaneous injection, the peak concentration (Cmax ; 14.99 ± 2.29 µg/ml) was observed at 4.17 ± 0.41 hr, and the absorption half-life (t1/2ka ) and absolute bioavailability (F) were calculated as 2.83 ± 0.46 hr and 82.95%±9.59%, respectively. The pharmacokinetic profiles of ceftiofur sodium and its related metabolites demonstrated their relatively slow, however, good absorption after subcutaneous administration, poor distribution, and slow elimination in cats. Based on the time of drug concentration above the minimum inhibitory concentration (MIC) (T>MIC) calculated in the current study, an intravenous or subcutaneous dose at 5 mg/kg BW of ceftiofur sodium once daily is predicted to be effective for treating feline bacteria with a MIC value of ≤4.0 µg/ml.

Force-induced Caspase-1-dependent pyroptosis regulates orthodontic tooth movement.

Pyroptosis, an inflammatory caspase-dependent programmed cell death, plays a vital role in maintaining tissue homeostasis and activating inflammatory responses. Orthodontic tooth movement (OTM) is an aseptic force-induced inflammatory bone remodeling process mediated by the activation of periodontal ligament (PDL) progenitor cells. However, whether and how force induces PDL progenitor cell pyroptosis, thereby influencing OTM and alveolar bone remodeling remains unknown. In this study, we found that mechanical force induced the expression of pyroptosis-related markers in rat OTM and alveolar bone remodeling process. Blocking or enhancing pyroptosis level could suppress or promote OTM and alveolar bone remodeling respectively. Using Caspase-1-/- mice, we further demonstrated that the functional role of the force-induced pyroptosis in PDL progenitor cells depended on Caspase-1. Moreover, mechanical force could also induce pyroptosis in human ex-vivo force-treated PDL progenitor cells and in compressive force-loaded PDL progenitor cells in vitro, which influenced osteoclastogenesis. Mechanistically, transient receptor potential subfamily V member 4 signaling was involved in force-induced Caspase-1-dependent pyroptosis in PDL progenitor cells. Overall, this study suggested a novel mechanism contributing to the modulation of osteoclastogenesis and alveolar bone remodeling under mechanical stimuli, indicating a promising approach to accelerate OTM by targeting Caspase-1.

Implant Survival and Complication Prevalence in Complete-Arch Implant-Supported Fixed Dental Prostheses: A Retrospective Study with a Mean Follow-up of 5 Years.

Purpose: To evaluate the implant survival and the prevalence of biologic and mechanical complications in edentulous patients restored with complete-arch implant-supported fixed dental prostheses (IFDPs). Materials and Methods: Patients restored with complete-arch screw-retained IFDPs between January 2012 and December 2019 with a minimum 2-year follow-up were included. Outcome measures were cumulative survival rate (CSR) for implants and prostheses, biologic complications, and mechanical complications. A generalized estimating equation model was used to estimate potential risk factors for mechanical complications. Patient satisfaction was investigated using a standardized questionnaire. Results: A total of 44 prostheses supported by 268 implants in 30 patients were included for a mean duration of 4.8 years (range: 2 to 9 years). Eighteen of the prostheses were zirconia-ceramic (group ZC), and 26 were titanium-ceramic (group TC). The CSR for the implants and IFDPs was 99.3% (95% CI: 98.2% to 100.3%) and 92.5% (95% CI: 84.2% to 100.8%), respectively. The most common biologic complication was peri-implant mucositis (4.5%), followed by peri-implantitis (3.0%). The most common mechanical complication was ceramic chipping (45.5%), followed by crown debonding (13.6%) and framework fracture (4.5%). There was no significant difference in the prevalence of complications between groups TC and ZC (P > .050). The presence of cantilever (OR = 5.54, P = .048) and maxillary arch (OR = 5.94, P = .041) were significantly associated with mechanical complications. Patient satisfaction scores were generally high, but some continued to be bothered by speech problems (13.6%). Conclusion: Complete-arch IFDPs presented reliable clinical outcomes for edentulous patients with a high implant survival rate and a high level of patient satisfaction. However, a high incidence of mechanical complications occurred in the long term.

Immediately or delayed sinus augmentation after pseudocyst removal: A randomized trial.

PURPOSE: To compare clinical and histological outcomes of sinus augmentation performed immediately or 3 months after pseudocyst removal through a prospective randomized controlled study. MATERIALS AND METHODS: In total, 33 sinus augmentation procedures were performed in 31 patients. Augmentation was performed either immediately after pseudocyst removal (one-stage intervention) or after 3 months (two-stage intervention). Six months postoperatively, bone specimens were harvested, and histomorphometric analysis was performed as primary outcome. Data were recorded and evaluated for implant survival rates, marginal bone resorption, complication rate, and patient-centered outcomes (visual analogue scale [VAS]). RESULTS: There were no baseline differences between groups or dropouts. Twelve biopsies obtained for histomorphometric analysis showed that delayed sinus augmentation, when compared to immediated led to a 1.1% increased mineralized bone ratio (95% confidence interval [CI]: -15.9 to 13.7). Graft leakage and acute sinusitis occurred in one patient in the one-stage group, none in the two-stage group. No pseudocyst recurrence was observed until the end of 1-year follow-up. Median VAS scores for overall acceptance were significantly increase of 1.4 (95% CI: 0.3-2.56) in immediate group. The degree of post-operative discomfort was not significantly different, although an increase of VAS (0.52, 95% CI: -0.32 to 1.37) was observed in delay group. CONCLUSIONS: Both procedures of sinus augmentation immediately and 3 months after pseudocyst removal could obtain comparable histological outcomes and had low complication rates. Patients who underwent the one-stage procedure had a short treatment course and high satisfaction rates, but this procedure is technically challenging to perform. This clinical trial was not registered prior to participant recruitment and randomization. The clinical trial registration number is ChiCTR2200063121. The hyperlink is as follows: https://www.chictr.org.cn/showproj.html?proj=172755.

Craniofacial therapy: advanced local therapies from nano-engineered titanium implants to treat craniofacial conditions.

Nano-engineering-based tissue regeneration and local therapeutic delivery strategies show significant potential to reduce the health and economic burden associated with craniofacial defects, including traumas and tumours. Critical to the success of such nano-engineered non-resorbable craniofacial implants include load-bearing functioning and survival in complex local trauma conditions. Further, race to invade between multiple cells and pathogens is an important criterion that dictates the fate of the implant. In this pioneering review, we compare the therapeutic efficacy of nano-engineered titanium-based craniofacial implants towards maximised local therapy addressing bone formation/resorption, soft-tissue integration, bacterial infection and cancers/tumours. We present the various strategies to engineer titanium-based craniofacial implants in the macro-, micro- and nano-scales, using topographical, chemical, electrochemical, biological and therapeutic modifications. A particular focus is electrochemically anodised titanium implants with controlled nanotopographies that enable tailored and enhanced bioactivity and local therapeutic release. Next, we review the clinical translation challenges associated with such implants. This review will inform the readers of the latest developments and challenges related to therapeutic nano-engineered craniofacial implants.

Photoinduced Carbonyl Radical Luminescence in Host-Guest Systems.

Developing a free radical emission system in different states, especially in water, is highly challenging and desired. Herein, a host-guest coassembly strategy was used to protect the in situ photoactivated radical emission of carbonyl compounds in solid and aqueous solutions by doping them into a series of small molecules with hydroxyl groups. The intermolecular interactions between host and guest and the electron-donating ability of the hydroxyl group can significantly promote the formation and stabilization of luminescence by carbonyl radicals. Accordingly, the stimuli-responsive property of the free radical system was investigated in detail, and the self-assembled aggregates showed photoactive and thermoresponsive behaviors. In addition, an advanced ammonia compound identification system can be built based on a radical emission system. Our design strategy sheds light on developing free radical systems that can emit in various states, which will greatly broaden the application range of free radicals.

Self-promoted electroactive biomimetic mineralized scaffolds for bacteria-infected bone regeneration.

Infected bone defects are a major challenge in orthopedic treatment. Native bone tissue possesses an endogenous electroactive interface that induces stem cell differentiation and inhibits bacterial adhesion and activity. However, traditional bone substitutes have difficulty in reconstructing the electrical environment of bone. In this study, we develop a self-promoted electroactive mineralized scaffold (sp-EMS) that generates weak currents via spontaneous electrochemical reactions to activate voltage-gated Ca2+ channels, enhance adenosine triphosphate-induced actin remodeling, and ultimately achieve osteogenic differentiation of mesenchymal stem cells by activating the BMP2/Smad5 pathway. Furthermore, we show that the electroactive interface provided by the sp-EMS inhibits bacterial adhesion and activity via electrochemical products and concomitantly generated reactive oxygen species. We find that the osteogenic and antibacterial dual functions of the sp-EMS depend on its self-promoting electrical stimulation. We demonstrate that in vivo, the sp-EMS achieves complete or nearly complete in situ infected bone healing, from a rat calvarial defect model with single bacterial infection, to a rabbit open alveolar bone defect model and a beagle dog vertical bone defect model with the complex oral bacterial microenvironment. This translational study demonstrates that the electroactive bone graft presents a promising therapeutic platform for complex defect repair.

Histologic and Clinical Evaluation of Ridge Augmentation of Extraction Sockets with Severe Bone Defects: A Clinical Prospective Study.

PURPOSE: To primarily evaluate the dimensional changes of bone and soft tissue following ridge augmentation in compromised molar regions. The secondary objective was to evaluate the histologic composition of augmented sites. MATERIALS AND METHODS: The study included 27 patients who underwent augmentation of extraction sites with grafts covered by a collagen membrane. CBCT was taken immediately after augmentation (T2) and after 8 months of healing, before implant placement (T3). The width and height of the extraction sites were recorded at extraction (T1) and reentry surgery (T4). A histomorphometric analysis was performed. Data were evaluated in terms of bone crest level, implant survival rates, and change in mucogingival junction. RESULTS: According to clinical measurement, horizontal and vertical bone gain was 10.15 ± 1.00 mm and 8.80 ± 1.86 mm, respectively. Radiographic measurement showed that the horizontal width changes were 1.46 ± 0.52 mm, 0.98 ± 1.29 mm, and 1.29 ± 0.82 mm, respectively, at 1, 3, and 5 mm apical to the crestal level. Vertical bone change was 2.34 ± 0.90 mm in the center of the socket. Histomorphometric analysis showed that percentages of mineralized bone, nonmineralized tissue, and bone substitute were 32.31% ± 13.25%, 25.36% ± 12.24%, and 42.34% ± 9.54%, respectively. The mucogingival junction shift was 0.6 ± 1.1 mm. Implant survival rates and crestal bone resorption were 100% and 0.78 ± 0.58 mm, respectively, after 1 year of loading. CONCLUSION: Ridge augmentation can be performed successfully to manage extraction sockets. Membrane coverage combined with primary wound closure could be conducive to new bone regeneration and peri-implant tissue health.

Influence of buccal emergence profile designs on peri-implant tissues: A randomized controlled trial.

BACKGROUND: The prosthetic emergence profile design might be an important factor in postsurgical mucosal recession etiology. Therefore, a restorative buccal emergence profile designed correctly might reduce gingival margin recession. PURPOSE: To compare the marginal gingival level and the width/height (W/H) ratio between two profile configurations of single implant-supported restorations at molar sites. MATERIALS AND METHODS: Twenty-one patients requiring a single mandibular molar tooth replacement with supracrestal mucosal thickness ≥2 mm were recruited and randomly assigned to a prosthesis buccal emergence profile design based on the buccal mucosal W/H ratio (Test Group) or maintained the original emergence profile of the healing abutment (Control Group). Assessments were made before delivery of the definitive restoration (T0), at prosthesis placement (T1), one (T2), and 12 (T3) months after loading. The gingival margin level change (△GM), initial emergence angle, buccal mucosal W/H ratio, marginal bone loss (MBL), implant failure, and complications were assessed. RESULTS: The gingival recession in the test group (0.13 ± 0.32 mm) was significantly lower than in the control group (0.63 ± 0.38 mm) at T3 (p = 0.006). The initial emergence angle in the test group (31.4 ± 7.22 degrees) was significantly lower than the control group (40.0 ± 7.60 degrees) (p = 0.025). The W/H ratio in the test group at T2 was significantly higher than at T0 but remained stable thereafter. The W/H ratio presented a continued rising trend in the control group. CONCLUSIONS: When the initial supracrestal soft tissue thickness was ≥2 mm, a restorative emergence profile based on the W/H ratio significantly reduced gingival margin recession. An emergence angle of 32.4 degrees showed better behavior in maintaining the gingival margin than 40 degrees. CLINICAL TRIAL REGISTRATION NUMBER: ChiCTR190002210.

Does a Severely Resorbed Subantral Ridge Decrease Long-Term Implant Survival Rate with Sinus Floor Augmentation?

PURPOSE: To identify the impact of residual bone height on 5-year implant survival and prosthetic complication rates in patients who underwent maxillary sinus grafting. MATERIALS AND METHODS: A total of 87 consecutive patients were treated with 104 lateral approach maxillary sinus floor augmentation procedures with 100% deproteinized bovine bone and received 169 implants. The analysis considered patient age, sex, time of implant placement, and residual bone height. Patients with < 3 mm residual bone height were assigned to the study group; otherwise, they were placed in the control group. RESULTS: The mean follow-up was 68.2 months (0 to 103 months). The mean residual bone height was 1.8 mm in the study group and 4.1 mm in the control group. The 5-year implant survival and prosthetic complication rates were, respectively, 97.4% and 8.0% in the study group and 100% and 12.5% in the control group. Residual bone height, sex, age, and time of implant placement were not significant factors for the 5-year implant survival or prosthetic complication rate. The lateral bone wall was significantly thinner in the study group. The grafted bone height reduction was significantly different at 6 months and 2 years postoperation in both groups, but there was no difference in the change in grafted bone height reduction over time between the two groups. CONCLUSION: A residual bone height < 3 mm did not impact the survival rates of implants placed in grafted maxillary sinuses or the prosthetic complication rate after 5 years of functional loading.

A novel combined fluorescent probe staining method for circulating tumor cell identification.

Background: To develop a novel highly accurate circulating tumor cell (CTC) identification method and to validate its application in cancer diagnostics and/or prognostics. Methods: We verified and validated the combined fluorescent probe staining protocol (combination of three fluorescent probes: Dil, Hoechst 33342, and PY) through CTC and non-CTC (white blood cell) morphological comparison of five tumor cell lines (THP-1, HEC, HEPG2, Eca-109, HeLa) in vitro and 32 patient tumor samples from the Shandong Cancer Hospital and Institute. Wright's Giemsa staining and cluster differentiation 45 (CD45) immunocytochemistry (ICC) staining were used as reference control methods. The association between the developed method and clinicopathology was also investigated. Results: We successfully developed and optimized the protocol, and validated the use of combined fluorescent probe staining for the identification of CTCs in the peripheral blood (PB) of tumor cell lines and tumor patients. Comparable CTC and non-CTC morphologies were observed for combined fluorescent probe staining and Giemsa staining methods in vitro. However, in vivo comparison between the three staining methods revealed that the identified CTCs differed in cell diameter and nucleo-cytoplasmic ratio. In addition, a higher CTC detection rate of 14/32, lower standard deviation (SD), and higher area under the receiver operating characteristic (ROC) curve (AUC) value of 0.844 were noted for combined fluorescence staining. Clinicopathological analysis revealed that CTCs were correlated with platelet levels (P=0.031), but not with age, gender, drinking history, or granule ratio. Conclusions: We developed a combined fluorescent probe staining method with higher CTC identification accuracy than Wright's Giemsa staining, and propose this technique as a novel clinical diagnostic/prognostic tool.

Force-Induced Autophagy in Periodontal Ligament Stem Cells Modulates M1 Macrophage Polarization via AKT Signaling.

Autophagy, a lysosomal degradation pathway, serves as a protective cellular mechanism in maintaining cell and tissue homeostasis under mechanical stimulation. As the mechanosensitive cells, periodontal ligament stem cells (PDLSCs) play an important role in the force-induced inflammatory bone remodeling and tooth movement process. However, whether and how autophagy in PDLSCs influences the inflammatory bone remodeling process under mechanical force stimuli is still unknown. In this study, we found that mechanical force stimuli increased the expression of the autophagy protein LC3, the number of M1 macrophages and osteoclasts, as well as the ratio of M1/M2 macrophages in the compression side of the periodontal ligament in vivo. These biological changes induced by mechanical force were repressed by the application of an autophagy inhibitor 3-methyladenine. Moreover, autophagy was activated in the force-loaded PDLSCs, and force-stimulated PDLSC autophagy further induced M1 macrophage polarization in vitro. The macrophage polarization could be partially blocked by the administration of autophagy inhibitor 3-methyladenine or enhanced by the administration of autophagy activator rapamycin in PDLSCs. Mechanistically, force-induced PDLSC autophagy promoted M1 macrophage polarization via the inhibition of the AKT signaling pathway. These data suggest a novel mechanism that force-stimulated PDLSC autophagy steers macrophages into the M1 phenotype via the AKT signaling pathway, which contributes to the inflammatory bone remodeling and tooth movement process.

Influence of crown-to-implant ratio and different prosthetic designs on the clinical conditions of short implants in posterior regions: A 4-year retrospective clinical and radiographic study.

BACKGROUND: Short implants (intra-bony length ≤ 8 mm) are generally considered as an alternative to bone augmentation in challenging situations; however, clinical evidence from large-scale studies with long follow-up regarding the application of short implants remains deficient. PURPOSE: The present study aimed to assess the mid-term clinical outcomes of short implants supporting fixed prostheses in the posterior region, and to investigate the effects of the crown-to-implant ratio (C/I), and other patient-, implant-, prosthesis-relevant factors on the clinical conditions around short implants. MATERIALS AND METHODS: 180 Thommen short implants in 130 partially edentulous patients were enrolled in the study after 3 to 7 (mean 4.2) years of follow-up. Potential risk factors (patient sex and age, implant diameter and location, splinted vs single-tooth restorations, retention mode, anatomical and clinical C/I ratios) were evaluated according to the following outcomes: Implant survival, marginal bone loss (MBL), and mechanical and biological complications. RESULTS: In total, four implants in four patients failed as a result of peri-implantitis. The cumulative survival rate was 97.8% for implant-based analysis. The peri-implant MBL around 180 short implants was 0.90 ± 0.78 mm. The mean clinical C/I ratio was 1.16 ± 0.36. Correlation analysis revealed that the influence of the clinical C/I ratio and patient age were significant for MBL (P < .05), whereas other potential risk factors showed no significant association with the outcome. Among 180 short implants, 24 cases (13.3%) had biological complications and 32 cases (17.8%) had mechanical complications, respectively. Peri-implant MBL and complication rates around splinted and non-splinted implants were not statistically different. CONCLUSION: Within the limitations of this study, short implants supporting fixed prostheses in the posterior region achieved predictable clinical outcomes over a 3 to 7 year period. Within the range of 0.47 to 3.01, the higher the C/I ratio, the less the peri-implant MBL.

Mechanical load-induced H2S production by periodontal ligament stem cells activates M1 macrophages to promote bone remodeling and tooth movement via STAT1.

BACKGROUND: Tooth movement is a unique bone remodeling process induced by mechanical stimulation. Macrophages are important in mediating inflammatory processes during mechanical load-induced tooth movement. However, how macrophages are regulated under mechanical stimulation remains unclear. Mesenchymal stem cells (MSCs) can modulate macrophage polarization during bone remodeling. Hydrogen sulfide (H2S) can be produced by MSCs and have been linked to bone homeostasis. Therefore, this study aimed to investigate whether H2S contributed to periodontal ligament stem cell (PDLSC)-regulated macrophage polarization and bone remodeling under mechanical stimulation. METHODS: An experimental mechanical load-induced tooth movement animal model was established. Changes in cystathionine-ß-synthase (CBS), markers of M1/M2 macrophages, tooth movement distance, and the number of osteoclasts were examined. The conditioned medium of PDLSCs with or without mechanical loading was utilized to treat THP-1 derived macrophages for 24 h to further investigate the effect of PDLSCs on macrophage polarization. Different treatments with H2S donor, CBS inhibitor, or the inhibitor of STAT1 were used to investigate the related mechanism. Markers of M1/M2 polarization and STAT1 pathway expression were evaluated in macrophages. RESULTS: Mechanical load promoted tooth movement and increased the number of M1-like macrophages, M1-associated pro-inflammatory cytokines, and the expression of CBS on the compression side of the periodontal ligament. The injection of CBS inhibitor or H2S donor could further repress or increase the number of M1-like macrophages, tartrate-resistant acid phosphatase-positive osteoclasts and the distance of tooth movement. Mechanistically, load-induced PDLSCs enhanced H2S production, which increased the expression of M1-associated cytokines in macrophages. These effects could be blocked by the administration of CBS inhibitor. Moreover, load-induced H2S steered M1 macrophage polarization via the STAT1 signaling pathway. CONCLUSIONS: These data suggest a novel mechanism indicating that mechanical load-stimulated PDLSCs produce H2S to polarize macrophages toward the M1 phenotype via the STAT1 signaling pathway, which contributes to bone remodeling and tooth movement process. These results provide new insights into the role of PDLSCs in regulating macrophage polarization and mediating bone remodeling under mechanical stimulation, and indicate that appropriate H2S supplementation may accelerate tooth movement.

Mechanical force modulates periodontal ligament stem cell characteristics during bone remodelling via TRPV4.

OBJECTIVES: Mechanical force plays an important role in modulating stem cell fate and behaviours. However, how periodontal ligament stem cells (PDLSCs) perceive mechanical stimulus and transfer it into biological signals, and thereby promote alveolar bone remodelling, is unclear. MATERIALS AND METHODS: An animal model of force-induced tooth movement and a compressive force in vitro was used. After force application, tooth movement distance, mesenchymal stem cell and osteoclast number, and proinflammatory cytokine expression were detected in periodontal tissues. Then, rat primary PDLSCs with or without force loading were isolated, and their stem cell characteristics including clonogenicity, proliferation, multipotent differentiation and immunoregulatory properties were evaluated. Under compressive force in vitro, the effects of the ERK signalling pathway on PDLSC characteristics were evaluated by Western blotting. RESULTS: Mechanical force in vivo induced PDLSC proliferation, which was accompanied with inflammatory cytokine accumulation, osteoclast differentiation and TRPV4 activation; the force-stimulated PDLSCs showed greater clonogenicity and proliferation, reduced differentiation ability, improved induction of macrophage migration, osteoclast differentiation and proinflammatory factor expression. The biological changes induced by mechanical force could be partially suppressed by TRPV4 inhibition. Mechanistically, force-induced activation of TRPV4 in PDLSCs regulated osteoclast differentiation by affecting the RANKL/OPG system via ERK signalling. CONCLUSIONS: Taken together, we show here that TRPV4 activation in PDLSCs under mechanical force contributes to changing their stem cell characteristics and modulates bone remodelling during tooth movement.

Histological and clinical outcomes of lateral sinus floor elevation with simultaneous removal of a maxillary sinus pseudocyst.

BACKGROUND: Maxillary sinus pathologies are a potential risk for failure of implant and bone augmentation. Management of lateral sinus floor elevation in the presence of a pseudocyst remains controversial, and reports on histological outcomes of endo-sinus bone augmentation with maxillary cysts are scarce. PURPOSE: To present a modified surgical technique for removal of maxillary pseudocyst with simultaneous sinus floor elevation, and to evaluate clinical and histological outcomes of the bone grafting. MATERIALS AND METHODS: Patients with a radiographic dome-shaped opacity in the posterior maxillary sinus were included to receive lateral sinus floor elevation with simultaneous pseudocyst removal. Bone core specimens harvested from the lateral aspect of the augmentation sites were histomorphometrically analyzed. Data were recorded and evaluated in terms of survival rates and complications. RESULTS: A total of 15 patients were included who underwent 17 maxillary sinus augmentation surgeries. Implant survival rate was 97.0%. Bone biopsy specimens were obtained at 6 months after surgery. Histomorphometric analysis revealed that mean percentages of mineralized bone, bone substitute, and nonmineralized tissue were 24.9% ± 18.1%, 14.4% ± 12.5%, and 60.1% ± 12.44%, respectively. No recurrence of the pseudocyst was detected on radiographic examination. CONCLUSIONS: The described technique could be successfully applied in clinical practice to perform sinus augmentation in the presence of pseudocysts.

Efficacy of the split-thickness labial flap method for soft tissue management in anterior ridge horizontal augmentation procedures: A clinical prospective study in the anterior maxilla.

OBJECTIVE: To introduce a novel method of split-thickness labial flap in maxillary anterior ridge horizontal augmentation and to evaluate its efficacy and morbidity. MATERIALS AND METHODS: 230 patients were selected to receive either particulate or onlay grafting. A split-thickness labial flap was applied to cover the grafted area and close the wound. The incidence of postsurgical complications and the level of patient discomfort were evaluated. A visual analog scale was used to quantify the amount of pain and swelling in the patients. RESULTS: In all 375 surgical sites, passive primary closure was achieved with the split-thickness labial flap method. Membrane exposure after surgery was seen in 6 cases in the onlay group and in 4 in the particulate group. No long-lasting pain (>1 week), paresthesia, or signs of infection occurred during the follow-up period of 6 months. The mean pain and swelling scores in the particulate graft group (2.75 ± 3.01 and 2.02 ± 2.51, respectively) were lower than the scores in the onlay graft group (3.18 ± 2.79 and 3.85 ± 2.25, respectively). CONCLUSIONS: The flap advancement technique presented in this study facilitates clinically passive primary closure. This technique can be used successfully in both particulate and onlay horizontal graft procedures.

Onlay grafting with bovine bone mineral block for horizontal reconstruction of severely atrophic alveolar ridges in anterior maxillae: A 6-year prospective study.

PURPOSE: The aim of this prospective study was to evaluate the efficacy and long-term outcomes of onlay grafting with bovine bone mineral block for reconstruction of horizontal alveolar ridge defects in anterior maxillae. MATERIALS AND METHODS: Fourteen patients requiring rehabilitation of edentulous anterior maxillae were enrolled to receive onlay grafting in two layers. A cortical block harvested from the lateral aspect of the mandibular ramus was split to acquire approximately 1-mm-thick bone laminae. The cortical bone plate and block graft were compressed and fixed to the recipient sites. After 6 months, the width of the augmentation was recorded, and implants were inserted. Provisional and definitive prostheses were delivered 3 and a further 6 months later. Implant success and associated complications were assessed. RESULTS: The horizontal bone gain was 8.73 ± 0.82, with a resorption rate of 7.03%. Severe bone resorption was noticed 6 months and 2 years after loading. Fistula occurred with the nonintegrated bovine block on the labial sides of the augmented sites 6 years after loading. CONCLUSION: Onlay grafting with bovine bone mineral block in the anterior maxilla may yield optimal horizontal gain with low resorption rates, under the condition of at least 6 months' healing time, mixation with autogenous particulate bone, and application of a membrane to cover the graft site.