Accuracy of digital implant impressions obtained using intraoral scanners: a systematic review and meta-analysis of in vivo studies.

PURPOSE: This systematic review aimed to investigate the accuracy of intraoral scan (IOS) impressions of implant-supported restorations in in vivo studies. METHODS: A systematic electronic search and review of studies on the accuracy of IOS implant impressions were conducted to analyze the peer-reviewed literature published between 1989 and August 2023. The bias analysis was performed by two reviewers. Data on the study characteristics, accuracy outcomes, and related variables were extracted. A meta-analysis of randomized control trials was performed to investigate the impact of IOS on peri-implant crestal bone loss and the time involved in the impression procedure. RESULTS: Ten in vivo studies were included in this systematic review for final analysis. Six studies investigated the trueness of IOS impressions, but did not reach the same conclusions. One study assessed the precision of IOS impressions for a single implant. Four clinical studies examined the accuracy of IOS implant impressions with a follow-up of 1-2 years. In full arches, IOS impression procedure needed significantly less time than conventional one (mean difference for procedure time was 8.59 min [6.78, 10.40 min], P < 0.001), prosthetic survival rate was 100%, and marginal bone levels of all participants could be stably maintained (mean difference in marginal bone loss at 12 months was 0.03 mm [-0.08, 0.14 mm], P = 0.55). CONCLUSIONS: The accuracy of IOS impressions of implant-supported restorations varied greatly depending on the scanning strategy. The trueness and precision of IOS in the partial and complete arches remain unclear and require further assessment. Based on follow-up clinical studies, IOS impressions were accurate in clinical practice. However, these results should be interpreted with caution, as some evidences are obtained from the same research group.

Interaction between ferroptosis and TNF-α: Impact in obesity-related osteoporosis.

The relationship of obesity and osteoporosis has been widely studied over the past years. However, the implications of obesity for bone health remain controversial, and the underlying molecular mechanism is not yet fully understood. This study demonstrated that high-fat diet-induced obesity leads to significantly decreased bone volume/tissue volume (BV/TV), trabecular number (Tb.N), and cortical thickness (Ct.Th) of male rat femur after mechanical loading effects of body weight were controlled. HFD-induced obese rats exhibited attenuated expression of ferroptosis inhibitory protein SLC7A11 and GPX4 in bone tissues, which was correlated with elevated serum TNF-α concentration. Ferroptosis inhibitor administration could effectively rescue decreased osteogenesis-associated type H vessels and osteoprogenitors, and downregulate serum levels of TNF-α to ameliorate bone loss in obese rats. Since ferroptosis and TNF-α both affect bone and vessel formation, we further investigated the interaction between ferroptosis and TNF-α, and its impact in osteogenesis and angiogenesis in vitro. In human osteoblast-like MG63 and umbilical vein endothelial cells (HUVEC), TNF-α/TNFR2 signaling promoted cystine uptake and GSH biosynthesis to provide protection against low-dose ferroptosis inducer erastin. While, TNF-α/TNFR1 facilitated ferroptosis in the presence of high-dose erastin through ROS accumulation. Moreover, TNF-α regulated ferroptosis-induced osteogenic and angiogenic dysfunctions based on its ferroptosis regulatory role. Meanwhile, ferroptosis inhibitors could reduce intracellular ROS overproduction and enhance osteogenesis and angiogenesis in TNF-α-treated MG63 and HUVECs. This study revealed the interaction between ferroptosis and TNF-α and its impact in osteogenesis and angiogenesis, which provides new insights into the pathogenesis and regenerative therapy of obesity-related osteoporosis.

Strontium Ranelate Inhibits Osteoclastogenesis through NF-κB-Pathway-Dependent Autophagy.

Strontium ranelate (SR) is a pharmaceutical agent used for the prevention and treatment of osteoporosis and fragility fracture. However, little attention has been paid to the effect of SR on alveolar bone remodeling during orthodontic tooth movement and its underlying mechanism. Here, we investigated the influence of SR on orthodontic tooth movement and tooth resorption in Sprague-Dawley rats and the relationship between the nuclear factor-kappa B (NF-κB) pathway, autophagy, and osteoclastogenesis after the administration of SR in vitro and in vivo. In this study, it was found that SR reduced the expression of autophagy-related proteins at the pressure side of the first molars during orthodontic tooth movement. Similarly, the expression of these autophagy-related proteins and the size and number of autophagosomes were downregulated by SR in vitro. The results also showed that SR reduced the number of osteoclasts and suppressed orthodontic tooth movement and root resorption in rats, which could be partially restored using rapamycin, an autophagy inducer. Autophagy was attenuated after pre-osteoclasts were treated with Bay 11-7082, an NF-κB pathway inhibitor, while SR reduced the expression of the proteins central to the NF-κB pathway. Collectively, this study revealed that SR might suppress osteoclastogenesis through NF-κB-pathway-dependent autophagy, resulting in the inhibition of orthodontic tooth movement and root resorption in rats, which might offer a new insight into the treatment of malocclusion and bone metabolic diseases.

Dual Role of Interleukin-20 in Different Stages of Osteoclast Differentiation and Its Osteoimmune Regulation during Alveolar Bone Remodeling.

Osteoimmunology mediators are critical to balance osteoblastogenesis and osteoclastogenesis to maintain bone homeostasis. A lot of the osteoimmunology mediators are regulated by interleukin-20 (IL-20). However, little is known about the role of IL-20 in bone remodeling. Here, we showed that IL-20 expression was correlated with osteoclast (OC) activity in remodeled alveolar bone during orthodontic tooth movement (OTM). Ovariectomize (OVX) in rats promoted OC activity and enhanced IL-20 expression, while blocking OC inhibited IL-20 expression in osteoclasts. In vitro, IL-20 treatment promoted survival, inhibited apoptosis of the preosteoclast at the early stages of osteoclast differentiation, and boosted the formation of osteoclasts and their bone resorption function at the late stages. More importantly, anti-IL-20 antibody treatment blocked IL-20-induced osteoclastogenesis and the subsequent bone resorption function. Mechanistically, we showed that IL-20 synergistically acts with RANKL to activate the NF-κB signaling pathway to promote the expression of c-Fos and NFATc1 to promote osteoclastogenesis. Moreover, we found that local injection of IL-20 or anti-IL-20 antibody enhanced osteoclast activity and accelerated OTM in rats, while blocking IL-20 reversed this phenomenon. This study revealed a previously unknown role of IL-20 in regulating alveolar bone remodeling and implies the application of IL-20 to accelerated OTM.

Stiffness-tuned and ROS-sensitive hydrogel incorporating complement C5a receptor antagonist modulates antibacterial activity of macrophages for periodontitis treatment.

Periodontitis is admittedly a microbe-driven intractable infectious disease, in which Porphyromonas gingivalis (Pg) plays a keystone role. Pg can selectively impair the antimicrobial responses of periodontal resident macrophages including their phagocytic and bactericidal activity without interfering their proinflammatory activity, which leads to microflora disturbance, destructive periodontal inflammation and alveolar bone loss eventually. Here, an injectable ROS-sensitive hydrogel is developed for releasing active bone marrow-derived macrophages (named ex-situ macrophages hereafter) and a complement C5a receptor antagonist (C5A) to the gingival crevice. Through appropriately tuning the hydrogel stiffness, the phagocytic activity of these macrophages is greatly enhanced, reaching an optimal performance at the elastic modulus of 106 kPa. Meanwhile, C5A avoids undesired C5a receptor activation by Pg to ensure the bacterial killing activity of both the ex-situ and in-situ macrophages. Besides, the ROS-sensitive hydrogels show another distinct feature of decreasing the ROS level in periodontal niche, which contributes to the alleviated periodontal inflammation and attenuated bone loss as well. This study highlights the potential of utilizing hydrogels with tailored biomechanical properties to remodel the functions of therapeutic cells, which is expected to find wide applications even beyond periodontitis treatment.

Inhibitory effect of infliximab on orthodontic tooth movement in male rats.

OBJECTIVE: This study aimed to investigate the effect of infliximab on orthodontic tooth movement in rats. MATERIALS AND METHODS: Sixty male Sprague-Dawley rats were randomly divided into two groups: saline group and infliximab group. The two groups of rats received weekly intraperitoneally injection of saline or infliximab (5 mg/kg), respectively. After four weeks of injection, five rats in each group were euthanized and orthodontic appliances were placed in the other twenty-five rats each. On days 1, 3, 7, 14 and 21, five rats from each group were euthanised. Maxillae of all the rats were collected and examined by micro-computed tomography, haematoxylin and eosin staining, tartrate-resistant acid phosphatase staining, and immunohistochemical staining of tumour necrosis factor (TNF)-α, receptor activator of nuclear factor κB ligand (RANKL), receptor activator of nuclear factor κB (RANK), and osteoprotegerin (OPG). All data were analysed with Mann-Whitney test. RESULTS: Infliximab inhibited orthodontic tooth movement and decreased osteoclastogenesis on the compression side during orthodontic tooth movement. The elevated TNF-α level, induced by orthodontic force, was decreased by infliximab. Furthermore, infliximab reduced the expression of RANKL and RANK, while increased the expression of OPG on the compression side. CONCLUSION: Infliximab inhibits orthodontic tooth movement by reducing levels of TNF-α, RANKL, and RANK, while increasing level of OPG, and decreasing osteoclastogenesis on the compression side of periodontium.

γ-Secretase inhibitors suppress IL-20-mediated osteoclastogenesis via Notch signalling and are affected by Notch2 in vitro.

Rheumatoid arthritis (RA) is a chronic immune disease involving the small joints, which often causes irreversible damage. In recent years, elevated interleukin 20 (IL-20) has been observed in synovial fluid, while IL-20 receptor overexpression has been observed in synovial cells. IL-20 is a pleiotropic cytokine that participates in various immune diseases. Further understanding of the relationship between IL-20 and RA can help to identify a potential clinical treatment for RA. This study demonstrated that IL-20 can regulate osteoclast differentiation and function in a dose-dependent manner, while influencing the expression of Notch signalling. Quantitative reverse transcription polymerase chain reaction and western blotting showed that γ-secretase-inhibiting drugs can reverse the effects of IL-20. The effects of Notch2 on IL-20-induced osteoclastogenesis were investigated by immunofluorescence and Notch2 gene silencing via transfection of small interfering RNA; the results showed that Notch2 obviously affected the expression levels of the key protein NFATc1 and downstream osteoclastic proteins. In conclusion, we found that IL-20 regulated the osteoclastogenesis in a dose-dependent manner via Notch signalling, primarily by means of Notch2 activity. This study may help to find new targets for RA treatment.

PRMT5 inhibition modulates murine dendritic cells activation by inhibiting the metabolism switch: a new therapeutic target in periodontitis.

BACKGROUND: Protein arginine methyltransferase 5 (PRMT5) catalyzes the methylation of arginine residues in multiple proteins. Recent reports have highlighted the anti-inflammatory role of PRMT5. Dendritic cells (DCs) are well-known professional antigen-presenting cells that are crucial for immune response initiation. However, whether PRMT5 participates in DC immunity processes is unknown. METHODS: In an in vitro experiment, a PRMT5 inhibitor (EPZ015666) was used to inhibit PRMT5 expression, and lipopolysaccharide (LPS) stimulation was applied to mimic the inflammation context. Proinflammatory cytokine production, interferon-stimulated genes (ISGs), costimulatory molecules, major histocompatibility complex (MHC) expression and DC metabolism were measured following PRMT5 inhibition and LPS stimulation. In an in vivo study, we first tested PRMT5 mRNA and protein expression in a BALB/c mouse ligature-induced periodontitis model. Then, we evaluated changes in periodontal tissue and DC migration to cervical lymph nodes after local treatment with the PRMT5 inhibitor. RESULTS: The in vitro results revealed that PRMT5 inhibition attenuated DC activation and maturation by inhibiting the expression of proinflammatory cytokines, ISGs, costimulatory molecules, and MHC induced by LPS stimulation. We also found that inhibition of PRMT5 blocked the DC metabolic switch to glycolysis. In the in vivo study, we found that PRMT5 inhibition reversed the severity of the lesions and slowed the migration of DCs to cervical lymph nodes. CONCLUSIONS: The results show a critical role of PRMT5 in the control of DC activation through inhibition of the metabolic switch and indicate that PRMT5 is a promising therapeutic target in periodontitis.

Interleukin-20 Acts as a Promotor of Osteoclastogenesis and Orthodontic Tooth Movement.

OBJECTIVES: Bones constitute organs that are engaged in constant self-remodelling. Osteoblast and osteoclast homeostasis during remodelling contribute to overall skeletal status. Orthodontics is a clinical discipline that involves the investigation and implementation of moving teeth through the bone. The application of mechanical force to the teeth causes an imbalance between osteogenesis and osteogenesis in alveolar bone, leading to tooth movement. Osteoimmunology comprises the crosstalk between the immune and skeletal systems that regulate osteoclast-osteoblast homeostasis. Interleukin- (IL-) 20, an IL-10 family member, is regarded as a proinflammatory factor for autoimmune diseases and has been implicated in bone loss disease. However, the mechanism by which IL-20 regulates osteoclast differentiation and osteoclastogenesis activation remains unclear. This study investigated the effects of IL-20 on osteoclast differentiation in a rat model; it explored the underlying molecular mechanism in vitro and the specific effects on orthodontic tooth movement in vivo. METHODS: For in vitro analyses, primary rat bone marrow-derived macrophages (BMMs) were prepared from Sprague-Dawley rats for osteoclast induction. After BMMs had been treated with combinations of recombinant IL-20 protein, siRNA, and plasmids, the expression levels of osteoclast-specific factors and signalling pathway proteins were detected through real-time polymerase chain reaction, western blotting, and immunofluorescence staining. For in vivo analyses, IL-20 was injected into the rat intraperitoneal cavity after the establishment of a rat orthodontic tooth movement (OTM) model. OTM distance was detected by Micro-CT and HE staining; the expression levels of protein were detected through immunofluorescence staining. RESULTS: In vitro analyses showed that a low concentration of IL-20 promoted preosteoclast proliferation and osteoclastogenesis. However, a high concentration of IL-20 inhibited BMM proliferation and osteoclastogenesis. IL-20 knockdown decreased the expression of osteoclast specific-markers, while IL-20 overexpression increased the expression of osteoclast specific-markers. Furthermore, IL-20 regulated osteoclast differentiation through the OPG/RANKL/RANK pathway. Overexpression of IL-20 could significantly upregulate RANKL-mediated osteoclast differentiation and osteoclast specific-marker expression; moreover, RANKL/NF-κB/NFATc1 acted as downstream signalling molecule for IL-20. In vivo analysis showed that OTM speed was significantly increased after intraperitoneal injection of IL-20; additionally, mechanical stress sensing proteins were markedly activated. CONCLUSIONS: IL-20 augments osteoclastogenesis and osteoclast-mediated bone erosion through the RANKL/NF-κB/NFATc1 signalling pathway. IL-20 inhibition can effectively reduce osteoclast differentiation and diminish bone resorption. Furthermore, IL-20 can accelerate orthodontic tooth movement and activate mechanical stress sensing proteins.

Interleukin-20 inhibits the osteogenic differentiation of MC3T3-E1 cells via the GSK3ß/ß-catenin signalling pathway.

OBJECTIVE: To investigate the effects of interleukin-20 (IL-20) on the osteogenic differentiation of MC3T3-E1 cells. METHODS: The pre-osteoblast line MC3T3-E1 was treated with different concentrations of IL-20 (0, 2, 20 and 100 ng/mL), and the cell viability was detected by the CCK8 assay. To assess the influence of IL-20 on osteogenic differentiation, alkaline phosphatase (ALP) activity and Alizarin red staining were performed at predetermined times. The expression levels of Runt-related transcription factor 2 (RUNX2), Osterix (Osx), glycogen synthase kinase-3ß (GSK-3ß) and ß-catenin were detected by qRT-PCR and Western blotting analyses. 5 nmol/L lithium chloride (LiCl) was used as GSK-3ß inhibitor. RESULTS: IL-20 promoted cell proliferation but decreased ALP activity and mineralization. Moreover, IL-20 downregulated the expression of RUNX2, Osx and ß-catenin but upregulated the level of GSK-3ß. CONCLUSIONS: The results suggest that IL-20 could inhibit the osteogenic differentiation of MC3T3-E1 cells via the GSK3ß/ß-catenin signalling pathway.

The combination of multi-functional ingredients-loaded hydrogels and three-dimensional printed porous titanium alloys for infective bone defect treatment.

Biomaterial with the dual-functions of bone regeneration and antibacterial is a novel therapy for infective bone defects. Three-dimensional (3D)-printed porous titanium (pTi) benefits bone ingrowth, but its microporous structure conducive to bacteria reproduction. Herein, a multifunctional hydrogel was prepared from dynamic supramolecular assembly of sodium tetraborate (Na2B4O7), polyvinyl alcohol (PVA), silver nanoparticles (AgNPs) and tetraethyl orthosilicate (TEOS), and composited with pTi as an implant system. The pTi scaffolds have ideal pore size and porosity matching with bone, while the supramolecular hydrogel endows pTi scaffolds with antibacterial and biological activity. In vitro assessments indicated the 3D composite implant was biocompatible, promoted bone marrow mesenchymal stem cells (BMSCs) proliferation and osteogenic differentiation, and inhibited bacteria, simultaneously. In vivo experiments further demonstrated that the implant showed effective antibacterial ability while promoting bone regeneration. Besides distal femur defect, the innovative scaffolds may also serve as an ideal biomaterial (e.g. dental implants) for other contaminated defects.

Oral microbial profile variation during canine ligature-induced peri-implantitis development.

BACKGROUND: Dental implants have become well-established in oral rehabilitation for fully or partially edentulous patients. However, peri-implantitis often leads to the failure of dental implants. The aim of this study was to understand the core microbiome associated with peri-implantitis and evaluate potential peri-implantitis pathogens based on canine peri-implantitis model. RESULTS: In this study, three beagle dogs were used to build peri-implantitis models with ligature-induced strategy. The peri-implant sulcular fluids were collected at four different phases based on disease severity during the peri-implantitis development. Microbial compositions during peri-implantitis development were monitored and evaluated. The microbes were presented with operational taxonomic unit (OTU) classified at 97% identity of the high-throughput 16S rRNA gene fragments. Microbial diversity and richness varied during peri-implantitis. At the phylum-level, Firmicutes decreased and Bacteroides increased during peri-implantitis development. At the genus-level, Peptostreptococcus decreased and Porphyromonas increased, suggesting peri-implantitis pathogens might be assigned to these two genera. Further species-level and co-occurrence network analyses identified several potential keystone species during peri-implantitis development, and some OTUs were potential peri-implantitis pathogens. CONCLUSION: In summary, canine peri-implantitis models help to identify several potential keystone peri-implantitis associated species. The canine model can give insight into human peri-implantitis associated microbiota.

Design of high-ductile medium entropy alloys for dental implants.

Developing new materials with high strength and ductility, low modulus and high biocompatibility is a continuing demand in the field of surgical implants. Inspired by the high-entropy design philosophy, two medium entropy alloys (MEAs), i.e. equiatomic TiZrHf and equi-weight Ti40Zr20Hf10Nb20Ta10 were designed and their mechanical properties and biocompatibility were assessed. Both the single-phase hexagonal close-packed (HCP) structured TiZrHf alloy and the single-phase body-centered cubic (BCC) structured Ti40Zr20Hf10Nb20Ta10 alloy show high strength-ductility combinations close to commercial Ti-6Al-4V wrought alloy and remarkably lower young's modulus than commercial pure titanium (CP-Ti) and Ti-6Al-4V. From the aspects of adhesion, proliferation, toxicity and related gene expression of human gingival fibroblasts (HGFs), the Ti40Zr20Hf10Nb20Ta10 alloy exhibits distinctively better biocompatibility than that of CP-Ti while the TiZrHf shows only slightly better biocompatibility as compared with CP-Ti. These results indicate that these two ductile MEAs are potential candidates for dental application.

Interleukin-20 differentially regulates bone mesenchymal stem cell activities in RANKL-induced osteoclastogenesis through the OPG/RANKL/RANK axis and the NF-κB, MAPK and AKT signalling pathways.

The immune and skeletal systems share common mechanisms, and the crosstalk between the two has been termed osteoimmunology. Osteoimmunology mainly focuses on diseases between the immune and bone systems including bone loss diseases, and imbalances in osteoimmune regulation affect skeletal homeostasis between osteoclasts and osteoblasts. The immune mediator interleukin-20 (IL-20), a member of the IL-10 family, enhances inflammation, chemotaxis and angiogenesis in diseases related to bone loss. However, it is unclear how IL-20 regulates the balance between osteoclastogenesis and osteoblastogenesis; therefore, we explored the mechanisms by which IL-20 affects bone mesenchymal stem cells (BMSCs) in osteoclastogenesis in primary cells during differentiation, proliferation, apoptosis and signalling. We initially found that IL-20 differentially regulated preosteoclast proliferation and apoptosis; BMSC-conditioned medium (CM) significantly enhanced osteoclast formation and bone resorption, which was dose-dependently regulated by IL-20; IL-20 inhibited OPG expression and promoted M-CSF, RANKL and RANKL/OPG expression; and IL-20 differentially regulated the expression of osteoclast-specific gene and transcription factors through the OPG/RANKL/RANK axis and the NF-kB, MAPK and AKT pathways. Therefore, IL-20 differentially regulates BMSCs in osteoclastogenesis and exerts its function by activating the OPG/RANKL/RANK axis and the NF-κB, MAPK and AKT pathways, which make targeting IL-20 a promising direction for targeted regulation in diseases related to bone loss.

The effect of risedronate on orthodontic tooth movement in ovariectomized rats.

OBJECTIVE: This study aimed to investigate the effect of risedronate on orthodontic tooth movement in ovariectomized rats. METHODS: Forty-five female Sprague-Dawley rats were divided into three groups. Bilateral ovariectomies were performed on the rats in the ovariectomy and ovariectomy + risedronate groups. Two weeks after ovariectomy, risedronate was administered intraperitoneally every three days in the ovariectomy + risedronate group, while rats in the ovariectomy and sham groups were administered saline until they were sacrificed. One month after ovariectomy, nickel-titanium alloy closed-coil springs were placed between the maxillary left first molar and the maxillary left incisor. On days 3, 7 and 14, five rats from each group were sacrificed. The distance of orthodontic tooth movement was measured by a digital caliper, and slides were obtained for histological analysis. RESULTS: The distance of orthodontic tooth movement and the number of tartar-resistant acid phosphatase (TRAP)-positive cells were the highest in the ovariectomy group, followed by those in the ovariectomy + risedronate group, on days 3, 7 and 14. The positive expression levels of receptor activator of nuclear factor-kappa ß (RANK) ligand and cathepsin K were the strongest while the positive expression of osteoprotegerin in the ovariectomy group was the weakest, followed by the corresponding expression levels in the ovariectomy + risedronate group, on days 3, 7 and 14. CONCLUSIONS: Risedronate can inhibit orthodontic tooth movement in ovariectomized rats and may function by regulating the RANK/RANK ligand/osteoprotegerin pathway.

Antinociceptive effects of the adenylyl cyclase inhibitor ST034307 on tooth-movement-induced nociception in rats.

OBJECTIVE: This study aimed to investigate the antinociceptive effects of the selective adenylyl cyclase type 1 (AC1) inhibitor ST034307 on tooth movement nociception through orofacial nociceptive behavior tests and molecular examination. METHODS: We placed fixed nickel-titanium alloy closed-coil springs around the incisors of male Sprague-Dawley rats to induce tooth movement. We subsequently administered ST034307 (3 mg/kg), for 2 days, intraperitoneally, and then subjected the rats to a battery of behavioral tests (n = 10/group) to assess orofacial nociception. The changes in the expression of key molecules in the anterior cingulate cortex were measured by ELISA (n = 8/group) and Western blotting (n = 8/group). RESULTS: Tooth movement increased face-grooming activities and rat grimace scale scores. Tooth movement was also associated with enhanced cyclic adenosine monophosphate (cAMP) generation as well as protein kinase A (PKA) activation. Moreover, the phosphorylation of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors and expression of N-methyl-d-aspartate (NMDA) receptors in the anterior cingulate cortex increased during tooth movement. ST034307 significantly decreased mouth wiping and rat grimace scale scores, accompanied by reductions in cAMP generation, PKA activation, AMPA receptor phosphorylation, and NMDA receptor expression in the anterior cingulate cortex. CONCLUSIONS: These results suggest that adenylyl cyclase type 1 plays an important role in the development of orthodontic tooth movement nociception. Furthermore, ST034307 can be used as an effective pharmacotherapy for orthodontic nociception.