The effect of compressive force in bone tissue induced by implants of different primary stabilities on macrophage polarization and bone regeneration.

Dental implants with different primary stabilities give rise to distinct stress distributions at the implant-bone interface after placement and exert mechanical force on the cells in the bone tissue. This study aimed to investigate whether the mechanical forces in peri-implant bone participate in the body's immune response and influence macrophage polarization. Therefore, an in vivo rat implantation model with different primary implant stabilities was established. The osteoimmune response and macrophage polarization were investigated, and the osseointegration of the implants was evaluated. In an in vitro experiment, an external compressive force was applied to RAW264.7 cells, and the polarization phenotype was observed. MC3T3-E1 cells were cultured in macrophage-conditioned medium to investigate the regulatory effect of the macrophage-secreted cytokines on the osteogenic differentiation of osteoblasts. In vivo experimental results indicated that the primary stability of implants is positively correlated with the mechanical force. The osteoimmune response was significantly amplified by compressive force generated from implants. This compressive force first induced both M1 and M2 macrophage polarization and then accelerated the progression of the transition to M2 macrophages in the bone repair phase. In vitro, compressive force significantly upregulated the M1 and M2 macrophage polarization. In addition, the suppressive effect of macrophages on the osteogenesis of MC3T3 cells was relieved by cytokines secreted by macrophages under compressive force loading, which promoted their osteogenesis. Overall, these results clarify that compressive force from different primary stabilities is an important influencing factor regulating the osteoimmunne response and macrophage polarization in addition to maintaining the implant.

Fabrication of a micro/nanocomposite structure on the surface of high oxygen concentration titanium to promote bone formation.

This study investigated the properties of the micro/nano composite structure on the surface of high oxygen concentration titanium (HOC-Ti) after anodic oxidation modification (HOC-NT) and evaluated its biocompatibility as a dental implant material in vitro and in vivo. HOC-Ti was produced by titanium powders and rutile powders using the powder metallurgy method. Its surface was modified by anodic oxidation. After detecting the electrochemical characteristics, the surface properties of HOC-NT were investigated. MC3T3 and MLO-Y4 cells were employed to evaluate the biocompatibility of HOC-NT and cocultured to study the effects of the changes in osteocytes induced by HOC-NT on osteoblasts. While, its possible mechanism was investigated. In addition, osseointegration around the HOC-NT implant was investigated through in vivo experiments. The results showed that a unique micronano composite structure on the HOC-Ti surface with excellent hydrophilicity and suitable surface roughness was created after anodic oxidation promoted by its electrochemical characteristics. The YAP protein may play an important role in regulating bone remodeling by ß-catenin and Rankl/OPG Signaling Pathways. An in vivo study also revealed an accelerated formation rate of new bone and more stable osseointegration around the HOC-NT implant. In view of all experimental results, it could be concluded that the unique morphology of HOC-NT has enhanced physicochemical and biological properties. The promotion of bone formation around implants indicated the feasibility of HOC-NT for applications in oral implants.

Inflammation-associated ectopic mineralization.

Ectopic mineralization refers to the deposition of mineralized complexes in the extracellular matrix of soft tissues. Calcific aortic valve disease, vascular calcification, gallstones, kidney stones, and abnormal mineralization in arthritis are common examples of ectopic mineralization. They are debilitating diseases and exhibit excess mortality, disability, and morbidity, which impose on patients with limited social or financial resources. Recent recognition that inflammation plays an important role in ectopic mineralization has attracted the attention of scientists from different research fields. In the present review, we summarize the origin of inflammation in ectopic mineralization and different channels whereby inflammation drives the initiation and progression of ectopic mineralization. The current knowledge of inflammatory milieu in pathological mineralization is reviewed, including how immune cells, pro-inflammatory mediators, and osteogenic signaling pathways induce the osteogenic transition of connective tissue cells, providing nucleating sites and assembly of aberrant minerals. Advances in the understanding of the underlying mechanisms involved in inflammatory-mediated ectopic mineralization enable novel strategies to be developed that may lead to the resolution of these enervating conditions.

Nerve electrical stimulation treatment of xerostomia / 口腔疾病防治

@#Patients with impaired quality of life associated with xerostomia need long-term treatment, and a nerve stimulator has the advantage of providing natural saliva and long-term management for patients with xerostomia by electrically stimulating the relevant secretory nerves to promote saliva production. A number of clinical trials have preliminarily demonstrated the efficacy of nerve electrical stimulation in the treatment of xerostomia. However, electrical stimulation has not yet become the mainstream treatment for xerostomia. Large prospective randomized controlled clinical trials are still needed to confirm its long-term effectiveness and safety. In addition, the design of nerve stimulators is of great significance for clinical application. The large volume and inconvenient treatment associated with the extra oral nerve stimulator and the first generation intraoral nerve stimulator hinder their clinical application and popularization. The second- and third-generation intraoral nerve stimulator devices are small, convenient to use and have great application prospects. Research on electrical nerve stimulators for xerostomia treatment is mainly concentrated in European and American countries, while there is very little domestic research. It is urgent to master the core technology for the research and development of electrical nerve stimulators. The innovation of miniaturization, efficient power supply, data feedback and packaging will be the key issues of electrical nerve stimulators in the future. In this paper, the treatment and research of electrical nerve stimulation for xerostomia are reviewed to provide a reference for related basic research and the clinical application of electrical stimulators treating xerostomia in China.

Mechanical properties and biocompatibility of titanium with a high oxygen concentration for dental implants.

In order to improve the strength of commercially pure Ti (CP-Ti) for oral implants, the high oxygen content Ti (HOC-Ti) was prepared via powder metallurgy. Its composition and mechanical properties were then characterized. After surface treatment by sandblasting and acid etching (SLA), the surface morphology, wettability and roughness of the HOC-Ti and CP-Ti sample were examined. In an in vitro test that followed an evaluation of the protein adsorption capacity of HOC-Ti, the mouse preosteoblast cells were inoculated onto the specimens to evaluate their biocompatibility, in comparison with those of CP-Ti. The oxygen concentration of the HOC-Ti increased to 0.62 wt%, which is higher than the 0.26 wt% of the CP-Ti, while their compositions and microstructures were very similar. The tensile and compressive yield strength of the HOC-Ti (800 MPa) was improved significantly in comparison to that of the CP-Ti (530 MPa). After surface treatment, a unique structure of micropores with a diameter of 380 nm was observed on the entire surface of the HOC-Ti that facilitates cell adhesion and proliferation. The wettability of the HOC-Ti was obviously superior (p < 0.05). The in vitro study showed that the MC3T3-E1 cells inoculated on the surface of HOC-Ti exhibited a homogeneous microstructure, and the viability was higher than that of the control group on days 4 and 7 (p < 0.05). In addition, the number and differentiation activity of cells that adhered to the surface of the HOC-Ti increased significantly on day 7 (p < 0.05). The experimental results showed that, in view of its mechanical properties and biocompatibility, HOC-Ti is superior to CP-Ti and is promising for oral implant applications.

Simulation analysis of impact damage to the bone tissue surrounding a dental implant.

Dental implant may suffer transient external impacts. To simulate the effect of impact forces on bone damage is very important for evaluation of damage and guiding treatment in clinics. In this study, an animal model was established by inserting an implant into the femoral condyle of New Zealand rabbit. Implant with good osseointegration was loaded with impact force. A three-dimensional finite element model was established based on the data of the animal model. Damage process to bone tissue was simulated with Abaqus 6.13 software combining dynamic mechanical properties of the femur. The characteristics of bone damage were analyzed by comparing the results of animal testing with numerical simulation data. After impact, cortical bone around the implant and trabecular at the bottom of the implant were prone to damage. The degree of damage correlated with the direction of loading and the magnitude of the impact. Lateral loading was most likely performed to damage cancellous bone. The stress wave formed by the impact force can damage the implant-bone interface and peri-implant trabeculae. The data from numerical simulations were consistent with data from animal experiments, highlighting the importance of a thorough examination and evaluation based on the patient's medical history.

Fracture Strength and Osseointegration of an Ultrafine-Grained Titanium Mini Dental Implant after Macromorphology Optimization.

The aim of this in vitro and in vivo study was to evaluate the fracture strength and osseointegration of an ultrafine-grained pure titanium (UFG-Ti) mini dental implant, prepared by equal channel angular pressing (ECAP) after macro-morphology optimization. UFG-Ti was prepared by ECAP using four passes in route Bc with the internal channel angle of 120° at room temperature. Furthermore, its microstructure and mechanical properties were studied. In optimization, a three-dimensional finite element model (FEM) composed of an UFG-Ti mini implant and alveolar bone was established to improve the implant surface area and decrease the stress distribution. Then, optimized mini implants were fabricated using UFG-Ti, and a fracture strength test was performed. For the in vivo study, UFG-Ti mini implants were inserted into rabbit femurs. A histological assessment and a pull-out test were performed to evaluate its osseointegration ability. The results show that the ultimate tensile strength of UFG-Ti (685 ± 35 MPa) was significantly higher than that of commercial pure titanium (CP-Ti grade 4, 454 ± 27 MPa). After optimization, the surface area of the 2.5 mm diameter mini implant was 19% higher than that of the standard-thread mini implant, and the maximum equivalent stress (Max EQV stress) decreased by 28% in cortical bone and by 33.1% in cancellous bone, when the thread height was 0.3 mm and the pitch was 0.67 mm. The fracture strength of the UFG-Ti mini implants (328 ± 21 N) was significantly higher than that of CP-Ti grade 4 mini implants (197 ± 11 N). The in vivo study showed favorable osseointegration in both the UFG-Ti and CP-Ti groups, but the osseointegration strength of the optimized mini implants was higher than that of the standard-thread mini implants. In conclusion, the fracture and osseointegration strength had been significantly improved for UFG-Ti mini dental implant after optimization. The excellent mechanical properties and osseointegration of the UFG-Ti mini implant suggest its feasibility for clinical application.

Surface Characteristics and Biocompatibility of Ultrafine-Grain Ti after Sandblasting and Acid Etching for Dental Implants.

This study investigated the surface characteristics and biocompatibility of ultrafine-grain pure titanium (UFG Ti) after sandblasting and acid etching (SLA) treatment to determine an effective method for modification of UFG Ti dental implants. The UFG Ti was processed by equal-channel angular pressing (ECAP). The micromorphology, roughness, and wettability of its surface were studied after SLA modification in different conditions. Rat bone marrow mesenchymal stem cells were subsequently seeded onto the specimens to evaluate the biocompatibility of cell adhesion, proliferation, and differentiation compared with commercially pure titanium (CP Ti). The results showed that surface characteristics of UFG Ti were affected by the pressure of sandblasting and acid etching time in addition to material properties. The favorable hierarchical porous structure that would benefit cell adhesion was formed on the UFG Ti surface when the pressure of sandblasting was 0.6 MPa and the acid etching time was 5 min; at this time, UFG Ti promoted proliferation and differentiation to a greater extent than CP Ti because of its excellent wettability. From this study, it could be seen that UFG Ti can be used as a dental implant material after proper surface modification.

The Microdamage and Expression of Sclerostin in Peri-implant Bone under One-time Shock Force Generated by Impact.

Osseointegration is the key to implant stability and occlusal support. Biomechanical response and remodeling of peri-implant bone occurs under impact loading. Sclerostin participates in bone formation and resorption through Wnt and RANKL pathways. However the mechanism of microdamage and expression of sclerostin in peri-implant bone under impact load is still unclear. In present study, specific impact forces were applied to the implants with favorable osseointegration in rabbits. The microdamage of peri-implant bone and the expression of sclerostin, ß-catenin and RANKL during the process of bone damage and remodeling were investigated by micro-CT, histology, immunofluorescence and RT-qPCR analysis. Interface separation and trabecular fracture were found histologically, which were consistent with micro-CT analyses. Throughout remodeling, bone resorption was observed during the first 14 days after impact, and osseointegration and normal trabecular structure were found by 28 d. The expression of sclerostin and RANKL increased after impact and reached a maximum by 14 d, then decreased gradually to normal levels by 28 d. And ß-catenin expression was opposite. Results indicated that sclerostin may involve in the peri-implant bone damage caused by impact and remodeling through Wnt/ß-catenin and RANKL/RANK pathways. It will provide a new insight in the diagnosis and treatment for patients suffering impact.

In vitro and in vivo studies of ultrafine-grain Ti as dental implant material processed by ECAP.

The aim of this study was to investigate the surface characterization of ultrafine-grain pure titanium (UFG-Ti) after sandblasting and acid-etching (SLA) and to evaluate its biocompatibility as dental implant material in vitro and in vivo. UFG-Ti was produced by equal channel angular pressing (ECAP) using commercially pure titanium (CP-Ti). Microstructure and yield strength were investigated. The morphology, wettability and roughness of the specimens were analyzed after they were modified by SLA. MC3T3-E1 osteoblasts were seeded onto the specimens to evaluate its biocompatibility in vitro. For the in vivo study, UFG-Ti implants after SLA were embedded into the femurs of New Zealand rabbits. Osseointegration was investigated though micro-CT analysis, histological assessment and pull-out test. The control group was CP-Ti. UFG-Ti with enhanced mechanical properties was produced by four passes of ECAP in BC route at room temperature. After SLA modification, the hierarchical porous structure on its surface exhibited excellent wettability. The adhesion, proliferation and viability of cells cultured on the UFG-Ti were superior to that of CP-Ti. In the in vivo study, favorable osseointegration occurred between the implant and bone in CP and UFG-Ti groups. The combination intensity of UF- Ti with bone was higher according to the pull-out test. This study supports the claim that UFG-Ti has grain refinement with outstanding mechanical properties and, with its excellent biocompatibility, has potential for use as dental implant material.