Diabetes has long been considered a risk factor in implant therapy and impaired wound healing in soft and hard oral tissues. Magnesium has been proved to promote bone healing under normal conditions. Here, we elucidate the mechanism by which Mg²⁺ promotes angiogenesis and osseointegration in diabetic status. We generated a diabetic mice model and demonstrated the alveolar bone healing was compromised, with significantly decreased angiogenesis. We then developed Mg-coating implants with hydrothermal synthesis. These implants successfully improved the vascularization and osseointegration in diabetic status. Mechanically, Mg²⁺ promoted the degradation of Kelch-like ECH-associated protein 1 (Keap1) and the nucleation of nuclear factor erythroid 2-related factor 2 (Nrf2) by up-regulating the expression of sestrin 2 (SESN2) in endothelial cells, thus reducing the elevated levels of oxidative stress in mitochondria and relieving endothelial cell dysfunction under hyperglycemia. Altogether, our data suggested that Mg²⁺ promoted angiogenesis and osseointegration in diabetic mice by regulating endothelial mitochondrial metabolism.
Mice ; Animals ; Kelch-Like ECH-Associated Protein 1/metabolism* ; Magnesium/metabolism* ; Osseointegration ; Diabetes Mellitus, Experimental/metabolism* ; Endothelial Cells/metabolism* ; NF-E2-Related Factor 2/metabolism*

Implant treatment in the esthetic area requires stable osseointegration and successful esthetic outcomes. Achieving this goal requires careful consideration of accurate implant axis and ideal three-dimensional position. Owing to the high esthetics and the special anatomical structure of the maxillary, a successful implant means a synthesized deli-beration of the residual bone dimensions, soft-tissue thickness, and the relationship of the residual alveolar ridge with the planned restoration. This article offers an in-depth analysis of the clinical decisions and key factors affecting the implant direction in the esthetic area.
Dental Implantation, Endosseous/methods* ; Dental Implants ; Esthetics, Dental ; Alveolar Ridge Augmentation/methods* ; Osseointegration ; Maxilla/surgery* ; Dental Implants, Single-Tooth

Retrograde peri-implantitis (RPI), a kind of rare biological complication in implant-supported prosthetic rehabilitation, has been reported more frequently in recent years. RPI is defined as the periapical lesion that occurs following implant placement while the coronal part of the implant achieves normal osseointegration. Due to the possibilities of asymptomatic clinical scenarios, RPI can easily be ignored if routine radiographic examination is absent postoperatively, which may postpone treatment and affect long-term outcome. The common cause is infection originating from the periapical lesion of the neighboring teeth, the residual bacteria at the implant site, the contaminated implant apex and etc. Treatment methods rely on the infection source and severity of defect. This article discusses the diagnosis, classification, etiology, and pathology as well as prevention and treatment of RPI in order to provide evidence for clinical decisions in the future.
Dental Implantation, Endosseous ; Dental Implants/adverse effects* ; Humans ; Osseointegration ; Peri-Implantitis/prevention & control*

OBJECTIVES: This study was performed to fabricate a bionic coating with titanium (Ti) phosphate to promote the osseointegration of Ti substrate implants. METHODS: Phosphorylated micro/nanocoating was prepared on the surface of pure titanium (i.e., TiP-Ti) by hydrothermal process under special pressure, and the untreated smooth pure titanium (cp-Ti) was selected as the control. To evaluate the characteristics of the coating surface, scanning electron microscopy, X-ray diffraction, atomic force microscopy, and contact-angle measurement were performed. In addition, the effects of TiP-Ti on the proliferation, adhesion, and differentiation of rat bone marrow mesenchymal stem cells (BMSCs) were investigated by using RESULTS: The TiP-Ti surface presented a bionic structure with coexisting nanoscale 3D spatial structure and microscale pores. CONCLUSIONS A bionic structure with TiP-Ti micro/nanoscale coating was successfully fabricated, indicating a promising method for modifying the surface of implants.
Animals ; Dental Implants ; Osseointegration ; Osteogenesis ; Oxides ; Phosphates ; Rats ; Surface Properties ; Titanium

OBJECTIVE: To develop dexamethasone plus minocycline-loaded liposomes (Dex/Mino liposomes) and apply them to improve bioinert polyetheretherketone (PEEK) surface, which could prevent post-operative bacterial contamination, enhance ossification for physiologic osseointegration, and finally reduce implant failure rates. METHODS: Dex/Mino liposomes were covalently grafted onto the PEEK surface using polydopamine (pDA) coating as a medium. Confocal laser scanning microscopy was used to confirm the binding of fluorescently labeled liposomes onto the PEEK substrate, and a microplate reader was used to semiquantitatively measure the average fluorescence intensity of fluorescently labeled liposome-decorated PEEK surfaces. Moreover, the mouse subcutaneous infection model and the beagle femur implantation model were respectively conducted to verify the bioactivity of Dex/Mino liposome-modified PEEK in vivo, by means of micro computed tomography (micro-CT) and hematoxylin and eosin (HE) staining analysis. RESULTS: The qualitative and quantitative results of fluorescently labeled liposomes showed that, the red fluorescence intensity of the PEEK-pDA-lipo group was stronger than that of the PEEK-NF-lipo group (P < 0.05); the liposomes were successfully and uniformly decorated on the PEEK surfaces due to the pDA coating. After mouse subcutaneous implantation of PEEKs for 24 hours, HE staining results showed that the number of inflammatory cells in the PEEK-Dex/Mino lipo group were lower than that in the inert PEEK group (P < 0.05), indicating a lower degree of infection in the test group. These results suggested that the Mino released from the liposome-functionalized surface provided an effective bacteriostasis in vivo. After beagle femoral implantation of PEEK for 8 weeks, micro-CT results showed that the PEEK-Dex/Mino lipo group newly formed more continuous bone when compared with the inert PEEK group; HE staining results showed that more new bones were formed in the PEEK-Dex/Mino lipo group than in the inert PEEK group, which were firmly bonded to the functionalized PEEK surface and extended along the PEEK interface. These results suggested that the Dex released from the liposome-functionalized surface induced effective bone regeneration in vivo. CONCLUSION Dex/Mino liposome modification enhanced the bioactivity of inert PEEK, the functionalized PEEK with enhanced antibacterial and osseointegrative capacity has great potential as an orthopedic/dental implant material for clinical application.
Animals ; Benzophenones ; Dogs ; Ketones ; Liposomes ; Mice ; Osseointegration ; Polyethylene Glycols ; Polymers ; Surface Properties ; X-Ray Microtomography

BACKGROUND: Three-dimensional (3D) printing with a direct metal fabrication (DMF) technology has been innovatively introduced in the field of surface treatment of prostheses. The purpose of this study was to determine whether such modifications on the surface of cobalt-chromium (CoCr) alloy by titanium powder coating using DMF improves the osseointegration ability of CoCr alloy. METHODS: We compared the in vitro and in vivo ability of cells to adhere to DMF-coated CoCr alloy with machining. Biological and morphological responses to human osteoblast cell lines were examined by measuring cell proliferation rate and observing expression of actin filament. For in vivo study, we inserted different specimens in each medulla of the distal femurs of rabbit. After 3 months, the distal femurs were harvested, and a push-out test and histomorphometric analyses were performed. RESULTS: The cell proliferation rate and cell adhesion in the DMF group were higher compared with those in the machined group. Human osteoblast cells on the DMF-coated surface were more strongly adhered and well-proliferated compared with those on the other surface. In the in vivo test, there was a significant difference in the ultimate shear strength between the DMF and machined groups (2.49 MPa vs. 0.87 MPa, respectively, p = 0.001). In the histomorphometric analysis, there was a significant difference in the mean bone-to-implant contact percentages between the DMF and machined groups (72.3 ± 6.2% vs. 47.6 ± 6.9%, respectively, p < 0.001). CONCLUSION: Titanium coating of CoCr alloy with 3D metal printing provides optimal surface characteristics and a good biological surface both in vitro and in vivo.
Actin Cytoskeleton ; Alloys ; Cell Adhesion ; Cell Line ; Cell Proliferation ; Femur ; Humans ; In Vitro Techniques ; Osseointegration ; Osteoblasts ; Printing, Three-Dimensional ; Prostheses and Implants ; Shear Strength ; Titanium

The aim of this study was to examine the bioactivity and osseointegration of Ti-6Al-4V alloy implant which was modified by an anodic oxidation and a cyclic precalcification treatments. After blasting treatment using HAp (Hydroxyapatitie; HAp) powder which is resorbable blasting media (RBM) on the surface of Ti-6Al-4V alloy implants, the anodic oxidation treatment and the cyclic precalcification treatment were conducted to form nanotube TiO2 layer and HAp precipitation respectively. The surface morphology of the surface-treated Ti-6Al-4V alloy implant was investigated after immersion in the simulated body fluid(SBF) for 3 days to investigate the bioactivity. To investigate the effect of surface treatment on bonding between the implant and bone, RBM treated implant and RBM-anodization-cyclic precalcification(RACP) treated implant were placed on the distal side of both tibia diaphysis of rats, and then the removal torque of the implant was measured after 4 weeks. On the surface of RACP treated group, bone-like apatite precipitation was observed after immersion in SBF for 3 days. The removal torque was significantly higher in the RACP treated group than in the RBM treated group. The interfacial fracture between the implant and the new bone was observed in the RBM treated group, but both the cohesive fracture at the new bone and the interfacial fractures between the implant and the new bone were observed in the RACP treated group.
Alloys ; Animals ; Diaphyses ; Immersion ; Nanotubes ; Osseointegration ; Rats ; Tibia ; Torque

OBJECTIVE: This work aimed to study and identify the influence and target gene of microRNA-29a-3p (miR-29a-3p) in the osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) in a high-fat environment in vitro and in vivo. METHODS: 1) In vitro: BMSCs were randomly allocated into two groups and were then induced to undergo osteogenic differentiation in a normal or high-fat environment. Next, a miR-29a-3p mimic/inhibitor was transfected into the two groups of cells. The mRNA expression levels of alkaline phosphatase (ALP), Runt related gene 2 (Runx2), and miR-29a-3p and the protein expression levels of ALP and Runx2 were detected before and after transfection through reverse transcription-quantitative real-time polymerase chain reaction (RT-qPCR) and Western blot analyses. Moreover, Frizzled (Fzd) 4 was predicted as the target gene of miR-29a-3p by using an online database (Target Scan, MiRNA.org). The interactive relationship between miR-29a-3p and Fzd4 was confirmed through dual-luciferase assays. 2) In vivo: Rats were randomly divided into two groups and fed with a standard or high-fat diet. Titanium implants were grown in rats. Then, the expression levels of miR-29a-3p, ALP, and Runx2 were detected in bone tissues surrounding implants. Moreover, hard tissue sections were subjected to methylene blue-acid magenta staining and observed under microscopy to study bone formation around implants. In addition, miR-29a-3p-overexpressing lentiviral vectors were transfected into rats, and the expression levels of ALP, Runx2, and miR-29a-3p in bone tissues surrounding implants were detected at 3 and 10 days after transfection. RESULTS: The expression levels of ALP, Runx2, and miR-29a-3p and the osteogenic differentiation of BMSCs were suppressed in high-fat groups in vitro and in vivo. CONCLUSIONS MiR-29a-3p plays a positive role in the regulation of BMSCs in a high-fat environment. It can increase ALP and Runx2 expression levels in bone tissues surrounding implants in hyperlipidemia models. This result implies that miR-29a-3p can promote implant osseointergration in a rat model of hyperlipidemia.
Animals ; Cell Differentiation ; Dental Implants ; Hyperlipidemias ; MicroRNAs ; Osseointegration ; Osteoblasts ; Osteogenesis ; Random Allocation ; Rats

Titanium dental implants have wide clinical application due to their many advantages, including comfort, aesthetics, lack of damage to adjacent teeth, and significant clinical effects. However, the failure of osseointegration, bone resorption, and peri-implantitis limits their application. Physical-chemical and bioactive coatings on the surface of titanium implants could improve the successful rate of dental implants and meet the clinical application requirements. This paper reviews the characteristics of surface modification of titanium implants from the aspects of physics, chemistry, and biology. Results provide information for research and clinical application of dental implant materials.
Coated Materials, Biocompatible ; Dental Implants ; Esthetics, Dental ; Osseointegration ; Surface Properties ; Titanium

Bone and soft tissue conditions are important for successful implant treatment. But, the placement itself is also very important. Implants which is installed in the wrong position result in the biological, esthetical and mechanical problems. In order to place an implant in the correct position, the final restoration and diagnostic wax-up should be considered prior to the surgery. If the artificial teeth for the interim denture are directly transferred from the diagnostic wax-up, the operator can try the form of diagnostic wax-up in the mouth. If the surgical template is produced by duplicating the interim denture, the implant can be placed in the planned position. In this case, the polymethyl methacrylate (PMMA) artificial tooth was precisely milled by the digital duplication of diagnostic wax-up. And interim denture was fabricated by using these milled teeth. After the patient adapted for a sufficient period, the implant was placed at the planned position with surgical template produced by duplicating the interim denture. After confirming sufficient osseointegration, the final prostheses were made to reflect the shape of diagnostic wax-up. Through this procedure, the satisfactory functional and esthetic outcome could be acquired.
Dental Implants ; Dental Prosthesis ; Dentures ; Humans ; Mouth ; Osseointegration ; Polymethyl Methacrylate ; Prostheses and Implants ; Rehabilitation ; Tooth ; Tooth, Artificial