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*

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

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

PURPOSE: This study evaluated differences in bone healing and remodeling among 3 implants with different surfaces: sandblasting and large-grit acid etching (SLA; IS-III Active®), SLA with hydroxyapatite nanocoating (IS-III Bioactive®), and SLA stored in sodium chloride solution (SLActive®). METHODS: The mandibular second, third, and fourth premolars of 9 dogs were extracted. After 4 weeks, 9 dogs with edentulous alveolar ridges underwent surgical placement of 3 implants bilaterally and were allowed to heal for 2, 4, or 12 weeks. Histologic and histomorphometric analyses were performed on 54 stained slides based on the following parameters: vertical marginal bone loss at the buccal and lingual aspects of the implant (b-MBL and l-MBL, respectively), mineralized bone-to-implant contact (mBIC), osteoid-to-implant contact (OIC), total bone-to-implant contact (tBIC), mineralized bone area fraction occupied (mBAFO), osteoid area fraction occupied (OAFO), and total bone area fraction occupied (tBAFO) in the threads of the region of interest. Two-way analysis of variance (3 types of implant surface×3 healing time periods) and additional analyses for simple effects were performed. RESULTS: Statistically significant differences were observed across the implant surfaces for OIC, mBIC, tBIC, OAFO, and tBAFO. Statistically significant differences were observed over time for l-MBL, mBIC, tBIC, mBAFO, and tBAFO. In addition, an interaction effect between the implant surface and the healing time period was observed for mBIC, tBIC, and mBAFO. CONCLUSIONS: Our results suggest that implant surface wettability facilitates bone healing dynamics, which could be attributed to the improvement of early osseointegration. In addition, osteoblasts might become more activated with the use of HA-coated surface implants than with hydrophobic surface implants in the remodeling phase.
Animals ; Bicuspid ; Bone Remodeling ; Bone-Implant Interface ; Dogs ; Durapatite ; Miners ; Osseointegration ; Osteoblasts ; Sodium Chloride ; Wettability

PURPOSE: The aim of this retrospective study was to determine the prevalence of early implant failure using a single implant system and to identify the factors contributing to early implant failure. METHODS: Patients who received implant treatment with a single implant system (Luna®, Shinhung, Seoul, Korea) at Dankook University Dental Hospital from 2015 to 2017 were enrolled. The following data were collected for analysis: sex and age of the patient, seniority of the surgeon, diameter and length of the implant, position in the dental arch, access approach for sinus-floor elevation, and type of guided bone regeneration (GBR) procedure. The effect of each predictor was evaluated using the crude hazard ratio and the adjusted hazard ratio (aHR) in univariate and multivariate Cox regression analyses, respectively. RESULTS: This study analyzed 1,031 implants in 409 patients, who comprised 169 females and 240 males with a median age of 54 years (interquartile range [IQR], 47–61 years) and were followed up for a median of 7.2 months (IQR, 5.6–9.9 months) after implant placement. Thirty-five implants were removed prior to final prosthesis delivery, and the cumulative survival rate in the early phase at the implant level was 95.6%. Multivariate regression analysis revealed that seniority of the surgeon (residents: aHR=2.86; 95% confidence interval [CI], 1.37–5.94) and the jaw in which the implant was placed (mandible: aHR=2.31; 95% CI, 1.12–4.76) exerted statistically significant effects on early implant failure after adjusting for sex, age, dimensions of the implant, and type of GBR procedure (preoperative and/or simultaneous) (P<0.05). CONCLUSIONS: Prospective studies are warranted to further elucidate the factors contributing to early implant failure. In the meantime, surgeons should receive appropriate training and carefully select the bone bed in order to minimize the risk of early implant failure.
Bone Regeneration ; Dental Arch ; Dental Implants ; Female ; Humans ; Jaw ; Male ; Osseointegration ; Prevalence ; Prospective Studies ; Prostheses and Implants ; Retrospective Studies ; Risk Factors ; Seoul ; Surgeons ; Surgical Procedures, Operative ; Survival Rate

OBJECTIVES: This study aimed to investigate the effects of chronic restraint stress on the osseointegration of titanium implants. MATERIALS AND METHODS: Twenty adult male Wistar albino rats were used in the study. After surgical insertion of titanium implants into the metaphyseal part of the tibial bone, rats were randomly divided into two groups: a control group (CNT group) and an experimental restraint stress group (RS group). In the CNT group, titanium implants were inserted surgically, and rats received no further treatment during the 47-day experimental period. In the RS group, restraint stress was applied for 3 hours per day for 45 days, beginning 2 days after implant surgery. Weight of the rats was measured prior to surgery and at the end of the study to analyze the effects of stress. At the end of the experimental period, rats were euthanized, and implants and surrounding bone tissues were used for undecalcified histological analysis. Serum cortisol levels were assessed in cardiac blood samples from the rats following centrifugation. RESULTS: Average weight of rats in the RS group was lower than that of rats in the CNT group after the experimental protocol had been completed (P<0.05). Further, serum cortisol levels were higher in the RS group than in the CNT group (P<0.05). There were no significant differences in bone-implant connection levels between the two groups (P>0.05). CONCLUSION: The data analyzed in this study suggest that chronic restraint stress did not adversely affect rats during a 45-day osseointegration period.
Adult ; Animals ; Bone and Bones ; Centrifugation ; Humans ; Hydrocortisone ; Male ; Osseointegration ; Rats ; Tibia ; Titanium

OBJECTIVES: This study sought to investigate the association between the systemic intake of proton pump inhibitors (PPI) and the early failure of dental implants. MATERIALS AND METHODS: A retrospective cohort study involving 1,918 dental implants in 592 patients (69 implants in 24 PPI users and 1,849 implants in 568 nonusers, respectively) was conducted. The effect of PPI intake on the osseointegration of dental implants was evaluated using patient- and implant-level models. RESULTS: Among 24 PPI users, two patients experienced implant failure, one of whom had three and the other of whom had one failed implant, respectively. Thus, the rate of failure for this population was 8.3%. Separately, 11 nonusers each experienced one implant failure, and the failure rate for these patients was 1.9%. Fisher's exact test revealed statistically significant differences between PPI users and nonusers at the implant level (P=0.002) but failed to show any significance at the patient level (P=0.094). The odds of implant failure were 4.60 times greater among PPI users versus nonusers. Dental implants that were placed in patients using PPIs were found to be 4.30 times more likely to fail prior to loading. CONCLUSION: The findings of this study suggest that PPI intake may be associated with an increased risk of early dental implant failure.
Cohort Studies ; Dental Implantation ; Dental Implants ; Humans ; Morinda ; Osseointegration ; Proton Pump Inhibitors ; Proton Pumps ; Protons ; Rehabilitation ; Retrospective Studies ; Risk Factors

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