Titanium (Ti) and its corresponding alloys have been widely applied in dental and orthopedic implants. Owing to abrasion and corrosion of implants in the unfavorable electrolytic aqueous environment of the host body, Ti ions could be released from implants and accumulated in local tissues. Recent studies have found that excessive Ti ions were toxic to osteoblasts in adjacent bone tissues and subsequently influenced long-term effects on implant prostheses. However, the potential molecular mechanisms underlying the damage to osteoblasts induced by Ti ions remained unclear. Hippo signaling has been confirmed to be involved in organ size and tissue regeneration in many organs, while its roles in osteoblasts differentiation and bone repair remained elusive. Therefore, we hypothesize that YAP, a regulator of Hippo pathway, inhibited osteoblast growth, skeletal development and bone repair, as well as excessive Ti ions promoted the progression of YAP activation. This study aimed to explore the role of Hippo/YAP signaling pathway in the biotoxicity effect of Ti ions on osteoblast behaviors. Here, we confirmed that 10 ppm Ti ions, a minimum concentration gradient previously reported that was capable of suppressing osteoblasts growth, induced nuclear expression of YAP in osteoblasts in our study. Furthermore, 10 ppm Ti ion-induced YAP activation was found to downregulate osteogenic differentiation of MC3T3-E1 cells. Most importantly, the hypothesis we proposed that knockdown of YAP did reverse the inhibitory effect of 10 ppm Ti ions on osteogenesis has been verified. Taken together, our work provides insights into the mechanism of which YAP is involved in regulating osteoblast behaviors under the effect of Ti ions, which may help to develop therapeutic applications for Ti implant failures and peri-implantitis.

Titanium (Ti) and its alloys as bio-implants have excellent biocompatibilities and osteogenic properties after modification of chemical composition and topography via various methods. The corrosion resistance of these modified materials is of great importance for changing oral system, while few researches have reported this point. Recently, oxidative corrosion induced by cellular metabolites has been well concerned. In this study, we explored the corrosion behaviors of four common materials (commercially pure Ti, cp-Ti; Sandblasting and acid etching-modified Ti, Ti-SLA; nanowires-modified Ti, Ti-NW; and zinc-containing nanowires-modified Ti, Ti-NW-Zn) with excellent biocompatibilities and osteogenic capacities under the macrophages induced-oxidizing microenvironment. The results showed that the materials immersed into a high oxidizing environment were more vulnerable to corrode. Meanwhile, different surfaces also showed various corrosion susceptibilities under oxidizing condition. Samples embed with zinc element exhibited more excellent corrosion resistance compared with other three surfaces exposure to excessive H 2 O 2 . Besides, we found that zinc-decorated Ti surfaces inhibited the adhesion and proliferation of macrophages on its surface and induced the M2 states of macrophages to better healing and tissue reconstruction. Most importantly, zinc-decorated Ti surfaces markedly increased the expressions of antioxidant enzyme relative genes in macrophages. It improved the oxidation microenvironment around the materials and further protected their properties. In summary, our results demonstrated that Ti-NW-Zn surfaces not only provided excellent corrosion resistance properties, but also inhibited the adhesion of macrophages. These aspects were necessary for maintaining osseointegration capacity and enhancing the corrosion resistance of Ti in numerous medical applications, particularly in dentistry.

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Objective: This study aims to investigate the influence of fluoride exposure on implant osseointegration.Methods: A total of 24 male New Zealand white rabbits were randomly divided into the control group and the fluoride exposure group. Rabbits in the control group were fed with tap water, while those in the fluoride exposure group were given 200 mg/L sodium fluoride solution. After 2-month feeding, implants were inserted into the extraction socket immediately after extraction of rabbit mandibular anterior teeth.Four rabbits in each group were sacrificed to collect the implants samples at 1, 2, and 3 months post-implantation, respectively. Radiographic and histomorphometry examinations were performed to evaluate the condition of implant osseointegration.Results: Bone volume around the implants increased in a time-dependent manner in both groups. Micro-CT images illustrated that the bone mineral density (BMD) in the fluoride exposure group was significantly lower than that in the control group after implantation for 2 and 3 months. The bone-implant contact ratio (BIC) in the fluoride exposure group was much lower than that of the control group at 3 months post-implantation according to histomorphometry examination. Conclusions:In rabbit animal model, high fluoride exposure affected the quality of bone surrounding the implant and significantly reduced bone integration of the implant, especially in the late stage of osseointegration. K E Y W O R D Sfluoride exposure, implant osseointegration, peri-implant bone, rabbit

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