Objective: To fabricate TiO₂ nanotube material functionalized by antimicrobial peptide LL-37, and to explore its effects on biological behaviors such as adhesion and migration of human keratinocytes (HaCaT) and its antibacterial properties. Methods: The TiO₂ nanotube array (NT) was constructed on the surface of polished titanium (PT) by anodization, and the antimicrobial peptide LL-37 was loaded on the surface of TiO₂ nanotube (LL-37/NT) by physical adsorption. Three samples were selected by simple random sampling in each group. Surface morphology, roughness, hydrophilicity and release characteristics of LL-37 of the samples were analyzed with a field emission scanning electron microscope, an atomic force microscope, a contact angle measuring device and a microplate absorbance reader. HaCaT cells were respectively cultured on the surface of three groups of titanium samples. Each group had 3 replicates. The morphology of cell was observed by field emission scanning electron microscope. The number of cell adhesion was observed by cellular immunofluorescence staining. Cell counting kit-8 (CCK-8) assay was used to detect cell proliferation. Wound scratch assay was used to observe the migration of HaCaT. The above experiments were used to evaluate the effect of each group on the biological behavior of HaCaT cells. To evaluate their antibacterial effects, Porphyromonas gingivalis (Pg) was respectively inoculated on the surface of three groups of titanium samples. Each group had 3 replicates. The morphology of bacteria was observed by field emission scanning electron microscope. Bacterial viability was determined by live/dead bacterial staining. Results: A uniform array of nanotubes could be seen on the surface of titanium samples in LL-37/NT group, and the top of the tube was covered with granular LL-37. Compared with PT group [the roughness was (2.30±0.18) nm, the contact angle was 71.8°±1.7°], the roughness [(20.40±3.10) and (19.10±4.11) nm] and hydrophilicity (the contact angles were 22.4°±3.1° and 25.3°±2.2°, respectively) of titanium samples increased in NT and LL-37/NT group (P<0.001). The results of in vitro release test showed that the release of antimicrobial peptide LL-37 was characterized by early sudden release (1-4 h) and long-term (1-7 d) slow release. With the immunofluorescence, more cell attachment was found on NT and LL-37/NT than that on PT at the first 0.5 and 2.0 h of culture (P<0.05). The results of CCK-8 showed that there was no significant difference in the proliferation of cells among groups at 1, 3 and 5 days after culture. Wound scratch assay showed that compared with PT and NT group, the cell moved fastest on the surface of titanium samples in LL-37/NT group at 24 h of culture [(96.4±4.9)%] (F=35.55, P<0.001). A monolayer cells could be formed and filled with the scratch in 24 h at LL-37/NT group. The results of bacterial test in vitro showed that compared with the PT group, the bacterial morphology in the NT and LL-37/NT groups was significantly wrinkled, and obvious bacterial rupture could be seen on the surface of titanium samples in LL-37/NT group. The results of bacteria staining showed that the green fluorescence intensity of titanium samples in LL-37/NT group was the lowest in all groups (F=66.54,P<0.001). Conclusions: LL-37/NT is beneficial to the adhesion and migration of HaCaT cells and has excellent antibacterial properties, this provides a new strategy for the optimal design of implant neck materials.
Humans ; Titanium/chemistry* ; Antimicrobial Peptides ; Cathelicidins ; Sincalide ; Anti-Bacterial Agents/pharmacology* ; Nanotubes/chemistry* ; Dental Materials ; Bacteria ; Keratinocytes ; Surface Properties

OBJECTIVE: To investigate whether 3D-printed artificial vertebral body can reduce prosthesis subsidence rate for patients with cervical chordomas, through comparing the rates of prosthesis subsidence between 3D printing artificial vertebral body and titanium mesh for anterior spinal reconstruction after total spondylectomy. METHODS: This was a retrospective analysis of patients who underwent surgical treatment for cervical chordoma at our hospital from March 2005 to September 2019. There were nine patients in the group of 3D artificial vertebral body (3D group), and 15 patients in the group of titanium mesh cage (Mesh group). The patients' characteristics and treatment data were extracted from the medical records, including age, gender, CT hounsfield unit of cervical vertebra and surgical information, such as the surgical segments, time and blood loss of surgery, frequency and degree of prosthesis subsidence after surgery. Radiographic observations of prosthesis subsidence during the follow-up, including X-rays, CT, and magnetic resonance imaging were also collected. SPSS 22.0 was used to analysis the data. RESULTS: There was no significant difference between the two groups in gender, age, CT hounsfield unit, surgical segments, time of surgery, blood loss of posterior surgery and total blood loss. Blood loss of anterior surgery was 700 (300, 825) mL in 3D group and 1 500 (750, 2 800) mL in Mesh group (P < 0.05). The prosthesis subsidence during the follow-up, 3 months after surgery, there was significant difference between the two groups in mild prosthesis subsidence (P < 0.05). The vertebral height of the 3D group decreased less than 1 mm in eight cases (no prosthesis subsidence) and more than 1 mm in one case (mild prosthesis subsidence). The vertebral height of the Mesh group decreased less than 1 mm in five cases (no prosthesis subsidence), and more than 1 mm in eight cases (mild prosthesis subsidence). Two patients did not have X-rays in 3 months after surgery. There was a statistically significant difference between the two groups in the prosthesis subsidence rate at the end of 12 months (P < 0.01). The vertebral height of eight cases in the 3D group decreased less than 1 mm (no prosthesis subsidence) and one case more than 3 mm (severe prosthesis subsidence). Four of the 15 cases in the Mesh group decreased less than 1 mm (no prosthesis subsidence), two cases more than 1 mm (mild prosthesis subsidence), and nine cases more than 3 mm (severe prosthesis subsidence). There was a statistically significant difference between the two groups in the prosthesis subsidence rate at the end of 24 months (P < 0.01). The vertebral height of seven cases in the 3D group decreased less than 1 mm (no prosthesis subsidence), one case more than 3 mm (severe prosthesis subsidence), and one case died with tumor. One case in the Mesh group decreased less than 1 mm (no prosthesis subsidence), one case more than 1 mm (mild prosthesis subsidence), 11 case more than 3 mm (severe prosthesis subsidence), one case died with tumor and one lost the follow-up. Moreover, at the end of 12 months and 24 months, there was significant difference between the two groups in severe prosthesis subsidence rate (P < 0.01). CONCLUSION 3D-printed artificial vertebral body for anterior spinal reconstruction after total spondylectomy for patients with cervical chordoma can provide reliable spinal stability, and reduce the incidence of prosthesis subsidence after 2-year follow-up.
Humans ; Chordoma/surgery* ; Retrospective Studies ; Vertebral Body ; Titanium ; Cervical Vertebrae/surgery* ; Printing, Three-Dimensional ; Spinal Fusion/methods* ; Treatment Outcome

The purpose of this study is to establish and apply a correction method for titanium alloy implant in spinal IMRT plan, a corrected CT-density table was revised from normal CT-density table to include the density of titanium alloy implant. Dose distribution after and before correction were calculated and compared to evaluate the dose deviation. Plans were also copied to a spinal cancer simulation phantom. A titanium alloy fixation system for spine was implanted in this phantom. Plans were recalculated and compared with the measurement result. The result of this study shows that the max dose of spinal cord showed significant difference after correction, and the deviation between calculation results and measurement results was reduced after correction. The method for expanding the range CT-density table, which means that the density of titanium alloy was included, can reduce the error in calculation.
Radiotherapy, Intensity-Modulated/methods* ; Titanium ; Radiotherapy Dosage ; Alloys ; Radiometry/methods* ; Radiotherapy Planning, Computer-Assisted/methods*

Nano-engineering-based tissue regeneration and local therapeutic delivery strategies show significant potential to reduce the health and economic burden associated with craniofacial defects, including traumas and tumours. Critical to the success of such nano-engineered non-resorbable craniofacial implants include load-bearing functioning and survival in complex local trauma conditions. Further, race to invade between multiple cells and pathogens is an important criterion that dictates the fate of the implant. In this pioneering review, we compare the therapeutic efficacy of nano-engineered titanium-based craniofacial implants towards maximised local therapy addressing bone formation/resorption, soft-tissue integration, bacterial infection and cancers/tumours. We present the various strategies to engineer titanium-based craniofacial implants in the macro-, micro- and nano-scales, using topographical, chemical, electrochemical, biological and therapeutic modifications. A particular focus is electrochemically anodised titanium implants with controlled nanotopographies that enable tailored and enhanced bioactivity and local therapeutic release. Next, we review the clinical translation challenges associated with such implants. This review will inform the readers of the latest developments and challenges related to therapeutic nano-engineered craniofacial implants.
Humans ; Titanium ; Dental Implants ; Wound Healing ; Surface Properties

Objective: To construct a kind of neural network for eliminating the metal artifacts in CT images by training the generative adversarial networks (GAN) model, so as to provide reference for clinical practice. Methods: The CT data of patients treated in the Department of Radiology, West China Hospital of Stomatology, Sichuan University from January 2017 to June 2022 were collected. A total of 1 000 cases of artifact-free CT data and 620 cases of metal artifact CT data were obtained, including 5 types of metal restorative materials, namely, fillings, crowns, titanium plates and screws, orthodontic brackets and metal foreign bodies. Four hundred metal artifact CT data and 1 000 artifact-free CT data were utilized for simulation synthesis, and 1 000 pairs of simulated artifacts and metal images and simulated metal images (200 pairs of each type) were constructed. Under the condition that the data of the five metal artifacts were equal, the entire data set was randomly (computer random) divided into a training set (800 pairs) and a test set (200 pairs). The former was used to train the GAN model, and the latter was used to evaluate the performance of the GAN model. The test set was evaluated quantitatively and the quantitative indexes were root-mean-square error (RMSE) and structural similarity index measure (SSIM). The trained GAN model was employed to eliminate the metal artifacts from the CT data of the remaining 220 clinical cases of metal artifact CT data, and the elimination results were evaluated by two senior attending doctors using the modified LiKert scale. Results: The RMSE values for artifact elimination of fillings, crowns, titanium plates and screws, orthodontic brackets and metal foreign bodies in test set were 0.018±0.004, 0.023±0.007, 0.015±0.003, 0.019±0.004, 0.024±0.008, respectively (F=1.29, P=0.274). The SSIM values were 0.963±0.023, 0.961±0.023, 0.965±0.013, 0.958±0.022, 0.957±0.026, respectively (F=2.22, P=0.069). The intra-group correlation coefficient of 2 evaluators was 0.972. For 220 clinical cases, the overall score of the modified LiKert scale was (3.73±1.13), indicating a satisfactory performance. The scores of modified LiKert scale for fillings, crowns, titanium plates and screws, orthodontic brackets and metal foreign bodies were (3.68±1.13), (3.67±1.16), (3.97±1.03), (3.83±1.14), (3.33±1.12), respectively (F=1.44, P=0.145). Conclusions: The metal artifact reduction GAN model constructed in this study can effectively remove the interference of metal artifacts and improve the image quality.
Humans ; Tomography, X-Ray Computed/methods* ; Deep Learning ; Titanium ; Neural Networks, Computer ; Metals ; Image Processing, Computer-Assisted/methods* ; Algorithms

OBJECTIVE: To study the effect of various intracanal materials on the accuracy of oral maxillofacial cone-beam computed tomography (CBCT) for the diagnosis of vertical root fracture (VRF). METHODS: A total of twenty-four structurally intact single root canal dried and isolated teeth extracted for orthodontic treatment or periodontal disease were collected. The teeth were decrowned along the cemento-enamel junction (CEJ) and then used as samples for the study after conventional root canal preparation and post preparation. The 24 samples were divided into two groups with 12 samples in each group. Group A was the control group (no VRF group). According to intracanal materials, they were divided into five subgroups: blank group, fiber post group, gutta-percha point group, titanium post group and gold-palladium post group. Group B was the experimental group (VRF group), and subgroups were grouped as above. The VRF model was prepared by a unified method in the VRF group: the root was completely fractured in the buccolingual direction with a custom root canal nail and then cemented and reset. The control group was not subjected to the simulation of VRF. Titanium post and gold-palladium post were made according to the individuality of the root canal preparation, and the tightness of the post to the root canal wall was confirmed by X-ray radiograph. Then all the samples were scanned by CBCT in the isolate swine mandibular alveolar sockets. The diagnostic accuracy was statistically analyzed via blind interpretation by experienced endodontic specialists and oral and maxillofacial medical imaging specialists. RESULTS: The accuracy of the diagnosis of VRF in the blank group, fiber post group, gutta-percha point group, titanium post group, and gold-palladium post group in CBCT was 95.83%, 91.67%, 87.50%, 79.17%, and 45.83%, respectively. Compared with the blank group, the differences were not statistically significant in the fiber post group (P>0.999), the gutta-percha point group (P=0.500) and the titanium post group (P=0.125). The lowest diagnostic accuracy of VRF was found in the gold-palladium post group, and the difference was statistically significant compared with all other groups (P < 0.001). CONCLUSION Various intracanal materials have different degrees of influence on the diagnostic accuracy of VRF diagnosis in CBCT. The influence of fiber post, gutta-percha point and titanium post was small, while the influence of gold-palladium post was significant.
Animals ; Cone-Beam Computed Tomography/methods* ; Gold ; Gutta-Percha ; Palladium ; Swine ; Titanium ; Tooth Fractures/diagnostic imaging* ; Tooth Root/injuries* ; Reproducibility of Results

OBJECTIVE: To investigate the effect of titanium dioxide nanoparticles (TiO₂ NPs) on the expression profile of circular ribonucleic acid (circRNA) in human hepatocytes through in vitro cell experiments, and to attempt to understand the potential mechanism of hepatotoxicity through bioinformatics analysis. METHODS: TiO₂ NPs were characterized from the aspects of particle size, shape and agglomeration state. The cell counting kit-8 (CCK8) was used to detect the cytotoxicity of TiO₂ NPs against human hepatocellular carcinoma cells (HepG2) after exposure to 0, 1.56, 3.13, 6.25, 12.5, 25, 50, 100, and 200 mg/L TiO₂ NPs for 24 h or 48 h. The cells were treated at doses of 0 mg/L TiO₂ NPs (control group) and 100 mg/L TiO₂ NPs (treatment group), and collected after exposure for 48 h, and then RNA from the extracted cell samples was collected and sequenced. The differential circRNAs between the control and the TiO₂ NPs treatment groups were screened, and then the enrichment pathway of the differential circRNA target gene was analyzed by multivariate statistics. According to the sequencing results, significantly altered genes and important genes in the significant enrichment pathways were screened, and real-time reverse transcription-polymerase chain reaction (real-time RT-PCR) was performed to verify the results. RESULTS: TiO₂ NPs were spherical anatase with a hydrated particle size of (323.50±85.44) nm and a Zeta potential of (-21.00±0.72) mV in a serum-free medium. The results of the CCK8 cytotoxicity assay showed that with the increase of TiO₂ NPs concentration, cell viability gradually decreased. A total of 11 478 circRNAs were found by RNA sequencing. Compared with the control groups, TiO₂ NPs treatment groups (100 mg/L) had a total of 89 differential circRNAs, of which 59 were up-regulated and 30 were down-regulated. Analysis of the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway showed that the targeted genes of differential circRNAs were mainly enriched in fatty acid degradation, Fanconi anemia pathway, and fatty acid metabolism. The expression levels of circRNA.6730, circRNA.3650 and circRNA.4321 were significantly different between the TiO₂ NPs treatment group and the control group, which were consistent with the sequencing results. CONCLUSION TiO₂ NPs can induce changes in circRNA expression profile, and epigenetics may play an important role in the mechanism of hepatotoxicity.
Humans ; RNA/genetics* ; RNA, Circular/genetics* ; Carcinoma, Hepatocellular/genetics* ; Liver Neoplasms/genetics* ; Titanium ; Nanoparticles ; Chemical and Drug Induced Liver Injury ; Fatty Acids

OBJECTIVE: To review antibacterial/osteogenesis dual-functional surface modification strategy of titanium-based implants, so as to provide reference for subsequent research. METHODS: The related research literature on antibacterial/osteogenesis dual-functional surface modification strategy of titanium-based implants in recent years was reviewed, and the research progress was summarized based on different kinds of antibacterial substances and osteogenic active substances. RESULTS: At present, the antibacterial/osteogenesis dual-functional surface modification strategy of titanium-based implants includes: ① Combined coating strategy of antibiotics and osteogenic active substances. It is characterized in that antibiotics can be directly released around titanium-based implants, which can improve the bioavailability of drugs and reduce systemic toxicity. ② Combined coating strategy of antimicrobial peptides and osteogenic active substances. The antibacterial peptides have a wide antibacterial spectrum, and bacteria are not easy to produce drug resistance to them. ③ Combined coating strategy of inorganic antibacterial agent and osteogenic active substances. Metal ions or metal nanoparticles antibacterial agents have broad-spectrum antibacterial properties and various antibacterial mechanisms, but their high-dose application usually has cytotoxicity, so they are often combined with substances that osteogenic activity to reduce or eliminate cytotoxicity. In addition, inorganic coatings such as silicon nitride, calcium silicate, and graphene also have good antibacterial and osteogenic properties. ④ Combined coating strategy of metal organic frameworks/osteogenic active substances. The high specific surface area and porosity of metal organic frameworks can effectively package and transport antibacterial substances and bioactive molecules. ⑤ Combined coating strategy of organic substances/osteogenic active substancecs. Quaternary ammonium compounds, polyethylene glycol, N-haloamine, and other organic compounds have good antibacterial properties, and are often combined with hydroxyapatite and other substances that osteogenic activity. CONCLUSION The factors that affect the antibacterial and osteogenesis properties of titanium-based implants mainly include the structure and types of antibacterial substances, the structure and types of osteogenesis substances, and the coating process. At present, there is a lack of clinical verification of various strategies for antibacterial/osteogenesis dual-functional surface modification of titanium-based implants. The optimal combination, ratio, dose-effect mechanism, and corresponding coating preparation process of antibacterial substances and bone-active substances are needed to be constantly studied and improved.
Anti-Bacterial Agents/pharmacology* ; Coated Materials, Biocompatible/chemistry* ; Metal-Organic Frameworks/pharmacology* ; Osteogenesis ; Surface Properties ; Titanium/pharmacology* ; Prostheses and Implants

OBJECTIVE: To investigate the early effectiveness of the Ti-Robot assisted femoral neck system (FNS) in the treatment of elderly Garden type Ⅱ and Ⅲ femoral neck fractures. METHODS: A retrospective analysis was conducted on the clinical data of 41 elderly patients with Garden type Ⅱ and Ⅲ femoral neck fractures who were admitted between December 2019 and August 2022 and met the selection criteria. Among them, 21 cases were treated with Ti-Robot assisted FNS internal fixation (study group), and 20 cases were treated solely with FNS internal fixation (control group). There was no significant difference in baseline data, including gender, age, side, cause of injury, time from injury to surgery, fracture Garden classification, and fracture line classification, between the two groups ( P>0.05). Surgical effectiveness was evaluated based on parameters such as operation time (including incision time and total operation time), reduction level, number of dominant pin insertions, intraoperative fluoroscopy frequency, incision length, whether to extend the incision, need for assisted reduction, postoperative hospital stay, fracture healing time, incidence of osteonecrosis of the femoral head, postoperative visual analogue scale (VAS) score at 1 day, and Harris hip score at last follow-up. RESULTS: The study group showed significantly shorter incision time, fewer dominant pin insertions, fewer instances of extended incisions, fewer intraoperative fluoroscopy frequency, and smaller incisions than the control group ( P<0.05). There was no significant difference in total operation time, reduction level, and assisted reduction frequency between the two groups ( P>0.05). Both groups achieved primary wound healing postoperatively, with no complications such as incision leakage or skin infection. All patients were followed up 12-24 months with an average of 14.6 months. Fractures healed in both groups, with no significant difference in healing time ( P>0.05). There was no significant difference in postoperative hospital stay between the two groups ( P>0.05). The study group showed significantly better VAS score at 1 day after operation and Harris hip score at last follow-up when compared to the control group ( P<0.05). No complication such as internal fixation failure, fracture displacement, or hip joint varus occurred in both groups during the follow-up. Osteonecrosis of the femoral head occurred in 1 patient of the control group, while no was observed in the study group, and the difference in the incidence of osteonecrosis of the femoral head between the two groups was not significant ( P=0.488). CONCLUSION Compared to sole FNS internal fixation treatment, Ti-Robot assisted FNS internal fixation for elderly Garden typeⅡ and Ⅲ femoral neck fractures can reduce incision time, achieve minimally invasive and accurate nail implantation, and decrease intraoperative fluoroscopy frequency, leading to improved postoperative hip joint function recovery.
Humans ; Aged ; Femur Neck ; Robotics ; Retrospective Studies ; Treatment Outcome ; Titanium ; Femoral Neck Fractures/surgery* ; Fracture Fixation, Internal ; Osteonecrosis ; Surgical Wound

Peri-implantitis is one of the most important biological complications in the field of oral implantology. Identifying the causative factors of peri-implant inflammation and osteolysis is crucial for the disease's prevention and treatment. The underlying risk factors and detailed pathogenesis of peri-implantitis remain to be elucidated. Titanium-based implants as the most widely used implant inevitably release titanium particles into the surrounding tissue. Notably, the concentration of titanium particles increases significantly at peri-implantitis sites, suggesting titanium particles as a potential risk factor for the condition. Previous studies have indicated that titanium particles can induce peripheral osteolysis and foster the development of aseptic osteoarthritis in orthopedic joint replacement. However, it remains unconfirmed whether this phenomenon also triggers inflammation and bone resorption in peri-implant tissues. This review summarizes the distribution of titanium particles around the implant, the potential roles in peri-implantitis and the prevalent prevention strategies, which expects to provide new directions for the study of the pathogenesis and treatment of peri-implantitis.
Humans ; Peri-Implantitis/pathology* ; Titanium/pharmacology* ; Dental Implants/adverse effects* ; Osteolysis/pathology* ; Inflammation/chemically induced*