Improved Biocompatibility and Angiogenesis of the Bone Titanium Scaffold through ERK1/2 Signaling Mediated by an Attached Strontium Element.

The promotion of early osseointegration is crucial for the success of biomedical titanium implants. Physical and chemical modifications to the material surface can significantly compensate for the lack of biocompatibility and early osseointegration of the implant. In this study, we implanted strontium onto titanium plates and analyzed the effect of strontium-doped materials on angiogenesis and biocompatibility in the human bone structure. Our findings demonstrated that strontium-loaded titanium sheet materials effectively promote human umbilical vein endothelial cell (HUVEC) biocompatibility and vascular differentiation ability, as evidenced by proliferation-apoptosis assays, RT-qPCR for vascular neogenesis markers, ELISA for vascular endothelial growth factor (VEGF) levels, and nitric oxide (NO) analysis. Mechanism studies based on RNAseq and Western blotting analysis revealed that strontium can promote titanium material biocompatibility with HUVEC cells and vascular neovascularization ability by activating the extracellular signal-regulated kinase 1/2 (ERK1/2) signaling pathway. Meanwhile, blocking the ERK1/2 signaling pathway could reverse the promotional effect of vascular formation. Overall, we have successfully fabricated a multifunctional biocompatible bone implant with better histocompatibility and angiogenesis compared to uncoated implants.

Castleman's disease with submaxillary lymphadenectasis as the main manifestation: a case report.

Castleman's disease is a lymphoproliferative disease that is rare and hard to diagnose. As a result of untypical manifestations, missed diagnosis and misdiagnosis of Castleman's disease are common in clinical practice. In this paper, we report one patient with clinical manifestations of painless submaxillary lymphadenectasis. The patient was finally diagnosed with Castleman's disease by clinical, laboratory, and pathological examinations. This report may promote the understanding and diagnosis of Castleman's disease for clinicians.

Superior CKIP-1 sensitivity of orofacial bone-derived mesenchymal stem cells in proliferation and osteogenic differentiation compared to long bone-derived mesenchymal stem cells.

Maxillofacial bone defects caused by multiple factors, including congenital deformations and tumors, have become a research focus in the field of oral medicine. Bone tissue engineering is increasingly regarded as a potential approach for maxillofacial bone repair. Mesenchymal stem cells (MSCs) with different origins display various biological characteristics. The aim of the present study was to investigate the effects of casein kinase­2 interaction protein­1 (CKIP­1) on MSCs, including femoral bone marrow­derived MSCs (BMMSCs) and orofacial bone­derived MSCs (OMSCs), isolated from the femoral and orofacial bones of wild­type (WT) and CKIP­1 knockout (KO) mice. MSCs were isolated using collagenase II and the main biological characteristics, including proliferation, apoptosis and osteogenic differentiation, were investigated. Subcutaneous transplantation of MSCs in mice was also performed to assess ectopic bone formation. MTT and clone formation assay results indicated that cell proliferation in the KO group was increased compared with the WT group, and OMSCs exhibited significantly increased levels of proliferation compared with BMMSCs. However, the proportion of apoptotic cells was not significantly different between CKIP­1 KO OMSCs and BMMSCs. Furthermore, it was revealed that osteogenic differentiation was increased in CKIP­1 KO MSCs compared with WT MSCs, particularly in OMSCs. Consistent with the in vitro results, enhanced ectopic bone formation was observed in CKIP­1 KO mice compared with WT mice, particularly in OMSCs compared with BMMSCs. In conclusion, the present results indicated that OMSCs may have a superior sensitivity to CKIP­1 in promoting osteogenesis compared with BMMSCs; therefore, CKIP­1 KO in OMSCs may serve as an efficient strategy for maxillofacial bone repair.

Nomograms forecasting long-term overall and cancer-specific survival of patients with oral squamous cell carcinoma.

Our aim was to establish a "nomogram" model to forecast the overall survival (OS) and cancer-specific survival (CSS) of oral squamous cell carcinoma (OSCC) patients. The clinicopathological data for the 10,533 OSCC patients were collected from the Surveillance, Epidemiology and End Results (SEER) database. We used a credible random split-sample method to divide 10,533 patients into two cohorts: 7046 patients in the modeling cohort and 3487 patients in the external validation cohort (split-ratio = 2:1). The median follow-up period was 32 months (1-119 months). We developed nomograms to predict 5- and 8-year OS and CSS of OSCC patients with a Cox proportional hazards model. The precision of the nomograms was assessed by the concordance index (C-index) and calibration curves through internal and external validation. The C-indexes of internal validation regarding 5- and 8-year OS and CSS were 0.762 and 0.783, respectively. In addition, the external validation's C-indexes were 0.772 and 0.800. Based on a large-sample analysis targeting the SEER database, we established two nomograms to predict long-term OS and CSS for OSCC patients successfully, which can assist surgeons in developing a more effective therapeutic regimen and conducting personalized prognostic evaluations.

Osteogenic activity of titanium surfaces with hierarchical micro-/nano-structures obtained by hydrofluoric acid treatment.

An easier method for constructing the hierarchical micro-/nano-structures on the surface of dental implants in the clinic is needed. In this study, three different titanium surfaces with microscale grooves (width 0.5-1, 1-1.5, and 1.5-2 µm) and nanoscale nanoparticles (diameter 20-30, 30-50, and 50-100 nm, respectively) were obtained by treatment with different concentrations of hydrofluoric acid (HF) and at different etching times (1%, 3 min; 0.5%, 12 min; and 1.5%, 12 min, respectively; denoted as groups HF1, HF2, and HF3). The biological response to the three different titanium surfaces was evaluated by in vitro human bone marrow-derived mesenchymal stem cell (hBMMSC) experiments and in vivo animal experiments. The results showed that cell adhesion, proliferation, alkaline phosphatase activity, and mineralization of hBMMSCs were increased in the HF3 group. After the different surface implants were inserted into the distal femurs of 40 rats, the bone-implant contact in groups HF1, HF2, and HF3 was 33.17%±2.2%, 33.82%±3.42%, and 41.04%±3.08%, respectively. Moreover, the maximal pullout force in groups HF1, HF2, and HF3 was 57.92±2.88, 57.83±4.09, and 67.44±6.14 N, respectively. The results showed that group HF3 with large micron grooves (1.5-2.0 µm) and large nanoparticles (50-100 nm) showed the best bio-functionality for the hBMMSC response and osseointegration in animal experiments compared with other groups.

Effects of different hierarchical hybrid micro/nanostructure surfaces on implant osseointegration.

BACKGROUND: Hierarchical hybrid micro/nanostructure implant surfaces are considered to better mimic the hierarchical structure of bone and the nanostructures substantively influence osseointegration through managing cell behaviors. PURPOSE: To enhance implant osseointegration for further clinical application, we evaluated the material properties and osseointegration effects of hierarchical surfaces with different nano-morphologies, using a rat model. MATERIALS AND METHODS: Two representative surface fabrication methods, hydrofluoric (HF) acid etching combined with anodization (HF + AN) or magnetron sputtering (HF + MS), were selected. Sample material properties were evaluated by scanning electron microscopy, atomic force microscopy, X-ray diffraction, X-ray photoemission spectroscopy, and epoxy resin docking tensile test. Implants with different surfaces were inserted into the distal femurs of rats. After 12 weeks, osseointegration was examined by microcomputed tomography (micro-CT), histological, and biomechanical tests. RESULTS: Tensile testing demonstrated high bonding strength at coating/implant in the HF + MS group. Micro-CT revealed increased bone volume/total volume and significantly reduced trabecular separation in HF + MS versus other groups. Histological analysis showed significantly higher HF + MS bone-to-implant contact (74.78 ± 4.40%) versus HF + AN (65.11 ± 5.10%) and machined samples (56.03 ± 3.23%). The maximal HF + MS pull-out force increased by 33.7% versus HF + AN. CONCLUSIONS: These results indicated that HF + MS surfaces exhibited superior material property in terms of bonding strength and favorable implant osseointegration compared to other groups.

The Effect of Hierarchical Micro/Nanotextured Titanium Implants on Osseointegration Immediately After Tooth Extraction in Beagle Dogs.

BACKGROUND: Owing to simplify the operation and shorten the overall duration of treatment, immediate implantation earned much satisfactory from patients and dentists. The results of immediate implantation determined by osseointegration, we fabricated a micro/nanotextured titanium implants to improve osseointegration immediately after tooth extraction. PURPOSE: The aim of this study was to investigate the effect of hierarchical micro/nanotextured titanium implant on osseointegration immediately after tooth extraction. MATERIAL AND METHODS: The micro/nanotextured titanium implants were fabricated by etching with 0.5 wt% hydrofluoric (HF) acid followed by anodization in HF electrolytes. Implants with a machined surface as well as implants a microtextured surface prepared by 0.5 wt% HF etching served as control groups. The machined, microtextured, and micro/nanotextured implants were inserted into fresh sockets immediately after tooth extraction in beagle dogs. Twelve weeks after implantation, the animals were sacrificed for micro-CT scanning, histological analysis and biomechanical test. RESULTS: The micro-CT imaging revealed that the bone volume/total volume (BV/TV) and trabecular thickness (Tb.Th) in the micro/nanotextured group was significantly higher than that in the machined group and microtextured group, and the trabecular separation (Tb.Sp) in the micro/nanotextured group was significantly lower than that in the other groups. For the histological analysis, the bone-to-implant contact in the machined, micro and micro/nanotextured groups were 47.13 ± 6.2%, 54.29 ± 4.18%, and 63.38 ± 7.63%, respectively, and the differences significant. The maximum pull-out force in the machined, micro, and micro/nanotextured groups were 216.58 ± 38.71 N, 259.42 ± 28.93 N, and 284.73 ± 47.09 N, respectively. CONCLUSIONS: The results indicated that implants with a hierarchical micro/nanotextured can promote osseointegration immediately after tooth extraction.