Mussel-inspired cortical bone-adherent bioactive composite hydrogels promote bone augmentation through sequential regulation of endochondral ossification.

Endochondral ossification (ECO) plays an integral part in bone augmentation, which undergoes sequential processes including mesenchymal stem cells (MSC) condensation, chondrocyte differentiation, chondrocyte hypertrophy, and mineralized bone formation. Thus, accelerating these steps will speed up the osteogenesis process through ECO. Herein, inspired by the marine mussels' adhesive mechanism, a bioactive glass-dopamine (BG-Dopa) hydrogel was prepared by distributing the micro-nano BG to aldehyde modified hyaluronic acid with dopamine-modified gelatin. By in vitro and in vivo experiments, we confirm that after implanting in the bone augmentation position, the hydrogel can adhere to the cortical bone surface firmly without sliding. Moreover, the condensation and hypertrophy of stem cells were accelerated at the early stage of ECO. Whereafter, the osteogenic differentiation of the hypertrophic chondrocytes was promoted, which lead to accelerating the late stage of ECO process to achieve more bone augmentation. This experiment provides a new idea for the design of bone augmentation materials.

The role of titanium surface micromorphology in MG-63 cell motility during osteogenesis.

Different surface micromorphologies influence osteoblast movements and impact the osteogenesis around implants. In this study, a biomimetic chip that simulates the microenvironment of the implant and bone in vitro was developed (tissue-on-chip of group T and group C) to study the correlation of cell movement velocity (CMV), direction (CMD), acceleration (CMA), and cell attachment number (CA) with the surface micromorphology of the Titanium material. Computational fluid dynamics (CFD) was used for flow analysis. Changes in intraosseous pressure (IOP), local blood perfusion index (LBPI), new bone microstructure, microvessel density (MVD), and bone-implant contact (BIC) in beagle dogs were detected as implant surface alterations. Surface skewness (Ssk) and surface arithmetic mean height (Sa) were the most important negative factors for high CMV, accounting for 51% and 32%, respectively, of all the influencing factors. Higher Ssk (SskT > 0, SskC < 0) and Sa (SaT > SaC) resulted in lower CMV (CMVT:CMVC = 0.41:1), greater CA (CAT:CAC = 1.44:1), and higher BIC (BICT:BICC = 3.06:1) (P < 0.05). The surface micromorphology influenced the CMD of MG-63 cells within 20 µm from the material surface. However, it could not regulate the IOP, LBPI, MVD, new bone microstructure, or CMD (P > 0.05).

MiR-874-3p inhibits osteogenic differentiation of human periodontal ligament fibroblasts through regulating Wnt/ß-catenin pathway.

BACKGROUND/PURPOSE: Previous studies have shown that miR-874 is considered to be an important regulatory factor that participated in osteoclast differentiation. The role of miR-874-3p on osteoclast differentiation of human periodontal ligament fibroblast(hPDLF), however, is still unclear. This study was aimed to delve into the related molecular mechanism of miR-874-3p on hPDLF osteoclast differentiation. MATERIALS AND METHODS: The qRT-PCR assays were applied to check miR-874-3p and WNT3A expression levels during the osteoclast differentiation of hPDLF. Alkaline phosphatase (ALP) activity assays and alizarin red staining assays were applied to appraise the degree of hPDLF osteoclast differentiation. Bioinformatics method and dual-luciferase reporter assay were employed together to anticipate and certify the interaction between miR-874-3p and WNT3A. Western blot assay was applied to examine the ß-catenin and WNT3A expression in transfected hPDLF. RESULTS: In this study, the results indicated that the expression level of miR-874-3p was gradually down-regulated while WNT3A was concomitantly increased during osteogenic differentiation of hPDLF. Overexpression or knockdown of miR-874-3p would inhibit or promote WNT3A and ß-catenin protein expression as well as osteogenic differentiation of hPDLF, respectively. Further research indicated that miR-874-3p directly regulated WNT3A expression via coupling with the 3'-UTR of WNT3A. Finally, upregulation of WNT3A expression levels rescues ß-catenin expression levels and osteogenic differentiation of hPDLF inhibited by miR-874-3p was explored. CONCLUSION: MiR-874-3p inhibits osteogenic differentiation of hPDLF through regulating Wnt/ß-catenin pathway.

The Cleaning Effect of the Photocatalysis of TiO2-Bï¼ anatase Nanowires on Biological Activity on a Titanium Surface.

BACKGROUND: Improvements in the early osseointegration of titanium implants require investigations on the bone-implant interface, which is a critical and complex challenge. The surface cleanliness of titanium implants plays an important role at this interface. However, the implant surface would inevitably absorb contamination such as organic hydrocarbons, which is not conductive to the establishment of early osseointegration. Herein, an optimized approach for removing contamination from titanium surfaces was studied. METHODS: The TiO2-Bï¼ anatase NWs (nanowires) were prepared on titanium substrates through a hydrothermal process. A methylene blue degradation experiment was performed to assess the photodegradation activity. The cleaning effect of the photocatalysis of TiO2-Bï¼ anatase NWs on a titanium surface and the cellular early response was determined by analyzing cell morphology, attachment, proliferation and differentiation. RESULTS: The results indicated that the photocatalysis of TiO2-Bï¼ anatase NWs could effectively remove hydrocarbons on titanium surfaces without sacrificing the favourable titanium surface morphology. The methylene blue degradation experiment revealed that the photocatalysis of TiO2-Bï¼ anatase NWs had powerful degradation activity, which is attributed to the presence of strong oxidants such as ·OH. In addition, compared to the merely ultraviolet-treated titanium surfaces, the titanium surfaces treated after the NWs photocatalytic cleaning process markedly enhanced cellular early response. CONCLUSION: The photocatalysis of TiO2-Bï¼ anatase NWs for the removal of contamination from titanium surfaces has the potential to enable the rapid and complete establishment of early osseointegration.

A quantitative analysis of the potential biomarkers of non-small cell lung cancer by circulating cell-free DNA.

The study was conducted to ascertain whether the quantification of circulating cell-free DNA (cfDNA) in serum has value as a diagnostic or for monitoring the progression of non-small cell lung cancer (NSCLC). The serum/plasma cfDNA concentration was quantified by absolute qPCR of long interspersed nuclear element-1 (LINE1) in 60 NSCLC patients and 68 controls in good health. Receiver operating characteristic (ROC) curve analysis was performed to determine the diagnostic utility and cut-off levels of cfDNA, CEA, and CYFRA21-1 in NSCLC patients. Correlations between cfDNA and age, sex, tumour stage and progression-free survival (PFS) were analysed. A follow-up study was conducted on 4 NSCLC patients, and serum cfDNA, CEA, and CYFRA21-1 were quantified throughout disease progression. Serum cfDNA levels were significantly higher in NSCLC patients than those in normal controls. Elevated serum cfDNA concentration was also significantly associated with advanced tumour stage. Serum cfDNA had a ROC area under the curve comparable to that of CEA and CYFRA21-1 for the diagnosis of NSCLC, and the combined cfDNA/CEA/CYFRA21-1 indicator had the highest diagnostic efficiency. Moreover, increased serum cfDNA levels were strongly correlated with tumour progression and poor PFS. This study preliminarily confirmed that cfDNA can monitor disease progression in NSCLC patients, and the lead time was 1-7 months compared with clinical medical imaging. Serum cfDNA may be useful in monitoring NSCLC progression, suggesting that the non-invasive quantification of serum cfDNA by LINE1 qPCR is a viable option for predicting progression and disease severity when repeated invasive tissue biopsy is not possible.

Interrelationships among hydrogen permeation, physiochemical properties and early adsorption abilities of titanium.

This study aimed to investigate if the titanium samples with low hydrogen permeation which treated with a novel etching combination: phosphoric acid and sodium fluoride could influence the surface physiochemical properties and early adsorption ability. Titanium samples were treated with three different concentrations of the new formula, as groups A, B and C, and treated with the traditional etching formula, as group T. Zeta potential, contact angle, X-ray photoelectron spectroscopy (XPS) and fibronectin (FN)/vitronectin (VN) adsorption of Sprague-Dawley (SD) rat tibial osteotomies in the initial 30min and MG-63 adsorption in the initial 24 h were detected. Basing on the results of trails and pearson correlation analysis, the low hydrogen permeation into titanium didn't exert an impact on the surface morphology and surface stability. The adsorptions of F, P, S, acid hydroxyl and basic hydroxyl on the surfaces brought no bear on them as well. Surface concave depth and surface skewness showed highly positive correlation and moderate negative correlation with adsorption ability, respectively. Therefore, the surface morphology of titanium treated with the novel etching formula plays the only and primary role on the early adsorption. Because of its specific surface topography, group C showed the best performance which possessed slightly superiority than those of group B and group T, and with the lowest being group A. The low hydrogen permeation into titanium substrate was just benefit for improving the titanium mechanical properties, but not for the surface biochemical traits.

In vivo evaluation of a simvastatin-loaded nanostructured lipid carrier for bone tissue regeneration.

Alveolar bone loss has long been a challenge in clinical dental implant therapy. Simvastatin (SV) has been demonstrated to exert excellent anabolic effects on bone. However, the successful use of SV to increase bone formation in vivo largely depends on the local concentration of SV at the site of action, and there have been continuing efforts to develop an appropriate delivery system. Specifically, nanostructured lipid carrier (NLC) systems have become a popular type of encapsulation carrier system. Therefore, SV-loaded NLCs (SNs) (179.4 nm in diameter) were fabricated in this study, and the osteogenic effect of the SNs was evaluated in a critical-sized rabbit calvarial defect. Our results revealed that the SNs significantly enhanced bone formation in vivo, as evaluated by hematoxylin and eosin (HE) staining, immunohistochemistry, and a fluorescence analysis. Thus, this novel nanostructured carrier system could be a potential encapsulation carrier system for SV in bone regeneration applications.

[Short-term outcome of the acellular dermal matrix in dental implant surgical sites].

OBJECTIVE: To evaluate the clinical short-term results of the acellular dermal matrix for guided bone regeneration. METHODS: Sixty-four patients with bone defect in anterior maxillary area (average bone width: 3 mm) were included. Ridge-splitting technique with simultaneous placement of implants and artificial bone material implantation was performed in 21 patients (non-membrane group). Forty-three patients received the same procedure but with acellular dermal matrix covering the surgical sites (membrane group). The patients were followed up for three months and the new bone formation was checked in clinic and by X-ray. RESULTS: Three months after operation, the membrane group showed good osseointegration and high bone density over the implant cover screws. In the second operation, the membranes became thinner and the new bone fully covered the implant in the membrane group. The labial bone exhibited slight absorption and labial surface of 7 implants in 7 patients was exposed in non-membrane group. The width and the height of the ridge in the second operation were greater in membrane group than in non-membrane group (P < 0.05). CONCLUSIONS: The acellular dermal matrix can effectively resist the growth of soft tissue to allow bone regeneration around the implant.