Accelerated Bone Regeneration on the Metal Surface through Controllable Surface Potential.

Surface potential is rarely investigated as an independent factor in influencing tissue regeneration on the metal surface. In this work, the surface potential on the titanium (Ti) surface was designed to be tailored and adjusted independently, which arises from the ferroelectricity and piezoelectricity of poled poly(vinylidene fluoride-trifluoroethylene) (PVTF). Notably, it is found that such controllable surface potential on the metal surface significantly promotes osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) in vitro as well as bone regeneration in vivo. In addition, the intracellular calcium ion (Ca2+) concentration measurement further proves that such controllable surface potential on the metal surface could activate the transmembrane calcium channels and allow the influx of extracellular Ca2+ into the cytoplasm. That might be the reason for improved osteogenic differentiation of BMSCs and bone regeneration. These findings reveal the potential of the metal surface with improved bioactivity for stimulation of osteogenesis and show great prospects for fabricable implantable medical devices with adjustable surface potential.

Polarized P(VDF-TrFE) film promotes skin wound healing through controllable surface potential.

Surface potential of biomaterials is found to be important for wound healing. Here, poly(vinylidenefluoride-co-trifluoroethylene) (P(VDF-TrFE)) films with different surface potentials and piezoelectric responses were prepared and explored for the effect of surface potential on wound healing. The crystalline state of P(VDF-TrFE) films were characterized with X-ray diffraction (XRD), differential scanning calorimetry (DSC) and Fourier-transformed infrared spectroscopy (FTIR), illustrated that the electric polarization will promote the crystallization of the ß phase of P(VDF-TrFE), in which the content of ß phase increased from 82.9 % to 86.8 % compared with the control. Then, Kelvin potential and piezoelectric coefficient d33 were to evaluate surface potential and polarization performance. Moreover, bovine serum albumin (BSA) adsorption and cell culture results showed that high surface potential can promote protein adsorption as well as fibroblast proliferation and macrophage polarization. Finally, in vivo experiments indicated that high voltage polarized P(VDF-TrFE) films can generate higher dynamic potential up to 2.3 V, and promoted wound healing from the phases of inflammation, proliferation and remodeling, the wound healing rate of which was 88.8 % ± 0.8 %, significantly higher than 79.1 % ± 2.5 % and 86.4 % ± 1.8 % of blank and control. In general, this work revealed that polarized P(VDF-TrFE) films can promote wound healing, shed light on designing wound healing materials with similar properties.

Identifying Depressed Essential Tremor Using Resting-State Voxel-Wise Global Brain Connectivity: A Multivariate Pattern Analysis.

Background and Objective: Although depression is one of the most common non-motor symptoms in essential tremor (ET), its pathogenesis and diagnosis biomarker are still unknown. Recently, machine learning multivariate pattern analysis (MVPA) combined with connectivity mapping of resting-state fMRI has provided a promising way to identify patients with depressed ET at the individual level and help to reveal the brain network pathogenesis of depression in patients with ET. Methods: Based on global brain connectivity (GBC) mapping from 41 depressed ET, 49 non-depressed ET, 45 primary depression, and 43 healthy controls (HCs), multiclass Gaussian process classification (GPC) and binary support vector machine (SVM) algorithms were used to identify patients with depressed ET from non-depressed ET, primary depression, and HCs, and the accuracy and permutation tests were used to assess the classification performance. Results: While the total accuracy (40.45%) of four-class GPC was poor, the four-class GPC could discriminate depressed ET from non-depressed ET, primary depression, and HCs with a sensitivity of 70.73% (P < 0.001). At the same time, the sensitivity of using binary SVM to discriminate depressed ET from non-depressed ET, primary depression, and HCs was 73.17, 80.49, and 75.61%, respectively (P < 0.001). The significant discriminative features were mainly located in cerebellar-motor-prefrontal cortex circuits (P < 0.001), and a further correlation analysis showed that the GBC values of significant discriminative features in the right middle prefrontal gyrus, bilateral cerebellum VI, and Crus 1 were correlated with clinical depression severity in patients with depressed ET. Conclusion: Our findings demonstrated that GBC mapping combined with machine learning MVPA could be used to identify patients with depressed ET, and the GBC changes in cerebellar-prefrontal cortex circuits not only posed as the significant discriminative features but also helped to understand the network pathogenesis underlying depression in patients with ET.

Altered local and matrix functional connectivity in depressed essential tremor patients.

BACKGROUND: Depression in essential tremor (ET) has been constantly studied and reported, while the associated brain activity changes remain unclear. Recently, regional homogeneity (ReHo), a voxel-wise local functional connectivity (FC) analysis of resting-state functional magnetic resonance imaging, has provided a promising way to observe spontaneous brain activity. METHODS: Local FC analyses were performed in forty-one depressed ET patients, 49 non-depressed ET patients and 43 healthy controls (HCs), and then matrix FC and clinical depression severity correlation analyses were further performed to reveal spontaneous neural activity changes in depressed ET patients. RESULTS: Compared with the non-depressed ET patients, the depressed ET patients showed decreased ReHo in the bilateral cerebellum lobules IX, and increased ReHo in the bilateral anterior cingulate cortices and middle prefrontal cortices. Twenty-five significant changes of ReHo clusters were observed in the depressed ET patients compared with the HCs, and matrix FC analysis further revealed that inter-ROI FC differences were also observed in the frontal-cerebellar-anterior cingulate cortex pathway. Correlation analyses showed that clinical depression severity was positively correlated with the inter-ROI FC values between the anterior cingulate cortex and bilateral middle prefrontal cortices and was negatively correlated with the inter-ROI FC values of the anterior cingulate cortex and bilateral cerebellum lobules IX. CONCLUSION: Our findings revealed local and inter-ROI FC differences in frontal-cerebellar-anterior cingulate cortex circuits in depressed ET patients, and among these regions, the cerebellum lobules IX, middle prefrontal cortices and anterior cingulate cortices could function as pathogenic structures underlying depression in ET patients.

Gr/TiO2 Films with Light-Controlled Positive/Negative Charge for Cell Harvesting Application.

Light-induced cell harvest shows much potential in in vitro cell culture. In this work, a light-responsive monolayer graphene (Gr)/titanium dioxide nanodot (TN) film is designed and used for light-induced cell harvest. It is found that after 20 min of 365 nm UV or 450 nm visible light illumination, different types of cells could be detached from the surface effectively. The highest cell detachment ratio reaches about 95%. The mechanism of such a cell detachment is contributed to light illumination generates charge accumulation, which, in turn, changes the conformation of the extracellular matrix protein molecules adsorbed to a more disordered state, and eventually leads to the cells detachment. Such UV and visible light responsive Gr/TiO2 film could be a good candidate for a surface with light-induced cell detachment property.

Cell-Sheet-Derived ECM Coatings and Their Effects on BMSCs Responses.

Extracellular matrix (ECM) provides a dynamic and complex environment to determine the fate of stem cells. In this work, light harvested cell sheets were treated with paraformaldehyde or ethanol, which eventually become ECM. Such ECM was then immobilized on titanium substrates via polydopamine chemistry. Their effects on bone marrow mesenchymal stromal cells (BMSCs) behaviors were investigated. It was found that paraformaldehyde-treated ECM coating (PT-ECM) showed a well-maintained microstructure, whereas that of ethanol-treated (ET-ECM) was completely changed. As a result, different amide structures and distributions of ECM components, such as laminin and collagen I, were exhibited. Alkaline phosphatase activity, osteocalcin secretion, related gene expression, and mineral deposition were evaluated for BMSCs cultured on both ECM coatings. PT-ECM was demonstrated to promote osteogenic differentiation much more efficiently than that of ET-ECM. That is ascribed to the preservation of native ECM milieu of PT-ECM. Such ECM acquirement and immobilization method could establish surfaces being able to direct stem cell responses on various materials. That shows promising potential in bone tissue engineering and other related biomedical applications.