Functionalization of Electrospun Polycaprolactone Scaffolds with Matrix-Binding Osteocyte-Derived Extracellular Vesicles Promotes Osteoblastic Differentiation and Mineralization.

Synthetic polymeric materials have demonstrated great promise for bone tissue engineering based on their compatibility with a wide array of scaffold-manufacturing techniques, but are limited in terms of the bioactivity when compared to naturally occurring materials. To enhance the regenerative properties of these materials, they are commonly functionalised with bioactive factors to guide growth within the developing tissue. Extracellular matrix vesicles (EVs) play an important role in facilitating endochondral ossification during long bone development and have recently emerged as important mediators of cell-cell communication coordinating bone regeneration, and thus represent an ideal target to enhance the regenerative properties of synthetic scaffolds. Therefore, in this paper we developed tools and protocols to enable the attachment of MLO-Y4 osteocyte-derived EVs onto electrospun polycaprolactone (PCL) scaffolds for bone repair. Initially, we optimize a method for the functionalization of PCL materials with collagen type-1 and fibronectin, inspired by the behaviour of matrix vesicles during endochondral ossification, and demonstrate that this is an effective method for the adhesion of EVs to the material surface. We then used this functionalization process to attach osteogenic EVs, collected from mechanically stimulated MLO-Y4 osteocytes, to collagen-coated electrospun PCL scaffolds. The EV-functionalized scaffold promoted osteogenic differentiation (measured by increased ALP activity) and mineralization of the matrix. In particular, EV-functionalised scaffolds exhibited significant increases in matrix mineralization particularly at earlier time points compared to uncoated and collagen-coated controls. This approach to matrix-based adhesion of EVs provides a mechanism for incorporating vesicle signalling into polyester scaffolds and demonstrates the potential of osteocyte derived EVs to enhance the rate of bone tissue regeneration.

Circ-E2F3 acts as a ceRNA for miR-204-5p to promote proliferation, metastasis and apoptosis inhibition in retinoblastoma by regulating ROCK1 expression.

BACKGROUND: Circular RNA (circRNA) plays an important role in the malignant progression of many tumors, including retinoblastoma (RB). However, the role and regulatory mechanism of circ-E2F3 in RB have not been fully elucidated. METHODS: Quantitative real-time PCR was used to measure circ-E2F3, miR-204-5p and Rho-associated protein kinase 1 (ROCK1) expression. Cell proliferation, apoptosis and metastasis were monitored by MTT, colony formation, flow cytometry, transwell and wound healing assays. Dual-luciferase reporter assay was employed to verify the relationship between miR-204-5p and circ-E2F3 or ROCK1. ROCK1 protein expression was detected by western blot assay. Mice xenograft models were built to assess the role of circ-E2F3 on RB tumor growth. RESULTS: Circ-E2F3 was upregulated in RB tissues and cells. Silencing of circ-E2F3 inhibited the proliferation, migration, invasion, and induced the apoptosis of RB cells in vitro, as well as reduced RB tumor growth in vivo. MiR-204-5p could be sponged by circ-E2F3, and its inhibitor reversed the suppressive effect of circ-E2F3 silencing on RB progression. In addition, ROCK1 was confirmed to interact with miR-204-5p. MiR-204-5p regulated RB progression by targeting ROCK1. Also, circ-E2F3 positively regulated ROCK1 expression by sponging miR-204-5p. CONCLUSION: Circ-E2F3 functioned as a tumor promoter in RB through the miR-204-5p/ROCK1 axis.

Effects of e-cigarette on retinal histology and ultrastructure in mice / 国际眼科杂志(Guoji Yanke Zazhi)

@#AIM: To study the histological and ultrastructural changes of mouse retina after exposure to e-cigarette and the potential mechanism.<p>METHODS: Totally 18 male c57BL mice aged 8-week-old were divided into control group(<i>n</i>=6), 0mg nicotine group(<i>n</i>=6)and 12mg nicotine group(<i>n</i>=6). The histological and ultrastructural changes of retina were evaluated by hematoxylin and eosin(HE)staining and transmission electron microscope(TEM), respectively. Additionally, the expression of Tuj1 and 8-OHdG was examined using immunofluorescent staining. <p>RESULTS: In comparison with control group, the thickness of whole retina, nerve fiber layer(NFL)and inner plexiform layer(IPL)was significantly decreased in experimental groups(0mg and 12mg nicotine group)(<i>P</i><0.01), but no significant difference was observed between 0mg and 12mg nicotine group(<i>P</i>>0.05). The dramatically reduced microvilli of RPE cells were also observed in experimental groups using TEM. Furthermore, residual microvilli were shortened. The expression of Tuj1 was decreased in ganglion cell layer(GCL), NFL and IPL, but no significant changes in the number of retinal ganglion cells were shown among three groups(<i>P</i>>0.05). In addition, the increased expression of 8-OHdG was observed in GCL and inner nuclear layer(INL)in experimental groups.<p>CONCLUSION: E-cigarette can lead to the retinal damages in mice, which might be due to oxidative stress.

Human bone marrow stem/stromal cell osteogenesis is regulated via mechanically activated osteocyte-derived extracellular vesicles.

Bone formation or regeneration requires the recruitment, proliferation, and osteogenic differentiation of stem/stromal progenitor cells. A potent stimulus driving this process is mechanical loading. Osteocytes are mechanosensitive cells that play fundamental roles in coordinating loading-induced bone formation via the secretion of paracrine factors. However, the exact mechanisms by which osteocytes relay mechanical signals to these progenitor cells are poorly understood. Therefore, this study aimed to demonstrate the potency of the mechanically stimulated osteocyte secretome in driving human bone marrow stem/stromal cell (hMSC) recruitment and differentiation, and characterize the secretome to identify potential factors regulating stem cell behavior and bone mechanobiology. We demonstrate that osteocytes subjected to fluid shear secrete a distinct collection of factors that significantly enhance hMSC recruitment and osteogenesis and demonstrate the key role of extracellular vesicles (EVs) in driving these effects. This demonstrates the pro-osteogenic potential of osteocyte-derived mechanically activated extracellular vesicles, which have great potential as a cell-free therapy to enhance bone regeneration and repair in diseases such as osteoporosis.

Experimental Realization of an Extreme-Parameter Omnidirectional Cloak.

An ideal transformation-based omnidirectional cloak always relies on metamaterials with extreme parameters, which were previously thought to be too difficult to realize. For such a reason, in previous experimental proposals of invisibility cloaks, the extreme parameters requirements are usually abandoned, leading to inherent scattering. Here, we report on the first experimental demonstration of an omnidirectional cloak that satisfies the extreme parameters requirement, which can hide objects in a homogenous background. Instead of using resonant metamaterials that usually involve unavoidable absorptive loss, the extreme parameters are achieved using a nonresonant metamaterial comprising arrays of subwavelength metallic channels manufactured with 3D metal printing technology. A high level transmission of electromagnetic wave propagating through the present omnidirectional cloak, as well as significant reduction of scattering field, is demonstrated both numerically and experimentally. Our work may also inspire experimental realizations of the other full-parameter omnidirectional optical devices such as concentrator, rotators, and optical illusion apparatuses.

Merging organoid and organ-on-a-chip technology to generate complex multi-layer tissue models in a human retina-on-a-chip platform.

The devastating effects and incurable nature of hereditary and sporadic retinal diseases such as Stargardt disease, age-related macular degeneration or retinitis pigmentosa urgently require the development of new therapeutic strategies. Additionally, a high prevalence of retinal toxicities is becoming more and more an issue of novel targeted therapeutic agents. Ophthalmologic drug development, to date, largely relies on animal models, which often do not provide results that are translatable to human patients. Hence, the establishment of sophisticated human tissue-based in vitro models is of upmost importance. The discovery of self-forming retinal organoids (ROs) derived from human embryonic stem cells (hESCs) or human induced pluripotent stem cells (hiPSCs) is a promising approach to model the complex stratified retinal tissue. Yet, ROs lack vascularization and cannot recapitulate the important physiological interactions of matured photoreceptors and the retinal pigment epithelium (RPE). In this study, we present the retina-on-a-chip (RoC), a novel microphysiological model of the human retina integrating more than seven different essential retinal cell types derived from hiPSCs. It provides vasculature-like perfusion and enables, for the first time, the recapitulation of the interaction of mature photoreceptor segments with RPE in vitro. We show that this interaction enhances the formation of outer segment-like structures and the establishment of in vivo-like physiological processes such as outer segment phagocytosis and calcium dynamics. In addition, we demonstrate the applicability of the RoC for drug testing, by reproducing the retinopathic side-effects of the anti-malaria drug chloroquine and the antibiotic gentamicin. The developed hiPSC-based RoC has the potential to promote drug development and provide new insights into the underlying pathology of retinal diseases.

Phase-Modulated Scattering Manipulation for Exterior Cloaking in Metal-Dielectric Hybrid Metamaterials.

Artificially structured metamaterials with metallic or dielectric inclusions are extensively studied for exotic light manipulations via controlling the local-resonant modes in the microstructures. The coupling between these resonant modes has drawn growing interest in recent years due to the advanced functional metamaterial making the microstructures more and more complex. Here, the suppression of magnetic resonance of a dielectric cuboid, an analogue to the scattering cancellation effect or radiation control system, realized with an exterior cloaking in a hybrid metamaterial system, is demonstrated. Furthermore, the significant modulation of the absorption of the dielectric resonator in the hybrid metamaterial is also demonstrated. The physical insight of the experimental results is well illuminated with a classical double-harmonic-oscillator model, from which it is revealed that the complex coupling, i.e., the phase of coupling coefficient, plays a crucial role in the overall response of the metal-dielectric hybrid system. The proposed design strategy is anticipated to form a more straightforward and efficient paradigm for practical applications based on radiation control via versatile mode couplings.

Nonlinearity in the Dark: Broadband Terahertz Generation with Extremely High Efficiency.

Plasmonic metamaterials and metasurfaces offer new opportunities in developing high performance terahertz emitters and detectors beyond the limitations of conventional nonlinear materials. However, simple meta-atoms for second-order nonlinear applications encounter fundamental trade-offs in the necessary symmetry breaking and local-field enhancement due to radiation damping that is inherent to the operating resonant mode and cannot be controlled separately. Here we present a novel concept that eliminates this restriction obstructing the improvement of terahertz generation efficiency in nonlinear metasurfaces based on metallic nanoresonators. This is achieved by combining a resonant dark-state metasurface, which locally drives nonlinear nanoresonators in the near field, with a specific spatial symmetry that enables destructive interference of the radiating linear moments of the nanoresonators, and perfect absorption via simultaneous electric and magnetic critical coupling of the pump radiation to the dark mode. Our proposal allows eliminating linear radiation damping, while maintaining constructive interference and effective radiation of the nonlinear components. We numerically demonstrate a giant second-order nonlinear susceptibility ∼10^{-11} m/V, a one order improvement compared with the previously reported split-ring-resonator metasurface, and correspondingly, a 2 orders of magnitude enhanced terahertz energy extraction should be expected with our configuration under the same conditions. Our study offers a paradigm of high efficiency tunable nonlinear metadevices and paves the way to revolutionary terahertz technologies and optoelectronic nanocircuitry.

Controlling optical polarization conversion with Ge2Sb2Te5-based phase-change dielectric metamaterials.

Recent progress in the metamaterial-based polarization manipulation of light highlights the promise of novel polarization-dependent optical components and systems. To overcome the limited frequency bandwidth of metamaterials resulting from their resonant nature, it is desirable to incorporate tunability into metamaterial-based polarization manipulations. Here, we propose a dielectric metamaterial for controlling linear polarization conversion using the phase-change characteristic of Ge2Sb2Te5 (GST), whose refractive index changes significantly when transforming from the amorphous phase to the crystalline phase under external stimuli. The polarization conversion phenomena are systematically studied using different arrangements of GST in this metamaterial. The performance of linear polarization conversion and the tunability are also analyzed and compared in three different designs. It is found that phase-change materials such as GST can be employed in dielectric materials for tunable and switchable linear polarization conversion in the telecom band. The conversion efficiency can be significantly modulated during the phase transition. Our results provide useful insights for incorporating phase-change materials with metamaterials for tunable polarization manipulation.

Electroconductive Biohybrid Collagen/Pristine Graphene Composite Biomaterials with Enhanced Biological Activity.

Electroconductive substrates are emerging as promising functional materials for biomedical applications. Here, the development of biohybrids of collagen and pristine graphene that effectively harness both the biofunctionality of the protein component and the increased stiffness and enhanced electrical conductivity (matching native cardiac tissue) obtainable with pristine graphene is reported. As well as improving substrate physical properties, the addition of pristine graphene also enhances human cardiac fibroblast growth while simultaneously inhibiting bacterial attachment (Staphylococcus aureus). When embryonic-stem-cell-derived cardiomyocytes (ESC-CMs) are cultured on the substrates, biohybrids containing 32 wt% graphene significantly increase metabolic activity and cross-striated sarcomeric structures, indicative of the improved substrate suitability. By then applying electrical stimulation to these conductive biohybrid substrates, an enhancement of the alignment and maturation of the ESC-CMs is achieved. While this in vitro work has clearly shown the potential of these materials to be translated for cardiac applications, it is proposed that these graphene-based biohybrid platforms have potential for a myriad of other applications-particularly in electrically sensitive tissues, such as neural and neural and musculoskeletal tissues.

A flow bioreactor system compatible with real-time two-photon fluorescence lifetime imaging microscopy.

Bioreactors are essential cell and tissue culture tools that allow the introduction of biophysical signals into in vitro cultures. One major limitation is the need to interrupt experiments and sacrifice samples at certain time points for analyses. To address this issue, we designed a bioreactor that combines high-resolution contact-free imaging and continuous flow in a closed system that is compatible with various types of microscopes. The high throughput fluid flow bioreactor was combined with two-photon fluorescence lifetime imaging microscopy (2P-FLIM) and validated. The hydrodynamics of the bioreactor chamber were characterized using COMSOL. The simulation of shear stress indicated that the bioreactor system provides homogeneous and reproducible flow conditions. The designed bioreactor was used to investigate the effects of low shear stress on human umbilical vein endothelial cells (HUVECs). In a scratch assay, we observed decreased migration of HUVECs under shear stress conditions. Furthermore, metabolic activity shifts from glycolysis to oxidative phosphorylation-dependent mechanisms in HUVECs cultured under low shear stress conditions were detected using 2P-FLIM. Future applications for this bioreactor range from observing cell fate development in real-time to monitoring the environmental effects on cells or metabolic changes due to drug applications.

Freeze-Drying as a Novel Biofabrication Method for Achieving a Controlled Microarchitecture within Large, Complex Natural Biomaterial Scaffolds.

The biofabrication of large natural biomaterial scaffolds into complex 3D shapes which have a controlled microarchitecture remains a major challenge. Freeze-drying (or lyophilization) is a technique used to generate scaffolds in planar 3D geometries. Here we report the development of a new biofabrication process to form a collagen-based scaffold into a large, complex geometry which has a large height to width ratio, and a controlled porous microarchitecture. This biofabrication process is validated through the successful development of a heart valve shaped scaffold, fabricated from a collagen-glycosaminoglycan co-polymer. Notably, despite the significant challenges in using freeze-drying to create such a structure, the resultant scaffold has a uniform, homogenous pore architecture throughout. This is achieved through optimization of the freeze-drying mold and the freezing parameters. We believe this to be the first demonstration of using freeze-drying to create a large, complex scaffold geometry with a controlled, porous architecture for natural biomaterials. This study validates the potential of using freeze-drying for development of organ-specific scaffold geometries for tissue engineering applications, which up until now might not have been considered feasible.

Steps toward Maturation of Embryonic Stem Cell-Derived Cardiomyocytes by Defined Physical Signals.

Cardiovascular disease remains a leading cause of mortality and morbidity worldwide. Embryonic stem cell-derived cardiomyocytes (ESC-CMs) may offer significant advances in creating in vitro cardiac tissues for disease modeling, drug testing, and elucidating developmental processes; however, the induction of ESCs to a more adult-like CM phenotype remains challenging. In this study, we developed a bioreactor system to employ pulsatile flow (1.48 mL/min), cyclic strain (5%), and extended culture time to improve the maturation of murine and human ESC-CMs. Dynamically-cultured ESC-CMs showed an increased expression of cardiac-associated proteins and genes, cardiac ion channel genes, as well as increased SERCA activity and a Raman fingerprint with the presence of maturation-associated peaks similar to primary CMs. We present a bioreactor platform that can serve as a foundation for the development of human-based cardiac in vitro models to verify drug candidates, and facilitates the study of cardiovascular development and disease.

Enhanced elastin synthesis and maturation in human vascular smooth muscle tissue derived from induced-pluripotent stem cells.

Obtaining vascular smooth muscle tissue with mature, functional elastic fibers is a key obstacle in tissue-engineered blood vessels. Poor elastin secretion and organization leads to a loss of specialization in contractile smooth muscle cells, resulting in over proliferation and graft failure. In this study, human induced-pluripotent stem cells (hiPSCs) were differentiated into early smooth muscle cells, seeded onto a hybrid poly(ethylene glycol) dimethacrylate/poly (l-lactide) (PEGdma-PLA) scaffold and cultured in a bioreactor while exposed to pulsatile flow, towards maturation into contractile smooth muscle tissue. We evaluated the effects of pulsatile flow on cellular organization as well as elastin expression and assembly in the engineered tissue compared to a static control through immunohistochemistry, gene expression and functionality assays. We show that culturing under pulsatile flow resulted in organized and functional hiPSC derived smooth muscle tissue. Immunohistochemistry analysis revealed hiPSC-smooth muscle tissue with robust, well-organized cells and elastic fibers and the supporting microfibril proteins necessary for elastic fiber assembly. Through qRT-PCR analysis, we found significantly increased expression of elastin, fibronectin, and collagen I, indicating the synthesis of necessary extracellular matrix components. Functionality assays revealed that hiPSC-smooth muscle tissue cultured in the bioreactor had an increased calcium signaling and contraction in response to a cholinergic agonist, significantly higher mature elastin content and improved mechanical properties in comparison to the static control. The findings presented here detail an effective approach to engineering elastic human vascular smooth muscle tissue with the functionality necessary for tissue engineering and regenerative medicine applications. STATEMENT OF SIGNIFICANCE: Obtaining robust, mature elastic fibers is a key obstacle in tissue-engineered blood vessels. Human induced-pluripotent stem cells have become of interest due to their ability to supplement tissue engineered scaffolds. Their ability to differentiate into cells of vascular lineages with defined phenotypes serves as a potential solution to a major cause of graft failure in which phenotypic shifts in smooth muscle cells lead to over proliferation and occlusion of the graft. Herein, we have differentiated human induced-pluripotent stem cells in a pulsatile flow bioreactor, resulting in vascular smooth muscle tissue with robust elastic fibers and enhanced functionality. This study highlights an effective approach to engineering elastic functional vascular smooth muscle tissue for tissue engineering and regenerative medicine applications.

Non-invasive Chamber-Specific Identification of Cardiomyocytes in Differentiating Pluripotent Stem Cells.

One major obstacle to the application of stem cell-derived cardiomyocytes (CMs) for disease modeling and clinical therapies is the inability to identify the developmental stage of these cells without the need for genetic manipulation or utilization of exogenous markers. In this study, we demonstrate that Raman microspectroscopy can non-invasively identify embryonic stem cell (ESC)-derived chamber-specific CMs and monitor cell maturation. Using this marker-free approach, Raman peaks were identified for atrial and ventricular CMs, ESCs were successfully discriminated from their cardiac derivatives, a distinct phenotypic spectrum for ESC-derived CMs was confirmed, and unique spectral differences between fetal versus adult CMs were detected. The real-time identification and characterization of CMs, their progenitors, and subpopulations by Raman microspectroscopy strongly correlated to the phenotypical features of these cells. Due to its high molecular resolution, Raman microspectroscopy offers distinct analytical characterization for differentiating cardiovascular cell populations.

Tailorable Zero-Phase Delay of Subwavelength Particles toward Miniaturized Wave Manipulation Devices.

Adjustable zero-phase delay and equiphase control are demonstrated in single and multilayer dielectric particle arrays with high index and low loss. The polarization-independent near-zero permeability is the origin of the wave control near the first Mie magnetic resonance. The proposed design paves the way for subwavelength devices and opens up new avenues for the miniaturization and integration of THz and optical components.

Engineering of a bio-functionalized hybrid off-the-shelf heart valve.

Currently available heart valve replacements are limited in long-term performance or fail due to leaflet thickening, lack of growth or remodeling potential. In order to address these issues, it is necessary to mimic multiple factors of the native valvular extracellular matrix (ECM) such as architecture, mechanical behavior and biochemical signals. Here, we successfully generated an electrospun PEGdma-PLA scaffold adapted to the structure and mechanical properties of native valve leaflets. Valvular interstitial cells (VICs) and valvular endothelial cells (VECs) were seeded on the scaffold and when cultured under physiological conditions in a bioreactor, the construct performed like a native leaflet. Atomic force microscopy (AFM) was employed to obtain detailed mechanical information from the leaflets, which enabled the first layer-specific measurement of the Young's modulus. Interestingly, spongiosa stiffness was much lower compared to the fibrosa and ventricularis. Moreover, investigations into human fetal heart valve development identified collagen type I and versican as important structural proteins. As a proof of principle, these proteins were introduced to the scaffold, demonstrating the ability to bio-functionalize the hybrid valve based on natures' blueprint.

A case-control study on risk factors of breast cancer in China.

INTRODUCTION: To screen the risk factors associated with breast cancer among Chinese women in order to evaluate the individual risk of developing breast cancer among women in China. MATERIAL AND METHODS: A case-control study on 416 breast cancer patients and 1156 matched controls was conducted in 14 hospitals in 8 provinces of China in 2008. Controls were age- and region-matched to the cases. Clinicians conducted in-person interviews with the subjects to collect information on demographics and suspected risk factors for breast cancer that are known worldwide. Conditional logistic regression was used to derive odds ratios (OR) and 95% confidence intervals (CI) for the associations between risk factors and breast cancer. RESULTS: Compared with matched controls, women with breast cancer were significantly more likely to have higher body mass index (BMI, OR = 4.07, 95% CI: 2.98-5.55), history of benign breast disease (BBD) biopsy (OR = 1.68, 95% CI: 1.19-2.38), older age of menarche (AOM) (OR = 1.41, 95% CI: 1.07-1.87), stress anticipation (SA), for grade 1-4, OR = 2.15, 95% CI: 1.26-3.66; for grade 5-9, OR = 3.48, 95% CI: 2.03-5.95) and menopause (OR = 2.22, 95% CI: 1.50-3.282) at the level of p < 0.05. Family history of breast cancer (FHBC) in first-degree relatives (OR = 1.66, 95% CI: 0.77-3.59) and use of oral contraceptives (OC) (OR = 1.59, 95% CI: 0.83-3.05) were associated with an increased risk of breast cancer at the level of p < 0.20. CONCLUSIONS: Our results showed that BMI, history of BBD biopsy, older AOM, SA and menopause were associated with increased risk of breast cancer among Chinese women. The findings derived from the study provided some suggestions for population-based prevention and control of breast cancer in China.

Connective tissue growth factor, a regulator related with 10-hydroxy-2-decenoic acid down-regulate MMPs in rheumatoid arthritis.

10-hydroxy-2-decenoic acid (10H2DA) is suggested to be a potential medication for rheumatoid arthritis (RA) by activation of matrix metalloproteinases (MMPs) via mitogen-activated protein kinase signaling pathways. The aim of the present work was to seek differentially expressed proteins in rheumatoid arthritis synovial fibroblasts (RASFs) treated with 10H2DA by comparative proteomics analysis. Two-dimensional electrophoresis (2-DE) and LC-MS/MS were performed to identify changes in protein expression after 24-h 10H2DA treatment. Differentially expressed proteins were identified by real-time PCR and Western blot analysis. Influence of down-regulation of connective tissue growth factor (CTGF) expression on MMPs was studied by RNAi. Ten proteins were up-regulated and 9 proteins were down-regulated after 24-h 10H2DA treatment. A total of 19 differentially expressed proteins were identified and found to be associated with glycolysis, lipid metabolism, cell adhesion, ATP synthesis, oxidation reduction, and anti-apoptosis. CTGF, a member of the C-terminal cystein-rich proteins (CCN) family, was down-regulated after 24-h 10H2DA treatment. MMPs were down-regulated after RNAi (CTGFi). These results suggest that CTGF is a regulator factor in the expression of MMPs, and 10H2DA down-regulate the concentration of MMPs probably by down-regulating the expression of CTGF.

Optically implemented broadband blueshift switch in the terahertz regime.

We experimentally demonstrate, for the first time, an optically implemented blueshift tunable metamaterial in the terahertz (THz) regime. The design implies two potential resonance states, and the photoconductive semiconductor (silicon) settled in the critical region plays the role of intermediary for switching the resonator from mode 1 to mode 2. The observed tuning range of the fabricated device is as high as 26% (from 0.76 THz to 0.96 THz) through optical control to silicon. The realization of broadband blueshift tunable metamaterial offers opportunities for achieving switchable metamaterials with simultaneous redshift and blueshift tunability and cascade tunable devices. Our experimental approach is compatible with semiconductor technologies and can be used for other applications in the THz regime.