The surgical procedure was performed in accordance with the protocol approved by the Animal Care and Use Committee, National Tsing Hua University, Hsinchu, Taiwan. The GelMA MBs were immersed in PBS for full swelling. C57BL/6 mice (Female, 7 weeks) were divided into four groups ( n = 6): (1) phosphate buffered saline (PBS), (2) MBs, (3) CMH, and (4) CMH + HFMF groups. An electric drill was first used to drill a hole on the skull when applying TBI to mice. Afterwards, a punch with 2 mm in diameter was adopted to give a 1.5 mm injury in depth. After removing the brain tissue, 10 μL of MBs or CMH (based on fractional void volume of CMH, the volume of gel was 61%(v/v) of gel in PBS solution) were injected by syringe. For HFMF treatment group, HFMF was applied 5 min/day until mice were sacrificed. To quantify the results, 25 slices per animals and 3 ROIs in lesion/trauma regions were randomly chosen and calculated. Brain collection and immunofluorescence staining

In addition to immune cell infiltration, activated resident microglia cells produce pro-inflammatory cytokines, such as IL1β, IL6, IL12, and TNFα, resulting in increased inflammatory activity and secondary cell death 42. IL-6 is a pro-inflammatory cytokine, which is usually used to elevate the inflammatory responses after tissue injury or an inflammatory stimulus 43. After 7 days postinjection, CLSM images in Supplementary Fig. 12a displayed the intensity of interleukin-6 (IL-6) expression at the peri-trauma area treated by MBs, where CMH and CMH + HFMF were lower than that treated by the PBS group (Supplementary Fig. 12b), indicating the reduction of the inflammatory response. This trend is consistent with the tendency of IBa-1 staining (Fig. 5d). These results support an at the present underexplored geometric component to immune stimulation with what has been observed in other microporous scaffolds that are cast ex vivo and implanted in vivo 17. The materials corroborated the greater ease of cell mobility and better infiltration of inflammatory cells. Furthermore, the MB scaffold and its surrounding tissue exhibited a lower number of microglia when compared with the PBS group. van der Zwaag, W. et al. fMRI at 1.5, 3 and 7 T: characterising BOLD signal changes. Neuroimage 47, 1425–1434 (2009). Zhang, L. G. et al. An NT-3-releasing bioscaffold supports the formation of TrkC-modified neural stem cell-derived neural network tissue with efficacy in repairing spinal cord injury. Bioact. Mater. 6, 3766–3781 (2021). Not only will this radiator blend beautifully with your house, but it also offers functionality as well. The double bar design provides optimal heat output and is by far the most efficient heating option. We offer a selection of sizes too so you can be sure we will have the perfect option regardless of room-size or need. Built from high-quality, durable steel means it will stand the test of time too and comes with a 10-year guarantee.The use of electrical stimulation for manipulating the proliferation and differentiation of neural stem cells into neuronal cells by activating intracellular signaling pathways and intracellular microenvironments has also attracted great attention 28, 29. To explore the effects of eddy currents on GYB-treated NSCs, NSCs were cultured with GYBs and treated with a HFMF for 5 min (Supplementary Fig. 7). At 4 days posttreatment, compared to the cells treated with GYBs or HFMF alone, the NSCs treated with GYBs and HFMF together exhibited obvious sprouting, indicating the current-induced neural-related cell differentiation of NSCs. Furthermore, the expression of a neuron marker (microtubule-associated protein 2, MAP-2) and astrocyte marker (glial fibrillary acidic protein, GFAP) was analyzed to assess the differentiation fate. In Fig. 4c, in the control group (without application of GYBs+HFMF) or the group treated with HFMF alone, the neural stem cells preferred to differentiate into astrocytes rather than neurons. However, compared with the other groups, the group treated with cys-GYBs exposed to a HFMF (The power was 3.2 kW with a strength of 4 kA/m at a frequency of 1 MHz) exhibited efficient neuron differentiation with an increase in the number of MAP-2-positive neurons. GYBs were observed in the neurospheres and sprout cells, and most GYBs were located close to the nuclei (Fig. 4d and Supplementary Fig. 8). The results indicated that the cys-GYBs demonstrated good affinity and low cell toxicity. These results also demonstrated that the electromagnetized GYBs promoted stem cell differentiation and neurite outgrowth.

To measure electrical conductivity of each gel, the cylindrical hydrogels were prepared (cross-sectional area: 3.14 × 1.0 cm 2; length: 1.0 cm). Then, two-terminal electrical resistance (Ω) was monitored using digital multimeter (Dawson), and the electrical conductivity was calculated as follows: Electrical conductivity (S cm −1) = L/ R × A, where R is (electrical resistance, Ω), A is (Atra of cross-sectional (cm 2) = 3.14 × radius 2), and L is (length, cm). Furthermore, LED emission was visualized while hydrogel was serially connected. In vitro cell culture Hofer, A. S. & Schwab, M. E. Enhancing rehabilitation and functional recovery after brain and spinal cord trauma with electrical neuromodulation. Curr. Opin. Neurol. 32, 828–835 (2019). The animal use and experimental protocols were approved by the Institutional Animal Care and Use Committee (IACUC) of National Tsing Hua University (Approval No. 10704). Synthesis and modification of gold nanoyarn-ball (GYBs) Ensuring that our fMRI-BOLD experiment with enrolling the enough number of animals used in each group to ensure reproducibility and spatial agreement of stimulus-evoked BOLD responses was a critical aspect of experimental design. Power, or the ability to reliably detect magnitude differences between evoked BOLD responses between stimulus ON and OFF, was used to determine their corresponding effect sizes and powers using open source toolbox, G ∗Power (version 3, Institut fürExperimentelle Psychologie, Dusseldorf, Germany) 61, and Cohen’s d equation 62. The magnitude of evoked BOLD signal in response to the forepaw stimulation showed a significant difference between stimulus ON and OFF in the ROIs of M1 (PBS: 1.7 ± 0.2%, p< 0.05, n = 6; MBs: 1.9 ± 0.2%, p< 0.05, n = 6; CMH: 1.5 ± 0.1%, p< 0.05, n = 6; CMH + HFMF: 2.2 ± 0.3%, p< 0.05, n = 6) and S1FL (PBS: 4.1 ± 0.2%, p< 0.05, n = 6; MBs: 4.3 ± 0.3%, p< 0.05, n = 6; CMH: 4.0 ± 0.1%, p< 0.05, n = 6; CMH + HFMF: 5.8 ± 0.4%, p< 0.05, n = 6), the power were more than 0.8 in M1 (PBS: effect size = 4.966, power = 0.986; MBs: effect size = 9.118, power = 0.959; CMH: effect size = 6.591, power = 0.999; CMH + HFMF: effect size = 12.329, power = 0.997) and S1FL (PBS: effect size = 5.784, power = 0.998; MBs: effect size = 11.931, power = 0.995; CMH: effect size = 8.541, power = 0.999; CMH + HFMF: effect size = 14.907, power = 0.999). According to the power analyses and effect size test, there were sufficient statistical powers (> 0.8) and medium to large effect sizes each group as shown in Supplementary Table 1, which complied with the Three Rs (3Rs) principle for more ethical use of animals in this study 63. Western blotting These adaptable properties were visualized by labeling cys-GYB and MBs with Cy5.5 and RITC, respectively. By simply mixing two particles at various ratios (cys-GYB 1 indicates that 1 mg of cys-GYB was mixed with 1 mL of MBs (0.61 g/mL)), the cys-GYBs (represented in yellow) were able to attach to the MBs rapidly (Fig. 2 l). While increasing the concentrations of cys-GYBs (5 and 10 mg), the coverage on the MBs was also increased (the cys-GYBs 5 and 10 groups in Fig. 2l). The fractional coverages of cys-GYB on the surface of microbeads were quantified by Imaris software. As shown in Supplementary Fig. 4a, the GYBs coverage on selected MBs were calculated by the overlapping fluoresce of GYBs and MBs, and the surface-exposed MBs were selected for evaluation. Based on the electrostatic attraction, the fractional coverage was increased from 29.5 ± 15.5% to 57.9 ± 16.0% with an increased ratio of GYBs/MBs from 1/1 to 10/1 mg/mL. Furthermore, the similar fractional coverage of 10/1 group at different periods under HFMF also revealed the stability of CMH after treatment (Supplementary Fig. 4b–d). Therefore, based on the stability and coverages, CMH with 10 mg/ml of cys-GYBs/MBs was applied in this study. Moreover, SEM images of the lyophilized CMH are presented in Supplementary Fig. 5. The amounts of GYBs were increased on the surface of MBs while increasing the GYBs ratios.Graham, N. S. Understanding neurodegeneration after traumatic brain injury: from mechanisms to clinical trials in dementia. J. Neurol. Neurosurg. Psychiatry 90, 1221–1233 (2019). The samples of crosslinked GelMA at different concentration were prepared as previously described 32. Then, the cylindrical hydrogels were compressed at a rate of 20% strain/min by a mechanical tester (Instron 5542). Elastic modulus was calculated as the slope of the linear region corresponding with 0-5% strain of a stress−strain curve. Preparation of conductive microporous hydrogel Chen, Z. et al. Microglial displacement of inhibitory synapses provides neuroprotection in the adult brain. Nat. Commun. 5, 4486 (2014).

For years, Honda have built all their lawn, garden and power equipment around clean 4-stroke engine technology. That’s because they’re committed to making their products as user-friendly, fuel-efficient and reliable as they can, without compromising performance.Being a 4-stroke engine, it means that it meets the worlds most stringent environmental legislation and emits very few emissions, has low fuel and oil consumption and reduced vibration and noise levels. Lovett, M. L., Nieland, T. J. F., Dingle, Y.-T. L. & Kaplan, D. L. Innovations in 3D tissue models of human brain physiology and diseases. Adv. Funct. Mater. 30, 1909146 (2020). Bosshard, S. C. et al. Assessment of brain responses to innocuous and noxious electrical forepaw stimulation in mice using BOLD fMRI. Pain 151, 655–663 (2010).