Scalability and device integration have been prevailing issues limiting our ability in harnessing the potential of small-diameter conducting fibers. We report inflight fiber printing (iFP), a one-step process that integrates conducting fiber production and fiber-to-circuit connection. Inorganic (silver) or organic {PEDOT:PSS [poly(3,4-ethylenedioxythiophene) polystyrene sulfonate]} fibers with 1- to 3-μm diameters are fabricated, with the fiber arrays exhibiting more than 95% transmittance (350 to 750 nm). The high surface area–to–volume ratio, permissiveness, and transparency of the fiber arrays were exploited to construct sensing and optoelectronic architectures. We show the PEDOT:PSS fibers as a cell-interfaced impedimetric sensor, a three-dimensional (3D) moisture flow sensor, and noncontact, wearable/portable respiratory sensors. The capability to design suspended fibers, networks of homo cross-junctions and hetero cross-junctions, and coupling iFP fibers with 3D-printed parts paves the way to additive manufacturing of fiber-based 3D devices with multilatitude functions and superior spatiotemporal resolution, beyond conventional film-based device architectures.

Neural crest cells arise from the border of the neural plate and epidermal ectoderm, migrate extensively and differentiate into diverse cell types during vertebrate embryogenesis. Although much has been learnt about growth factor signals and gene regulatory networks that regulate neural crest development, limited information is available on how epigenetic mechanisms control this process. In this study, we show that Polycomb repressive complex 2 (PRC2) cooperates with the transcription factor Snail2/Slug to modulate neural crest development in Xenopus. The PRC2 core components Eed, Ezh2 and Suz12 are expressed in the neural crest cells and are required for neural crest marker expression. Knockdown of Ezh2, the catalytic subunit of PRC2 for histone H3K27 methylation, results in defects in neural crest specification, migration and craniofacial cartilage formation. EZH2 interacts directly with Snail2, and Snail2 fails to expand the neural crest domains in the absence of Ezh2. Chromatin immunoprecipitation analysis shows that Snail2 regulates EZH2 occupancy and histone H3K27 trimethylation levels at the promoter region of the Snail2 target E-cadherin. Our results indicate that Snail2 cooperates with EZH2 and PRC2 to control expression of the genes important for neural crest specification and migration during neural crest development.

Glioblastomas (GBMs) are deadly tumors of the central nervous system. Most GBM exhibit homozygous deletions of the CDKN2A and CDKN2B tumor suppressors at 9p21.3, although loss of CDKN2A/B alone is insufficient to drive gliomagenesis. MIR31HG, which encodes microRNA-31 (miR-31), is a novel non-coding tumor suppressor positioned adjacent to CDKN2A/B at 9p21.3. We have determined that miR-31 expression is compromised in >72% of all GBM, and for patients, this predicts significantly shortened survival times independent of CDKN2A/B status. We show that miR-31 inhibits NF-κB signaling by targeting TRADD, its upstream activator. Moreover, upon reintroduction, miR-31 significantly reduces tumor burden and lengthens survival times in animal models. As such, our work identifies loss of miR-31 as a novel non-coding tumor-driving event in GBM.

In glioma, microglia and macrophages are the largest population of tumor-infiltrating cells, referred to as glioma associated macrophages (GAMs). Herein, we sought to determine the role of Suppressor of Cytokine Signaling 3 (SOCS3), a negative regulator of Signal Transducer and Activator of Transcription 3 (STAT3), in GAM functionality in glioma. We utilized a conditional model in which SOCS3 deletion is restricted to the myeloid cell population. We found that SOCS3-deficient bone marrow-derived macrophages display enhanced and prolonged expression of pro-inflammatory M1 cytokines when exposed to glioma tumor cell conditioned medium in vitro. Moreover, we found that deletion of SOCS3 in the myeloid cell population delays intracranial tumor growth and increases survival of mice bearing orthotopic glioma tumors in vivo. Although intracranial tumors from mice with SOCS3-deficient myeloid cells appear histologically similar to control mice, we observed that loss of SOCS3 in myeloid cells results in decreased M2 polarized macrophage infiltration in the tumors. Furthermore, loss of SOCS3 in myeloid cells results in increased CD8+ T-cell and decreased regulatory T-cell infiltration in the tumors. These findings demonstrate a beneficial effect of M1 polarized macrophages on suppressing glioma tumor growth, and highlight the importance of immune cells in the tumor microenvironment.

Building two-dimensional (2D) and three-dimensional (3D) fibrous structures in the micro- and nanoscale will offer exciting prospects for numerous applications spanning from sensors to energy storage and tissue engineering scaffolds. Electrospinning is a well-suited technique for drawing micro- to nanoscale fibers, but current methods of building electrospun fibers in 3D are restrictive in terms of printed height, design of macroscopic fiber networks, and choice of polymer. Here, we combine low-voltage electrospinning and additive manufacturing as a method to pattern layers of suspended mesofibers. Layers of fibers are suspended between 3D-printed supports in situ in multiple fiber layers and designable orientations. We examine the key working parameters to attain a threshold for fiber suspension, use those behavioral observations to establish a “fiber suspension indicator”, and demonstrate its utility through design of intricate suspended fiber architectures. Individual fibers produced by this method approach the micrometer/submicrometer scale, while the overall suspended 3D fiber architecture can span over a centimeter in height. We demonstrate an application of suspended fiber architectures in 3D cell culture, utilizing patterned fiber topography to guide the assembly of suspended high-cellular-density structures. The solution-based fiber suspension patterning process we report offers a unique competence in patterning soft polymers, including extracellular matrix-like materials, in a high resolution and aspect ratio. The platform could thus offer new design and manufacturing capabilities of devices and functional products by incorporating functional fibrous elements.