Glioblastoma (GBM) is the most lethal primary adult brain tumor and its pathology is hallmarked by distorted neovascularization, diffuse tumor-associated macrophage infiltration, and potent immunosuppression. Reconstituting organotypic tumor angiogenesis models with biomimetic cell heterogeneity and interactions, pro-/anti-inflammatory milieu and extracellular matrix (ECM) mechanics is critical for preclinical anti-angiogenic therapeutic screening. However, current in vitro systems do not accurately mirror in vivo human brain tumor microenvironment. Here, we engineered a three-dimensional (3D), microfluidic angiogenesis model with controllable and biomimetic immunosuppressive conditions, immune-vascular and cell-matrix interactions. We demonstrate in vitro, GL261 and CT-2A GBM-like tumors steer macrophage polarization towards a M2-like phenotype for fostering an immunosuppressive and proangiogenic niche, which is consistent with human brain tumors. We distinguished that GBM and M2-like immunosuppressive macrophages promote angiogenesis, while M1-like pro-inflammatory macrophages suppress angiogenesis, which we coin "inflammation-driven angiogenesis." We observed soluble immunosuppressive cytokines, predominantly TGF-β1, and surface integrin (αβ) endothelial-macrophage interactions are required in inflammation-driven angiogenesis. We demonstrated tuning cell-adhesion receptors using an integrin (αβ)-specific collagen hydrogel regulated inflammation-driven angiogenesis through Src-PI3K-YAP signaling, highlighting the importance of altered cell-ECM interactions in inflammation. To validate the preclinical applications of our 3D organoid model and mechanistic findings of inflammation-driven angiogenesis, we screened a novel dual integrin (αβ) and cytokine receptor (TGFβ-R1) blockade that suppresses GBM tumor neovascularization by simultaneously targeting macrophage-associated immunosuppression, endothelial-macrophage interactions, and altered ECM. Hence, we provide an interactive and controllable GBM tumor microenvironment and highlight the importance of macrophage-associated immunosuppression in GBM angiogenesis, paving a new direction of screening novel anti-angiogenic therapies.

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To meet the growing demands in flexible and wearable electronics, various sensors have been designed for detecting and monitoring the physical quantity changes. However, most of these sensors can only detect one certain kind of physical quantity based on a single mechanism. In this paper, we have fabricated a multifunctional sensor made from carbonized electrospun polyacrylonitrile/barium titanate (PAN-C/BTO) nanofiber film. It can detect two physical quantities (pressure and curvature), independently and simultaneously, by integrating piezoresistive, piezoelectric, and triboelectric effects. For flex sensing with the impedance change of PAN-C/BTO nanofiber films during bending, it had a sensitivity of 1.12 deg from 58.9° to 120.2° and a working range of 28°-150°. For self-powered force sensing, it had a gauge factor of 1.44 V·N within the range of 0.15-25 N. The sensor had a long stability over 60 000 cycles at both sensing modes. The inclusion of barium titanate nanoparticles (BTO NPs) into the nanofiber film had an over 2.4 times enhancement of sensitivity for pressure sensing because of the synergy of piezoelectric and triboelectric effects. On the basis of multifunction and modularity, a series of potential applications of the sensor were demonstrated, including sensing human's swallowing, walking gaits, finger flexure, and finger-tapping. The self-powered flexible dual-mode sensor has great application potential in human-computer interactive and smart wearable sensing systems.

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