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Abstract The prognosis of glioblastoma multiforme (GBM) remains dismal, despite standard treatment regimens. A key challenge in treating GBM is the persistence of glioma stem cells (GSCs) within the perivascular niche (PVN) – a protective tumor microenvironment (TME) that is often associated with inadequate drug penetration. Current preclinical models do not capture complexity of the human TME, particularly the vasculature and niche‐specific interactions that drive GBM progression. To overcome these limitations, an innovative 3Dex‐vivotumor‐on‐a‐chip (TOC) platform is engineered to accurately replicate the structural and functional characteristics of the PVN. Using this platform, this study demonstrates that monocyte membrane‐coated nanoparticles (MoNP) effectively target the abnormal tumor microvasculature, offering a promising approach to enhance drug delivery to these hard‐to‐reach GSCs. The results show that the therapeutic agent verteporfin, when delivered via MoNP, significantly inhibited GSC growth and invasiveness, while the free‐form drug showed minimal efficacy. Comprehensive transcriptomic profiling and cytokine analysis validated the TOC model's ability to reflect authentic GSC responses and confirmed that MoNP‐mediated verteporfin delivery effectively modulates key tumor‐related signaling pathways. This integrated TOC‐MoNP platform represents a clinically relevant tool that bridges the gap between traditional preclinical models and human disease, providing new opportunities for developing more effective GBM therapies. 

Cardiac tissue engineering is an emerging field providing tools to treat and study cardiovascular diseases (CVDs). In the past years, the integration of stem cell technologies with micro- and nanoengineering techniques has enabled the creation of novel engineered cardiac tissues (ECTs) with potential applications in disease modeling, drug screening, and regenerative medicine. However, a major unaddressed limitation of stem cell-derived ECTs is their immature state, resembling a neonatal phenotype and genotype. The modulation of the cellular microenvironment within the ECTs has been proposed as an efficient mechanism to promote cellular maturation and improve features such as cellular coupling and synchronization. The integration of biological and nanoscale cues in the ECTs could serve as a tool for the modification and control of the engineered tissue microenvironment. Here we present a proof-of-concept study for the integration of biofunctionalized gold nanoribbons (AuNRs) with hiPSC-derived isogenic cardiac organoids to enhance tissue function and maturation. We first present extensive characterization of the synthesized AuNRs, their PEGylation and cytotoxicity evaluation. We then evaluated the functional contractility and transcriptomic profile of cardiac organoids fabricated with hiPSC-derived cardiomyocytes (mono-culture) as well as with hiPSC-derived cardiomyocytes and cardiac fibroblasts (co-culture). We demonstrated that PEGylated AuNRs are biocompatible and do not induce cell death in hiPSC-derived cardiac cells and organoids. We also found an improved transcriptomic profile of the co-cultured organoids indicating maturation of the hiPSC-derived cardiomyocytes in the presence of cardiac fibroblasts. Overall, we present for the first time the integration of AuNRs into cardiac organoids, showing promising results for improved tissue function. 

An organotypic heart on-a-chip modeling long QT syndrome type 2 was created to study effect of R531W mutation in LQTS2 pathology.