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Exogenous matrix‐free biomanufacturing of glioblastoma organoids enables autonomous assembly of neurovascular‐like structures and extracellular matrix

2026-08-05 · Bioengineering & Translational Medicine

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One-line summary

Here, we present an exogenous ECM‐free biomanufacturing process for GBM organoids (GBOs) that recapitulate pathological development relative to size and spatial distribution.

Engineering notes

Trajectory analyses of neurovascular unit (NVU) zonation, cell‐type differentiation, and basement membrane converged with clinical benchmarks highlighting a critical developmental milestone at the 2 mm diameter stage.

Chinese explanation / 中文解读

中文解读待补充:本站会优先为端到端自动驾驶、BEV感知、3D目标检测、轨迹预测、路径规划、LiDAR感知等高价值论文补充中文说明。

Original abstract

Abstract Current glioblastoma (GBM) models often rely on chemically undefined exogenous extracellular matrices (ECMs) and serums that limit understanding of autonomous cellular behaviors driving tumor progression. Here, we present an exogenous ECM‐free biomanufacturing process for GBM organoids (GBOs) that recapitulate pathological development relative to size and spatial distribution. These GBOs exhibit a conserved glioma signature established from The Cancer Genome Atlas clinical datasets. Trajectory analyses of neurovascular unit (NVU) zonation, cell‐type differentiation, and basement membrane converged with clinical benchmarks highlighting a critical developmental milestone at the 2 mm diameter stage. Immunofluorescence revealed a matrix‐priming cascade of tenascin‐C (TNC) at 1 mm diameter and fibronectin (FN) at 1.5 mm diameter to provide the necessary biochemical cues and biophysical assembly for endothelial cells at 2 mm diameter. Lastly, the 2 mm diameter GBOs displayed a distinct vascular‐like area characterized by capillary‐scale lumen distributions (5–15 μm) and peak junctional complexity, similar to in vivo capillary beds. However, transcriptional divergences in arterial and proteoglycan markers suggest biochemical cues and morphology are insufficient for full physiological maturation without confirmed internal hemodynamic shear stress. Despite these results, our GBOs serve as a high‐fidelity structural framework for modeling GBM NVU‐like regions that may be used as a translatable platform for TNC‐ and FN‐targeted therapies designed to enhance drug delivery across the NVU.

5.0Engineering value
7.0Research novelty
5.0Business relevance

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