ArticleResearch (Washington, D.C.)2026
Microenvironment-Driven 3-Dimensional Biofabrication Enables Sequential Maturation of the Blood-Brain Barrier.
Article in Research (Washington, D.C.), 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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14 authors.
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Abstract
Three-dimensional (3D) in vitro blood-brain barrier (BBB) models are essential for studying neurovascular development, drug permeability, and disease mechanisms, yet most fail to recapitulate the temporal sequence of cellular maturation. Here, we present a spatiotemporally organized 3D BBB model engineered via dynamic microenvironmental regulation. Temporally controlled enzymatic modulation of an alginate/collagen dual-network hydrogel enabled transition in matrix properties from strong to weak mechanical confinement, thereby triggering the embedded cells to shift from a quiescent to an active state and further enabling the construction of a BBB model with sequential endothelial and supporting cell development. The resulting 3D BBB model exhibits improved barrier integrity, reduced macromolecular leakage, and physiologically relevant drug-selective permeability. This strategy demonstrates that temporally controlled microenvironmental cues can guide multicellular tissue development, providing a versatile platform for neurovascular research and central-nervous-system-targeted drug evaluation.
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