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Fast and early detection of low-dose chemical toxicity is a critical unmet need in toxicology and human health, as conventional 2D culture models often fail to capture subtle cellular responses induced by sub-toxic exposures. Here, we present a bioengineered three-dimensional (3D) electrospun nanofibrous scaffold composed of polycaprolactone that enhances chromatin accessibility and primes fibroblasts for improved sensitivity to low-dose chemical stimuli in a short period. The scaffold mimics the extracellular matrix, providing topographical cues that reduce cytoskeletal tension and promote nuclear deformation, thereby increasing chromatin openness.
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