An innervated and vascularized HNSCC-on-a-chip model built on defined and tunable engineered extracellular matrices.

An innervated and vascularized HNSCC-on-a-chip platform built on fully defined, tunable engineered extracellular matrices enables ECM-dependent transcriptional states, collective invasion, and chemotherapeutic sensitivity.

• Why it matters: Tumor microenvironment studies need experimental systems that include key components together while controlling extracellular matrix properties.
• What they did: The platform stepwise cocultured patient-derived HNSCC cells, cancer-associated fibroblasts, and endothelial cells in tailored eECMs, then added a cancer–vasculature interface and trigeminal innervation via injectable 3D human bioengineered trigeminal ganglia.
• The result: ECM-dependent differences were observed in transcriptional state, multicellular self-organization, chemotherapeutic sensitivity, and directional collective migration and invasion within the modular human microenvironment.