Abstract

Intrahepatic cholangiocarcinoma (ICC) is a highly aggressive malignancy with a dismal prognosis, and pronounced interpatient heterogeneity severely limits the efficacy of systemic therapies, underscoring the need for rapid and accurate functional platforms to guide individualized drug selection. Here, we develop a clinically oriented, patient-derived, 3D bioprinted in vitro model for personalized drug sensitivity assessment in ICC. Using a compositionally defined and cost-effective GelMA/HAMA composite hydrogel, we reconstruct a tumor microenvironment that supports rapid self-organization and sustained viability of primary ICC cells. Histological analyses, marker expression profiling, and bright-field imaging demonstrate close similarity to matched patient tumor tissues. Genomic and transcriptomic fidelity are further confirmed by whole-exome and RNA sequencing, revealing preserved driver mutations and transcriptional programs. Drug sensitivity testing was performed on tumor samples from 21 ICC patients using clinically relevant agents. Notably, in patients receiving neoadjuvant therapy, in vitro drug responses were fully consistent with clinical outcomes. Longitudinal follow-up further showed that recurrence occurred exclusively in patients who did not receive the predicted sensitive therapies. Importantly, clinically actionable drug response profiles were generated within 10 days. Collectively, this platform provides a rapid, reproducible, and patient-specific functional drug testing strategy with strong potential for clinical translation.