Embedded Coaxial Bioprinting of Vascularized Tissue Models for Drug Evaluation

Abstract Vascularized tissue models represent a pivotal approach for enhancing the accuracy of clinical drug prediction by recapitulating the in vivo microenvironment. However, replicating the structural complexity, functional integration, and long‐term stability inherent in native vascular tissues remains a significant challenge within the tissue engineering field. Herein, a novel strategy employing aqueous‐embedded coaxial bioprinting is proposed. By optimizing the rheological compatibility between alginate‐collagen (Alg‐Col) bioink and xanthan gum‐collagen (XG‐Col) support bath, the high‐fidelity and efficient fabrication of vascularized tissue models is achieved. Utilizing a triaxial nozzle, synchronous deposition of a bilayered vascular construct containing human umbilical vein endothelial cells (HUVECs) and human lung fibroblasts (HLFs) is performed directly within a tumor cell (human lung adenocarcinoma PC‐9 cell line)‐laden support bath, resulting in the construction of a perfusable vascularized lung cancer tissue model. Drug assessment revealed significantly lower sensitivity of PC‐9 cells to erlotinib within the 3D vascularized model compared to controls. In addition to the physical barrier effect, the vascularized microenvironment activated cancer cell survival pathways primarily through paracrine signaling from endothelial cells and fibroblasts. Gene expression analysis further demonstrated the induction of epithelial‐mesenchymal transition (EMT) in the vascularized model. This integrated platform more accurately recapitulates in vivo drug diffusion kinetics and resistance mechanisms, thereby providing an innovative preclinical platform for enhanced anticancer drug screening.