患者来源肿瘤的可重复3D生物打印实现高保真临床前药物测试

Traditional 2D cancer cell culture systems have substantially advanced our understanding of tumor biology but fail to recapitulate the architectural organization, ECM composition, and spatial nutrient and oxygen gradients present in vivo. Consequently, they show weak correlation between in vitro drug sensitivity and clinical response. This translational gap contributes to high attrition in cancer drug development, with many therapies performing well preclinically but failing clinically due to the insufficient predictive power of early models, including in vivo systems that lack patient-specific biology and exhibit species-specific differences. Developments in 3D bioprinting enable reconstruction of tumor tissues containing epithelial, stromal, and immune populations embedded within physiological matrix analogs, more accurately reproducing the tumor microenvironment and retaining cell-cell and cell-matrix interactions. Bioprinting allows standardized, scalable tumor models while maintaining biologically relevant complexity. Early studies established feasibility, but systemic validation using fresh human tumor tissue, including compositional and functional fidelity, remains incomplete. We demonstrate that patient-derived ovarian and HER2+ breast tumors can be dissociated, bioprinted, and maintained in 3D culture while preserving key cellular populations and functional behaviors, and that treatment responses in these models correlate with known patient outcomes and standard-of-care drug efficacy. Constructs were generated using biomimetic hydrogels supplemented with ECM-derived proteins and primary tumor cells, and evaluated for viability, structural stability, and microarchitecture by live/dead imaging, histology, flow cytometry, and quantitative microscopy. Drug-response assays with standard-of-care chemotherapies and targeted anti-HER2 agents were performed. Optimized initial cell density supported sustained survival, proliferation, and hierarchical reorganization. Evaluation of our printing strategy showed we can achieve constructs with coefficients of variation below 10% for both bioprint structural integrity and cell viability at one day post-print and that this could be maintained over prolonged culture. This degree of reproducibility permitted attribution of drug responses to the treatment and supported investigation of optimal pre-treatment culture duration. Drug-response profiles differed from those in 2D cultures, indicating greater physiological relevance. Collectively, these findings highlight the predictive validity of bioprinted tumor constructs as a promising tool for preclinical efficacy assessment. Ongoing work will expand multicellular complexity, incorporate immune components, and benchmark against clinical datasets.