Long-term modelization of cancer as it changes in the human body is a difficult goal, particularly when designing and testing new therapeutic strategies. This becomes even more difficult with metastasis modeling to show chemotherapeutic molecule delivery directly to tumoral cells. Advanced therapeutics, including oncolytic viruses, antibody-based and cell-based therapies are increasing. The question is, are screening tests also evolving? Next-generation therapeutics need equally advanced screening tests, which whilst difficult to achieve, are the goal of our work here, creating models of micro- and macrotumors using 3D bioprinting. We developed advanced colorectal cancer tumor processing techniques to provide options for cellular expansion, microtumor printing, and long-term models, which allow for the evaluation of the kinetics of penetration testing, therapeutic success, targeted therapies, and personalized medicine. We describe how we tested tumors from a primary colorectal patient and, applying 3D bioprinting, matured long-term models for oncolytic metastatic screening. Three-dimensional microtumors were kept alive for the longest time ever recorded in vitro, allowing longitudinal studies, screening of oncolytic viruses and realistic modelization of colorectal cancer. These 3D bioprinted models were maintained for around 6 months and were able to demonstrate the effective delivery of a product to the tumoral environment and represent a step forward in therapeutic screening.
对人体内不断变化的癌症进行长期建模是一项艰巨的任务,尤其在设计和测试新型治疗策略时更具挑战性。当涉及建立转移模型以展示化疗分子直接靶向肿瘤细胞的递送过程时,这一难题更为复杂。随着溶瘤病毒、抗体疗法及细胞疗法等先进治疗手段的日益增多,关键问题在于:筛选检测技术是否同步发展?新一代治疗方法需要与之匹配的先进筛选检测体系,尽管实现这一目标困难重重,但正是我们研究工作的核心方向——通过三维生物打印技术构建微观与宏观肿瘤模型。我们开发了先进的结直肠癌肿瘤处理技术,为细胞扩增、微肿瘤打印及长期模型构建提供解决方案,从而实现对药物渗透动力学、治疗效果、靶向治疗及个体化医疗的评估。本研究详细阐述了如何利用原发性结直肠癌患者的肿瘤组织,通过三维生物打印技术构建适用于溶瘤转移筛选的长期成熟模型。这些三维微肿瘤在体外存活时间创历史记录,为纵向研究、溶瘤病毒筛选及结直肠癌真实模拟提供了可能。这些三维生物打印模型可维持约六个月的生命周期,成功展示了药物在肿瘤微环境中的有效递送,标志着治疗筛选技术迈出了重要一步。