Abstract：
The mechanisms underlying the formation of necrotic regions within avascular tumors are complex and poorly understood. In this paper, we investigate the formation of a necrotic core in a 3D tumor cell culture within a microfluidic device, considering oxygen, nutrients, and the microenvironment acidification by means of a computational-mathematical model. Our objective is to simulate cell processes, including proliferation and death inside a microfluidic device, according to the microenvironmental conditions. We employed approximation utilizing finite element models taking into account glucose, oxygen, and hydrogen ions diffusion, consumption and production, as well as cell proliferation, migration and death, addressing how tumor cells evolve under different conditions. The resulting mathematical model was examined under different scenarios, being capable of reproducing cell death and proliferation under different cell concentrations, and the formation of a necrotic core, in good agreement with experimental data reported in the literature. This approach not only advances our fundamental understanding of necrotic core formation but also provides a robust computational platform to study personalized therapeutic strategies, offering an important tool in cancer research and treatment design.
摘要：
在无血管肿瘤内形成坏死区域的潜在机制是复杂的且知之甚少。在本文中,我们研究了微流体装置内3D肿瘤细胞培养物中坏死核心的形成，考虑到氧气，营养素,并通过计算数学模型对微环境酸化进行了研究。我们的目标是模拟细胞过程，包括微流体装置内的增殖和死亡，根据微环境条件。我们利用考虑葡萄糖的有限元模型进行近似，氧气,和氢离子扩散，消费和生产，以及细胞增殖，移民和死亡,解决肿瘤细胞在不同条件下如何进化。在不同的情况下检查了所得的数学模型，能够在不同的细胞浓度下复制细胞死亡和增殖，坏死核的形成，与文献中报道的实验数据非常吻合。这种方法不仅促进了我们对坏死核心形成的基本理解，而且还提供了一个强大的计算平台来研究个性化治疗策略。提供癌症研究和治疗设计的重要工具。
