Three‐dimensional (3D) biomimetic cell culture platforms offer more realistic microenvironments that cells naturally experience in vivo. We developed a tunable hyaluronan‐based hydrogels that could easily be modified to mimic healthy or malignant extracellular matrices (ECMs). For that, we pre‐functionalized our hydrogels with an adhesive polypeptide (poly‐l‐lysine, PLL) or ECM proteins (type III and type IV collagens), naturally present in tumorous tissues, and next, we tuned their stiffness by crosslinking with gradual concentrations of genipin (GnP). Then, we thoroughly characterized our substrates before testing them with glioblastoma and breast cancer cells, and thereafter with endothelial cells. Overall, our hydrogels exhibited (a) increasing stiffness with GnP concentration for every pre‐functionalization and (b) efficient enzyme resistance with PLL treatment, and also with type IV collagen but to a lesser extent. While PLL‐treated hydrogels were not favorable to the culture of any glioblastoma cell lines, they enhanced the proliferation of breast cancer cells in a stiffness‐dependent manner. Contrary to type III collagen, type IV collagen pre‐treated hydrogels supported the proliferation of glioblastoma cells. The as‐desired HA‐based 3D tumor‐like models we developed may provide a useful platform for the study of various cancer cells by simply tuning their biochemical composition and their mechanical properties.

中文翻译：

---

基于透明质酸的水凝胶作为多功能类肿瘤模型：可调节 ECM 和刚度与京尼平交联。

三维 (3D) 仿生细胞培养平台提供了细胞在体内自然体验的更真实的微环境。我们开发了一种基于透明质酸的可调水凝胶，可以很容易地对其进行修改以模拟健康或恶性细胞外基质 (ECM)。为此，我们用粘性多肽（poly- l‐赖氨酸，PLL）或 ECM 蛋白（III 型和 IV 型胶原蛋白），天然存在于肿瘤组织中，接下来，我们通过与逐渐浓度的京尼平（GnP）交联来调整它们的硬度。然后，我们在用胶质母细胞瘤和乳腺癌细胞以及内皮细胞对其进行测试之前彻底表征了我们的底物。总体而言，我们的水凝胶表现出（a）每个预功能化的 GnP 浓度随 GnP 浓度而增加刚度和（b）PLL 处理的有效酶抗性，以及 IV 型胶原蛋白，但程度较小。虽然 PLL 处理的水凝胶不利于任何胶质母细胞瘤细胞系的培养，但它们以刚度依赖性方式增强了乳腺癌细胞的增殖。与 III 型胶原蛋白相反，IV型胶原预处理水凝胶支持胶质母细胞瘤细胞的增殖。我们开发的基于 HA 的 3D 肿瘤样模型可以通过简单地调整它们的生化成分和机械性能，为研究各种癌细胞提供一个有用的平台。