Engineering viscoelastic hydrogels for mimicking the tumour microenvironment and stopping tumour progression

肿瘤间质是一个复杂的微环境，其中组分被募集或重塑以促进侵袭性肿瘤生长和肿瘤细胞向远处组织的扩散。因此，具体的重点放在了解周围的细胞外基质（ECM），主要是胶原蛋白和纤连蛋白，是如何改变介导肿瘤进展。水凝胶是水溶胀的细胞友好的生物材料，其机械、结构和生物化学性质可以被调节以模拟天然ECM，用于组织工程或作为体外模型。然而，用于细胞培养的标准水凝胶关注于它们的弹性机械性质，而忽略了考虑它们的粘性、动态性质。因此，研究人员正在开发具有受控粘性的粘弹性水凝胶，以控制细胞机械感应、干细胞的谱系定型或癌细胞的增殖/侵袭。在这个项目中，学生将制造和制备具有不同粘弹性的粘弹性水凝胶，目的是（i）模拟乳腺肿瘤微环境的粘弹性，（ii）了解癌细胞（将研究3种类型的癌细胞，从非侵袭性到高度侵袭性类型）和对照细胞如何感知微环境的变化并对这些特性做出反应。这些研究将在2D和更生理的3D环境中进行。该项目有望为如何改造体外微环境以改变细胞命运并阻止肿瘤进展、侵袭和转移提供新的见解。

The tumour stroma is a complex microenvironment in which components are recruited or remodelled to facilitate invasive tumour growth and spread of tumour cells to distant tissues. Therefore, specific focus is placed on understanding how the surrounding extracellular matrix (ECM), mainly collagen and fibronectin, is altered to mediate tumour progression. Hydrogels are water-swollen cell-friendly biomaterials, whose mechanical, structural, and biochemical properties can be tuned to mimic native ECMs, for application in tissue engineering or as in vitro models. However, standard hydrogels used in cell culture focus on their elastic mechanical properties and neglect to consider their viscous, dynamic nature. Hence, researchers are developing viscoelastic hydrogels with controlled viscous properties to control cell mechano-sensing, lineage commitment of stem cells, or proliferation / invasion of cancer cells. In this project, the student will fabricate and characterise viscoelastic hydrogels with varied viscoelastic properties with the aim of (i) mimicking the viscoelastic properties of the breast tumour microenvironment and (ii) understanding how cancer cells (3 types of cancer cells will be investigated, from non-aggressive to highly aggressive types) and control cells sense microenvironmental changes and respond to these properties. These studies will be performed both in 2D and more physiological 3D environments. The project is expected to provide novel insights into how the in vitro microenvironment can be engineered to alter cell fate and stop tumour progression, invasion, and metastasis.