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，其中的成分被招募或重塑，以促进侵袭性肿瘤的生长和肿瘤细胞向远处组织的扩散。因此，重点放在了解周围的细胞外基质(ECM)是如何改变的，主要是胶原和纤维连接蛋白，以介导肿瘤的进展。水凝胶是一种亲水溶胀的细胞友好型生物材料，其力学、结构和生化特性可以模拟天然的细胞外基质，应用于组织工程或体外模型。然而，用于细胞培养的标准水凝胶侧重于它们的弹性力学性能，而忽略了它们的粘性、动力学性质。因此，研究人员正在开发具有可控粘性的粘弹性水凝胶，以控制细胞机械传感、干细胞的谱系承诺或癌细胞的增殖/侵袭。在这个项目中，学生将制作和表征具有不同粘弹性属性的粘弹性水凝胶，目的是(I)模拟乳腺肿瘤微环境的粘弹性属性，(Ii)了解癌细胞(将研究三种类型的癌细胞，从非侵袭性到高度侵袭性)和控制细胞如何感知微环境的变化并对这些属性做出反应。这些研究将在2D和更具生理意义的3D环境中进行。该项目有望为如何设计体外微环境来改变细胞命运并阻止肿瘤的进展、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.