3D BioEngineered constructs for TE cancer research

In the context of tissue engineering and regenerative medicine, the pivotal role of the extracellular microenvironment, cell-matrix and cell-cell interactions in the signalling and regulation of pathophysiological states has been extensively studied. This work addresses challenges in cancer research, conceiving a more relevant in vitro model enabling to study the cross-talk between the primary tumour and the pre-metastatic niche site. In this study we report the use of manufacturing techniques to fabricate 3D cancer in vitro models by means of alginate based hydrogel-spheres and porous cryogels. In particular, the use of the encapsulating technique enables a precise control over the number of embedded cells per bead and bead size, both of them fundamental for a precise modelling of cancer signalling phenomena. By increasing the levels of complexity of the proposed tumour in vitro models enables us to follow not only the dynamics and characteristics of the primary tumour, but also the effects imposed to the distal metastatic site, e.g. the presence of cell-released factors (soluble factors and extracellular vesicles), controlled material properties (mechanical and diffusion properties), physiological relevance (co-culture of cancer with stromal cells, mimicking the connection between the primary tumour compartment and the pre-metastatic site). Here, emphasis is given to a relevant cancer-associated surface receptor (CD44 and its variants), characterised as a function of the cell culture methods i.e. 2D monolayer, encapsulation and porous 3D culture, co-culture. This approach will enable to develop and test targeted formulations for the delivery of drugs such as small nucleic acids to the tumours, but also to identify new targets to the stromal components to prevent the spreading of aggressive/metastatic cancers.