Silk hydrogels give third dimension to tumor model

Solid tumor as breast cancer exposes cells to a heterogeneous and complex extracellular matrix microenvironment. Tumor microenvironment has a strong impact on cancer proliferation, invasion and drug response. Many anticancer drugs show success in the preclinical studies but fail when they are administered to the patients. Three-dimensional (3D) cell cultures recently generate great attention because they promote levels of cells differentiation and tissue organization not possible in conventional two-dimensional culture systems. For this reason, there is an emerging need to develop 3D tumor model in which different cell types are embedded in a matrix copycatting the in vivo microenvironment. At same time they are easily accessible for experimental manipulation. One of the main challenge in tissue engineering application in biomedical field is to find the ideal biomaterial and the perfect configuration to copycat the tumor microenvironment. The reason is to obtain a robust 3D tumor model. The answer to this issue may arise from the use of natural hydrogel-based materials because of their chemical/physical properties. Hydrogels can be the right matrices for the development of a 3D tumor model fabrication and silk fibroin (SF) and gellan gum (GG) are taken into consideration. SF from mulberry silkworm Bombyx mori is used for the good biocompatibility, elasticity, toughness, suitable mechanical properties and biodegradability with controllable degradation rates. GG is an anionic extracellular polysaccharide and it can be used as transparent, soft, elastic and flexible gels. A SF/GG blend hydrogel with modulated chemical composition and cross-linking density, is customized in order to obtain the best condition for biocompatibility. Breast cancer cells and cancer associated fibroblast are seeded in natural derived extracellular matrix to better mimic the tumor microenvironment and the crosstalk between cancer cells and stroma. This 3D breast cancer model may be used as physiologically relevant 3D platform for screening the drug response in a complex system. The combination of SF and GG, as protein and polysaccharides composite hydrogels will improve the properties of the extracellular matrices for the tumor model. The use of the bioengineered platform will shorten the evaluation time of a drug response and will offer a more realistic tool to study the mechanism of action of the drugs.