Tuning Biochemical and Mechanical Properties of 3D Hydrogel Tweak Stem and Cancer Cells Cross-talk

Osteosarcoma (OS), is the second most typical primary malignancy after multiple myeloma. Solid tumors like osteosarcomas are commonly considered as "organs", comprise of cancer cells and tumor stroma. Tumor stroma is made from tumor microenvironment, which includes extracellular matrix, stem cells, immune cells, endothelial cells, diverse networks of cytokines and growth factors¹. Tumor microenvironment works silently, while largely governs the cellular fate. Therefore, an attempt is made to investigate the effect of tumor microenvironment by means of extracellular matrix and stem cells on osteosarcoma development and progression. Looking for a biomimetic biomaterial other than collagen for osteosarcoma modeling is challenging. Silk protein fibroin can be a suitable alternative due to its well recognition in bone tissue engineering² and can readily be blended with other polymers like gellan gum. Blended spongy-like hydrogel library of silk - gellan gum³ with tunable structural and mechanical properties are fabricated. Human osteosarcoma and adipose derived stem cells are co-cultured using this biomaterial library. The resultant constructs are then screened for formation of spheroid, which is the typical phenomenon of solid tumor. The formation of spheroids in selective spongy-like hydrogels is suggestive of regulatory influence of biophysical cues in cancer (spheroid) formation and succession. The heterogeneity of present model, both at structural and cellular level, recapitulates more closely the diversity of physiological tumor microenvironment. This is anticipated to be useful in predicting the efficacy of cancer chemotherapeutics.

Acknowledgement:This work is supported by the European Union Framework Programme for Research and Innovation Horizon 2020 under grant agreement nº 668983 — FoReCaST. VM Correlo acknowledges Investigator FCT program (IF/01214/2014) and JM Oliveira to the program Investigador FCT2015 (IF/01285/2015).

References

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