We have developed a bilayer hydrogel system that simulates the crosstalk between tumor associated stroma and cancer cells via growth factor signaling to support tumoroids formation in vitro. To prepare the hydrogels, hyaluronic acid (HA) derivatives containing either acrylate groups (HA-AC) or thiols (HA-SH) were synthesized and characterized. Simple mixing of HA-AC and HA-SH resulted in the formation of viscoelastic gels under physiological conditions. The top hydrogel layer contained entrapped HA-based hydrogel particles (HGPs) presenting heparin-binding epidermal growth factor-like growth factor (HB-EGF) in a sustained manner. LNCaP prostate cancer cells were embedded within the bottom hydrogel layer and receive the inductive stimuli from the top. After 7 days of culture, the obtained spherical tumoroids exhibited an average size of 85 �m. Upregulation of pro-angiogenic factors, both on gene and protein levels, were detected. The HA-based, bilayer hydrogel system provides a useful platform for studies of tumor biology and drug evaluation.

3D in vitro bioengineered tumors based on bilayer hyaluronic acid hydrogels

244th National Meeting (2012)

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