Tumor Growth Suppression Induced by Biomimetic Silk Fibroin Hydrogels

Protein-based hydrogels with distinct conformations which enable encapsulation or differentiation of
cells are of great interest in 3D cancer research models. Conformational changes may cause macroscopic
shifts in the hydrogels, allowing for its use as biosensors and drug carriers. In depth knowledge on
how 3D conformational changes in proteins may affect cell fate and tumor formation is required. Thus,
this study reports an enzymatically crosslinked silk fibroin (SF) hydrogel system that can undergo
intrinsic conformation changes from random coil to β-sheet conformation. In random coil status, the
SF hydrogels are transparent, elastic, and present ionic strength and pH stimuli-responses. The random
coil hydrogels become β-sheet conformation after 10 days in vitro incubation and 14 days in vivo
subcutaneous implantation in rat. When encapsulated with ATDC-5 cells, the random coil SF hydrogel
promotes cell survival up to 7 days, whereas the subsequent β-sheet transition induces cell apoptosis
in vitro. HeLa cells are further incorporated in SF hydrogels and the constructs are investigated in vitro
and in an in vivo chick chorioallantoic membrane model for tumor formation. In vivo, Angiogenesis and
tumor formation are suppressed in SF hydrogels. Therefore, these hydrogels provide new insights for
cancer research and uses of biomaterials.