@article {19493,
	title = {Rapidly responsive silk fibroin hydrogels as an artificial matrix for the programmed tumor cells death},
	journal = {PLoS ONE},
	volume = {13},
	year = {2018},
	month = {2018-04-04 00:00:00},
	pages = {e0194441},
	publisher = {PLOS},
	abstract = {
Timely and spatially-regulated injectable hydrogels, able to suppress growing tumors in
response to conformational transitions of proteins, are of great interest in cancer research
and treatment. Herein, we report rapidly responsive silk fibroin (SF) hydrogels formed by a
horseradish peroxidase (HRP) crosslinking reaction at physiological conditions, and demonstrate
their use as an artificial biomimetic three-dimensional (3D) matrix. The proposed SF
hydrogels presented a viscoelastic nature of injectable hydrogels and spontaneous conformational
changes from random coil to β-sheet conformation under physiological conditions.
A human neuronal glioblastoma (U251) cell line was used for screening cell encapsulation
and in vitro evaluation within the SF hydrogels. The transparent random coil SF hydrogels
promoted cell viability and proliferation up to 10 days of culturing, while the crystalline SF
hydrogels converted into β-sheet structure induced the formation of TUNEL-positive apoptotic
cells. Therefore, this work provides a powerful tool for the investigation of the microenvironment
on the programed tumor cells death, by using rapidly responsive SF hydrogels as
3D in vitro tumor models.
},
	keywords = {3D in vitro models, Apoptosis, Enzymatically crosslinked hydrogels, Silk Fibroin},
	issn = {1932-6203},
	doi = {10.1371/journal.pone.0194441},
	url = {http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0194441},
	author = {Ribeiro, V. P. and Silva-Correia, J. and Gon{\c c}alves, C. and Pina, S. and Radhouani, H. and Hyttinen, J. and Roy, A. and Oliveira, A. L. and Reis, R. L. and Oliveira, J. M.}
}