The mechanical microenvironment plays a crucial role
in the evolution
of colorectal cancer, a complex disease characterized by heterogeneous
tumors with varying elasticity. Toward setting up distinct scenarios,
herein, we describe the preparation and characterization of gelatin
methacrylamide (GelMA)-based hydrogels via two different
mechanisms: free-radical photopolymerization and photo-induced thiol-ene
reaction. A precise stiffness modulation of covalently crosslinked
scaffolds was achieved through the application of well-defined irradiation
times while keeping the intensity constant. Besides, the incorporation
of thiol chemistry strongly increased stiffness with low to moderate
curing times. This wide range of finely tuned mechanical properties
successfully covered from healthy tissue to colorectal cancer stages.
Hydrogels prepared in phosphate-buffered saline or Dulbecco’s
modified Eagle’s medium resulted in different mechanical and
swelling properties, although a similar trend was observed for both
conditions: thiol-ene systems exhibited higher stiffness and, at the
same time, higher swelling capacity than free-radical photopolymerized
networks. In terms of biological behavior, three of the substrates
showed good cell proliferation rates according to the formation of
a confluent monolayer of Caco-2 cells after 14 days of cell culture.
Likewise, a characteristic apical-basal polarization of cells was
observed for these three hydrogels. These results demonstrate the
versatility of the presented platform of biomimetic materials as in vitro cell culture scaffolds.