Gellan Gum Hydrogels with Enzyme-Sensitive Biodegradation and Endothelial Cell Biorecognition Sites

The survival of a biomaterial or tissue engineered construct is mainly
hampered by the deficient microcirculation in its core, and limited nutrients
and oxygen availability to the implanted or colonizing host cells. Aiming
to address these issues, we herein propose bioresponsive gellan gum (GG)
hydrogels that are biodegradable by metalloproteinase 1 (MMP-1) and enable
endothelial cells adhesion and proliferation. GG is chemically functionalized
with divinyl sulfone (DVS) and then biofunctionalized with thiol cell-adhesive
peptides (T1 or C16) to confer GG endothelial cell biorecognition cues. Biodegradable
hydrogels are then formed by Michael type addition of GGDVS or/
and peptide-functionalized GGDVS with a dithiol peptide crosslinker sensitive
to MMP-1. The mechanical properties (6 to 5580 Pa), swelling (17 to 11),
MMP-1-driven degradation (up to 70%), and molecules diffusion coefficients
of hydrogels are tuned by increasing the polymer amount and crosslinking
density. Human umbilical cord vein endothelial cells depict a polarized
elongated morphology when encapsulated within T1-containing hydrogels, in
contrast to the round morphology observed in C16-containing hydrogels. Cell
organization is favored as early as 1 d of cell culture within the T1-modified
hydrogels with higher concentration of peptide, while cell proliferation is
higher in T1-modified hydrogels with higher modulus. In conclusion, biodegradable
and bioresponsive GGDVS hydrogels are promising endothelial cell
responsive materials that can be used for vascularization strategies.