Improving Network Crosslinking of Peptide- immobilized Hydrogels formed by Visible Light-initiated Thiol-acrylate Photopolymerization

摘要

Photopolymerization has been a favorable method for preparing poly(ethylene glycol) (PEG) based hydrogels for in situ cell encapsulation. Since PEG contains no bioactive motif for receptor recognition, pendent peptides/proteins are routinely co-polymerized within the crosslinked PEG network to increase survival and function of the encapsulated cells. We recently reported a visible light initiated mixed-mode thiol-acrylate photopolymerization for preparing peptide immobilized hydrogels suitable for in situ cell encapsulation. 1,2 Briefly, a non-cleavage type visible light photosensitizer eosin-Y was used to generate thiyl radicals from thiol-containing cross-linkers and initiates rapid gelation. To render the otherwise inert PEG-based hydrogels bioactive, either acrylated or mono-cysteine bearing peptide could be co-polymerized within the hydrogel network. 2 Unfortunately, the immobilization efficiency of acrylated pendent peptide in the hydrogels was relatively low (~60%). Alternatively, pendent peptide bearing a cysteine residue (e.g., Cys-Arg-Gly-Asp-Ser or CRGDS) could be effectively immobilized (~90%) within the covalent hydrogel network through radical-mediated thiol-acrylate conjugation for improving cell adhesion in 3D. The use of mono-cysteine pendent peptide, however, caused significant chain transfer of the growing polymer chains and drastically reduced the cross-linking density of the hydrogels. 2 Therefore, this project aimed at creating an effective peptide immobilization strategy without compromising network crosslinking density in the visible light-initiated thiol-acrylate hydrogels.