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A combination of 'orthogonal' thiol-ene 'click' reactions is utilized for fabrication and functionalization of micro-patterned hydrogels. A furan-protected maleimide-containing parent copolymer is partially activated via the retro Diels-Alder reaction to obtain an 'orthogonally' functionalizable copolymer, where the different functional groups can be exploited for multi-functionalization or fabrication of functional hydrogels using combination of the nucleophilic and radical thiol-ene reactions.

In this study, we report a facile fabrication of poly(ethylene glycol) (PEG) based bulk and micro-patterned hydrogels that are amenable to functionalization with thiol-bearing molecules using the metal-free radical 'thiol-ene' click reaction. The hydrogels were synthesized using photopolymerization of commercially available monomers, namely allyl methacrylate and PEG-methacrylate in the presence of a PEG-dimethacrylate based crosslinker. Swelling behaviour of these hydrogels could be tailored by varying the amount of the hydrophilic monomer in the feed as well as varying the length of the PEG-chain in the methacrylate monomer. Importantly, the extent of functionalization of these hydrogels could be readily tuned by varying the amount of the reactive allyl methacrylate monomer. Analysis of nitrogen content in the hydrogels after conjugation of cysteamine demonstrated that the amount of cysteamine incorporation was in correlation with the amount of allyl groups in the hydrogels. Three-dimensional hydrogel patterns were fabricated using micromolding in capillaries. Tuneable conjugation of a thiol-containing dye molecule and a ligand-mediated immobilization of streptavidin onto these hydrogel patterns were realized. It was found that the swellability of the hydrogel patterns control the diffusion of streptavidin into the interior of the hydrogel matrix. These bio-inert hydrogels could be appended with peptides to promote cellular adhesion. Furthermore, it was demonstrated that the photochemical thiol-ene based method of conjugation enables localized attachment of thiol-containing molecules within these reactive hydrogels.