Macroporous cryogels that are amenable to facile functionalization are attractive platforms for biomolecular immobilization, a vital step for fabrication of scaffolds necessary for areas like tissue engineering and diagnostic sensing. In this work, thiol-reactive porous cryogels are obtained via photopolymerization of a furanprotected maleimide-containing poly(ethylene glycol) (PEG)-based methacrylate (PEGFuMaMA) monomer. A series of cryogels are prepared using varying amounts of the masked hydrophilic PEGFuMaMA monomer, along with poly(ethylene glycol) methyl ether methacrylate and poly(ethylene glycol) dimethacrylate, a hydrophilic monomer and cross-linker, respectively, in the presence of a photoinitiator. Subsequent activation to the thiol-reactive form of the furan-protected maleimide groups is performed through the retro Diels−Alder reaction. As a demonstration of direct protein immobilization, bovine serum albumin is immobilized onto the cryogels. Furthermore, ligand-directed immobilization of proteins is achieved by first attaching mannose− or biotin−thiol onto the maleimide-containing platforms, followed by ligand-directed immobilization of concanavalin A or streptavidin, respectively. Additionally, we demonstrate that the extent of immobilized proteins can be controlled by varying the amount of thiol-reactive maleimide groups present in the cryogel matrix. Compared to traditional hydrogels, cryogels demonstrate enhanced protein immobilization/detection. Additionally, it is concluded that utilization of a longer linker, distancing the thiol-reactive maleimide group from the gel scaffold, considerably increases protein immobilization. It can be envisioned that the facile fabrication, conjugation, and control over the extent of functionalization of these cryogels will make these materials desirable scaffolds for numerous biomedical applications.

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