Poly(2-hydroxyethyl methacrylate) (PHEMA) hydrogels were prepared with a disulfide containing crosslinker bis(2-methacryloxyethyl) disulfide (DSDMA) that exhibited enhanced release in the presence of glutathione (GSH), a biologically available reducing agent. Varying concentrations of the DSDMA crosslinker were incorporated into the prepolymer before the radical polymerization, enabling the crosslink density to be easily tuned. Dye release studies were performed using rhodamine B and rhodamine 6G dyes, and the UV response of the dyes released into the supernatant measured with the addition of GSH. Using ether-based cross-linkers as a control, the disulfide cross-linkers exhibited a substantial increase in release rates, confirming the responsive nature of the hydrogels to biological reducing agents. The polymers were also tested in a cell culture system for their ability to release the anti-fibroproliferative agent, mitomycin C (MMC). Polymers cross-linked with DSDMA delivered MMC over a slightly longer time period than control polymers prepared with a conventional ether cross-linker. (C) 2011 Elsevier Ltd. All rights reserved.