Mixed mode thiol-acrylate photopolymerizations for the synthesis of PEG-peptide hydrogels

Thiol-acrylate mixed mode photopolymerizations provide an easy, robust, cost-efficient, and cytocompatible reaction scheme for the incorporation of cysteine-containing peptide sequences into PEG hydrogels. With an acrylate: cysteine ratio of 4:1, similar to 95% of the peptide is incorporated after 10 min of reaction with similar to 5 mW/cm(2) of 365 nm light. Specifically, thiol monomers, with thiol-presenting peptide groups in the form of CGGGGG, CRGGGG, CWGGGG, CDGGGG, CSGGGG, and CGGGGC, copolymerized with PEG4600 diacrylate were characterized. The chain transfer constant of acrylates to thiols was determined to range from 1.5 to 2, depending on the amino acid sequence. Complete conversion of the functional groups occurred after similar to 40 s for all systems, excluding the tryptophan-containing peptide sequence which had a retarded polymerization, taking similar to 60 s. The cross-linking densities of the final gels ranged from 1.5 x 10(-2) to 2.0 x 10(-2) mol/L when 10 mM of peptide was reacted with 40 mM of acrylate groups. Efficient incorporation of high amounts of peptide functionalities with this polymerization method provides a facile technique for the covalent incorporation of cell-specific peptides important for directing cellular function in a gel environment and the purposes of 3D cell culture, which are critical in applications such as tissue engineering.