Polymethacrylate hydrogels are useful scaffolds for tissue engineering and cell-based therapies provided they can be modified to give good cell adhesion characteristics. They have advantages over non-swollen materials, such as good diffusion properties, tunable moduli and porosities. However, conventional non-charged hydrogels are essentially non-adhesive for cells and they are poor substrates for cell culture. In a previous volume in this series of symposia from the Polymer Networks Group, we described how both amphiphilic conetworks and alkyl-aminated hydrogels were excellent substrates for cell culture.([1]) In this article we report our most recent work on understanding how to modify hydrogels for cell attachment. We report how the choice of photoinitiator affects the viability of human dermal fibroblasts (HDFs). Next, we provide further results involving the use of an enzyme deprotection strategy that can be carried out after copolymerization of a GRGDS methacrylate monomer. We show that the peptide enhanced the culture of HDFs in serum when the peptide was attached to poly(1,2-propane diol methacrylate-co-ethane diol dimethacrylate). On the other hand, poly(n-butyl methacrylate-co-ethane diol dimethacrylate) networks adsorb larger amounts of protein non-specifically, and they are reasonable substrates for adhesion of HDFs without peptide modification. Attachment of GRGDS to an example of these networks did not increase the attachment and proliferation of HDFs in serum containing media. We also describe the attachment of fibrinogen/fibrin coatings by the transglutaminase mediated reaction of alkyl amines attached to a poly(1,2-propane diol methacrylate-co-ethane diol dimethacrylate-co-dodecyl methacrylate) network. This work illustrates the reactivity of alkyl-aminated hydrogels in transglutaminase catalyzed reactions, although the addition of the fibrin coating did not improve the performance of the material for cell culture which was already good on these hydrogels.