A reactive electrospinning strategy is used to fabricate viable and proliferative cell-loaded nanofibrous hydrogel scaffolds in a single step using an all-aqueous approach. In situ gelling and degradable hydrazone-cross-linked poly(oligo ethylene glycol methacrylate)-based hydrogel nanofibrous networks can be produced directly in the presence of cells to support long-term cell viability, adhesion, and proliferation, in contrast to bulk hydrogels of the same composition. Furthermore, the capacity of the gel nanofibers to retain bound water maintains this high cell viability and proliferative capacity following a freeze/thaw cycle without requiring any cryoprotectant additives, ideal properties for ready-to-use functional tissue patches.