Multicellular Layered Nanofibrous Poly(Oligo Ethylene Glycol Methacrylate) (POEGMA)‐Based Hydrogel Scaffolds via Reactive Cell Electrospinning

While hydrogels are demonstrated to be effective scaffolds for soft tissue engineering, existing fabrication techniques pose limitations in terms of being able to reproduce both the micro/nanofibrous structures of native extracellular matrix as well as the spatial arrangement of different cell types inherent of more complex tissues. Herein, a reactive cell electrospinning strategy is described using hydrazide and aldehyde-functionalized poly(oligoethylene glycol methacrylate) precursor polymers that can create nanofibrous hydrogel scaffolds with controllable local cell gradients using a sequential all-aqueous process that does not require additives or external energy. Cells can be encapsulated directly during the fabrication process in different layers within the scaffold, enabling localized segregation of different cell types within the structures without compromising their capacity to proliferate (≈4-fold increase in cell density over a 14 day incubation period). This sequential reactive electrospinning approach thus offers promise to generate coculture fibrous hydrogel networks in which both the nanoscale architecture and the cell distribution can be controlled, as it is essential to recreate more complex types of tissues.