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NanoES are freestanding, flexible 3D structures assembled via the stepwise integration of electronic and biological building blocks. Planar lithography is used to pattern and deposit silicon nanowire field-effect transistors (NWFETs), which serve as the sensor elements of the scaffold and are capable of detecting extra- and intracellular potentials with subcellular resolution. NWFETs are subsequently arranged and integrated into freestanding 3D structures (nanoES) via self-organization, manual folding or rolling of planar mesh matrices, and/or by hybridization with synthetic or natural extracellular matrix (ECM) components. Cells are subsequently seeded into the nanoES, affording opportunities for developmental modification via growth factors and the spatiotemporal monitoring of electrochemical activity in the context of therapeutic assays.