We present a discussion of the use of vertically-aligned carbon nanofibers (VACNFs) as nanoscale elements that directly interface to biological whole-cell systems. VACNFs are compatible with a large subset of microfabrication processes, thereby enabling their incorporation into mesoscale hybrid systems that provide addressability of the VACNFs as either bulk electrode material, or as individually addressed nanoelectrodes. These VACNF devices are compatible with cell cultures, and electrochemical addressability of nanofibers can be maintained for extended periods within cell cultures. We present results that demonstrate possible use of VACNF devices as electrical and genetic substrates for tissue scaffolding applications.