Microelectrode assemblies and related methods are disclosed for bio-stimulating and/or bio-sensing a target tissue. The assemblies can include a two-side substrate, an array of microelectrodes, each of the microelectrodes including a nano-wire embedded within the substrate and extending from a proximal end to a distal end and through the substrate, each nano-wire having a diameter preferably less than 1 μm. The substrate can include portions made of nano-porous material(s) through which the microelectrodes pass. The substrate with the embedded nano-wires can effectively be fluid impermeable. The proximal ends of the nano-wires can be adapted to be connected to an electronic device and the distal ends are adapted to be disposed in a biological environment for bio-stimulating a target tissue and/or bio-sensing activities of the target tissue. Suitable alloys such as platinum, platinum-iridium, and/or other noble-metal-alloyed compositions can be used for the nano-wires.