ED-E bought the farm in the gas explosion to kill the spores. Does he regenerate back at another location or is my little friend gone for good?

If your playing hardcoe mode then he is dead but if not then he should be back at either primm or lucky 38 if you wait for 3 - 7 days.

Or.. If he was just knocked unconscious, then he may still be in the vault. ED-E has some issues getting stuck in areas with low ceilings.