I thought i can use Buffers to input Nuclear Fuel and output the depleted fuel - but this does not work. Is it supposed to work?

You need to use fission ports to access the controller. Buffers are for getting fluids to active coolers ;)

Okay, i now tried the same with Fission Ports - i was able to remove the depleted cells, but i'm not able to put in new, fresh cells. What might be the reason for that?

See the following screenshots with the guis being from the left cable to the right (so first left chest, fission port, right chest).

@turbodiesel4598
Tried around with Mekanism Pipes - same result. Inputting does not work. Do i need to input them from a special side (front instead of downside)?

This is a sort-of bug which I'll get fixed - basically, it's because you're trying to insert into the bottom of the port, which corresponds to the bottom of the controller. If you try piping into the side, it should work.