I think there's a need to have resistances or defence, and my preference is scaling resistances for the theme of taking damage and healing it up. I'd really like the health bar to fluctate up and down to simulate what the name 'regeneration' is suggesting in a defence set.
Regeneration itself is a strictly linear mechanic - you heal a set amount, and it doesn't care how much damage is incoming. If it is 50 damage/second or 500 damage/second, regeneration is going to heal a flat amount. That's your mitigation. If things get worse, you spiral very fast.
Resistances however scale to what's incoming. 90% resistance protects you from 45 out of 50 damage, or 450 out of 500. Resistance works harder the more danger you're in.
I think Regeneration needs resistances so that it functions as a set against more difficult enemies. It needs that initial cushion so it can take a heavy hitter on.