In yesterday's stream you showed us that there will be a difficulty above Nightmare in the future. I don't think you have to overcomplicate things.
All that you need to do to make survival a victory for veterans of the game, is to remove the automatic heal-up of wounds and blood plague entirely. Of course, you may tune up zombie density and stuff like that, but that probably won't change the way I play the game that much.
If a character is injured, he needs to be put into the infirmary's treatment bed to heal up - and it should take quite a while. Painkillers only temporarily removes the negative effects of the injury, similarly to how coffee works on tiredness.
If a character has got a full-on blood plague infection (with timer), he needs the cure, but it only removes the timer. The character still needs to be put in a treatment bed to actually remove the negative effects and the built-up infection.
The heal-up costs -1 meds per day per patient. So 0 cost if you don't have anyone being treated. Bump the Field Hospital's treatment beds to at least 4. Infirmary 1 has got 1 bed, lvl 2 and 3 adds another bed each.
This also means that any neck bite, lunge attack that downs you, Feral attack of any kind, Bloater Gas injury... basically any zombie attack that is not just a regular clawing, is going to give your character an injury. The same with any fire damage, explosive damage, fall damage and Juggernaut attack.
Each injury should take 30 minutes to heal, while regular health damage from regular zombie swipes (as well as blood plague) should be healed at a 33% per 30 minutes rate. Pathology/surgeon skills should add a 25% rate to that, respectively, and Medicine 25% to both. You could make the infirmary beds part of the total bed count of the base and have the AI automatically put the most hurt characters in them, and rotate as needed. The injuries should be removed first, so that a character can have "internal bleeding" + "chunk of flesh missing" + "sprained wrist" constituting a near-death sliver of health left. That would mean 1,5 days to remove all 3 injuries, and then another 1,5 days to fully recover. The pathologist and surgeon both have abilities that would speed this up, for a hefty cost, of course. A First Aid kit should remove an injury each - but not recover health.
In this way, we would have an incentive to actually use the infirmary facility mods, heal-up abilities and the medicine skill, and we would have to play more carefully out in the wild since the hospitalized characters won't participate in base defense (at least not efficiently) and will be useless until healed up.