Hard to describe how cool this paper is in Science. This carries the potential to change surgery dramatically, and offer the amazing potential of scar-free surgery. A https://science.sciencemag.org/content/372/6540/eaba2374

Most surgical residents notice in their training how different scarring is between different patients, from those who have the potential to develop keloid scars, to the tendency of children and neonates to heal almost scar-free, there is enormous variability in healing response.

We've had various explanations, from hyaluronic acid and persistent inflammation etc., but these authors appear to come up with a far more elegant explanation, and powerfully demonstrate the mechanism behind scarring.

Briefly, the were able to sort out the healing response of two different populations of fibroblasts. One, that is active when you are developing, heals and *regenerates* tissue - no scar, normal tension, hair follicles etc. This is ideal.

But after we're born the priority, probably an evolutionary benefit, is rapid closure of the wound to re-establish a microbe-proof seal. The fibroblasts that do this have slightly different gene expression, do not regenerate tissue, and create a more disordered collagen matrix.

This is scar. Scar is weaker than native skin. It is often unsightly. It will never be as strong. You know that nonsense that what doesn't kill you makes you stronger? Idiocy. Scar is weaker.

So imagine if we could reprogram the body to only use the natal fibroblast population to heal wounds? After all, surgery, done sterilely, isn't like the wounds we've faced throughout our evolutionary development. It's not so important to be a *fast* healer.

That's where this paper gets really cool, first by genetically forcing this change to have mice heal a wound by tissue regeneration, but then *also doing this with an established drug* verteporfin.

Now I have *never* used this drug, perhaps @DGlaucomflecken has as it has something to do with eyeballs, but it also happens to inhibit the "scar" fibroblasts, allowing the "regenerative" fibroblasts resident in your skin to take over.

If this translates to humans, the potential would be to treat skin at the time of surgery by injecting around the wound, or impregnate dressings (it's a lipophilic drug so transdermal delivery is conceivable via a drug patch). It can also be given systemically.

It has some side effects, but not terrible, and it's not clear you wound need to be on it for long. But it also raises lots of other, very interesting questions. Would it increase infectious risk? If you had fixed, say, bowel, would it interfere with an anastomosis?

Or, would it be better? Since it causes regeneration, maybe instead of scarred anastomosis, you end up with regenerated bowel? It would be just as possible you would heal with less leak, and fewer adhesions (another type of scar). This has big implications.

Adhesive scar tissue - it makes you weaker remember - sets you up for future problems and complications - like bowel obstructions. If this drug did not interfere with anastomotic healing (bowel-bowel, vessel-vessel or other connections), could it result in regeneration elsewhere?

Imagine, no more bowel obstructions after surgery, healing to native tissue function, less complicated re-operative surgery, etc.

Now this is very speculative, we're still in *mice* after all, but this is why science is so cool.

Mice are a model organism, but they, despite being so different, have a lot of genetic homology to us because we have a common ancestor. Now, as we know, all models are wrong, but some are useful. Is this a case of a useful model?

Probably so. If not a homolog humans likely have orthologs or paralogs with similar function. Wound healing is well conserved across mammals. If not directly applicable, it is highly probable it will lead us to a similar mechanism!

I'm excited. I want to get some of this drug and make two little cuts - maybe one on each of my thighs - and try drug vs saline to see if I heal without scar! I mean, why not? What's two little cuts? Science!