Verteporfin - Experimental Scarless Healing
Some description on current state of Verteporfin
Day 29/30 of writing daily. I have been reading about this for a while, and write some notes here, but they are still not as clean as I would like.
If you have a wound that is large, then typically, while healing, then typically this forms scar tissue rather than normal skin tissue.
However, there might eventually be ways of healing that doesn’t cause the scar to form. But this is still a highly experimental technique.
Why does scarring occur?
When you get a wound, you want to close it up as soon as possible to reduce chance of infection. The body naturally does this by having platelets form a scab, and then heal the wound underneath the scab more gradually.
However, in healing, the body optimizes for speed, and thus uses fibrous tissue to scaffold a fix that can be done sooner.
There is a time period over which you can determine whether the wound will cause scar tissue or normal healing. This is typically determined in the first 24-48 hours.
This process can be altered. If one physically closes the wound, with stitches, then one typically gets less scarring. But are there other ways we can try work on this.
Verteporfin
One pathway that seems to affect this, is the YES-Activating-Protein (YAP) route. Verteporfin is an experimental drug that has been repurposed to try affect YAP.
This was mostly found as a contender from being an existing drug with a new possible use, and such, it is difficult to fund large scale trials for researching this.
Thus, current science relies on small-scale animal studies with a few people doing self-tests too.
Case studies
Most of these are taken from the telegram server on verteporfin.net. The site also has some old case examples.
I try to list a couple, but they are limited and varied. Initial experiments were via injection, but there is some reason to think that a topical gel might work even better. I guess both are understudies.
Animal Studies
Most of the inferred research is form looking at a pig study, where they made a scar, then sewed it up, and used a different dose of a single verteporfin injection.
Mouse incision showed almost scar tissue with saline solution, vs close to perfect healing after 30 days with a single verteporfin injection.
Pig skin also was tried, “Tested 1, 2, 4, 8 mg/mL. "Wounds (1 and 2 mg/mL) had minimal apparent scarring by 8 weeks, whereas some scarring was observed at higher doses (4 or 8 mg/mL)...”
But there are few studies even on animals
Case study: Dr Bloxham
They studied using this to try induce hair regrowth instead of scarring.
“highest dose seems to work the best”
Some noticeable results, where there were a few different doses tried to induce head hair to grow back instead of hairless scar tissue on the head.
The best result was the highest dose, which was ~0.8mg/cm², which showed some better than the smaller doses.
Since then people have continued to do 0.8mg/cm^2 though it seems like possibly higher could be better too.
Case Study: Lucy & Sage
These people tried two times.
first a basic solution when there was some scar, didn’t work that well since it didn’t dissolve
second, they made a real solution, but maybe didn’t use enough (hard to tell)
First attempt
The Verteporfin was purchased from MedChemExpress (https://www.medchemexpress.com/Verteporfin.html, 50 mg for $552) in preparation of an upcoming reconstructive surgery in May next year for which I wanted to evaluate its usefulness in scarless wound healing. We were preparing to compound some Verteporfin following the Hydrogel preparation described by Jiang-Tao Yang, Dingwei Wu, Jianping Li et al this weekend, but after I cut myself in a woodshop accident this Thursday I kinda improvised and did a preliminary trial of using the unprocessed Verteporfin powder in a suspension of Hank’s Balanced Salt Solution (HBS) by weighting out 10mg of Verteporfin into a presteralized 5ml amber glass vial. I then added 5ml of the freshly opened HBS which I had laying around for another project as a improvised PBS replacement and after crimping the vial i placed it on a vortexer for 60s until the Verteporfin was fully suspended (but not dissolved, as seen in the video). What followed is documented in the recording; I did all of this within an hour of injuring myself and before replacing the dressing I withdraw 1ml from the 5ml suspension using a 25G needle and injected 5x 0.2ml doses (ie a total of 2mg undissolved Verteporfin suspension) into the fresh wound as seen in the video.
Follow up:
I had a very bad reaction with non dissolvable vp
I don’t think it was a good idea that u used the non dissolvable VP into your wound
Cover your wound from the sun for more than 2 weeks
Because your body will take time to absorb the VP particles
Enrico, [20 Sep 2024 at 00:25:12]:
Any reason for injecting more?
Should be noted that there’s an upper limit to VP, after which results have been noted to get worse in animal studies
Also the fluid looked super clear, not sure if that’s alright
Lucy Vertoperfin, [20 Sep 2024 at 00:26:15]:
i just feel like when i did the initial wound care i didn’t really inject it into the tissue and as someone pointed out, a lot of it just ran down my arm so this time i wanted to make sure it actually ended up in the skin tissue
i think we are still far below that
well since its still not soluable it kinda just undissolved, suspended VP particles in solution that are hard to see in the video
but i am confident that 2mg of it ended up in my skin tissue
Enrico, [20 Sep 2024 at 00:28:19]:
I think bloxham said it’s supposed to become a thick green liquid
Lucy Vertoperfin, [20 Sep 2024 at 00:31:42]:
if you reconstitute the liposomeized version of it (ie Visudyne) or you dissolve the unprocessed VP in a solvent other than water (ie ether, ethanol or DMSO), yes
as i explained in #general there is a lot of confusion in this group around verteporfin as in verteporfin the raw benzoporphyrin derivative you can buy as a chemical reagent (not water soluable) and the FDA approved drug Visudyne
i have verteporfin powder, but as you pointed out it’s not water-soluble so it is useless for injection. all the papers that are cited by stanford etc say verteporfin but in the methods section they usually mention that they actually use Visudyne, which makes sense. i dont have the means to make the lipid myself from verteporfin but im wondering if i could still use it if i use DMSO for delivery
Second attempt
Sage, Ivy and I refined the protocol for preparing the verteporfin liposom from the verteporfin powder we obtained from medchemexpress. We plan to publish a paper on this some time soon, but im happy to share the protocol. if you end up replicating this research before we get a chance to publish, it would be appreciated if you credit our efforts appropriately
verteporfin simple liposome protocol:
verteporfin and soy lecithin are combined in a 1:8 molar ratio in a brown glass vial. They are dissolved using a minimal amount of methanol and chloroform in a 1:2 v:v ratio. The solution is gently agitated to get as much of the solids into solution. The non-polar solvents are removed by gently heating the glass vial at no higher than 55c. When all solvents have disappeared the vial is placed in a vacuum chamber to remove any remaining solvent (or heated further for another hour or more to ensure remaining solvent is driven off). The mixture is rehydrated using the desired final volume of saline, warmed above 30c. The vial is then placed in an ultrasonic bath at 40c for 20 minutes. After sonication the film should have dissolved into the saline and is ready for sterile filtration. Ensure that sterile filtration is performed with a liquit tempature at or above 30c.
ie to compound 4mg of VP in a 1mg / ml solution, you can follow these steps:
weight out 34mg of lecithin and 4 mg verteporfin on a microgram scale in a brown glass vial
dissolve lecithin and VP by adding 2ml of CHCl₃ + 1ml MeOH
plug the vial with a silicon stopper and agitate the vial on a vortex mixer for 2-3 minutes to help with dissolving the lecithin + VP in the organic solvent
remove stopper, place open vial on a hotplate set to 55C for about 20min to evaporate most of the organic solvent. i attached a TC probe to make sure the temperature inside the vial does not exceed 50C
after all solvent is evaporated, there should be a thin dark film in the bottom of the vial. remove any remaining solvent by placing the vial in a vacuum chamber down to ~1mbar, i used a vacuum desiccator
[video 1]
start warming up the some saline (i used presteralized 0.9% 5ml sodium chloride solution) to 40C in an incubator or water bath before for sonification
preheat sonicator (i used a vevor brand ultrasonic cleaner) water bath to 40C
add 4ml of the pre warmed saline to the vial and plug with a silicon stopper and crimp the vial using a hand vial crimper
[video 2]
shake the sealed vial with the redissolved VP + lecithin thin film and place it in the sonicator for 20min at 40C
[video 3]
prepare a second empty brown glass vial and sterilize in an autoclave or buy a presteralized, pre crimped vial. this is the vial we will fill with the filtered VP suspension.
use a 5ml or 10ml syringe with any (ie 18G) needle to withdraw the unfiltered VP solution while it is still warm. it is important to perform the filtration step quickly so the liquid temperature is at or above 30C during the filtration. use a 0.22um PTFE syringe sterile filter to filter and inject the VP solution into the empty sterile vial using a fresh needle following common practice for pharmaceutical compounding of sterile preparations like this (ie ideally working under a laminar flow hood, read “Compounding Sterile Preparations”, Fourth Edition, by E. Clyde Buchanan et all for advice).
the filtered and sterile VP is now ready for application following the protocols discussed in other channels in this group. if you follow this specific protocol, you end up with 4ml of saline with 1mg / ml VP.
we used the VP prepared this way for Sage about 48h after surgery. more to come and we will update with results of her recovery
results were not that good though:
I unfortunately don’t have good before/after pics. My very subjective review is: 0.4mg/cm^2 is not a large enough dose to make a significant effect. I am now about 8 months into recovery and I don’t see a huge difference between the treated and untreated parts of my wound.
Case Study: Dr. Taleb Barghouthi
Some notes from telegam on different trials being attempted
Dr. Bargouthi’s VP FUE trials
Yes, bargouthi recently tried 0.4, 0.6, 0.8 and 1 mg (in seemingly a single cm2)
Dr. Ted Miln is confirmed to do a VP trial in 2025. Likely a hairtransplant. https://www.hairrestorationnetwork.com/topic/64737-verteporfin-hair-regeneration-human-trial-dr-barghouthi-official-thread/page/114/#comment-782509
bargouthi had comparable results in both 0.8 and 1
Conclusion
Through some self-tests, we can see that some people have attempted various methods for using Verteporfin to get scar-free healing. However, the success is very mixed. There are some vert small scale clinical trials happening eventually, but things in this space are slow.
I guess it seems like it could potentially be used in conjunction with surgeries to prevent scar formation after (eg: post-FFS or something), but it’s unclear if the evidence is good enough for this yet.
I will try to edit and add more info on this when it comes up.