can’t really add much here…except:

• these products would be years and years away from being used at scale (if they get that far)
• if these new potential products present a better option it would be for very limited use cases? So how do these companies make this commercially viable. I would imagine that PNV could then maybe just acquire the tech and incorporate into a niche area that compliments BTM
• personally…if I had a burn…I would want to grow back my own skin using BTM.

thanks for the article!

One key point that I picked up from the article is that both BTM and engineered skin are needed.

"The BTM acts like the dermis, and buys time for engineered skin to be produced. Grafts can then be placed directly over the BTM dressing, which eventually breaks down."

They sound complimentary.

Hey @Scott - good catch. Yes, I think that's right. Here's how I understand things.

Picture below shows why BTM is getting so many indications in burns and trauma (including post amputation). The dermis regenerates into it, from bottom up. In severe wounds, it is essential to enable the dermis to repair.The biologics also do this, but the advantage of BTM is that there is no foreign organic matter involved, and its breakdown over time is complete, producing urea and water, which are perfectly managed naturally by the body.

While I'm not a medic, I wonder if laying an engineered skin on top of a damaged dermis might lead to scar tissue formation? Whereas, BTM essentially provides a protective covering, a scaffold for regeneration to grow into, while still technically being an open wound and delaying or reducing the scarring process. I say this because, as I understand, the mechanism of scar tissue formation is primarily generated frrom within the dermis layer, and we know that BTM leads to less scarring than skin grafts.

Any medically-qualified StrawPeople might be able to correct any misunderstandings but, if this is true, then the commercialisation of engineered skin might well enhance the adoption of BTM as a complementary product. After all, it is already true that the treatment of complex wounds often (usually?) involves the use of muliple products.

@mikebrisy @Scott thats pretty well right. The BTM is stitched or stapled over a wound, sealing it like a fancy bandaid, and its special sauce promotes dermal tissue to repair or regrow beneath it.

TL;DR - the tech are complementary as they all need a healthy dermal layer to support skin formation

If the dermis didn't repair properly, scar tissue would form as the body just tries to cover up the wound like crazy. Part of complex skin wound management is regularly scraping back dead, infected, or poorly healed tissue until decent clean dermis forms a base layer. The dermis, as shown in the graphic, contains all the supporting structures like blood vessels for healthy epidermis (which is what we think of as skin).

when the underlying tissue has healed well enough, the remaining btm membrane can be removed and the epidermis replaced by A split thickness skin graft (STSG). For this, a fancy razor is pushed across a patch of the patients own skin, to slice off epidermis and a small slither of dermis. This tissue is very stretchy, and it can have lots of little cuts put in it (called "meshing"), to make it stretch out even further - it ends up looking like a piece of fishnet stocking. In this way, a relatively small piece of donor skin can cover up a really large area if there is healthy tissue with decent blood supply under it. The donor site heals pretty quickly (a few days, like a bad sunburn), because enough healthy dermis is left that the superficial dermis and epidermis readily regrow.

So, for most wounds even a small donor site can go a long way to cover a large wound, but clearly there are limits. The more extensive the injury, there more wound and less remaining healthy skin. This is where RECELL comes in- it needs only about 5% as much skin tissue as an STSG to cover an equivalent area, so it can go even further. BUT it still needs healthy, vascularised tissue underneath... which can be fostered by a decent patch of BTM

Nb: im not sure that graft can be placed directly over BTM. Perhaps it can, but I have only ever seen the BTM removed then graft placed over the underlying tissue.

@Aaronfzr , @mikebrisy , the diagram and explanations are extremely helpful - many thanks for the insights!

Is it right to say then, that BTM and ReCell each deal with 2 different sections of the burn wound and while they both share the same objective of expediting wound healing and encourage regrowth, both play in distinctly different sections of the wound and as such are not interchangeable? Meaning, ReCell is all about the epidermis layer and BTM operates in the Dermis area and thats where each treatment is targeted at/stays?

Meaning that for each burn wound, depending on nature and severity, of course, the treatment can be (1) ReCell alone (2) BTM alone and in some cases (3) BTM and Recell co-existing together? If this "categorisation" is roughly right, what very broad % would you ascribe to each of these 3 categories?

I am trying to work out how ReCell and BTM co-exist/compete/complement to work out if it makes sense to have investment exposure to both AVH (already a holder) and PNV, given that both directly play in the same "burns wound care management" space.

Apologies if the questions don't make sense!

Thanks for the stimulating discussion - Its been a great motivator to read up on ReCell. Ive found the user guides which seem to answer your question @jcmleng , but also offer us more questions/opportunities in turn.

Short answer: yes, I believe there are use cases that would suit only ReCell for big-ish superficial-only injuries (as an alternative to split thickness skin grafting, STSG)(30%), OR BTM+ReCell Go (10-15%). Small deep injuries may suit BTM-only plus a STSG without ReCell being justified (the majority of cases, lets say 55ish%). My %s are a total guess, ill try to look at the epidemiology of surgical burns and clarify.

Although ReCell claims to be useable on full-thickness thermal burns (ie involving all of deep dermis, as well as superficial dermis/epidermis), it can only do so in conjunction with an autograft (a grafted slab of dermal tissue taken from the same patient). it cant rebuild a dermal layer (which the BTM can assist with), but it doesn't actually save much donor skin if it still needs grafting over a full-thickness defect. So you may as well just do a series of STSG as use the ReCell for these full thickness injuries.

As above, BTM does a pretty good job of rebuilding the dermal layer, and making a good target for a STSG. In this graphic (from polynovo), the BTM provides a matrix for the body to rebuild dermis, upon which epidermis can be placed (green/blue layers, either by own body process, STSG or ReCell-like tech).

But reading the manual shows some quirks of ReCell. For example, in the case of a superficial burn (epidermis and superficial dermis only), recell isnt approved for use on the hands or joints, or with burns >20% Total body surface area (TBSA). 20% is a pretty big area but not massive area- it would logically be EXACTLY what the product should be used for. As an indication, the front of the chest +stomach, or a whole leg/foot front and back, would be about 18% TBSA. To graft this area would probably need about 25-50% of injured skin, or if ReCell used about 5% of injured area. So its weird that it isn't approved for that, although presumably it will eventually be.

And, as i noted above, for a full thickness burn, you still need a graft to make functional deep dermis, so that too doesnt save much tissue. Its just quite strange that the approvals for both use-cases dont really reflect what would actually be needed for either scenario.

https://avitamedical.com/wp-content/uploads/2024/08/AW-IFU045-Instructions-for-Use-RECELL-GO™-Autologous-Cell-Harvesting-Device-AVRL0103-AVRL0104-Rev-3.pdf

@jcmleng as @Aaronfzr has given a more authoritative answer, I only add to thank @Aaronfzr for a more in depth and clinically informed response. That is directionally what my understanding was, but I’ve learned some more from the details you’ve given.

All I’d add is that this explains why $AVH has an explicit strategy to do deals to complement the range of solutions it offers.

Finding data to answer @jcmleng's question about the relative volume of the different use cases has been quite tricky.

The closest I have found so far is from a 2022 report by the Plastic Surgeon's society in Australia:

https://plasticsurgery.org.au/wp-content/uploads/2022/08/Burns-Report-16-February-2022-FINAL.pdf

I hope this adds some interesting context, but the data are a few years old, largely predate the commercial introduction of these products, and only loosely address the question.

On average, just under 2,000 adults per year had a major burn, 93% of which had a Total-body surface area burn (TBSA)<20>

In 2019/20, only 1% of major burns needed a product functionally similar to BTM,10% used a "skin cell product" (I'm not sure what this refers to - I don't think engineered skin), 70% received a skin graft, and 4% needed skin donation from another person - presumably

because they had too much injury to cover / too little remaining healthy skin (ReCell candidate).

In table 13, from 2018/19 data we can see that 1,679 adults ≥16yrs (21%) had some form of alternate skin graft (donated from another person's skin, animal skin/ product, engineered skin)(possible ReCell +/- BTM), while almost 35% underwent a STSG (possible role for ReCell, or BTM, or both). Only 2% needed a full thickness grafting (possible role for BTM+ReCell)

@Aaronfzr , I cannot thank you enough for your very insightful posts! As I work through them, I now wish I paid more attention during Biology back in high school to be able to more quickly comprehend what you have posted!

Morningstar Australia issued an updated report on $AVH, worth a read, happy to share if its behind a paywall. But their analyst includes a paragraph which seems to agree with our view:

"Other competitive products in burn and wound care include Polynovo’s NovoSorb, which is a synthetic membrane that biodegrades over time allowing the skin time to regenerate. A recent academic article in the Journal of Burn Care & Research concluded that using RECELL in conjunction with Novosorb produced better clinical outcomes than skin grafts. Thus, we believe the products are more complementary than competitive. Novosorb is approved in overlapping markets to RECELL but is further ahead in commercial roll-out."

https://premium.morningstar.com.au/investments/security/ST/0P00006WE0