Dr Mark Rubin talks about driving oxygen to the surface of the skin using Cutagenesis
By taking a deep breath, we know that oxygen is good for us. From even the most basic understanding of biology we learn that oxygen is a necessity for our body. Those of us interested in tissue growth and new collagen production, are also aware that oxygen is one of the essential ingredients needed for cell growth.
Oxygen enhances collagen synthesis and also has a very profound antimicrobial effect on wounds. It’s essential in order to be able to create ATP, and it is one of the rate limiting factors when it comes to re-epithelialisation.
Oxygen in the skin
Some oxygen enters the skin through blood, but research also shows that the uppermost 250-400 microns of your skin gets most of its oxygen supply from the atmosphere.
Oxygen diffuses into the dermis—the upper 400 microns of your skin, rather than coming through your bloodstream.
In many treatment modalities such as microneedling, that’s as deep as you reach, so if you’re trying to heal those areas, the oxygen that’s going to help healing is atmospheric oxygen; it’s the oxygen around you rather than in your blood supply.
Healthy skin has a mechanism for absorbing oxygen, but damaged or ageing tissue doesn’t function quite as well and the skin’s oxygen level decreases every year as we get older.
Using Cutagenesis, a super-saturated oxygen emulsion, it’s possible to drive oxygen through the surface of the skin and promote healing. The science is based on the idea of using perfluorodecalin—a material that has a very high affinity for oxygen.
Perfluorodecalin has been used by the military over the years as a blood substitute. It’s been used in trials in the United States for post-myocardial infection to try and oxygenate ischemic areas of the heart and save the heart muscle.
It’s possible to put a huge amount of oxygen under pressure into a container of perfluorodecalin. Applying this to the skin allows very slow outgassing into the tissue over several hours.
Research has shown that if you create a well, fill it with oxygen emulsion, then lay a 1mm thick piece of tissue over the well, and measure the oxygen that passes through the tissue, that oxygen will increase over the following 20 minutes and stay elevated for several hours (see Figs.1 and 2).
This particular research shows a starting reading of 160mm of mercury, and within 20 minutes it goes up to almost 500, illustrating that oxygen can diffuse through a 1mm thick piece of tissue within 20 minutes, and stay elevated over the course of several hours.
There is a multitude of products on the market that claim to include oxygen, but the technology used for the pressurised oxygen in perfluorodecalin is unique.
No other topical oxygen product has the same amount of oxygen, nor can they outgas it over the course of several hours.
In fact, measuring the amount of oxygen in all these products reveals an oxygen content no higher than atmospheric oxygen at 160mm of mercury. Instilling large amounts of oxygen in a product is impossible if it’s not pressurised.
Research and benefits
A study carried out in the 1990s tested different moisturisers with non-pressurised oxygen in them, and found that higher levels of oxygen within a product gave more profound reductions in wrinkles over the course of a month.
The technology that we have now, allowing pressurised oxygen, delivers over 100 times more oxygen than what they were capable of doing in the 1990s.
In a trial of 20 patients with photodamage, using the perfluorodecalin super-saturated oxygen emulsion product CutaVive, patients applied the product twice a day over the course of six weeks.
Skin oxygen content was measured using a radiometer and skin moisture content using a corneometer. A biopsy was taken from the face of several of the patients before the study and after six weeks to see what the difference was histologically.
The skin’s oxygen levels naturally reduce as we age—it’s much lower in middle aged skin than when we were 20 years old. CutaVive usage twice a day for 6 weeks created a rise in the resting oxygen level—the partial pressure of oxygen in their skin from them using the product twice a day.
The results showed around a 17% increase in moisture content, while the tissue’s oxygen levels increased by over 70%.
Patients were asked to rate the improvements in their skin at three weeks and then again at six weeks, considering elements ranging from colour, wrinkle improvement, blotchiness, dryness, pore size and firmness.
The results showed some improvement in all of these parameters within three weeks, The response in smokers is a little faster and more profound since they start with lower oxygen levels than non smokers
When asked to rate themselves, 76% of the patients rated that they had at least a moderate improvement in their skin overall.
Looking at the images below, in the first set we can see fine wrinkling in the periorbital area in this female patient after six weeks showing the degree of improvement, which is fairly significant.
The second patient is a smoker who used the product for six weeks in the trial, and then stopped the product; we waited four more weeks, and then photographed him. We can see an overall improvement in the quality of skin and in wrinkling and he’s also maintained the improvement a month after stopping use of CutaVive.
It’s important to realise that wrinkle improvement here is not because of increased moisturisation. Many products for wrinkle reduction work well because they hydrate the skin, and when the skin is hydrated it looks better.
However a 17% increase in moisturisation or hydration isn’t enough to give people the significant results in wrinkle reduction that this trial demonstrated.
We can see changes if we look histologically at biopsies in the preauricular area of patients (see opposite page), where facial skin was treated with the topical product for six weeks. There is new collagen production and there are new elastic tissues.
The before and after reticular stain shows all these new reticulin fibres at the end of six weeks.
A trichrome stain reveals fairly profound new collagen deposition, in the upper dermis and some thickening of the epidermis from the before and the after that goes along.
Oxygen is food for cellular growth. If we look at elastic tissue stains before and after CutaVive use, the dark material is all new elastic tissue which has grown at the end of six weeks.
We see improvements in the appearance of the skin because there are histologic changes in the skin. New collagen and new elastic tissue, doesn’t die afer a month, so you’d expect that those results are going to be ones that were maintained over time.
Now, in real life, obviously, the presumption is people are going to continue to use the product long term, but it’s important to realise that the persistence of the improvement that you see is not an artefact, but due to tissue changes.
Other uses for super-saturated oxygen
Super-saturated oxygen used after CO2 laser resurfacing, has shown to create improvement in healing and a reduction in complications. Photodynamic therapy, (PDT) for actinic keratoses, or for superficial basal cells, as a therapy can cause some significant tissue reactions.
In a recent study, ten patients with multiple actinic keratoses were treated with PDT, following a traditional PDT protocol.
After cleaning the skin with alcohol and acetone, topical aminolevulinic acid (ALA) was applied, left to incubate for two hours, and then subjects were put under blue light for 16 minutes to activate the ALA.
Immediately afterwards, Cutagenix was applied on one side of the face, and Aquaphor, which is a petrolatum-based product with chamomile in it, on the other half of the face. This was done three times a day for a week.
Almost all treated patients reported immediate relief in pain and stinging when they put the hyper-oxygenated product on that side of their face.
They had significantly less swelling and redness on the side treated with the supersaturated oxygen emulsion every day until they were completely healed at days five to seven.
At the end of six months, examination of the patients showed that there was no reduction in efficacy of the PDT therapy from the use of the oxygen product compared to the use of the petrolatum based product.
This patient in image 1 was injected with Restylane in the glabellar complex, and presented three days after the injection with necrosis in the forehead.
We began treatment with the Cutagenix product four times a day. This is a photograph of him three days later, and a photograph four days after that. You can see he has healed rapidly and has no evidence of full thickness necrosis in that area.
This was done with just the topical superstaurated oxygen emulsion without the need for hyperbaric oxygen therapy in a chamber.
The patient in image 2 shows a case of radiation dermatitis. Radiation dermatitis under the microscope is full of microembolic areas and microthrombi. All these superficial vessels are clotted off as part of the reaction to radiation and there are ischemic changes in the skin.
It’s very uncomfortable for these patients and their skin breaks down. If you can increase oxygen levels in tissue that has a very low oxygen level you’d expect it to heal well.
When you compare the result seven days after the end of the radiation therapy, there is a fairly profound degree of improvement in the radiation dermatitis, and 21 days later really profound improvement with excellent healing.
Image 3 shows a radiation dermatitis patient at the start of the topical oxygen therapy and then seven days later very significant changes in the overall quality of the skin as well as in the healing.
The Cutegensis product has also shown good results on thermal burns with rapid re-epithelialisation and improvement in the quality of the skin. When trying to heal from a burn, both healing time and final quality of the tissue are important.
The results in image 4 show the contrast in two treatment approaches to a thermal burn.
One area is treated with Silvadene and the other, with the Cutagenix product. After three days, the area treated with Cutagenix is already healed, and the eschar has fallen off. The area treated with Silvadene has had almost no change.
The results in image 5 show fairly significant improvement and rapid healing, very much unlike what you’d expect to see in burn tissue after ten days of traditional therapy.
It’s also possible to use this product for other conditions such as gangrene and it’s also been shown to be very effective for rosacea and for some patients with perioral dermatitis.
It’s also proved effective in patients who have eczema or rosacea, who are interested in anti-aging therapies but can’t tolerate AHAs, or retinoids, but they can tolerate topical oxygen easily.
So, Cutegenesis is a calming therapy, but also stimulates collagen, elastic tissue and healing.
Mark G. Rubin, M.D. is a board certified dermatologist in practice at the Lasky Skin Center in Beverly Hills, California. Dr Rubin’s practice is limited exclusively to cosmetic dermatology, with a specialty in skin resurfacing. He is one of the founding members of Cutagenesis.