Skin actives are an increasingly popular component of skin rejuvenation treatments, providing a cascade of collagen stimulation and wound healing. Dr Hema Sundaram describes the benefits of topical and injectable treatments, involving growth factors and platelet-rich fibrin matrix
In terms of skin ageing pathways, there are extrinsic and intrinsic ageing mechanisms. Extrinsic largely involves UV exposure, while intrinsic ageing is unavoidable—it involves our oxidative metabolism.
There are a number of key anti-ageing actives that can remediate or prevent these mechanisms from occurring. Growth factors play a particularly important role, helping to reverse the detrimental imbalance that causes reduction in dermal collagen. They can prevent the suppression of synthesis of pro-collagen —the precursor for collagen—and can also prevent collagen degradation.
We can combine growth factors with cytokines, and other anti-ageing actives for a synergistic approach to skin rejuvenation, including VEGF, PDGF, TGF-ß1 and TGF-ß2 and TIMP.
Supplemental growth factors can help the multiplication of cell growth and provide wound healing, ramping up fibroblast activity. It’s important to note that it isn’t actually essential to get down to the dermis, or deeper, to get these effects because there is a cascade.
Keratinocytes have receptors for growth factors and cytokines. If we’re injecting these actives superficially into the skin, or even applying them topically, we can potentially get an impact on the keratinocytes and initiate a cascade, leading to activity in the dermis.
Topical growth factors
Topically-applied growth factors include human-derived, animal-derived and plant-derived, and also recombinant growth factors.
One example of animal-derived growth factors is SCA, which stands for secretion of cryptomphalus aspersa. The secretion, or slime, is harvested from the cryptomphalus aspersa snail.
The snail’s secretion contains a growth factor complex that is secreted at times of stress and tissue damage. It also contains glycosaminoglycans and enzymatic antioxidants. Initial studies showed that SCA can regenerate damaged tissue in less than 48 hours so it has been developed for topical use.
These studies involved radiation therapy—a challenging situation—and showed good results in acute conditions. The ingredient has been used in Europe for over 15 years to treat radiation dermatitis.
From an evidence-based point of view, the growth factor increases fibroblast proliferation and stimulates fibroblast replication. It also optimises form and function so they’re in an active state. The greater the concentration, the greater the proliferation of fibroblasts.
An open label, double-blind study published in the Journal of Drugs and Dermatology involved the application of 8% SCA cream and 40% serum on patients with lighter Fitzpatrick skin types. Validated scales were used for the general ageing assessment, along with silicone impressions around the periocular region and punch biopsies. Following application of the cream in the morning and the serum at night, there was a significant decrease in wrinkles (p<0.05). There was an increase in the elasticity of the skin in all patients by day 19, dryness and roughness resolved and sallowness also was shown to be improved.
There was also an increase in microangiogenesis—the area occupied by the micro vessels—a and a reduction in epidermal thickness. It is important for these studies to be vehicle-controlled—we can compare the effect from lubricant or moisturising activity with the active ingredient.
Endocare Tensage includes the SCA complex and has been through rigorous testing, particularly for a cosmeceutical—there is still a grey zone for cosmeeuticals as far as evidence is concerned. Results are good for a topically applied treatment.
So can we facilitate healing and synergistically augment the results through growth factors in autologous injections? Platelets possess all the elements that are essential for tissue regeneration. Platelet-rich fibrin matrix, or PRFM (Selphyl), is a fibrin matrix scaffold. It essentially allows us to have a sustained and controlled release of growth factors and cytokines.
It’s very important that the platelets should be viable. Platelets are complex cells, and a number of growth factors and cytokines are associated with platelet function. These growth factors and cytokines provide tissue repair, cell growth, collagen production, angiogenesis, keratinocyte growth and generation as well as the promotion of wound healing—all important factors when dealing with ageing skin.
Platelets release growth factors, which stimulate angiogenesis, and stimulate the migration of fibroblasts and stem cells.
The fibrin matrix, which is unique to PRFM, provides a scaffold that can support the sustained, controlled and predictable release of growth factors and cytokines. Ultimately, the aim is to achieve the formation of new collagen and extracellular matrix in the dermis.
PRFM and PRP
So what’s the difference between PRFM and platelet-rich plasma (PRP)? The PRFM has minimal red cells in the plasma, which reduces the risk of hemosiderin staining. While that’s important all over the face, one of the areas we’re injecting PRFM the most is the tear troughs.
Many patients who come in for tear trough treatment already have an issue with hemosiderin, deposition which is one of the main causes of dark circles. We certainly don’t want to put any more there.
Minimal white cells in the plasma have been reported to reduce the risk of impaired tissue healing and remodelling. It’s a complex process that includes the activation of matrix metalloproteinases which break down collagen.
It’s a non-traumatic procedure; the PRFM injects as a liquid but then remains in place and provides a sustained effect from the fibrin matrix. The closed system, with minimal user interaction, minimises contamination.
The physiological platelet concentration is only two to three times the platelet concentration in blood. This is important—as it has been shown in some Asian studies that the manipulation and super-concentration of PRP may cause some side effects. Benign tumours in connective tissue have been reported anecdotally.
The closer we are to what’s physiologically occurring in the body, the safer we may be.
If this complex array of growth factors and cytokines is kept in the same proportions as those present in the blood—just concentrated slightly—we have a physiological balance.
The treatment is available as a closed kit with labelled tubes. The first step is to draw blood from the patient, then invert the tube gently and place it into the centrifuge. The machine spins for six minutes and, when it comes out, it is now platelet rich plasma.
Once this gets transferred into a tube with calcium chloride, it becomes platelet rich fibrin matrix. The entire preparation takes around 20 minutes which, up to this point, can be performed by ancillary staff. Then we go ahead and inject.
There are a number of potential applications. Core applications include fine lines and wrinkles, superficial volumetry, facial rejuvenation and improvement in skin tone, texture, colour and quality.
I prefer to use a multi-level superficial technique with PRFM. When injecting the tear troughs, for example, I use a blunt cannula in the superficial subdermal plane. Over-correction is not a concern as the liquid PRFM is very forgiving.
After this deeper injection with the cannula, I then use a sharp needle for intradermal layering of the PRFM. Typically, I use a 30 or 32 gauge needle. This combined cannula and needle protocol minimises tissue trauma and resultant bruising.
Treatment of the tear troughs with PRFM or PRP can be combined with hyaluronic acids to the lower face to provide additional volumisation if needed.
The synergy with PRFM provides improvement in dark circles, skin tone and texture. The procedure also provides a superficial volumising effect for hollowing, tear trough depth can be decreased and tissue quality can be improved after three months.
This is a safe, well-tolerated treatment that can yield significant improvement in some patients. Studies have shown that it can induce angiogenesis and fat cell synthesis.
Combining PRFM and PRP with other fillers and autologous fat provides an effective combined treatment approach. Ageing is multimodal so we need to think of multimodal means of rejuvenation.
Dr Hema Sunderam is a fellowship-trained board certified dermatologist, and the Founder and Director of her aesthetic dermatology practice in suburban Washington, D.C. Her new paper in collaboration with Dr Sabrina Fabi in Facial Plastic Surgery, “The Potential of Topical and Injectable Growth Factors and Cytokines for Skin Rejuvenation”, serves as an educational guide to this topic in conjunction with American Academy for Facial Plastic & Reconstructive Surgery International Symposium.