By Natasha MohrWe all know that growth factors stimulate biochemical pathways that regulate cellular growth, proliferation and differentiation under controlled conditions, which play an important part in maintaining healthy skin structure and function. This includes promoting the formation of collagen and elastic fibers. This carefully choreographed dance of cellular actions is a series of synergistic interactions of multiple growth factors with other proteins in the epidermis and dermis. We also know that growth factors do not exist in isolation and no single growth factor is solely determinant in the outcome of skin rejuvenation.
Early OnResearch on the potential benefits of applied growth factors was first conducted in the area of wound healing. A 1987 study examined the role of platelet-derived growth factor in the process through in vitro (laboratory benchtop) experiments. The result of the work showed PDGF (platelet-derived growth factor) “stimulates DNA synthesis and chemotaxis of fibroblasts and smooth muscle cells and stimulates collagen, glycosaminoglycan, and collagenase production by fibroblasts. These in vitro properties suggest that PDGF, delivered by platelets to the site of injury in vivo, may play an important role in the initiation of the wound repair process.” Lynch SE, Nixon JC, Colvin RB, Antoniades HN. Proc National Academy of Science USA. 1987 Nov;84(21):7696-700. The study further explained that IGF-1 (insulin-like growth factor 1) and EGF (epidermal growth factor), when combined with PDGF, provided additional synergistic benefit. Since the early 2000s researchers have been exploring the potential benefits of topically applied growth factors and cytokines. The research was promising and in 2007, Drs. Rahul C. Metha and Richard E. Fitzpatrick published a paper titled “Endogenous growth factors as cosmeceuticals.” In it they stated:
“Growth factors play an important role in reversing the effects of skin aging mediated by chronological and environmental factors . . . Topical application of human growth factors in multiple clinical studies has shown to reduce the signs and symptoms of skin aging, including statically significant reduction in the fine lines and wrinkles and increase in dermal collagen synthesis. More double-blind and controlled studies are needed to confirm the preliminary clinical effects of growth factor products and more controls on product quality and stability need to be established.”Mehta RC, Fitzpatrick RE. Endogenous growth factors as cosmeceuticals. Dermatologic Therapy 2007; Published online; DOI: 10.1111/j. 1529-8019.2007.00149.x From then on, it seemed anyone with an eye toward product development was off to the races.
The Current DebateLike many of her colleagues, Dr. Amy Taub of Chicago, IL, feels that Dr. Fitzpatrick’s work was vital to the development of growth factors as we know them today. “Dr. Richard Fitzpatrick was one of the first to realize that the wound healing pathway had many elements in common with skin aging mechanisms and tried to develop a skin care line to address this specific pathway. He helped to develop SkinMedica and TNS Essential Serum was the first product introducing human growth factors. Although many questioned whether they could be absorbed or even if they had any function, the overwhelming response by patients and the longevity of these products showing clinical benefits swayed me to believe. Most cosmeceuticals have small pilot type studies that show clinical or even some type of objective data. SkinMedica was one of the few skin care companies that did put together some data that was convincing.” But even with all of the advances made in the last 18 years, growth factors have still been steeped in controversy and concerns over carcinogenesis (thought they have not manifested clinically), have not been put completely to rest. This has opened the door to serious scrutiny and even some legal action. In a 2015 Dermatology Times Modern Medicine.com article, Dr. Zoe Diana Draelos, MD, summed up the legal woes then faced by the growth factor product industry: “Recently, there was a legal challenge…stating that the [GFs]…were responsible for the induction of skin cancers. The suit seemed to be a test case for a larger class action suit… [but] demonstrating that [GFs] caused the skin cancers when skin cancers are common in the general population was challenging and the suit did not progress.” Are Growth Factors Safe in Cosmetics? With all of the givens and the unknowns, it is understandable that there would be controversy around growth factors. From the sources from which they are derived to the potential for efficacy and need for technology to help them traverse the stratum corneum, it is no wonder that our very own Cosmetic Surgery Forum (CosmeticSurgeryForum.com) faculty do not all agree on the role of growth factors in skin care. Dr. Matt Zirwas of Columbus, OH, feels that “growth factors in skin care products are good for marketing, and totally worthless when it comes to actual results. Growth factors are proteins. Topically applied proteins cannot penetrate through intact stratum corneum to the living epidermis, hence cannot stimulate growth or the production of anything. Now, growth factors used in conjunction with microneedling, resurfacing, fractional resurfacing or injection are certainly effective.” In speaking further with Dr. Taub, she shared that in spite of the controversy over the last 18 years she finds growth factors to be instrumental to the skin care regimens she recommends for her patients. “I call them the ‘Core 4’: Sunscreen, Antioxidant, Exfoliant and Growth Factors. Albeit very simplified, it helps me to explain to patients why they might need multiple products or products with multiple ingredients to achieve all the functions necessary to keep the skin healthy. “Since Dr. Fitzpatrick first introduced SkinMedica we have had other growth factors available, particularly NEOCUTIS products, which to me are much more aesthetically pleasing and at least as effective. More recently the NEOCUTIS company wanted to put to rest the controversy regarding human-sourced products (used in both TNS and PSP) so they developed MPC, a mix of proprietary and non-proprietary peptides that stimulate our own internal growth factors instead of adding growth factors themselves. “The newest growth factor entrant is DefenAge, taking the idea one step further to stimulate an actual single stem cell component present in our hair follicles called LGR6+ that is the main loci of developing new basal cells in the epidermis after wounding. Instead of adding growth factors to enable wound healing/anti-aging, or to stimulate cells (which are old themselves) to produce more growth factors we are stimulating a stem cell locus within our own cells that can produce brand new cells. “I believe the growth factor story represents a significant step forward in our understanding of the biology of the skin and our attempts to modulate it to our advantage.” In Montclair, NJ, Jeanine Downie, MD, also says that the science has influenced her beliefs in the benefits of growth factors but that often it is the percentage of growth factor in the product that can be the problem. “I have looked at many studies over the years from SkinMedica and from the general scientific dermatology literature that have convinced me about the effectiveness of growth factors. I like the quality growth factors that are present in SkinMedica TNS Recovery Complex and Essential Serum. In my opinion, this is one of the cosmeceuticals that absolutely works the best for anti-aging. Growth factors in this product improve texture, tone, fine lines and sagging. The problem with growth factor products in general is that the percentage of growth factor can be very low so that the skin does not show any overall improvement. TNS has 93.5% growth factor so it is truly best in class for anti-aging serums on the market. I feel that growth factors are good for overall skin health.” Finally, Dr. Joel Schlessinger in his practice in Omaha, NE, says that while there is not a clear consensus, he himself has not seen any problems. “I have been offering products with growth factors to my patients for more than 12 years now and so far haven’t seen any problems. Clearly, they seem to have a huge following as the benefits seem to be enough that my patients keep coming back to repurchase.” However, he also offers an alternative for patients and colleagues looking for great anti-aging results without being left vulnerable to any perceived risks to growth factors: peptides. “Peptides also provide a great anti-aging benefit without exposure to growth factors and are achieving a large following as well. If a physician or a patient remains unconvinced about their safety or has personal objections of any kind, peptides offer a fantastic alternative with wonderful results. Some peptide-based products with which we’ve seen great patient satisfaction are: Obagi Professional-C Peptide Complex, Revision Skincare D·E·J Face and Eye Creams, Jan Marini Transformation Face Cream, SkinCeuticals Metacell Renewal B3 and HydroPeptide Power Lift: Advanced Ultra-Rich Moisturizer. And there are, of course, many others. It is great to have so many options and choices!” The debate surrounding growth factors will certainly go on… so, tell us what you think.