Ask any dermatologist for the most effective skin-care ingredients, and she or he will namecheck the members of an exclusive squad: sunscreen, retinol, antioxidants, alpha hydroxy acids, and peptides. These are your skin guardians, your glow cajolers, your wrinkle crushers — and they deliver nearly every single time.
Recently, though, another active ingredient has quietly entered the fold: growth factors. They were first discovered by two scientists back in the ‘50s — an achievement that earned the duo the Nobel Prize in 1986, fueling a flurry of modern research. Yet dermatologists only recently started semi-routinely endorsing the collagen-builders — and often, it seems, with a hint of hesitation. When pressed, some express a few qualms: Growth factors are steeped in confusion and controversy, precisely how they work is a bit of a mystery, and the current cache of data supporting growth factors’ skin-rejuvenating powers isn’t especially jaw-dropping.
Given the general mood here, I could only laugh when a dermatologist friend, catching wind of this story, remarked, “So brave of you to navigate the growth factors!” What can I say? Anything for the promise of smoother smile lines. Here, top beauty minds share all the knowledge on growth factors in skin care.
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What are growth factors, and why are they in my skin care?
Found in abundance throughout the body, growth factors are large proteins that float between cells communicating crucial messages relevant to growth, healing, and survival. They’re manufactured by all types of cells. In the skin, this includes those comprising both the outermost epidermal layer and the deeper dermis — so, we’re talking the keratinocytes you can plainly see in the mirror, and the fibroblasts (collagen factories) and melanocytes (pigment-making cells) nestled down below. When these “signaling proteins bind to receptors on cell surfaces, they can send commands to replicate, repair, and rejuvenate,” says New York City dermatologist Estee Williams, who played dermatologic cryptographer for this story, helping me decipher stacks of studies.
Gail Naughton, a regenerative medicine researcher and growth-factor formulator, likens growth factors to keys, and their respective receptors to locks. “When the key clicks into the lock, it activates the cell to do things, like grow and divide, make more collagen and elastin, or increase blood flow.” But by our late 20s, that lock-and-key mechanism begins to get rusty. The skin starts producing smaller quantities of growth factors — resulting in less cell growth, and thinner, less supple skin.
At the same time, collagen production drops off and elastic fibers begin to stiffen, laying the groundwork for wrinkles and sagging. And that’s just the inevitable intrinsic side of aging. Outside threats, like sun exposure and pollution, exacerbate the process. But growth factors, when applied regularly for several weeks, can act as a sort of “replacement therapy,” says Naughton, “restoring all of the normal signals that support healthy skin when we’re young.”
This knack for resuscitating basic skin functions, like cell turnover and collagen construction, makes growth factors a logical fit in product formulas aiming for lineless, even-toned, luminous effects. But researchers are also exploring their usefulness for correcting under-eye bags, sunken scars, and even acne, notes New York City dermatologist Dendy Engelman, as growth factors can temper inflammation while helping cells slough off at a healthy pace for clearer pores.
To be clear: There are no actual bits of foreskin or fetus in these
serums — merely the proteins they give off.
Where do the growth factors in my skin care come from?
Ah, the million-dollar question. The growth factors found in serums, gels, and creams are either bioengineered in a laboratory, or culled from human stem cells — but not necessarily human skin stem cells. Stem cells from any source — skin, fat, bone marrow, umbilical cord — can produce growth factors that give rise to a variety of different cell types in the body. “They take cues from the surrounding tissue to become those types of cells, so if you put them on the skin, they help generate new skin cells; hence, younger-looking skin," Engelman explains. SkinMedica TNS Recovery Complex— the first commercially available cosmetic product containing human growth factors, which was developed by Naughton in the ‘90s — boasts a blend of dermal proteins derived from the fibroblasts of neonatal foreskin (harvested from a single circumcision years ago).
The growth factors in Regenica Rejuvenating Dual Serum are also naturally secreted by human fibroblasts and have been “tricked” into reverting back to stem cells (more on that in a second), notes Naughton, the brand’s founder and chief scientific officer. Nugene Clinical relies on human fat stem cells to generate the factors in its Universal Serum. And to make the proprietary “processed skin proteins” for its Bio-Serum, NeoCutis uses fetal fibroblast cells. That’s right: fetal — and as you can imagine, they’ve caught some heat for this. According to the company, the cells originally came from a fetal skin biopsy donated to the University Hospital of Lausanne, Switzerland, following a terminated pregnancy that was deemed medically necessary. That single skin sample was then used to establish a “cell line” — think white coats duplicating cells in a lab — originally intended for burn treatments. The proteins released by the cultured cells are what’s used today by NeoCutis.
To be clear: There are no actual bits of foreskin or fetus in these serums — merely the proteins they give off. And while the association alone may seem icky, many experts consider these young human fibroblast cells the ideal source of growth factors for skin rejuvenation. “The embryonic environment is a unique one, in which you have rapid stem cell growth and the well-documented phenomenon of scarless healing,” says Naughton, referring to the fact embryos operated in utero often emerge from the womb without any scars. Using growth factors released by fetal cells in creams and serums would make a lot of sense — if they weren’t so heavily clocked in controversy.
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In an attempt to skirt at least some side-eyes, Regenica found a way to mimic the conditions of the womb by suspending newborn fibroblast cells on starch beads in a low-oxygen system, which causes them to quickly revert back into stem cells, and start secreting embryonic-like growth factors, which the company then collects for its prized serums.
Other brands choose to remove the human element completely. Both the Icelandic import Bioeffect and dermatologist Ronald Moy’s DNA Renewal line use a human-like epidermal growth factor (EGF) that’s made in bioengineered barley seeds. (Bioeffect’s chief scientific officer, Björn Örvar, says they provided Moy with this barley EGF in 2009 for use in his products and clinical trials.) By making DNA via genetic engineering, “we introduced a synthetic DNA into the barley stem cell, and from that stem cell grew a plant with seeds that are producing a human EGF replica,” explainsÖrvar. “This barley-made protein has the same amino acid sequence and 3-D structure as human EGF, so it can easily detect and bind to EGF receptors on human skin cells.”
And studies show it works as advertised. In one Bioeffect trial, 30 women applied the serum to one side of their face, twice a day, for eight weeks (on the other half, they used a placebo, which was essentially the same formula minus the EGF). After two months, the thickness of their skin on the EGF-serum side — when measured by tools that track biophysical changes — had increased by more than 60 percent.
One quick but critical side note about plant parts: While people often conflate stem cells and growth factors, this barley EGF — again, a human-like protein produced by a plant — is utterly unrelated to the miscellaneous plant stem cells cropping up in botanically-based serums, which may offer antioxidant benefits, but “are not able to bind with or signal human cells,” says Naughton.
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So which is better: human or synthetic?
There's a case to be made on both sides, and a lot of it comes down to how they're created in a lab.
According to Moy, barley EGF is purer and more stable in creams than its human counterpart, while Örvar points out that seed-generated EGF is simply more transparent: “We’re using a defined concentration of known [synthetic] growth factors, whereas companies working with human growth factors use an undefined extract, a ‘soup’ of many different proteins” — meaning not solely dermal growth factors but also cytokines (molecules that regenerate skin) and other kinds of growth factors that are tied to blood vessel formation, inflammation control, and more.
That “soup,” however, is vital to the creation of human growth factors for creams and serums. Naughton explains that human growth factors are made when “cells from donor skin samples are fed a liquid, called a cell culture medium, which gives them all the essential vitamins and nutrients to thrive and secrete growth factors and cytokines." That complete mixture — the so-called “soup” of growth factors, vitamins, nutrients, cytokines (everything our own cells make under normal wound-healing conditions in the body) — is collected every day or two, says Naughton, "and becomes the key ingredient in skin care.”
As a result of this process, the broth “contains a combination of hundreds of individual dermal growth factors and active proteins that is optimal for skin activity,” says Rahul Mehta, the vice president for research and development at SkinMedica. It’s the organic, synergistic interplay between these myriad molecules that’s said to give the ”soup” its potent edge — “with no single growth factor being solely determinant in the outcome of skin repair,” according to a 2009 SkinMedica-led article in the Journal of Drugs in Dermatology. This multifaceted cocktail, human growth-factor proponents assert, most closely resembles the mix of compounds involved in the body’s own repair process that’s impossible to copy in a lab. The insurmountable task of deconstructing this soup, researchers note, is akin to unlocking every intricacy and benefit of breast milk.
In a rare comparison study published in 2017 (and sponsored by Allergan, the company that owns SkinMedica and Regenica), “dermal growth factors outperformed growth factors derived from other kinds of human stem cells, like fat cells, as well as non-human sources of stem cells, such as snails and plants,” says Mehta, who co-authored the study. (The barley EGF was not included in this trial, however.) “This is a rigorous study looking at how different kinds of topical growth factors influence the genes responsible for turning on collagen and elastin production in the skin,” says Williams (who was not involved in the study).
Seeking unbiased opinions on the human-versus-synthetic debate, I reached out to Annie Chiu, a dermatologist in North Redondo Beach, California, who told us, “It is likely that naturally derived growth factors [i.e. those in the ‘soup’ that were culled from human stem cells] are more active, because they tend to work in tandem and amplify the effects of each other.” Los Angeles-based dermatologist Michael Kassardjian echoed her sentiment, saying, “Successful repair of damaged skin, and collagen synthesis, have been shown to require the involvement of growth factors and cytokines. Single factors [i.e. the synthetic ones] are less likely to mimic those complex interactions on their own.”
That said,“some of my patients feel uncomfortable with the idea of a human cell line producing the growth factors in their skin care,” notes Chiu. (Doctors, too: “Safety and efficacy aside, the human sourcing just doesn’t appeal to me, personally,” adds Williams.) The offputting smell of human proteins is another deterrent for some. Still, despite the cloud hovering over human growth factors, nearly every dermatologist I interviewed uses and recommends SkinMedica TNS.
With so much unclear, one thing is crystal: Further studies are needed comparing the efficacy of naturally secreted (but not entirely identifiable) human growth-factor blends, to specific growth factors harvested from other sources (plants, animals, bacteria), and to synthetic growth factors engineered in the lab.
I see growth factor products as the icing on the cake if you’re
looking to maximize your skin-care regimen.
Why do some experts doubt the efficacy of growth factor serums?
There’s debate among derms as to whether topically applied growth factors can penetrate the skin enough to be effective, says Kassardjian. Skeptics have long asserted that growth factors are too massive to slip past the skin barrier. The thing is, growth factor experts don’t dispute that fact.
“Growth factor molecules from any source are too large to penetrate intact skin, and there is no convincingly proven technology that can increase the penetration,” says Mehta. And, yet, dozens of topical growth factor studies show measurable increases in collagen and elastin, and improvements in skin thickness, radiance, moisturization, pigmentation, and texture. How can growth factors be so accomplished if they’re not even granted entry into the skin?
Leading researchers share a fascinating and widely accepted hypothesis, says Mehta: “When growth factors are applied to the skin in high concentrations, a very small fraction of them interact with the topmost layers of the skin, and initiates a communication chain that leads to stimulation of dermal fibroblasts,” sparking collagen growth. The aforementioned 2009 Journal of Drugs in Dermatology study expands on the theory, but the science is superheavy, and the language explaining it, convoluted, so here’s the gist: Growth factor serums essentially urge the living cells of your skin’s surface layer to call down to collagen cells, Hey, pump out more growth factors! This order then incites swifter cell turnover and more robust growth-factor output, which then triggers more collagen creation down below the surface for glowier, plumper, prettier skin.
Do they really work?
In a word? Yes. Granted, not every skin-focused growth factor study is an unequivocal home run. The majority involve fewer than 100 subjects, and only a handful meet the gold standard of scientific testing, says Williams — that is, being double-blinded and placebo-controlled to squash the potential for bias. Yet, the studies that are well done do, in fact, prove that both human-derived dermal growth factors (like those in TNS, Regenica, NeoCutis) and barley-grown EGFs (in Bioeffect and DNA Renewal) can switch on genes responsible for fibroblast activity, thereby revving up collagen production, and making skin look fresher and brighter.
While critics may argue that additional non-GF active ingredients in these products could be responsible for such perks, reputable brands actually test their growth factor compositions solo — independently of final formulations — and can attribute reported benefits to the growth factors directly.
Are growth factors safe?
“The whole point of using these products is to increase the rate of growth in cells, leading to thicker, firmer skin,” says Williams. But what does this notion of rapidly growing cells call to mind? Cancer. At this point, though, the risk is purely theoretical. Moy, a Mohs skin cancer surgeon and vice president of the Skin Cancer Foundation, tells us plainly, “There is no evidence that a natural EGF could speed the growth of a [malignant] lesion.” (Remember, adds Kassardjian, “these molecules are large, and high quantities can’t be adequately absorbed.”) While it’s true that “human growth factors cannot distinguish between normal healthy cells and potentially compromised cells,” says Mehta, SkinMedica hasn’t recorded “any serious adverse events” from TNS in the 15-plus years they’ve been collecting consumer feedback on the serum.
Do I really need a growth factor serum, and how can I work it in?
“I see growth factor products as the icing on the cake if you’re looking to maximize your skin-care regimen,” says Chiu, noting that sunscreen, antioxidants, and retinols should take precedence. If you find you’re too sensitive for retinoids, however, growth factors can make a solid stand-in, as “they yield similar effects — building collagen to help with lines, evening tone, decreasing roughness — but with far less irritation,” says Kassardjian.
Growth factors should be applied to damp skin, right after cleansing, before any other item in your lineup. “Acidic environments can break down growth factors,” so don’t pair them with vitamin C or alpha hydroxy acids, says Chiu, who routinely applies TNS Essential Serum (which is the Recovery Complex coupled with a separate antioxidant-peptide potion in a dual-chambered bottle), and then waits a few minutes before adding moisturizer and a prescription-strength retinoid.
The bottom line (finally, and thanks for sticking with me): Adopting a more-the-merrier approach to skin-plumping ingredients is a smart idea, especially as 40 nears. Growth factors — both the human- and barley-procured varieties — can bolster your existing beauty regimen without inflaming your face. Go for a research-backed formula that suits both your skin and sensibilities.
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