Featured Experts
Dr. John O’Neill, biomedical engineer and CSO of Xylyx Bio and Sweet Chemistry
Dr. Julie Russak, board-certified dermatologist in New York City
Dr. Sanjay Batra, founder of WeThrivv, PhD in medical physiology, and former adjunct professor at the Wake Forest Institute for Regenerative Medicine
Alec Batis, cosmetic chemist and CEO and founder of Sweet Chemistry
Dr. Jennifer Levine, board-certified facial plastic surgeon in New York City
The future of medicine, in our opinion, is regenerative medicine. It just makes sense: whether treating damage caused by disease, trauma, congenital defect, or just age, why wouldn’t you take advantage of innovations that can eliminate intensely invasive procedures? Current developments in the field of regenerative medicine include focuses on treatment tailored to a patient’s genome and how to stop—or even reverse—aging.
While we have a long way to go to harness the power of regenerative medicine, there are many exciting ingredients being studied that are already finding their way into the aesthetics and skin-care landscape. Here, with the help of experts, we’re breaking down five different ingredient categories for your most advanced regimen yet.
Peptides
Peptides are strings of amino acids, and they all have different functions. Dr. John O’Neill, biomedical engineer and CSO of Xylyx Bio and Sweet Chemistry, says to think of those strings of amino acids like letters of the alphabet—when organized differently, they create different words. “In the peptide world, ‘words’ (peptides) can communicate to cells specific signals,” he says. Thus, not all peptides are created the same.
For example, there are neurotransmitter-inhibiting peptides, like argireline, also known as acetyl hexapeptide-8, which is “known for its Botox-like effects in reducing expression lines,” says Dr. Julie Russak, board-certified dermatologist in New York City. (You can find this and many other peptides in Maskād Anti-Aging Serum, $125.) There are the oft-used copper peptides, which can promote wound healing. Some just work as moisture-binding agents. And many aren’t actually proven to be efficacious. “Unfortunately, the availability of peer-reviewed publications reporting rigorous randomized controlled studies that document evidence of benefits for [many] peptides is scarce,” says Dr. O’Neill. But then there are clinically proven peptides with regenerative benefits, like matrikines.
Matrikines are signal peptides, and they can tell your body (including your skin, of course) to repair cells, reverse tissue damage, and combat inflammation. “They are involved in a component of the human body called the extracellular matrix (ECM), which is essential to regulating cellular activity, proliferation, and migration—matrikines are unique,” says Dr. Sanjay Batra, founder of WeThrivv, PhD in medical physiology, and former adjunct professor at the Wake Forest Institute for Regenerative Medicine. Adds Alec Batis, cosmetic chemist and CEO and founder of Sweet Chemistry, “Due to their chemical nature, ECM peptides are very stable even when stored long-term at room temperature.”
Even if you think you’ve never heard of matrikines, there’s a chance you’ve used one of the most famous ones over the last 20 years: Matrixyl. Developed in 2000, Matrixyl is a blend of synthetic peptides, palmitoyl tripeptide-1 and palmitoyl tetrapeptide-7, found in products like The Ordinary Matrixyl 10% + HA ($11) and Tarte Shape Tape Pressed Powder ($35). Studies show it can actually increase collagen production for significantly denser skin in eight weeks. More recently, Dr. O’Neill created Matrikynes, which are formulated into products from the brand Sweet Chemistry, including the Elasticity Reinforcing Cream ($170). These are regenerative bone peptides ethically sourced from USDA-compliant upcycled bovine bones from the food industry. A clinical study of this ingredient shows that it not only improves the appearance of fine lines and wrinkles, reduces inflammaging, fades hyperpigmentation, and repairs the skin barrier but also can improve skin density in just four weeks, both faster and more effectively than its predecessor, Matrixyl.
Unlike other ingredients you’ll find further down on this list, there aren’t any risks to consider when using peptides beyond those you might experience when using any skin-care product, like irritation, burning, or itching, says Batis. You’ll just want to do your homework regarding the origins of your peptides and their efficacy. This is especially important when considering in-office peptide therapy. “In-office treatments typically use higher concentrations and may involve specialized delivery methods, such as microneedling, for deeper skin penetration,” says Dr. Jennifer Levine, board-certified facial plastic surgeon in New York City. “Some formulations may also have ingredients that provide improved delivery.”
Growth factors
Though technically peptides, growth factors are in a class of their own. “Growth factors are naturally occurring proteins capable of stimulating cellular growth, proliferation, healing, and differentiation,” says Dr. Russak. They’re naturally produced by a variety of organisms, from humans and animals to plants and insects. There are many different types, including fibroblast growth factor (FGF), which stimulates the production of fibroblasts, cells that secrete collagen, and keratinocyte growth factor (KGF), best known for helping to grow hair. However, the most famous in the category is epidermal growth factor, or EGF. “It’s an essential growth factor for the production of collagen proteins that you lose as a function of age,” says Dr. Batra.
According to Dr. O’Neill, this is one of the first growth factors to ever be identified. When used in skin care, EGF is recognized for its ability to promote skin renewal, fade wrinkles, and enhance elasticity. The most effective forms of EGF will be human derived, such as that in SkinMedica TNS Advanced+ Serum ($295) and the lab-synthesized sh-oligopeptide-1, which mimics human EGF. You can find the latter ingredient in Noble Panacea The Absolute Rejuvenation Night Balm ($430), Colorescience Pep Up Collagen Boost Face & Neck Serum ($179), and Drunk Elephant Protini Polypeptide Cream ($68).
You’ll see some plant-derived growth-factor serums out there, but you may not want to waste your time or money. “Plant-derived growth factors are meant to bind receptors in plant tissues—they do not have the specificity or protein conformation to bind receptors on human cells,” explains Batis. The only reason you might want to consider them is any concern you might have about using human-derived growth factors. For the most part, growth factors are “cleaned up” and replicated in a lab, but “the sourcing of human-derived growth factors can raise ethical questions, particularly regarding consent and the origin of the cells,” says Dr. Russak. (For example, the EGF in SkinMedica’s product is famously derived from foreskin cells harvested decades ago.)
There’s also potential for health risk, according to some. “There is ongoing debate and research about whether topical application of growth factors could stimulate the growth of cancer cells,” warns Dr. Russak. “While there is no conclusive evidence, it remains a topic of concern, especially for individuals with a history of skin cancer.” You should also speak with your physician before using growth factors if you have psoriasis, says Batis, as this condition is characterized by a hyperproliferation of skin cells.
Stem cells
Forget snail mucin or parabens—stem cells are the most controversial ingredients to pop up in skin care. Found in both plants and animals, stem cells are “one of the few cell types that can produce new cell types rather than simply dividing to make more copies of the same cell type,” says Dr. O’Neill They can also self-renew. Systemically, stem cells are critical to functions related to growth, maintenance, and repair, and in therapeutic use, human stem cells have been intravenously infused to help them circulate and target sites of tissue damage. In skin, “they repair primarily through the secretion of growth factors and cytokines, which communicate with surrounding skin cells to create new, healthy cells, reduce inflammation, and produce collagen,” says Dr. Levine.
The reason they’re so controversial is due to their source—which is, most frequently, human. Those most commonly used in aesthetics come from bone marrow or adult fat and are known as adult stem cells; those used in research and sometimes in skin-care formulations are embryonic stem cells. “They typically come from unused harvested embryos,” says Dr. Batra, who explains that the processed skin protein (PSP) in Neocutis Bio Cream Bio-Restorative Skin Cream with PSP ($178) is derived from an aborted fetuses. “If you’re pro-life, you may have some concerns about taking fetal tissue and using it for aesthetic application, but that’s a personal question,” he says. Adds Dr. Levine, “As this therapy becomes more common, there are concerns about how to ensure that stem cells are derived from consenting and healthy donors.”
There’s a variety of plant-derived stem cells on the market, many of which started to hit the scene in the ’80s and ’90s. “You hear of these very beautiful-sounding things from nature, like plants from the Swiss Alps, stem cells from the edelweiss flower, stem cells from an apple so it never rots, but that’s all marketing,” insists Dr. Batra. Batis agrees: “Since plants and humans have significant differences in cellular structure and function, skin-care products formulated with plant stem cells or plant stem-cell derivatives do not provide the same bioactivity or corresponding benefits as human-derived factors.” However, they may still offer some benefits. “Plant-derived extracts are effective for their antioxidant and anti-inflammatory properties but will not necessarily have regenerative properties,” says Dr. Levine.
The use of stem cells in skin-care treatments is complex. Although there is a body that provides guidelines for ethical research and use of stem cells, The International Society for Stem Cell Research, it’s worth noting that there are no clear FDA guidelines for the use of these products in skin care, says Dr. Russak. “It is up to the practitioner and consumer to really do their own due diligence, to understand whether the product has viable components or not.”
Platelet-rich plasma (PRP)
Thanks to treatments like Vampire Facials, there’s more awareness of the power of platelet-rich plasma, or PRP. “PRP is a blood product made by taking a small sample of blood from a patient, isolating platelets and plasma from red and white blood cells,” says Dr. Batra. “What you’re left with is a golden solution with an enriched amount of platelets and plasma.” Unlike some of the other ingredients on this list, PRP treatment is FDA approved, albeit for very specific purposes.
“PRP has been investigated to facilitate healing, regulate inflammation, and reduce pain in a wide variety of applications, including dentistry, orthopedics, sports medicine, and wound healing,” explains Dr. O’Neill. It’s also used in aesthetic treatments like the aforementioned Vampire Facial to help stimulate collagen production and tissue regeneration. Currently though, aesthetic treatments are off-label uses of PRP. FDA-approved treatments include bone regeneration and the treatment of nonhealing wounds.
The way platelets work is by releasing growth factors, which help repair tissue. You can see this process in action when you scrape your knee. The platelets in the wound’s blood will help stop the bleeding, then they’ll release growth factors to start creating a scab. “Underneath the scab, you’ll remember, there’s that yellow liquid—that’s your very own platelet-rich plasma,” says Dr. Batra. By using PRP in a clinical setting, providers are tricking the body into thinking there’s an injury at the site of the injection.
What’s nice about PRP is that there’s zero risk when it comes to treatments—it’s autologous, meaning it comes from your own blood and goes back to you. You’ll get the best results from it when a treatment is administered in a medical setting, where your PRP is freshly prepared and used immediately. “In-office treatments involve injecting PRP directly into the target area, ensuring maximum efficacy,” adds Dr. Russak.
There are also at-home products that use PRP, including SoMe Skincare and Dr. Barbara Sturm’s MC1 Blood Cream. These products are prepared by medical providers; your PRP is mixed into them before you’re sent home to add them into your regimen. While they’re exciting in concept, they may not be effective in practice. “Incorporating live platelets into commercial skin-care products raises concerns about stability and shelf life,” says Dr. Russak. Additionally, “the topical application of skin-care products may not allow adequate penetration or deliver a sufficient concentration of the PRP’s growth factors to the deeper layers of the skin,” she says. To get any benefit from topically applied PRP products, you will likely have to create micro injuries to your skin first, such as by dermarolling. “Platelet cells and large proteins are much too large to penetrate intact skin,” says Batis.
Exosomes
Exosomes are one of our favorite rising stars in regenerative medicine—and according to O’Neill, they’re one of the newest on the scene, only just having been discovered in 1983. Exosomes are vesicles that are secreted by many cell types and carry “molecular cargo” like RNA, proteins, and lipids between cells, says Dr. O’Neill. “If you think of exosomes as a cellular delivery method, like a care package with a note, you can begin to see how they could be leveraged to deliver specific beneficial factors to the skin,” he explains. They also have growth factors, cytokines, and genetic material and are derived from stem cells. A study shows that using them in skin tissues can promote the formation of new blood vessels, stimulate collagen production, and reduce inflammation. Dr. Russak notes that exosomes are being explored for their potential in skin rejuvenation, collagen synthesis, wound healing, and more; beyond aesthetics, they’re being studied for their value in immunology and oncology research.
But what’s important to remember is that a lot of work is left to be done when it comes to understanding exosomes. “They hold tremendous potential in human health, and we’re just beginning to learn about the power that they have—it’s still early days and highly investigational,” says Dr. Batra. “The FDA has not approved a single exosome product for any indication for use in the US … I really caution some guidance behind promoting exosomes.” In fact, the FDA issued a public safety warning about exosome treatment.
That’s not to say you won’t find them being used in aesthetic practices. Brands like Benev, Rion, and Exocel Bio all offer professional-grade exosome therapy products, using exosomes extracted from different sources. Exosomes are human-derived and can come from bone marrow; placenta; amniotic fluid; stem cells; and Wharton’s jelly, connective tissue found in the umbilical cord. You may have ethical hesitations here. “The source may be a concern for some patients,” says Dr. Levine, who notes that some exosomes are ethically sourced. For example, a tissue like placenta is frequently discarded during medical procedures, but this may still make you squeamish.
There are limitations to using exosomes in at-home skin care. The molecules are too large to penetrate the skin, which means they’re best used in clinical treatments. “They provide a powerful solution for those looking to improve the appearance of their skin and hair,” says Dr. Levine, who uses exosomes in conjunction with microneedling for hair restoration and after laser treatments. They’re also very delicate. “In the biomedical/research community, exosomes are widely recognized as extremely susceptible to rapid degradation and must be maintained at cold temperatures,” says Dr. O’Neill. For best results, they have to be stored at -20°C or -80°C (-4°F and -112°F, respectively), but their quality will deteriorate once they thaw. “In the right preservation media, exosomes can be stored at 4°C [39°F] for up to one week, although analysis has shown loss of greater than 50%,” he adds.
However, there are scant few brands using exosomes in over-the-counter formulas—such as (plated) Skin Science, a brand owned by Rion, a professional-grade exosome manufacturer. “This is the first brand to stabilize exosomes and maintain their viability,” says Dr. Yael Halaas, a board-certified facial plastic surgeon in New York City. The products, including the Intense Serum ($267), use a proprietary lyophilized form of exosomes. (Lyophilization is actually how neurotoxins are manufactured—they’re delivered in powdered form to providers, who then reconstitute them with saline solution.) Dr. Halaas uses the products at her practice and in her own regimen. “They’re a good option for those who can’t tolerate retinoids,” she adds. “Before using this product, I could never tolerate them, but now I can—this product helps my skin heal itself after using Retin-A.”
While many providers feel strongly that exosomes are largely safe and are a valuable addition to the aesthetic-treatment roster, they may not be without risk. “Risks include immune reactions, the possibility of transferring unwanted molecules or pathogens, and in the case of cancer-derived exosomes, the potential to influence tumor growth,” warns Dr. Russak. As exosomes are studied further, we’ll be able to understand potential risks.
