NeoGenesis’ New Topical Probiotic Products, MB-2 and MB-3, Feature 5 Strains of Live, Colonizing Symbiotic Bacteria

Based on many recent scientific studies of using live, symbiotic bacteria in a topical application, NeoGenesis has launched a new probiotic, topical skin care product (MB-2) and will be launching MB-3 soon. I briefly explain some of the science for using topical probiotic products in this post.

I’ve been publishing about (Maguire and Maguire, 2017) and developing topical probiotic products (MB-1 was launched in 2015) for well over a decade. The data for topical symbiotic bacteria colonizing and benefiting the skin are rapidly accumulating. For example, topically applied Lactobacilli have been found to temporarily colonize the skin and to directly compete with skin pathogens through adhesion inhibition, production of antimicrobial metabolites, and by influencing pathogen metabolism. The competitive anti-pathogenic action of Lactobacilli has been described mechanistically for common skin pathogens, such as Staphylococcus aureus, Cutibacterium acnes, and Candida albicans (DeLanghe et al, 2021). Recently, studies of live Lactobacillus crispatus (LBC) demonstrated benefit to the skin when compared to inactivated LBC biomass, stimulating collagen in vitro. Moreover, the live LBC was stable in formulations not containing antimicrobial preservatives and was found to improve dermis density and wrinkle appearance in vivo.

Microbes and human cells have co-evolved for billions of years, through which they have been exposed to many types of molecules produced by each other and acting in bidirectional signaling pathways (Wu et al, 2025). For example, Lactobacilli have an immunomodulatory capacity associated with a reduction in excessive skin inflammation (Delanghe et al, 2021). Their influence on the immune system is mediated by bacterial metabolites and cell wall-associated or excreted microbe-associated molecular patterns (MAMPs). Lactobacilli acting as immune modulators associated with a reduction in excessive skin inflammation exert their influence on the immune system by secreting many bacterial metabolites, a type of postbiotic (this is a term I introduced in 2019; Maguire and Maguire, 2019), along with the cell wall-associated MAMPs that are not released but integrated into the cell of the bacterium. In addition, Lactobacilli can also enhance the skin barrier function, which is often disrupted as a result of infection, trauma, or in inflammatory skin diseases such as eczema and psoriasis. Lebeer et al (2022) found that the Lactobacillis species L. crispatus, L. iners, L. gasseri, and L. jensenii, all still belonging to the genus Lactobacillus strictu sensu, have a broader human adaptation to stratified epithelium than merely the human vaginal epithelial cells, based on their association with healthy skin. In other words, Lactobacilli colonize the skin just as they do in other epithelial tissues. However, these colonies of bacteria on the skin can be disrupted by a number of extrinsic and intrinsic factors, such as harsh chemicals and aging. For example, aged skin contains significantly fewer L. crispatus (a beneficial symbiont) than young skin. Let’s now breiefly look at how symbiotic bacteria benefit the skin through quorum sensing and the release of post-biotic molecules, including molecules that will inhibit pathogenic bacteria such as certain strains of Staphlacoccus aureus.

Quorum Sensing and Post-Biotic Release

Mechanisms of quorum sensing is different for gram-positive versus gram-negative bacteria. Regardless, quorum sensing molecules (AIP or QS molecules) can work within species or on other species to control growth. This is an important means by which symbiotic bacteria, such as B. subtilis, can inhibit pathogenic bacteria such as S. aureus.

As bacteria grow, they secrete and sense signaling molecule in the surrounding environment. By detecting variations in the concentration of these signal molecules, bacteria can modulate the expression of related genes, thereby regulating associated behaviors. Consequently, interfering in bacterial QS signaling to either promote or inhibit the development of lactic acid bacteria (LAB) biofilms holds substantial significance in terms of enhancing skin immunity, promoting skin health.

Quorum sensing allows bacteria to communicate and coordinate collective behaviors by sensing population density through chemical signals, or autoinducers. While primarily species-specific, interspecies communication also occurs when different bacteria produce or detect shared autoinducers like autoinducer-2 (AI-2), a “universal” signal molecule used by many species. This interspecies communication can lead to either cooperation or competition, influencing functions such as biofilm formation, virulence, and resistance against other microbes.

For example, colonization of the skin by Staphylococcus aureus is associated with exacerbation of atopic dermatitis (AD). Proteases and phenol-soluble modulin α (PSMα) secreted by S. aureus leads to endogenous epidermal proteolysis and skin barrier damage that promotes inflammation (Williams et al, 2019). Other species of bacteria residing on normal skin can produce autoinducing peptides that inhibit the S. aureus agr system, in turn decreasing PSMα expression. A number of bacteria types, such as Bacillus subtilis (it secretes lactic acid), can quorum sense (Spacacan et al, 2020) and react to the S. aureus overcolonization by inhibiting the S. aureus through disruption of their QS system (Leistikow et al, 2024).

Quorum-sensing systems in the skin can be divided into two paradigmatic classes: LuxI/LuxR–type quorum-sensing systems in Gram-negative bacteria and oligopeptide/two-component–type quorum-sensing circuits in Gram-positive bacteria. All of this is very complicated, relaizing that bacteria have elaborate chemical signaling systems that enable them to communicate within and between species is only recently been explored and the field is emerging quickly. Based on our current knowledge, I’ve developed two new products, MB-2 and MB-3, using symbiotic, live bacteria known to perform QS or interfere with QS in other bacteria strains and promote skin benefits, including reduced inflammation and barrier function rebuild.

Interspecies Quorum Sensing Fosters Both Competition and Collaboration

To be clear, quorum sensing between different bacterial species occurs as well. For example, some species cannot produce their own autoinducers, but have receptors for the autoinducer molecules of other species, allowing them to sense and respond to others in their environment. Like human behavior, bacteria behavior operates on a continuum of individualism and collectivism. This quality can breed conflict, but also collaboration and interspecies quorum sensing can take both forms. In other words, the good guys, the symbiotic bacteria, can work together through quorum sensing among themselves (intraspecies quorum sensing) to inhibit the bad guys, the pathogenic bacteria, through interspecies quorum sensing. The good guys can be fighting some bacterial species, such as S. aureus, that use quorum sensing to enhance each other’s virulence.

Let’s now look at the five symbiotic bacteria that are contained in MB-2 and MB-3

Lactobacillus plantarum

Lactobacillus plantarum treatment reduced wound bacterial load, neutrophils, apoptotic and necrotic cells, modified IL-8 production and induced wound healing (Peral et al, 2010). When topically applied to a disease skin model for acne, L. plantarum induced a significant reduction in viability of virulent bacteria phylotypes, lipid production, and modulated inflammatory markers (Podrini et al, 2023). Further, L. plantarum whole cultures promote tissue repair, and this bacterium may also improve the healing of diabetic wounds in rats through the regulation of inflammatory cytokines (Ishi et al, 2023). In a study of 23 subjects, topical L. plantarum in a cream formulation was found to benefit skin aging properties, including TEWL, barrier function, and wrinkles (Elvebakken et al, 2023).

Lactobacillus crispatus

An oily suspension containing Lactobacillus crispatus and Lacticaseibacillus paracasei was found to benefit Seborrheic dermatitis (Truglio et al, 2024). In a study of 29 women with topical application of L. crispatus, the density of the sub-epidermal zone significantly increased vs baseline by 11% and of the dermis by 6% (+5% vs placebo). As I mentioned in the introduction,, studies of live Lactobacillus crispatus (LBC) demonstrated benefit to the skin when compared to inactivated LBC biomass, stimulating collagen in vitro. Moreover, the live LBC was stable in formulations not containing antimicrobial preservatives and was found to improve dermis density and wrinkle appearance in vivo.

Bacillus subtilis

Topical application of live Bacillus subtilis has been found to reduce the number of pathogenic bacteria in skin, including S. aureus (Moskovicz et al, 2021; Piewngam et al, 2023). Topical application also helps to reduce acne breakouts (Ma’or et al, 2023). B. subtilis is being developed for drug delivery for a number of reasons (Montgomery et al, 2024). It may have advantages over other candidate bacteria as a platform for drug delivery to the skin because of its safety profile and genetic tractability. It is found in the skin microflora and is metabolically active on the skin. It is nonpathogenic and has natural antimicrobial properties against pathogenic staphylococci and fungi. B. subtilis has generally regarded as safe status from the FDA, and multiple B. subtilis probiotic products as well as a genetically modified strain of B. subtilis are currently commercially available. Further, an important characteristic of B. subtilis is that it is commonly used in biotechnology for the production of proteins, vitamins, and antibiotics because of its efficient protein secretion system, and ease of cultivation, factors that mean it can work well when topically applied to the skin as a probiotic.

Bacillus coagulans

LactoSporin, a metabolite of Bacillus coagulens, cream topically applied for 10 weeks resulted in a significant reduction in visibility of wrinkles around crow’s feet, nasolabial folds, frown lines, and facial fine lines compared to baseline and placebo by dermatological and Antera imaging assessments (Majeed et al, 2023). . Optimal conditions for growth include a temperature range of 30–50°C and a pH level of 5.5–6.5, matching the surface of the skin. This bacterium exhibits weak adhesion to epithelial cells, which prevents long-term colonization, but allows temporary colonization and yielding positive effects.

Lactoccus lactis

Various strains of L. lactis have recently been reported to induce anti-inflammatory activity in vitro (Luerce et al, 2014). Administration of L. lactis LB 1022 improved clinical AD symptoms, decreased serum IgE and suppressed the Th2 cytokines secretion, such as IL4, IL-13, and TSLP in blood, which are factors found to be elevated by AD. Similarily, oral L. lactis LB 1022 may have a protective effect against AD by reducing high IgE serum levels and Th2-related responses that arise from an imbalance in the gut microbiota. Topical application of L. lactis is likely to have similar effects on AD, but given the likely lower colonization levels when topically applied, requires more frequent dosing to achieve similar positive results. It is also possible that L. lactis ferments glycans on the surface of the skin, thus producing beneficial lactic acid that may then be fermented into beneficial short chain fatty acids which then regulate the immune system and reduce inflammation.

Summary

As you can read here in the studies I’ve mentioned, there is much accumulating evidence for the benefits of the 5 types of symbiotic bacteria that I’ve chosen to include in our NeoGenesis MB-2 and MB-3 products. Working with a number of dermatologists in the USA, we’ve had remarkable postive results in compromised, inflammatory skin conditions where MB-2 (bacteria in an occlusive base) serves those conditions with interupted barrier function, such as atopic dermatitis and MB-3 (in a non-occlusive oil base) serves those conditions with a more intact barrier and oily and pustule-prone skin.

Why Seed Oils Are Great For Skin Care

Did you know scientists have discovered that topical sunflower seed oil helps to rebuild the stratum corneum and barrier function? Or that topical safflower oil can help to regrow hair and help to close wounds. Did you know that consuming seed oil, full of polyunstaurated fats, is healthier than eating coconut oil, which is 90% saturated fat. Consuming staurated fat leads to heart problems and dysbiosis, among other problems. Did you know that some seed oils, such as high oleic sunflower seed oil, tends to have higher stability than the high linoleic varieties of oils? Or that safflower seed oil contains extremely stable oleosomes? These are the reason why I formulate with these two oils. They provide essential oils (oils the skin needs to aquire to be healthy but are not made by the skin) and they provide numerous benefits to the skin. If the seed oils are extracted carefully, such as expeller pressed, and then formulated in a cold-process, the seed oils are of great benefit to the skin.

Listening to some unknowledgeable and outspoken people on TikTok, YouTube, including some pharmacists, or any of a number of podcasts, the oil extracted from plant seeds is poisoning us. RFK, Jr., who should have stuck with being an environmental lawyer, has jumped on this inane bandwagon. I think his cerebral arteries must be clogged with beef tallow (50% saturated fat) and advanced glycation end products from the fries he eats. Other people, such as the physician Mark Hyman are telling people to eat unhealthy coconut oil instead of seed oils – I guess he’s trying to drum-up business. Coconut oil induces inflammation and metabolic disorders, and a coconut oil- high fat diet has been found to cause dysbiosis associated with an increased risk of colorectal cancer. Further, diets rich in saturated fats, such as coconut oil, may contribute to mitochondrial dysfunction, protein aggregation, and neuronal degeneration. Recent studies (McCright et al, 2025) also find that saturated fats exacerbate asthma and promote lung myeloid cell inflammasome activation and IL-1β–mediated inflammation in mice and humans.

Instead of pseudoscience from RFK, Jr, try some science from Prof. Dr. Christopher Gardner, Ph.D. on a recent podcast. “It’s so odd that the internet has gone wild demonizing these things [seed oils],” said Dr. Christopher Gardner, Ph.D., a professor of medicine at Stanford University School of Medicine in California and a nutrition scientist at the Stanford Prevention Research Center. “They are not to be feared.” Dr. Gardner says seed oils contain high levels of omega-6 fatty acids, a polyunsaturated fat the body needs but cannot produce itself, so it must come from foods. Polyunsaturated fats help the body reduce bad cholesterol, lowering the risk for heart disease and stroke. The American Heart Association supports the inclusion of omega-6 fatty acids as part of a healthy diet. Studies of linoleic acid, found in seeds, finds the seed oils benefit cardiovascular function.

Seed Oils in Topical Skincare Products

Some seed oils, such as sunflower seed oil, are great for the skin. Sunflower seed oil helps to rebuild skin barrier function. In contrast to sunflower seed oil, topical treatment with olive oil significantly damages the skin barrier, and therefore has the potential to promote the development of, and exacerbate existing, atopic dermatitis.

Sunflower Seed Oil

Notice sunflower seed oil (SFSO) is used by dermatologists at UCSF, such as Prof. Dr. Peter Elias, M.D. and his colleagues, in an inexpensive product for building the epidermis and barrier function: https://pmc.ncbi.nlm.nih.gov/articles/PMC9078150/. There are other products that work better, but they are more expensive because of ingredients like oleosomes, Triple Lipid Technology and Natural Mositurizing Factors, things that I’ll explain later. The product developed by Prof. Elias and colleagues features sunflower seed oil, something that is less expensive but provides benefit to barrier function. SFSO activates PPAR-alpha, which has numerous benefits in the epidermis (increased lipid production and lamellar body formation, and differentiation of keratinocyes) that help to rebuild natural barrier function. Sunflower seed oil contains oleosomes if cold-processed and not refined. Oleosomes are specialized plant organelles that protect the oil, and I’ll describe in the next section.

From Elias et al (2022): The putative mechanisms by which a topical optimised mixture improves permeability barrier homeostasis. In the mixture, petrolatum and lanolin instantly improve the permeability barrier, while glycerol improves barrier (stratum corneum, SC) hydration and accelerates permeability barrier repair. Linoleic acid in both sunflower oil and borage oils activates peroxisome proliferator-activated receptors (PPAR), resulting in increased production of lipids and antimicrobial peptides, and stimulation of lamellar body secretion and membrane maturation. Consequently, both permeability barrier and antimicrobial barriers are improved.

Safflower Seed Oil and its Oleosomes

I’ll also described the benefits of safflower seed oil (SSO), and the oleosomes contained within. SSO has antioxidant and antimicrobial activity, helping to heal wounds. The potential uses of SSO for skin care are under intense investigation given what is already known of this oil. For example, recent results indicate that SSO and its active compound acacetin can prevent UVB-induced MMP-1 expression, which leads to skin photoaging.

From Karefyllakis et al (2019): 2D-model of an oleosome with an emphasis on the configuration of the membrane, composed from a monolayer of phospholipids with the hydrophobic oleosin proteins anchored in the triacylglyceride (TAG) core (sizes not to scale), and (b) CLSM (confocal laser scanning microcope) image of SFO stained by Nile Blue showing lipids in green and proteins in red.

Safflower oleosomes are of interest in part because the plant seeds uniquely contain a large amount of oil bodies (oleosomes) and low water content, resulting in decreased hydrolytic properties and lower protein degradation. Within the oil, tocopherol or vitamin E occurs naturally. Looking at the evolution of plant seeds, the primary function of oleosomes is to safely store the seed energy source in the form of triacyglycerols (vegetable oil) during dormancy of the seed and then use it during germination, and to protect the seeds against environmental stressors. To achieve this, a sophisticated structure has evolved where oleosomes are equipped with a membrane that covers the triacylglycerols (TAGs) core, imparting physical and chemical stability. The membrane acts as a shield, preventing the oxidation of the TAGs. The membrane is dilatable and consists of a continuous monolayer of phospholipids that contains a number of proteins, mostly oleosins, embedded in the membrane. Triacylglycerols, also known as triglycerides, are a type of lipid composed of a glycerol molecule bonded to three fatty acids. They are the main constituents of body fat in animals and vegetable fats. Triacylglycerols serve as a crucial energy reserve, storing more than six times the energy of glycogen per gram. The seeds need this energy to germinate.

The oleosomes we use at NeoGenesis are naturally and sustainably extracted from the seeds of safflower (Carthamus tinctorius). The herbaceous non-GMO plant is cultivated and harvested in California, USA, without the use pesticides and with low water requirements. The manufacturer with whom we work, Sharon, uses a proprietary aqueous extraction cold process, comprising: grinding the seeds with aqueous medium, centrifugation and separating the liquids from the solids by centrifugation again before isolating the oleosomes. This process keeps the oleosomes fully intact, maintaining the micro-oil bodies as they occur naturally, with their full qualities and capabilities. Further, cold processing retains the antioxidants, vitamins and minerals. The result is an oil-in-water (o/w) emulsion with natural properties that provide many skin benefits. Biophysical studies of the oleosome have characaterized the oleosomes’ high physical stability, and have called for bioinspired construction of oil structures capable of protection and delivery of ingredients to the skin, all based on the remarkable evolutionary structure of the oleosome.

Sea Buckthorn Oil (Berries, Pulp, and Seeds)

Sea Buckthorn Seed Oil (SBSO), which typically contains the oil from the berries and pulp too, is another highly prized oil for skin care. One of the key reasons I use it in my topical skin care formulations is the high level, about 50%, of Omega-7 fatty acids. SBSO has been found to aid wound healing and increases telomerase activity, and decrease 3-nitrotyrosine. Inhibiting 3-nitrotyrosine (3-NT) is huge because 3-NT is a stress factor and acts as a neoantigen leading to the production of autoantibodies that can destroy skin tissue.

More than Omega-7, sea buckthorn (Hippophae rhamnoides) is valued for its diverse array of bioactive compounds. Cold-pressed extraction is important for retaining the full spectrum of these compounds. The SBSO is typically derived from various parts of the plant, including the whole berry, pulp, and seed, each yielding unique profiles of fatty acids, vitamins (A, C, and E), phytosterols, flavonoids, and carotenoids. SBSO, in particular, is rich in polyunsaturated fatty acids like linoleic acid (omega-6) and linolenic acid (omega-3), as well as the monounsaturated fatty acid palmitoleic acid (Omega-7). SBSO also contains a small amount of saturated fatty acid palmitic acid, monounsaturated fatty acid oleic acid, and trace amounts of myristic and stearic acids, along with minerals such as selenium, copper, zinc, and silicon. Together, this remarkable array of components in SBSO enhance the epidermis’ skin barrier function, structural integrity, and and anti-inflammatory properties, making SBSO a valuable therapeutic agent for conditions such as skin wounds, atopic dermatitis and psoriasis, or any skin condition with inflammation and compromised barrier function.

Other seed oils have been found to provide benefit too. Raspberry seed oil, for example, improve barrier function as measured by decreases of TEWL in human subjects, whereas the comparator oil, coconut oil, had no effect. Let’s stop denegrating seed oils!

Beneficial Seed Oils for Skin

Oil	Key Components	Main Skin Benefits	Skin Types Best Suited For
Rosehip Seed Oil	Linoleic acid, α-linolenic acid, provitamin A (retinoids), tocopherols	Promotes skin regeneration, reduces scars and hyperpigmentation, improves elasticity	Dry, mature, scar-prone
Pomegranate Seed Oil	Punicic acid (omega-5), polyphenols	Strong anti-inflammatory and antioxidant activity, supports skin repair, calms redness	Sensitive, inflamed, aging skin
Black Cumin Seed Oil	Thymoquinone, linoleic acid	Antimicrobial, reduces acne inflammation, supports wound healing	Acne-prone, oily
Chia Seed Oil	α-linolenic acid, phytosterols	Improves hydration barrier, reduces trans-epidermal water loss, calms irritation	Dry, sensitive, eczema-prone
Hemp Seed Oil	Balanced omega-3 and omega-6, γ-linolenic acid	Regulates oil production, reduces inflammation, strengthens barrier	Oily, acne-prone, combination
Pumpkin Seed Oil	Zinc, tocopherols, phytosterols	Promotes firmness, antioxidant protection, may help with hormonal skin changes	Aging, combination
Sea Buckthorn Seed Oil	Palmitoleic acid, carotenoids, tocopherols	Heals damaged skin, boosts elasticity, protects against oxidative stress	Dry, sun-damaged
Raspberry Seed Oil	Ellagic acid, tocopherols, polyunsaturated fats	Antioxidant, anti-inflammatory, mild natural UV protection	Sensitive, aging, photo-exposed

Summary

Bottom line, if you’re using coconut oil or olive oil on your skin, your not improving epidermal function, you can be degrading it. Switch to products using evidence-based, scientific knowledge to formulate their products – and, yes, seed oils, providing essential oils, can be great for the epidermis and improving barrier function. For example, if you use the NeoGenesis Barrier Renewal Cream, you’ll benefit from safflower oleosomes, combined with our Triple Lipid Technology (free fatty acids, ceramide, cholesterol) and Natural Moisturizing Factors (NMF) to rebuild the stratum corneum and barrier function. No other company features this combination of ingredients to rebuild the epidermis. And for those with moderate to severe barrier dysfunction, our new MB-2 product provides instantaneous barrier function without the use of petrolatum, along with 5 types of symbiotic bacteria important to rebuilding barrier function and inhibiting Staphylococcus aureus overgrowth, commonly found in skin with disrupted barrier function. One last thing, NeoGenesis S2RM, containing adipose mesenchymal stem cell secretome, helps to rebuild barrier function too!

For those with disrupted barrier function in conditions such as eczema, including atopic dermatitis, I recommend Skin Serum, which contains S2RM and glycerol, Barrier Renewal Cream, which contains oleosomes+ Triple Lipid Technology +NMF, followed by MB-2, containing a non-petrolatum occlusive+5 live symbiotic bacteria. There’s no better way to improve epidermal health and barrier function, and seed oils are part of the rebuild!.

Forget the Collagen Supplements for Skin Health – It’s All Pay to Play When the Studies Are Analyzed

A new study analyzing 23 randomized clinical trials with 1474 participants has found that “collagen supplements” significantly improved skin hydration, elasticity, and wrinkles only if you include data from physician-investigators who were paid by pharmaceutical/supplement companies. However, an analysis of studies not receiving funding from pharmaceutical companies revealed no effect of collagen supplements for improving skin hydration, elasticity, and wrinkles, while those receiving funding from pharmaceutical companies did show significant effects. Similarly, high-quality studies of “collagen supplements” revealed no significant effect in all categories, while low-quality studies revealed a significant improvement in elasticity.

No evidence that collagen supplements improve skin health

First, “collagen supplements” don’t contain collagen – they contain hydrolyzed collagen, otherwise known as amino acids. Moreover, most “collagen supplements” contain many ingredients other than the hydrolyzed collagen. A new meta-analysis by scientists at two major universities casts doubt on the effectiveness of “collagen supplements” for improving signs of skin aging, raising questions about the role of industry-funded research in shaping health and wellness trends. As the authors conclude, “There is currently no clinical evidence to support the use of “collagen supplements” to prevent or treat skin aging.” This is nothing new. Many studies in the pharmaceutical and supplement industries are flawed, frequently using fraudulent data, to sell their products that actually don’t work.

Often times, pharma and supplement companies hire ghostwriters to perform and write-up the study. Then the company finds a physician who will put their name on the byline. The physician didn’t have anything to do with the study and had nothing to do with writing the study. Ghostwriting is a big problem, and growing. For example, “first author” of a medical paper on Vioxx, Jeffrey Lisse, M.D., has said in an interview that “Merck designed the trial, paid for the trial, ran the trial…Merck came to me after the study was completed and said, ‘We want your help to work on the paper.’ The initial paper was written at Merck (ghostwritten), and then it was sent to me for editing.” In other words, Mr. Lisse was not an author of the study but was paid to pretend he was. Not only were his actions immoral, they were dangerous. Vioxx was later removed from the market because it significantly increases cardiovascular adverse events – people died from heart attacks. As physician Adriane Fugh-Berman, M.D., professor at Georgetown University School of Medicine and PharmedOut, has said about ghostwriting, “But there’s also the fact that this is so common that it’s not considered unusual. There’s no shame attached to it.” The point here is that many studies of drugs and supplements are flawed, some are fraudulent, and the studies of collagen supplements seem to be highly flawed.

Collagen and its importance to skin function and health

From: Han et al (2021) Recent advances in skin collagen: functionality and non-medical applications

Skin Collagen is a scleroprotein (not water soluble) and a major structural protein found throughout the body, including in skin (Fig. 2), hair, nails, tendons and bones. Much collagen in the body, including in the skin, is long-lived. One estimate of human skin collagen half-life suggested 14.8 years. Specifically, type I and type III collagen are found in abundance in the skin. Elastic fibers also play an important structural role within the dermis. Elastic fibers are composed of elastin and fibrillin microfibrils. In contrast to collagen, the biochemical configuration of elastin allows for gliding, stretching, and recoiling of fibers. The reticular dermis comprises thick elastic fibers. Two subtypes of elastic fibers are noteworthy: elaunin and oxytalan fibers. Elaunin fibers are horizontally arranged elastic fibers found near the junction of the papillary and reticular dermis. Oxytalan fibers are perpendicular elastic fibers found in the papillary dermis. Fibers work alongside substances like glycosaminoglycans (GAGs), such as hyaluronic acid, to maintain skin elasticity, volume, and moisture. While the body naturally produces collagen using amino acids from foods like beans and tofu, production declines with age and can be further reduced by sun exposure and poor diet.

From Alcaide-Ruggiero et al (2021). Schematic representation of collagen biosynthesis. (1) Gene transcription. (2) Formation of α-chains. (3) Formation of triple helix procollagen and secretion into extracellular space. (4) Procollagen processing and formation of tropocollagen (non-soluble form of collagen). (5) Association of tropocollagen molecules to form collagen structures.

Many forms of collagen, such as type I, are abundant through a range of tissues and are fundamental structural building blocks. Type I collagen is the main component of fibrils that provide tissues with tensile strength. Type I collagen is a heterotrimeric protein assembled from the two α1(I) and one α2(I) polypeptides when they fold into a triple helix. After secretion of procollagen into the extracellular space, the terminal domains are removed by proteolytic cleavage and the rodlike triple helices of the central domain polymerize into fibrils and are covalently cross-linked.

Type I collagen is the most abundant collagen type in the skin, accounting for 80–85% of the dermal ECM. Other subtypes, like type III and type V collagen, can be found in skin, but type I collagen is fundamental to skin structure; it supplies considerable tensile strength and helps to determine the structure and durability of the dermis. As skin ages, there is a progressive loss, damage, and fragmentation of dermal collagen fibrils, leading to reduced skin thickness and biomechanical strength.

Type I collagen is also one of the longest-lasting of the long-lived protein in humans, and is a major fibrillar component of connective tissues such as skin, bone, and tendons. It has a triple-helix structure composed of two α1 chains encoded by the Collagen type I alpha 1 chain (COL1A1) gene and one α2 chain encoded by the Collagen type I alpha 2 chain (COL1A2) gene. Among these, COL1A1 expression has been identified as a biomarker of skin aging, as its levels decline with age. This organization of collagen along with other fibrils and matrix molecules endows connective tissues with mechanical strength and elasticity.

Collagen genetics

The COL1A1 gene provides instructions for making part of type I collagen. A component of type I collagen called the pro-α1(I) chain is produced from the COL1A1 gene. Collagens begin as rope-like procollagen molecules that are each made up of three chains. Type I collagen is composed of two pro-α1(I) chains and one pro-α2(I) chain (which is produced from the COL1A2 gene).

The triple-stranded procollagen molecules are processed by enzymes in a series of steps inside and outside the cell to create mature collagen. The collagen molecules then arrange themselves into long, thin fibrils that form stable interactions (cross-links) with one another in the spaces between cells. The cross-links result in the formation of very strong type I collagen fibers.

Industry funded pharmaceutical and supplement studies are often flawed

While collagen drinks, supplements, topical products and even prescription pharmaceuticals have gained market traction for their promised skin benefits, the stark difference between the overall results and the subgroup findings underscores how industry funding and study quality can sway outcomes, a longstanding concern in nutrition, pharmaceutical, and supplement research. Sadly, many medicines and supplements don’t work, including those for dermatological use. Allen Rogers, PharmD, worldwide vice president of genetics at Glaxo SmithKline, is reported on the front page of the Independent (8 December, p 1) as saying: “Our drugs don’t work on most patients.”

Confounding these studies of collagen, most of the trials used commercially available supplements that contained more than hydrolyzed collagen (amino acids), including vitamins, minerals, antioxidants, coenzyme Q10, hyaluronic acid and chondroitin sulfate were among the additional ingredients.

Too much amino acid consumption is bad for health, including heart health

Scientists have discovered a molecular mechanism by which excessive dietary protein could increase atherosclerosis risk. For example, amino-acid-mediated mammalian target of rapamycin (mTOR) signalling in macrophages has been implicated in the pathogenesis of ischemic cardiovascular disease. Specifically, ingestion of protein or amino acids in excess of ∼22% of dietary energy requirements drives atherosclerosis.

Further, an unbalanced, unnatural increased intake of one or more amino acids can cause imbalance in amino acid concentrations in the body, increase concentrations of its metabolites, and affect the transport of a group of amino acids into cells due to competition for a carrier at the cell membrane. The phenomenon of carrier competition can affect absorption of other amino acids in the gut and subsequently their appearance in the blood, transport across the blood-brain barrier, and supply for protein synthesis. Proteinopathies may result, leading to degenerative disorders. For example, too much leucine consumption can decrease autophagy in the brain. Autophagy, a cellular process of waste and debris removal, is known to decrease proteinopathy, and therefore too much leaucine may potentially lead to the buildup of toxic metabolites and neurodegeneration.

Summary

Skip the supplements made from hydrolyzed collagen. Eating a variety of plant-based protein sources—such as beans, soy, legumes and quinoa—means your body will have the amino acids it needs to make collagen, while also providing Vitamin C and antioxidants, all of which are important to the health status of the skin, particularly collagen formation and protection of the long-lived collagen.

Skin Pores – Reducing Their Size

Many endogenous and exogenous factors are known to cause enlarged pilosebaceous pores. Such factors include sex, ageing, diet, chronic ultraviolet light exposure, comedogenic xenobiotics, acne, genetic and epigenetic predisposition, and seborrhoea. Most of these causative factors of enlarged pores, being exogenous and controlled by enironmental factors, means you can do something about it. There are procedures and topical products you can use to reduce pore size.

From: Yousef et al (2024)

Although the pathogenesis of enlarged facial pores is still not fully understood, three factors are thought to be key to the pathology: 1) high sebum production, 2) decreased skin elasticity around pores, and 3) increased hair follicle volume. Other factors, including chronic recurrent acne, diet, sex hormones, and skin care regimens, such as inappropriate use of cosmetics, modern Western diets, washing habits, and sun exposure, also affect pore enlargement. Many of these factors will affect the epigenetics of the skin and therefore the skin’s health and potentially pore size. Epigenetics are regulated by your environment, so there is much you can do to reduce enlarged pores.

Causes of Large Pore Size

In cross-sectioned images of conspicuous, enlarged pores, a strongly undulated epidermal–dermal junction was commonly observed around a pore’s opening. Areas with this feature correlated well to the areas with larger hollows and an uneven skin tone. (Sugata et al, 2007).

Recent clinical studies have confirmed the cause of facial pore size to be multifactorial. A positive correlation of pore size and number with sebum output level has been confirmed by several studies (Roh et al, 2006; Kim et al, 2013). Enlarged pores increase with age, up to 40 years, and then stabilize or only slightly increase (Jung et al, 2018). Another significant correlation was detected between skin elasticity and pore number in two independent studies suggesting that the structure of dermis could be involved in pore widening (Kim et al, 2013; Hameed et al, 2019). Other observations found pore counts were related to wrinkle severity; and the loss of Microfibril-associated glycoprotein-1 in the hair follicle/pore area with aging and photo-exposure, indicating a lack of matrix support in the dermis (Zheng et al, 2013; Jung et al, 2018).

Both epidermal and dermal structual impairments have been identified as a cause of large pores. Microscopic imaging of pores revealed inner structural changes affecting skin, including a lower density of collagen in the deeper dermis, a thicker stroma and coarser collagen fibers forming a tubular structure around the follicle, and an irregular basement membrane ultrastructure, all of which may result in an altered distribution of skin tensions (Sugata et al, 2008; Sugiyama-Nakagiri et al, 2008; Mizukoshi and Takahashi, 2014). These ultrastructural alterations may result from inflammation, and recent data suggest inflammaging, mediated by complement activation (immune system proteins), as one of the possible inflammatory agents in the formation of enlarged facial pores (Qiu et al, 2024). Bacteria, such as Staphlacoccus aureus, infect hair follicles and pores, and the question remains, does the inflammation with this sort of infection enlarge the pore. Defects in epidermal morphology around pores have also been discovered, such as epidermis thickening and acanthosis (thickening of the stratum spinosum layer), likely indicating abnormal and possibly excessive keratinocyte proliferation ( Mizukoshi and Takahashi, 2014).

Procedures to Reuce Pore Size

Procedures, such as Micro-focused ultrasound with visualization (MFU-V), have been found to reduce pore size. MFU-V uses focused ultrasound energy to lift and tighten the skin by delivering heat to specific tissue layers beneath the skin’s surface, stimulating collagen production and causing skin tightening according to The Journal of Clinical and Aesthetic Dermatology. The visualization aspect of the procedure allows practitioners to see the underlying tissue during treatment, ensuring precise targeting and optimal results.

Topical S2RM to Reduce Pore Size – It’s Not Just the Exosome, It’s the Secretome

But are procedures needed to reduce pore size? No, the right choice of topical skin care products can significantly reduce pore size too. The secretome from adipose mesenchymal stem cells, something used in the NeoGenesis S2RM technology, significantly reduces pore size. That inflammation inducing the ultrastructual changes causing pores to enlarge can be reduced- reduce the inflammation with ADSC secretome found in the NeoGenesis S2RM technology. Remember, It’s Not Just the Exosome, It’s the Secretome that is optimal for reducing inflammation and regenerating tissue – including the tissue that constructs the pore. Changes of TEWL found that ADSC secretome can faciltate the recovery of the skin barrier function (Zhou et al, 2013), which can be explained by ADSC secretome normalizing the proliferation and migration of human primary keratinocytes as reported by Moon et al (2012). Both the epidermis (Ren et al, 2024) and dermis (Silveira et al, 2022) and hypodermis (An et al, 2021) are regenerated by ADSC secretome, with ADSC secretome containing collagen type IV needed to build the basment membrane, thereby regulating that “undulated epidermal–dermal junction” found to underly increased pore size.

I want to emphasie that inflammaging, inflammation that occurs as we age, is exposome induced. Those who eat well and live in an healthy envionment don’t suffer from inflammaging (Franck et al, 2025). As Franck et al write, “Inflammaging, as measured in this manner in these cohorts, thus appears to be largely a byproduct of industrialized lifestyles, with major variation across environments and populations.” In other words, if you live a healthy lifestyle, chronic inflammation, including inflammaging, is something you won’t suffer. This will reflect in your skin health, and your skin’s pore size.

Summary

Pore size in the skin depends on your envionment, your so-called exposome. Healthy skin is beautiful skin, including beautiful, healthy pores. Eat well to keep the skin healthy with sebum production levels normal and therefore reducing a risk factor for increased pore size. And the right choice of topical skin care products can help keep the skin healthy and pore size normal.

NeoGenesis’ New Vitamin C Product – Vibrant C Serum – Why It’s Different and Better

There are many topical vitamin C products on the market, but I needed to formulate something new because the other products are suboptimal for a number of reasons that I discuss here. Some Vitamin C products feature too much Vitamin C (15-20%) that inhibits elastin, and include alcohol at high levels to disrupt the skin barrier (penetration enhncement), resulting in the induction of inflammation in as little as 3 days of use. Alcohol-induced penetration across the skin is the result, at least in part, of stratum corneum intercellular lipid removal – in other words, alcohol destroys the fats in the skin’s barrier. Liposomal ascorbic acid is one reason the NeoGenesis vitamin C product, Vibrant C Serum, is better, and our built-in antioxidant cascade system is another. Unlike alcohol-based products with high levels of ascorbic acid (20% product and a 15% product; notice too that both of these products contain phenoxyethanol that kills cells), NeoGenesis’s Vitamin C product doesn’t destroy the skin’s barrier and doesn’t inhibit elastin, nor does it kill epithelial cells like some other Vitamin C products..

Primates, including humans, cannot synthesize vitamin C. Most other mammals (except guinea pigs), including our cats and dogs, can produce vitamin C, but primates have lost this ability due to a beneficial genetic mutation. Primates evolved to eat mostly, if not exclusively, plants and therefore obtained all the vitamin C they needed through their diets. Look at those big, strong Gorillas, they eat only plants. We primates evolved to eat plants, loaded with C, all that we needed for optimal health, and so we eventually lost the genetics to make vitamin C. In other words, we mutated, and that pesky DNA sequence for making vitamin C was a waste of energy and therefore to be efficient, evolution of primates dropped the unneeded sequence. Pretty cool how mother nature is so efficient and evolution is such as great designer, doing so without a designer. Thinking teleogically, what she said was, “you eat so much vitamin C, you don’t need to make it anymore.”

Reasons Why the Skin May Not Have Adequate Vitamin C Levels

But that was then, and this is now. People don’t eat so well these days and are stressed-out, both of which can lead to suboptimal levels of vitamin C in the skin. Even if you eat sufficent levels of Vitamin C, the transporters of vitamin C from the blood vessels don’t work well under conditions of chronic inflammation – therefore those with chronic inflammation in the skin may not be receiving adequate levels of dietary vitaimin C required for both dermal and epidermal function. The blood vessels bringing the vitamin C to the skin are no longer transporting it out of the blood into the skin – the process has been decommissoned by inflammation in the skin.

Ascorbic Acid (Vitamin C) Doesn’t Easily Penetrate the Skin

Vitaimin C (VC) has a molecular weight of only 176.12 g/mol, but it is a hydrophillic small molecule and because it interacts with water and not lipids, it dosen’t penetrate the fatty stratum coreum very well. Many companies put high levels of VC in their products, but the VC just lays on the surface of the skin.

High Levels of Vitamin C on the Skin’s Surface Oxidize (DHA an Anti-inflammatory) But Still Provide No Benefit

That 15% VC product you’re using may just sit on the surface of your skin where it will oxidize. Dehydroascorbic acid (DHA) is the oxidized form of VC, and it too has anti-inflammatory benefits just as VC does. If only it would penetrate the skin and provide benefit. Oxidized VC in the DHA form has benefits and cells, such as keratinocytes, readily take up DHA to convert it back to VC, but it needs to penetrate to the cells (keratinocytes) in the skin to give benefit. If the DHA sits on the surface of the skin too long, it can further breakdown to oxalic acid that can irritate the skin.

For those who would like to know, DHA is reduced to ascorbic acid by cytosolic reductases GSH-NADPH-dependent, lipoic acid-NADH-dependent, and thioredoxin reductase. The bottom line is that both AA and DHA are important to the skin, but longer term oxidation of AA and DHA into oxalic acid is likely detrimental.

Liposomes Carry Vitamin C Into the Skin

You’ll notice lecithin as part of the ingredient list on the Vibrant C Serum. Lecithin is part of the ingredient combination involved in making the liposomes that encapsulate the ascorbic acid. The liposomes not only protect the ascorbic acid, but importantly, carry the ascorbic acid through the stratum corneum to the deeper layers of the skin. The liposomes act without disrupting the stratum corneum and epithelial barrier function. This is different from some other Vitamin C skin care products that use alcohol as a penetration enhancer. Alcohol, especially at high concentrations, disrupts the lipid structure of the stratum corneum and reduces barrier function.

For example, some products use 15% ascorbic acid, along with an alcohol called Ethoxydiglycol, a type of ethanol. They use over 15% alcohol in their formula because the ethoxydiglycol is listed before the ascorbic acid on the product’s ingredient list – this alcohol is used as a penetration enhancer and using a high level of this alcohol in the formulation can disrupt the corneum stratum and induce irritation. In other words, this product is disrupting the stratum corneum’s barrier function.

Positive Epigenetic and Cellular Effects of Vitamin C Once It’s Absorbed Into the Skin

When VC penetrates to the keratinocytes, remarkable and beneficial physiological processes occur. VC increases epidermal thickness by promoting keratinocyte proliferation through the DNA demethylation of proliferation-related genes (Sato et al, 2025). This is an epigenetic effect, where VC helps to remove a methyl group that is attached to the DNA in the keratinocyte, so-called demethylation, and this allows the keratinocyte to proliferate. Part of what happens in life is that some of our DNA accumulates methyl group attachements, something that can “turn-off” the DNA. VC demethylates the DNA and turns it on again, allowing the keratinocyte to once again proliferate. It’s much more complicated than this, but for the keratinocytes this is the basic hypotheisis that scientists have brought forth.

In terms of the epidermis, L-ascorbic acid (vitamin C [VC]) is widely recognized for its antioxidant properties in the skin (Masaki, 2010), enhances collagen synthesis (Kishimoto et al, 2013), alleviates UV-induced damage to the epidermis (Kawashima et al, 2018), and inhibits melanin deposition (Sato et al, 2017). Long-term VC deficiency leads to epidermal atrophy in a mouse model with disrupted VC synthesis capabilities (Sato et al, 2012). VC promotes keratinocyte viability, induced expression of differentiation marker genes, and increased SC barrier lipids in monolayer or organotypic cultures of normal human keratinocytes (Boyce et al, 2002; Michalak et al, 2021). Together, these data suggest that VC is critical to epidermal cell proliferation and differentiation.

Collagen and Matrix Formation

Vitamin C is also crucial for the production of collagen, a protein that helps to form your skin’s overall structure and barrier and enhances your skin’s elasticity. Collagen is an important building block of the skin. In addition to stabilising the collagen molecule by hydroxylation, vitamin C also stimulates collagen mRNA production by fibroblasts in the dermis yiedling more collagen and stable collagen. Hydroxylation of collagen is a critical post-translational modification where specific amino acids, proline and lysine residues, are hydroxylated, forming hydroxyproline and hydroxylysine, respectively. This process is vital for collagen’s structural integrity, stability, and proper function, particularly within the extracellular matrix. So, Vitamin C helps to stabilize the collagen that is present, as well as to help produce new collagen.

Skin collagen is a long-lived protein, having a long half-life that is estimated to be approximately 15 years, so some skin collagen can exist for much of your life. In young, healthy skin, the amount of enzymes, such as MMP (proteases) that breaks down collagen is low, and therefore, collagen degrades very slowly. However, as we age and more MMP is present, collagen ages, it starts to degrade and fragment. Unfortunately, the degraded and fragmented collagen cannot be incorporated into new collagen fibers and it accumulates within the extracellular matrix of the dermis. The presence of fragmented collagen remainders in aged dermis inhibits both fibroblast proliferation and type I procollagen synthesis by these cells, further degrading the dermis.

It’s the supporting matrix, such as collagen and elastin, that gives the skin its tightness, thickness, and firmness, but over the years, it starts to break down. That’s why skin gets saggy and thin. Again, Vitamin C is one factor, a necessary factor, to protect collagen and to produce new collagen.

Using the Optimal Amount of Ascorbic Acid: Too Much Vitamin C Inhibits Elastin

Elastin helps form the dermal matrix and helps give elasticity to the skin. Like collagen, much of the eleastin is formed in the dermis by fibroblasts. Differential effects of ascorbic acid on collagen I and elastin mRNA abundance result from the combined, marked stabilization of collagen mRNA, the lesser stability of elastin mRNA, and the significant repression of elastin gene transcription. In other words, too much Vitamin C can inhibit elastic production. At NeoGenesis, we use a topical 5% of ascorbic acid, the natural form of Vitamin C, that has been found by scientists at major university in France to rebuld the skin’s ultratructure and provide clincially visible benefits to the skin, rebuilding collagen but not destroying elastin. Moreover, our stem cell-based S2RM technology stimulates fibroblasts to form collagen and elastin, a perfect complement to our Vitamin C product..

Notice we at NeoGenesis don’t use sodium ascorbate because sodium accululates in the skin and induces inflammation, including in skin conditions such as psoraisis and autoimmune diseases. Skin sodium content has been positively and significantly correlated with classical inflammatory markers such as CRP and white blood cell count. For example, dietary salt loading can result in hypertonic sodium storage in the skin by binding to glycosaminoglycans. Topical sodium can add to the accumulation, so wherever possible, we don’t use sodium molecules in our NeoGenesis formulations.

Antioxidant Cascade – Primary and Seconday Antioxidants

You’ll find a number of primary and secondary antioxidants (they work indirectly to prevent oxidation) in the Vibrant C Serum, including: Rose Geranium (Pelargonium spp.) water, Ascorbic Acid, Magnesium Ascorbyl Phosphate, Gluconolactone, Ferulic Acid, Panthenol (a secondary antioxidant), Resveratrol, Sodium Benzoate, Hydrolyzed Rice Protein, Potassium Ascorbyl Tocopheryl Phosphate, Chinese Senna (Cassia Obtusifolia) Seed Extract, Glutathione, Curcumin (encapsulated), Honokiol, Magnolol, Ergothioneine, Soybean (Glycine Soja) Protein, and Superoxide Dismutase.

The antioxidant cascade is a series of reactions where one antioxidant molecule neutralizes a free radical and, in doing so, becomes oxidized itself. This oxidized antioxidant can then be recycled back to its active, reduced state by another antioxidant, and so on, creating a chain reaction that efficiently eliminates harmful free radicals. Antioxidants working in a cascade is where one antioxidant type regenerates another type. For example, vitamin E neutralizes lipid radicals but becomes a radical itself; vitamin C can then restore vitamin E to its active form. Enzymatic antioxidants like SOD, CAT, and GPx (Glutathione peroxidase family of enzymes) handle different reactive species at various cellular locations, creating a layered defense This process helps maintain cellular redox balance and protect against oxidative stress. Thus, different types of antioxidants work together in a cascade process by complementing, supporting, and regenerating each other’s activity, resulting in a more robust and comprehensive defense against oxidative stress than any single antioxidant could provide alone. The pathways in cellular oxidation and antioxidation are complex, involving many pathways and may different types of antioxidants. While vitamin C is important, having the other antioxidants available concurrently is critical to the cellular redox balance, the the dynamic equilibrium within a cell between oxidation and reduction reactions. Both are critical to normal cellular function.

Summary

The antioxidant cascade, involving many antioxidant types, not just Vitamin C, is important for neutralizing free radicals, but also very important in regulating cellular signaling, gene expression, and repair mechanisms. Antioxidants, such as the encapsulated curcumin found in Vibrant C Serum, can modulate key pathways (like NF-κB and MAPK) to reduce inflammation and enhance cell survival and regeneration. Delivering these many antioxidants to the cells in the skin where they can provide benefit requires good formulations where, for example, liposome and encapsulation delivery technologies are used by NeoGenesis for its Vibrant C Serum product.

Safety and Efficacy: Adipose Mesenchymal Stem Cell (ADSC) Secretome Is Superior to Bone Marrow Mesenchymal Stem Cell (BMSC) and Umbilical Cord Mesenchymal Stem Cell (UCSC) Secretomes

I list here some of the reasons why I formulate my skin care products using the secretome of adipose mesenchymal stem cells (ADSCs) instead of bone marrow mesenchymal stem cells or umbilical cord mesenchymal stem cells. ADSCs are better at reducing inflammation and setting the innate and adaptive immune systems into a pro-regenerative state, inducing collagen formation, and laying down that collagen in a manner that is anti-fibrotic. This is a small excerpt of my upcomming peer-reviewed publication.

Listing Efficacy of ADSCs Versus BMSCs versus UCMSCs Secretome (Exosomes + Soluble Fraction)

Bone Marrow Mesenchymal Stem Cells (BMSCs), and the molecules they release, prolong and enhance inflammation by increasing survival and function of neutrophils (Casatella et al, 2011; Liang et al, 2024). BMSC secretome also reprograms hematopoietic stem cells to become inflammatory white blood cells (Ng et al, 2023). Under hypoxic conditions, which induces the activation of TRL4, BMSCs secrete pro-inflammatory factors and decrease the polarization of macrophages from the M1 to M2 phenotype, the M2 type being anti-inflammatory and therefore the BMSCs are promoting more inflammation (Faulknor et al, 2017; Waterman et al, 2010). Thus, BMSCs cultured in normal hypoxic conditions in the laboratory are secreting pro-inflammatory factors and when administered to wounded skin will induce inflammation by recruiting neutrophils and M1 type pro-inflammatory macrophages.

ADSCs have consistently exhibited much greater anti‑inflammatory capabilities, phagocytic activity, anti‑apoptotic capability activity and cell viability over BMSCs (Li et al, 2019).

ADSCs have been found to be highly immunomodulating cells, exceeding the suppressive effect of BMSCs by secreting more anti-inflammatory IL-6 and transforming growth factor-β1 (TGF-β1) Ceccarelli et al (2020).

When compared with the BMSCs- and UCSCs-treated groups, the ADSCs-treated group exhibited markedly accelerated healing efficiency, characterized by increased wound closure rates, enhanced angiogenesis, and collagen deposition at the wound site in an animal model (Cao et al, 2024).

ADSCs have biological advantages over BMSCs in the proliferative capacity, secreted proteins (basic fibroblast growth factor, interferon-γ, and insulin-like growth factor-1), and immunomodulatory, ant-inflammatory effects (Li et al, 2015).

Differences in cytokine secretion cause ADSCs to have more potent immunomodulatory effects than BMSCs (Melief et al, 2013)

ADSCs are better at preventing fibrosis than BMSCs (Yoshida et al, 2023).

Adipose mesenchymal stem cell secretome is superior to that of BMSCs because it preferentially helps to rebuild the epidermis by stimulating basal keratinocytes (Ademi et al, 2023).

BMSCs express much CTHRC1 protein (Turlo et al, 2023), which may help to promote fibrosis (Liu et al, 2023).

ADSC exosomes contain SIRT1 (Huang et al, 2020) and activate SIRT1 in other cells (Liu et al, 2021) to reduce inflammation, improve mitochondrial function, and reduce senescence.

ADSC exosomes reduce inflammation in endothelial cells (Heo and Kim, 2022).

ADSCs are considered more powerful suppressors of immune response than mesenchymal stem cells (MSCs) derived from different tissue sources, including trabecular bone, bone marrow, dental pulp, and umbilical cord (Ribeiro et al., 2013; Nancarrow-Lei et al., 2017).

ADSCs immunomodulatory effects exceed that of BMSCs (Melief et al., 2013).

ADSCs secrete higher amount of immune suppressive cytokines, such as IL-6 and transforming growth factor-β1 (TGF-β1) than do BMSCs (Soleymaninejadian et al., 2012; Melief et al., 2013; Montespan et al., 2014).

Bochev et al (2008) showed that ADSCs had a stronger ability to inhibit immunoglobulin (Ig) production by B cells than BMSCs.

Ivanova-Todorova E et al (2009) found that Adipose tissue-derived mesenchymal stem cells are more potent suppressors of the adaptive immune response through limiting dendritic cells differentiation compared to bone marrow-derived mesenchymal stem cells.

ADSC secretome inhibits LPS-induced proinflammatory cytokines (Li et al, 2018)

Human ADSCs are key regulators of immune tolerance, with the capacity to suppress T cell and inflammatory responses and to induce the generation/activation of antigen-specific regulatory T cells (Gonzalez-Rey et al, 2010).

ADSC secretome can suppress the activation, proliferation, and function of CD8+ T cells, which are inflammatory killer T cells (Kuca-Warnawin et al, 2020).

ADSC secretome was able to elevate expression of M2 macrophages and modified their cytokine expression to an anti-inflammatory profile (Hu et al, 2016; Zomer et al, 2020)

Exosomes secreted by human adipose mesenchymal stem cells promote scarless cutaneous repair by regulating extracellular matrix remodeling (Wang et al, 2017).

ADSC exosomes reduce inflammation and alleviate keloids by promoting mitochondrial autophagy through the PI3K/AKT/mTOR pathway (Liu et al, 2024).

ADSC exosomes reduce injury through the transfer of mitochondria components to neighboring cells (Xia et al, 2022).

ADSC secretome expedited wound healing and reduced inflammation in an animal model (Ma et al, 2021).

ADSC secretome promotes wound healing without leaving visible scars and was found safe when injected (An et al, 2021).

ADSC secretome has positive effects on granulation tissue formation and vascularization, and helps prevent fibrosis in pressure ulcers (Alexandrushkina et al, 2020).

Human ADSCs secrete functional neprilysin-bound exosomes that can degrade β-amyloid peptide (Aβ) that is found in the skin – cutaneous amyloidosis (Katsuda et al, 2013; Kucheryavykh et al, 2018).

In psoriasis and eczema the secretome from adipose mesenchymal stem cells (ADSCs), can regulate SOCS (suppressor of cytokine signaling) pathways, and modulate JAK pathways to reduce inflammation (Wang et al, 2022; Ko et al, 2023). Further, the secretome from ADSCs increases SOCS3 expression and, thus, the persistent and uninhibited expression of STAT3 by increased SOCS3 effectively ameliorates tissue injury by promoting tissue regeneration and decreasing inflammation and apoptosis (Lee et al, 2016).

ADSC and BMSC secretomes were characterized by the upregulation of proteins linked to ECM structure and organization and proteolytic processes compared to UCSCs, important to active involvement in tissue repair and microenvironment maintenance and suggesting their advantage for tissue-forming applications (Hodgson-Garms et al, 2025), but ADSCs are better at preventing fibrosis and reducing inflammation (Yoshida et al, 2023).

Fu et al (2025) found that hADSC-Exos are more effective in promoting hair follicle development compared to hUCMSC-Exos, and the secretome of ADSCs was more associated with growth processes such as nucleosome function than was the UCMSC secretome (Fu et al, 2025).

Mechanisms Of Action of NeoGenesis Hair Thickening Serum

Topical application of Hair Thickening Serum (HTS) promotes hair growth by two key means: Providing, 1. Skin and hair follicle endogenous molecules from skin and hair follicle stem cells (Adipose mesenchymal stem cells, fibroblasts, and dermal papillae) that drive and maintain the transition from telogen to anagen, and 2. Botanical ingredients normally derived from healthy diets that support hair growth.

Simple topical application of NeoGenesis Hair Thickening Serum, b.i.d., twice daily.

Let’s look at the hair growth cycle, and some of the many factors affecting hair growth. I’ll then explain some the mechanisms by which HTS drives the hair follicle to the anagen phase.

Figure 1. Schematic of the hair growth cycle and the factors that may influence a transition from anagen to telogen vs. telogen to anagen phase. From Natarelli et al, 2023.

HTS Mechanisms of Action in the Hair Growth Cycle

HTS’ mechanisms of action at the hair follicle are many. Here I consider a simplified summary of some of the pathways that the stem cell released molecules and botanical ingredients activate or inhibit to drive and maintain the follicle’s transition to the anagen phase.

Transition from Anagen to Telogen

Inflammation – An immunoprivileged state in the follicle is needed to drive anagen, and inflammation transitions the follicle to telogen instead (Bertolini et al, 2020). HTS reduces inflammation in the innate and adaptive immune systems by using the secretome from adipose mesenchymal stem cells – both the exosomal fraction and soluble fractions that act synergistically to optimally reduce inflammation (González-Cubero et al, 2022; Mitchell et al, 2019)

Hormone – ADSC secretome inhibits negative effects of DHT on hair growth (Tang et al, 2023; Fu et al, 2025).

Poor Nutrition – HTS contains nutrients to support hair growth. Larix Europaea Wood Extract, containing Dihydroquercetin-glucoside (polyphenol), EGCG (polyphenol catechin), glycine, zinc, Camellia Sinensis Leaf Extract, Santalum Acuminatum Fruit Extract, Citrus Glauca Fruit Extract, Acacia Victoriae Fruit Extract, Trifolium Pratense (Clover) Flower Extract (providing an abundance of polyphenols and antioxidants).

Stress – ADSC secretome mitigates immunological disturbances affecting the hair follicle (HF) and contributing to hair loss. ADSCs are able to suppress lymphocyte proliferation and, inhibit complement activation and dendritic cell differentiation from monocytes and therefore are considered natural immunosuppressants (Salhab et al, 2022).

Transition from Telogen to Anagen

Blood Flow – Secretome of ADSCs promotes angiogenesis and increased blood flow to follicles (Silveira et al, 2022; Zhu et al, 2020)

Direct stimulation of Hair Growth – Exosomes from dermal papillae cells drive hair follicle stem cell proliferation to rebuild hair follicle (Li et al, 2023), while fibroblasts provide many building-block proteins need to reconstruct the follicle architecture as it transitions from telogen to anagen (Suh et al, 2023).

Increased Local Growth factors – Fibroblasts (Lin et al, 2015), ADSCs (Won et al, 2017), and dermal papillae (HU et al, 2020) secretome all provide necessary growth factors to induce transition to anagen

References

Bertolini M et al (2020) Hair follicle immune privilege and its collapse in alopecia areata. Exp Dermatol. 29: 703–725.

Fu Y, Han YT, Xie JL, Liu RQ, Zhao B, Zhang XL, Zhang J, Zhang J. Mesenchymal stem cell exosomes enhance the development of hair follicle to ameliorate androgenetic alopecia. World J Stem Cells 2025; 17(3): 102088

González-Cubero, E et al (2022) María L. González-Fernández, Elias R. Olivera, Vega Villar-Suárez,Extracellular vesicle and soluble fractions of adipose tissue-derived mesenchymal stem cells secretome induce inflammatory cytokines modulation in an in vitro model of discogenic pain,The Spine Journal,Volume 22, Issue 7,2022, Pages 1222-1234

Li J, Zhao B, Yao S, Dai Y, Zhang X, Yang N, Bao Z, Cai J, Chen Y, Wu X. Dermal PapillaCell-Derived Exosomes Regulate Hair Follicle Stem Cell Proliferation via LEF1. Int J Mol Sci. 2023 Feb 16;24(4):3961.

Lin WH, Xiang LJ, Shi HX, Zhang J, Jiang LP, Cai PT, Lin ZL, Lin BB, Huang Y, Zhang HL, Fu XB, Guo DJ, Li XK, Wang XJ, Xiao J. Fibroblast growth factors stimulate hair growth through β-catenin and Shh expression in C57BL/6 mice. Biomed Res Int. 2015;2015:730139.

Mitchell R et al (2019) Secretome of adipose-derived mesenchymal stem cells promotes skeletal muscle regeneration through synergistic action of extracellular vesicle cargo and soluble proteins. Stem Cell Res Ther. 10(1):116.

Natarelli N, Gahoonia N, Sivamani RK (2023) Integrative and Mechanistic Approach to the Hair Growth Cycle and Hair Loss. J Clin Med. 2023 Jan 23;12(3):893.

Salhab O, Khayat L, Alaaeddine N (2022) Stem cell secretome as a mechanism for restoring hair loss due to stress, particularly alopecia areata: narrative review. J Biomed Sci. 2022 Oct 5;29(1):77.

Shiqi Hu et al. (2020) Dermal exosomes containing miR-218-5p promote hair regeneration by regulating β-catenin signaling.Sci. Adv.6,eaba1685(2020).

Silveira BM, Ribeiro TO, Freitas RS, Carreira ACO, Gonçalves MS, Sogayar M, et al. (2022) Secretome from human adipose-derived mesenchymal stem cells promotes blood vessel formation and pericyte coverage in experimental skin repair. PLoS ONE 17(12): e0277863.

Suh SB, Ahn KJ, Kim EJ, Suh JY, Cho SB. (2023) Proteomic Identification and Quantification of Secretory Proteins in Human Dermal Fibroblast-Conditioned Medium for Wound Repair and Hair Regeneration. Clin Cosmet Investig Dermatol. 2023;16:1145-1157

Tang, Xin, Cao, Cuixiang, Liang, Yunxiao, Han, Le, Tu, Bin, Yu, Miao, Wan, Miaojian, Adipose-Derived Stem Cell Exosomes Antagonize the Inhibitory Effect of Dihydrotestosterone on Hair Follicle Growth by Activating Wnt/β-Catenin Pathway, Stem Cells International, 2023, 5548112, 20 pages, 2023.

Won CH et al (2017) The Basic Mechanism of Hair Growth Stimulation by Adipose-derived Stem Cells and Their Secretory Factors. Curr Stem Cell Res Ther. 2017;12(7):535-543

Zhu, D., Johnson, T.K., Wang, Y. et al. (2020) Macrophage M2 polarization induced by exosomes from adipose-derived stem cells contributes to the exosomal proangiogenic effect on mouse ischemic hindlimb. Stem Cell Res Ther 11, 162.

Why I Formulate With Chondrus Crispus Extract, and Why It’s Not Comedogenic

Chondrus crispus extract is a polysachharide, which are not comedogenic, and is known for its anti-inflammatory, moisturizing, and wound-healing properties on human skin.

NeoGenesis is a biotech company that has the most advanced skin care products on the market, utilizing, for example, our S2RM – stem cell released molecules technology (exosomes, ectosomes, and soluble fraction) that is the most advanced penetration technology in the skin care marketplace. At NeoGenesis we feature science-to-market ingredients that work and are backed by scientific and clinical studies. Chondrus crispus extract is one the science-to-market ingredients used by NeoGenesis. I’ll dig into the science of Chondrus crispus extract (CCE) in the next paragraph, but even a cursory online search of the ingredient gives you an outline of how good this extract is for the skin. Whether it’s SpecialChem, EWG, or Paula’s Choice, scientists reviewing the studies of Chondrus crispus extract all extole its virtues in skin care. Little wonder the ingredient is widely used in skin care products.

Recent studies have found CCE mitigated inflammation and improved scratch-wound healing, and reduce environmental stress. A number of beneficial metabolites can be obtained from algae, including antioxidants, mycosporine-like amino acids, carotenoids, pigments, flavanoids, and polysaccharides. Further, CCE is sustainably sourced unlike a number of competing ingredients.

CCE also contains 15 of the 18 essential elements that make up the human body. This includes calcium, sulfur, magnesium, potassium, vitamin A, and vitamin K. Further, because CCE contains sulfur, it may help to reduce sebum production. CCE also contains omega-3 fatty acids, good for the skin, including acneic skin, whether topical or oral.

You can also read what other scientists and physicians say about the benefits CCE when topically applied to the skin in the popular press here, and here.

Why I Don’t Formulate Products with SLS

Despite the years of research on the ill effects of SLS (sodium lauryl sulfate), I continue to hear that people, including dermatologists, are using products with this ingredient, including shampoos.

If you’ve ever Googled the causes of a skin irritation or damaged hair, you’ve likely seen posts about SLS, or sodium lauryl (or laureth) sulfate, a common ingredient in beauty products, cleansers, shampoos, toothpastes, and cleaning products.

So what does this ingredient do, why is it in everything, and what does the evidence say about how safe it is?

When we use a cleanser or shampoo, the product usually contains a detergent. That detergent is called a surfactant. A surfactant allows the oil and water molecules to bind together – it’s what’s found in soaps and detergents so we can wash our oily faces or dishes with water and remove the grime.

Sodium lauryl sulfate (SLS) is a surfactant, and its efficacy, low cost, abundance and simplicity mean it’s used in a variety of cosmetic, dermatological, and consumer products.

Our skin’s outermost layer, the stratum corneum of the epidermis, is specially designed to keep harmful things out, and this is where a surfactant can cause problems. Using chemicals that weaken this barrier defence mechanism can potentially cause our skin harm.

As the outermost layer of the epidermis, the stratum corneum is the first line of defense for the body, serving an essential role as a protective skin barrier against the external environment. The stratum corneum aids in hydration and water retention, which prevents skin cracking, and is made up of corneocytes, which are anucleated keratinocytes that have reached the final stage of keratinocyte differentiation (From Murphrey et al, 2022).

Some surfactants are more irritating to our skin than others. For something to be harmful, irritating or allergenic, it has to fulfill two criteria. It has to have been found in studies to irritate human skin, and it has to have the ability to penetrate the skin. SLS does both. It penetrates the stratum corneum and induces an immune reaction, and degrades the structure of the barrier.

Scientists in Germany tested 1,600 patients for SLS irritancy and found 42% of the patients tested had an irritant reaction. Another study, on seven volunteers over a three and a half month period, found regular contact caused irritation, and the irritation subsided once the skin was no longer exposed to SLS. Another study found the warmer the water used with SLS, the more irritating it will be.

SLS is a well established irritatant and is used as a positive control in dermatological testing. That is, new products being tested to see how irritating they might be to human skin are compared to the known irritant, SLS. If a person is sensitive to SLS, they might find the area that has been in contact is red, dry, scaly, itchy or sore. It’s also important to note there’s no scientific evidence SLS causes cancer, despite what is often posted on the internet. So, it’s probably OK to use SLS in products that are used for household cleaners.

Who should avoid SLS?

Everyone, especially people with a history of sensitive skin, hyperirritable skin and patients suffering from skin conditions such as atopic dermatitis (eczema), rosacea, and psoriasis are best to avoid products containing SLS. If you think it might be SLS causing a skin irritation, stop the use of the product and look for products that don’t contain SLS.

Epithelial Barrier Dysfunction in Noncommunicable and Communicable Diseases

The modern world’s dramatic increase in the number and types of chemicals in which man is exposed, a major part of of someone’s exposome, responsible for about 90% of diseases (not genetics), is causing a dramatic rise in noncommunicable and communicable diseases. Over 350 000 chemicals and mixtures of chemicals have been registered for production and use, up to three times as many as previously estimated, and an underestimate of the true number of chemical types that have been produced and commercialized. As the skin and other epithelial tissues are compromised and exposed to communicable diseases, skin and epithelial transmitted diseases are on the rise. For example, the shingles virus can enter through the skin or the epithelial tissue in our respiratory tract, and having shingles can even lead to increased risk of dementia (2nd Ref). Further, a compromised skin epithelial barrier caused by environmental factors such as mechanical trauma, exposure to exogenous proteases in microorganisms and our food, detergents, and air pollution can activate the innate and adaptive immune systems, inducing keratinocytes to release pro-inflammatory cytokines and chemokines and enhancing the antigen presentation by intradermal Langerhans cells (LCs) and dermal DCs and activating T-cells. In turn, for example, activation of T2 type T-cells leads to IL-4, IL-5, and IL-13 secretion, provoking skin barrier alteration, immune cell infiltration into skin, and itch as observed in atopic dermatitis.

The first essential step to skin immunity is the epithelial barrier, as infection and resulting inflammation are impossible without first breaching it. Epithelia, coated with a sugary glycocalyx, not only comprise our skin but also the mucosal membranes that line our organs. Their ability to secrete squalene, mucus, lipids, and antimicrobials help protect against pathogen invasion. Additionally, epithelia can prevent inflammation by physically shoving out cells infested with toxins, allergens, antigens, pathogens, or other damage by seamlessly extruding them. This is a strategy employed by not only epithelia, but also our hair does the same as it sheds. Given that chronic inflammation could stem from a defective epithelial barrier, the current approach of treating only the inflammation will only partially mitigate symptoms of a more central problem, ongoing wound healing and disrupted barrier.

Scientists now understand that in patients with allergic disease, regardless of tissue location, the homeostatic balance of the epithelial tissue barrier is skewed toward loss of differentiation, reduced junctional integrity, and impaired innate defense and a hyperactive adaptive (trained immunity) immune system. Importantly, epithelial dysfunction characterized by these traits appears to pre-date a predisposition to immunological responses against a range of antigens or allergens, and development of allergic disease.

From the disease perspective, trained immunity is beneficial, as it improves the host’s defense against subsequent infection from pathogens. However, it can also be detrimental and result in overly active immune responses or chronic inflammation. Even the innate immune system has some memory, given evidence that components in House Dust Mite extract activate and likely train macrophages to produce high amounts of CCL17, IL-6, and cysteinyl leukotrienes following re-exposure to HDM through the TNF-α and PGE₂ pathways. Thus, an activated immune system, one that has memory and is primed to react, can lead to sensitivities that may be triggered by an overabundance of chemicals in the environment, and those sensitivities heightened by a disrupted barrier.

Evidence that epithelial barrier dysfunction explains the growing prevalence and exacerbations of inflammatory diseases such as eczema has grown through many studies performed world-wide. Diseases encompassed by the epithelial barrier theory share common features such as an increased prevalence after the 1960s that cannot be accounted soley by the emergence of improved diagnostic methods. They are indeed increasing in prevalence, i.e. the number of afflictions per 1,000 people.

Eepithelial barrier dysfunction enables the microbiome’s translocation from the skin’s surface to interepithelial and deeper subepithelial areas, doing in combination with allergens, toxins, pathogens, and pollutants. Thereafter, microbial dysbiosis and possible infection, characterized by colonization of opportunistic pathogenic bacteria and loss of the number and biodiversity of commensal bacteria results. Local inflammation, impaired tissue regeneration, and remodeling characterize the skin that suffers from impaired barrier. For example, commensal bacteria on the skin’s surface are important for epidermal lipid synthesis and improve barrier function. The skin’s microbiome is therefore critical to maintaining epidermal barrier function. The infiltration of inflammatory cells and inflammatory cytokines to affected tissues is part of the immune system’s response to erradicate invading bacteria, allergens, toxins, and pollutants away from the deep tissues. As Peter Elias, M.D. has written, “AD [atopic dermatitis] can be considered a disease of primary barrier failure, characterized by both a defective permeability (Proksch et al., 2006, and references therein) and antimicrobial function.” Further, inflammatory cells and inflammatory cytokines that migrate from the skin to other organs may play roles in the exacerbation of various inflammatory diseases in other organs. Thus, inflammation iniated in the skin may contribute to chronic inflammatory diseases in other tissues.

What Dr. Elias has been saying is that the permeability-barrier abnormality in AD is not merely an epiphenomenon but rather the “driver” of disease activity, an “outside–inside view of disease pathogenesis” (Elias and Feingold, 2001). The evidence for this is: (1) the extent of the permeability-barrier abnormality parallels severity of disease phenotype in AD, (2) both clinically uninvolved skin sites and skin cleared of inflammation for as long as 5 years continue to display significant barrier abnormalities, (3) topical artificial barrier therapy comprises effective ancillary therapy, and (4) specific replacement therapy, which targets the prominent lipid abnormalities that account for the barrier abnormality in AD, not only corrects the permeability-barrier abnormality but also comprises effective anti-inflammatory therapy for AD (Figure 1; Chamlin et al., 2002). Thus, inflammation in AD may begin with insults from without, i.e. the exposome.

That barrier insult can then activate epithelial cells in the skin, keratinocyes, which are non-professional immune cells, but do possess MHC-II molecules, that present antigens to professional immune cells, such as T-cells. Thus, with disrupted barriier, the keratinocytes can recognize antigens and present them to the immune system, leading to inflammation. More and more, scientists are discovering how epithelial cells are part of the immune system, regardless in which organ they exist. Key here is to protect barrier function in all of our epithelial tissues, including the skin.

So if inflammatory diseases such as eczema and psoriasis are environmentally triggered and lead to barrier dysfunction and resultant inflammation, what can we do?

First, calm the inflammation. It’s destructive and further degrades the epidermal barrier. S2RM technology (in NeoGenesis Recovery) is great for reducing inflammation, doing so in both the innate and adaptive immune systems.

Second, use a topical product that provides the 3 lipids and natural moisturizing factors that are needed to rebuild normal stratum corneum and barrier function. One product to use is NeoGenesis Barrier Renewal Cream (BRC).

Third, use a product that provides instantaneous barrier function and commensal bacteria. The instantaneous barrier allows the BRC to rebuld the natural barrier function over time, and the commensal bacteria help to rebuild the barrier through activation of lipid synthesis by skin cells. The commensal bacteria in Neogenesis MB-2 also help to reduce the Staphylococcus aureus infection often assicated with disrupted barrier function.

So remember, these inflammatory skin conditions are triggered by the environment. Therefore, their treatment and prevention means that if you change your environment, you can prevent or treat these diseases. Part of changing your environment is the careful choice of topical products to reduce inflammation and renormalize the structure and function of your skin.

Dr. Greg Maguire's Skin Care

The Science of Skin Care

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