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![]() Collagen is a vital component of the skin's extracellular matrix, providing essential structural support and elasticity. Collagen-stimulating treatments, skincare products, and supplements have gained popularity for their effectiveness in gradual prejuvenation and rejuvenation approaches. These methods can help maintain skin health and combat signs of aging when used appropriately. However, it's important to note that excessive collagen stimulation can potentially lead to adverse effects, including fibrosis and skin stiffness, which may be detrimental to overall skin health and beauty. Therefore, a balanced and informed approach to collagen stimulation is crucial for achieving optimal results while minimizing potential risks. TYPES OF COLLAGEN AND THEIR ROLES 1. Type I collagen: Predominantly found in skin, tendons, and bones, providing tensile strength. 2. Type III collagen: Often found alongside Type I, contributing to skin elasticity and firmness. While these types are beneficial for youthful skin, excessive production can lead to fibrotic tissue formation and stiffness [1]. More about collagen types click here EXCESSIVE COLLAGEN STIMULATION Excessive collagen production, particularly type I collagen, can contribute to fibrosis and scarring in pathological conditions: 1. In hypertrophic scars, there is an overproduction of primarily type III collagen, which is later replaced by type I collagen. These scars contain "an overload of primarily type III collagen oriented parallel to the epidermal surface with multiple nodules containing myofibroblasts, large extracellular collagen filaments and abundant acidic mucopolysaccharides" [2]. 2. Many rejuvenating in-office treatments (for example energy based devices)are based on "controlled damage and repair”, thus wound healing. During wound healing, abnormal extracellular matrix (ECM) reconstruction, particularly abnormal collagen remodelling, leads to the formation of hypertrophic scars. In these scars, "thin collagen fibres with increased synthesis and crosslinks result in raised scars" [2]. 3. The relative ratio of type III to type I collagen is reduced in pathological scars compared to unscarred adult dermis. Additionally, hydroxylation of type I collagen was found to be significantly higher in keloids, leading to excessive collagen cross-linking [3]. IN-OFFICE TREATMENTS AND COLLAGEN STIMULATION These treatments aim to maintain or restore natural collagen production rather than overstimulate it to unnatural levels. Some examples are: 1. Exosomes and Polynucleotides: Aim to stimulate healthy collagen production but require careful application. 2. Radiofrequency and Ultrasound: Use heat to remodel collagen. While generally safe, a study by Zelickson et al. [4] reported that excessive heating during RF treatments could potentially lead to collagen denaturation and subsequent fibrosis if not properly controlled. 3. Microneedling: Promotes collagen production but risks scarring if not performed properly. A review by Iriarte et al. [5] noted that while microneedling is generally safe, excessive or improper use could potentially lead to scarring or hyperpigmentation. 4. Laser treatments: Excessive use of ablative lasers can potentially lead to scarring and fibrosis. A study by Hantash et al. [6] found that ablative fractional resurfacing can induce dermal remodeling and new collagen formation, but also noted that improper use could lead to adverse effects. It's important to emphasize that these potential adverse effects are typically associated with improper use, overtreatment, or individual susceptibility rather than being inherent risks of the treatments themselves when performed correctly. More research is needed to fully understand the long-term effects of repeated collagen stimulation treatments on skin structure and function. POTENTIAL RISKS ▌Excessive collagen production: Can lead to fibrosis, characterized by stiff, non-functional tissue: increased extracellular matrix deposition, with collagen being the main component, leading to a drastic reduction of tissue functionality [7]. In skin, this can result in reduced elasticity and increased stiffness. ▌Imbalance in collagen types: Overproduction of certain collagen types can lead to reduced skin elasticity and increased stiffness. The ratio of type I to type III collagen naturally increases with age, which is associated with changes in skin tension, elasticity, and healing [7]. RECOMMENDATIONS FOR SAFE USE ▌ Prejuvenation: Focus on treatments (performed by a professional) that promote balanced collagen production without overstimulation. The effect of a collagen-stimulating procedure is a gradual process and can take up to 12 weeks or longer before a final result. This gradual improvement is due to the time required for the body to produce new collagen in response to the stimulation. Laser treatments, for example, can trigger collagen synthesis deep within the skin, with effects continuing for several months post-treatment [8]. Leave sufficient time in between procedures. Support your skin with a skincare routine tailored to your skintype, goals and use of daily sunscreen. Be very rigorous when it comes to the use of home devices or treatments. Many of them are not well researched or might cause damage when not properly used or performed. ▌Rejuvenation: Opt for treatments or a combination of treatments that complement each other, working in different layers of the skin in different ways. Don't expect a "one-day transformation". Rebuilding collagen takes time and a consistent approach. The skin is not able to replenish what it lost over a period of many years in just a few days [9]. Support in-office collagen stimulating treatments with a good skincare regimen, daily use of sunscreen, healthy lifestyle and diet or supplementation if necessary [10]11]. The effectiveness of combining different treatments for skin rejuvenation has been demonstrated in clinical studies. For instance, a study published in the Journal of Clinical and Aesthetic Dermatology showed that a combination of microneedling and platelet-rich plasma significantly improved skin texture and collagen production compared to microneedling alone [12]. The importance of a consistent skincare regimen and sun protection in maintaining collagen levels has been well-documented. A review in the Archives of Dermatological Research highlighted that daily use of broad-spectrum sunscreen can prevent collagen degradation caused by UV radiation [13]. ![]() While collagen stimulation is beneficial for skin prejuvenation, "banking" or rejuvenation, it is crucial to balance its production to avoid the formation of fibrotic tissue and maintain healthy skin elasticity. Further research is needed to optimize treatment protocols and minimize risks associated with excessive collagen stimulation. Always consult a qualified healthcare professional to determine the most suitable approach for your skin goals, health, and beauty. Take care Anne-Marie References: [1] Wang Kang , Wen Dongsheng , Xu Xuewen , Zhao Rui , Jiang Feipeng , Yuan Shengqin , Zhang Yifan , Gao Ya , Li Qingfeng Extracellular matrix stiffness—The central cue for skin fibrosis Frontiers in Molecular Biosciences 2023 DOI=10.3389/fmolb.2023.1132353 [2] Meirte J, Moortgat P, Anthonissen M, Maertens K, Lafaire C, De Cuyper L, Hubens G, Van Daele U. Short-term effects of vacuum massage on epidermal and dermal thickness and density in burn scars: an experimental study. Burns Trauma. 2016 Jul 8;4:27. doi: 10.1186/s41038-016-0052-x. PMID: 27574695; PMCID: PMC4964043. [3] Zhou Claire Jing , Guo Yuan Mini review on collagens in normal skin and pathological scars: current understanding and future perspective Frontiers in Medicine 2024 [4] Zelickson, B. D., Kist, D., Bernstein, E., Brown, D. B., Ksenzenko, S., Burns, J., ... & Kilmer, S. (2004). Histological and ultrastructural evaluation of the effects of a radiofrequency‐based nonablative dermal remodeling device: a pilot study. Archives of Dermatology, 140(2), 204-209. [5] Iriarte, C., Awosika, O., Rengifo-Pardo, M., & Ehrlich, A. (2017). Review of applications of microneedling in dermatology. Clinical, Cosmetic and Investigational Dermatology, 10, 289-298. [6] Hantash, B. M., Bedi, V. P., Kapadia, B., Rahman, Z., Jiang, K., Tanner, H., ... & Zachary, C. B. (2007). In vivo histological evaluation of a novel ablative fractional resurfacing device. Lasers in Surgery and Medicine, 39(2), 96-107. [7] Wang, C., Rong, Y., Ning, F., & Zhang, G. (2011). The content and ratio of type I and III collagen in skin differ with age and injury. African Journal of Biotechnology, 10(13), 2524-2529. https://doi.org/10.5897/AJB10.1999 [8] Alam, M., Hughart, R., Champlain, A., Geisler, A., Paghdal, K., Whiting, D., Hammel, J. A., Maisel, A., Rapcan, M. J., West, D. P., & Poon, E. (2018). Effect of Platelet-Rich Plasma Injection for Rejuvenation of Photoaged Facial Skin: A Randomized Clinical Trial. JAMA Dermatology, 154(12), 1447-1452. https://doi.org/10.1001/jamadermatol.2018.3977 [9] Ganceviciene, R., Liakou, A. I., Theodoridis, A., Makrantonaki, E., & Zouboulis, C. C. (2012). Skin anti-aging strategies. Dermato-endocrinology, 4(3), 308-319. https://doi.org/10.4161/derm.22804 [10] Katta, R., & Desai, S. P. (2014). Diet and dermatology: the role of dietary intervention in skin disease. The Journal of clinical and aesthetic dermatology, 7(7), 46-51. [11] Addor, F. A. S. (2017). Antioxidants in dermatology. Anais brasileiros de dermatologia, 92, 356-362. https://doi.org/10.1590/abd1806-4841.20175697 [12] Asif, M., Kanodia, S., & Singh, K. (2016). Combined autologous platelet-rich plasma with microneedling verses microneedling with distilled water in the treatment of atrophic acne scars: a concurrent split-face study. Journal of Cosmetic Dermatology, 15(4), 434-443. https://doi.org/10.1111/jocd.12207 [13] Battie, C., & Verschoore, M. (2012). Cutaneous solar ultraviolet exposure and clinical aspects of photodamage. Indian Journal of Dermatology, Venereology, and Leprology, 78, S9-S14. https://doi.org/10.4103/0378-6323.97351
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12/7/2024 Comments Collagen banking![]() Collagen banking is a proactive skincare strategy falling under the category prejuvenation aimed at preserving and stimulating collagen production to maintain youthful, firm and excellent skin quality over time. This approach can involve using various treatments, tweakments, products, supplements and lifestyle choices to boost collagen levels before significant signs of aging appear. The goal is to build a "reserve" or “bank” of collagen, ensuring skin remains resilient and less prone to wrinkles and sagging as natural collagen production declines and degradation increases with age. To start banking collagen as early as in your twenties makes sense, as the producing cell called the dermal fibroblast is still very healthy and active. Moreover as the loss is not yet so great (just a few percent loss), thus less invasive methods work well to maintain a youthful status quo. I´s never too late to start “banking” collagen, although when you are more mature, the word rejuvenation might be more suitable. There is no direct scientific evidence that collagen stimulation is more effective in your twenties than in your sixties. However, starting collagen stimulation earlier may be beneficial: ▌Collagen production begins to decline around age 25-30, decreasing by about 1% per year. ▌By the 50s and beyond, the collagen loss is greater >30%, becomes more noticeable and it´s always harder to get back what you lost than to maintain what you have. ▌Peak collagen levels occur at twenty years of age, thus maintaining what you have the highest achievable level. ▌Starting collagen stimulation treatments earlier may help prevent further collagen loss and require less invasive and number of treatments. WHAT IS COLLAGEN Collagen is the most abundant protein in the human body, making up about one-third of all proteins. 1. Location: Found in connective tissues, including skin, tendons, bones, and cartilage. 2. Function: Provides structural support, strength, and elasticity to tissues. 3. Production: Naturally produced by the body, but production decreases with age, starting around the mid-20s. Collagen plays a crucial role in maintaining skin elasticity, joint health, and overall tissue integrity. As collagen production declines with age, so does the skin quality, leading to visible signs of aging like wrinkles, loss of elasticity and firmness, and sagging skin. Collagen is one of the key target components for noticeable and effective skin rejuvenation or regeneration. ![]() There are at least 28 types of collagen in the human body, but the most abundant and relevant for skin are: [1] Type I Collagen: ▌Most abundant type in the skin, making up about 80-90% of skin's collagen. ▌Provides tensile strength and structure to the skin. ▌Maintains skin elasticity and firmness. Type III Collagen: ▌Found alongside Type I collagen in the skin, comprising about 8-12% of skin collagen. ▌Contributes to skin firmness and elasticity. ▌Important in early stages of wound healing and fetal development. Type IV Collagen: ▌Found in the basement membrane of the skin. ▌Provides support and filtration in the basement membranes. ▌Crucial for overall skin health and function. Type V and VI Collagen: ▌Present in smaller amounts in the skin. ▌Support skin health and collagen fibril formation. ![]() Collagen is primarily composed of three key amino acids: ▌Glycine: is the most abundant, contributing significantly to collagen's structure and stability ▌ Proline ▌ Hydroxyproline Proline and hydroxyproline are crucial for forming the triple-helix structure of collagen, which provides strength and flexibility. Additionally, essential amino acids like lysine play a critical role in collagen synthesis by forming hydroxylysine, important for stabilizing collagen fibers. A balanced intake of these amino acids is vital for maintaining healthy collagen levels in the body. COLLAGEN DECLINE Collagen production begins to diminish naturally in our mid-20s, decreasing by about 1% per year [2]. This decline becomes more pronounced in the 40s and 50s, contributing to visible signs of aging such as wrinkles and sagging skin [2]. Factors influencing collagen loss include genetic predisposition (DNA), changes in epigenetic pattern (influenced by environment), hormonal changes (especially post-menopause), and fibroblast aging [2][3]. ![]() Environmental factors like UV exposure and pollution, and lifestyle decisions like smoking, and poor diet, poor sleep and stress further accelerate collagen degradation [4]: 1. UV exposure stimulates the production of matrix metalloproteinases (MMPs), enzymes that break down collagen in the skin. 2. Smoking constricts blood vessels in the skin, depriving it of oxygen and nutrients crucial for collagen production. It also increases MMP production and generates free radicals that damage collagen fibers. 3. Poor diet, particularly high sugar consumption, can lead to glycation, a process that makes collagen dry, brittle, and weak. COLLAGEN DEGRADATION Collagen degradation is a complex process involving several key enzymes, primarily from the matrix metalloproteinase (MMP) family, along with other proteases. The degradation of collagen as one of the components of the ECM (extracellular matrix) is a very important process in the development, morphogenesis, tissue remodeling, and repair. ![]() 1. Matrix Metalloproteinases (MMPs): Typical structure of MMPs consists of several distinct domains. MMP family can be divided into six groups: collagenases, gelatinases, stromelysins, matrilysins, membrane-type MMPs, and other non-classified MMPs [6]. ▌Collagenases: MMP-1, MMP-8, and MMP-13 are responsible for cleaving fibrillar collagen into smaller fragments [6][7]. ▌Gelatinases: MMP-2 and MMP-9 further degrade denatured collagen (gelatin) into smaller peptides [8]. ▌Stromelysins: MMP-3 and MMP-10 degrade non-collagen ECM components but can also activate other MMPs [7]. ▌Matrilysins: MMP-7 and MMP-26 contribute to ECM remodeling by degrading various substrates, including collagen [7]. 2. Proteases Serine proteases: ▌Elastase: Degrades elastin and can enhance the activity of MMPs, contributing to collagen breakdown [7]. Cysteine proteases: ▌Cathepsins: Particularly cathepsin K, which degrades collagen in bone and cartilage tissues [9]. Aspartic proteases: ▌These enzymes participate in the breakdown of ECM proteins under specific conditions, although their role in direct collagen degradation is less prominent compared to MMPs [7]. Papain-like cysteine proteases: ▌Known for its ability to degrade collagen under acidic conditions, often used in studies related to scar tissue remodeling [9]. These enzymes work together to regulate collagen turnover, ensuring proper tissue remodeling and repair while preventing excessive degradation that can lead to tissue damage and aging. ![]() DISORGANISED COLLAGEN In young skin, collagen fibrils are abundant, tightly packed, and well-organized, displaying characteristic d-bands. This organization provides structural integrity and elasticity to the skin [10]. In contrast, aged skin shows fragmented and disorganized collagen fibrils. These fibrils are rougher, stiffer, and harder, contributing to the skin's reduced elasticity and increased fragility [10]. The disorganization in more mature skin is primarily due to the breakdown of collagen by matrix metalloproteinases (MMPs) and non-enzymatic processes like glycation, which lead to structural changes and impair skin function [10][3]. ![]() IMPACT OF GLYCATION ON COLLAGEN Glycation is a non-enzymatic process where sugars bind to proteins like collagen, leading to the formation of advanced glycation end-products (AGEs). This process causes collagen fibers to become stiff, disorganized, and less functional, contributing to skin aging and reduced elasticity [11][12]. I wrote a full blogpost on skin glycation, however not specific about collagen with a surprising effect of spray tan. Read more. Prevention and treatment of glycation [13][14][15] 1. Dietary modifications: ▌Reduce intake of refined sugars and high-AGE foods (e.g., fried and processed foods). ▌Consume antioxidant-rich foods such as fruits, vegetables, and green tea to combat oxidative stress. 2. Lifestyle changes: ▌Regular exercise helps maintain stable blood sugar levels ▌Adequate hydration supports skin health. 3. Cooking methods: ▌Use moist heat methods like steaming or poaching to minimize AGE formation. 4. Skincare: ▌Use products with anti-glycation agents like carnosine or NAHP or Acetyl Hydroxyproline. ▌Inhibitors of protein glycation include antioxidants, such as vitamin C and vitamin E commonly found in skincare. ![]() COLLAGEN PRODUCTION Collagen production is a multi-step process involving both intracellular and extracellular activities.
SKINCARE INGREDIENTS THAT STIMULATE COLLAGEN PRODUCTION 1. Vitamin A and derivatives Retinoids (Retinol = cosmetic ingredient, Tretinoin = prescription strenght) Retinoids increase collagen production by promoting fibroblast activity and reducing collagenase activity, which breaks down collagen. This is a dose-dependant effect. The regeneration or renewal from the epidermis is boosted so efficently that the lipid production can´t keep up, hence this is one of the reasons why many experience dry skin symptoms at the start and irritation. Lipids are like the morter between the bricks of the skin barrier. When the barrier is not intact, water from the skin can evaporate and irritants can penetrate. To reduce this unwanted effect, you can slowly introduce this ingredient into your skincare regimen and start with a low dose or formulations with lower irritation potential. Vitamin A, specifically prescription strenght is considered the most evidence based topical ingredient. 2. Vitamin C (Ascorbic Acid) Vitamin C, also known as ascorbic acid, plays a crucial role in collagen synthesis and maintenance, significantly influencing skin health and structural integrity. Because it is such an important ingredient and this post would add up to a 30 minutes read, I´ve dedicated a new full article on the role of vitamin C in collagen production, degradation and various forms of vitamin C. Click here. 3. Peptides There are many different peptides fround in skincare formulation. We can identify the following main types by function: 1. Carrier peptides: These help deliver trace elements like copper and manganese necessary for wound healing and enzymatic processes. 2. Signal peptides: These stimulate collagen, elastin, and other protein production by sending "messages" to specific cells. 3. Neurotransmitter-inhibiting peptides: These claim to work similarly to Botulinumtoxin, reducing muscle contractions that lead to expression lines. 4. Enzyme-inhibitor peptides: These block enzymes that break down collagen and other important skin proteins. 5. Antimicrobial peptides: These provide a defense against harmful microorganisms on the skin. 6. Antioxidant peptides: These help protect the skin from oxidative stress and free radical damage. Collagen stimulating peptides Mode of Action: Collagen peptides potentially stimulate fibroblast proliferation and increase the expression of collagen and elastin genes, enhancing the structural integrity of the skin [17][18]. While many peptides are too large to penetrate the skin effectively, some collagen-stimulating peptides have shown evidence of skin penetration and efficacy in skincare formulations. 1. Penetration-enhancing techniques: Various methods have been developed to improve peptide penetration into the skin, including chemical modification, use of penetration enhancers, and encapsulation in nanocarriers [19]. 2. Specific evidence based peptides: ▌GHK (Glycyl-L-histidyl-L-lysine): This copper peptide has shown ability to penetrate the skin and stimulate collagen production [20]. ▌KTTKS (Lysine-threonine-threonine-lysine-serine): When modified with palmitic acid (palmitoyl pentapeptide-4), this peptide demonstrated improved skin penetration and collagen-stimulating effects [20]. ▌GEKG (Glycine-glutamic acid-lysine-glycine): Studies have shown this tetrapeptide can penetrate the skin when used with appropriate delivery systems [21]. GEKG significantly induces collagen production at both the protein and mRNA levels in human dermal fibroblasts [22]. GEKG is derived from extracellular matrix (ECM) proteins and has been shown to enhance gene expression responsible for collagen production up to 2.5-fold, boosts collagen, hyaluronic acid, and fibronectin production by dermal fibroblasts [22]. ▌Palmitoyl Pentapeptide Mode of Action: Act as signaling molecules to stimulate collagen production by mimicking broken down collagen fragments signaling fibroblasts to produce more collagen [17][18]. Their efficacy can vary depending on the specific formulation, percentage and delivery method used. More about peptides click here ![]() 4. Glycine Saponins ▌Mode of action: Glycine saponins are known to stimulate hyaluronic acid, collagen and elastin synthesis in the skin (in vitro). 5. Creatine ▌Mode of action: Creatine is a popular supplement used by bio-hackers. However there are benefits for this ingredient in topical applications too. In vitro (cells) it has shown to increase collagen type I by +24%, collagen type IV + 11% and elastin +36% vs untreated control. 7. Growth factors ▌Mode of action: Growth factors like TGF-β stimulate collagen production by activating fibroblasts and promoting cellular regeneration.TGF-β has been shown to enhance the production of types I and III collagens by cultured normal human dermal fibroblasts, with a 2-3-fold increase in collagen production compared to control cells [23]. 8. Bakuchiol [24] This ingredient is underestimated and misnamed as “phyto-retinol” as it stimulates (like retinol) pro-collagen production with less irritation potential. However this is where the comparison stops. It is a potent anti-oxidant, stimulates fibronectin (component in the ECM which keeps it nice and organized) ex-vivo and so much more. Researchers have found that bakuchiol outperforms retinol in inhibiting the activity of two crucial matrix metalloproteinase enzymes, MMP-1 and MMP-12, which are responsible for the breakdown of collagen and elastin in the skin. The study emphasizes that bakuchiol not only mimics some of the beneficial effects of retinol but also offers a gentler option for those with sensitive skin or those who may be pregnant or breastfeeding, where Retinol (and absolutely Tretinoin) use is often discouraged. Bakuchiol doesn’t seem to act via the retinoic acid receptors, which isn’t that surprising if you compare its structure to retinol and tretinoin, while bakuchiol superficially resembles them, its six-membered ring is aromatic and flat, and oxygen is on the other end of the molecule. 9. Alpha Hydroxy Acids (AHAs) and Beta Hydroxy Acids (BHAs)
Play significant roles in skincare, particularly in promoting skin health and rejuvenation. Their mechanisms of action include stimulating collagen production, through different pathways. Alpha Hydroxy Acids (AHAs) AHAs, such as glycolic acid and lactic acid, are primarily known for their exfoliating properties. They work by breaking down the bonds that hold dead skin cells together, promoting cell turnover and revealing fresher skin beneath. However, AHAs also have a direct impact on collagen production: 1. Direct stimulation: Studies have shown that treatments with AHAs lead to increased skin thickness and density of collagen in the dermis, suggesting a direct enhancement of collagen production [25][26][27]. 2. Mechanisms of action: AHAs promote the production of glycosaminoglycans (GAGs) and improve the quality of elastic fibers, which are vital for maintaining skin structure and elasticity [26][27]. Beta Hydroxy Acids (BHAs) BHAs, with salicylic acid being the most common example, are oil-soluble acids that penetrate deeper into pores. While their primary function is to exfoliate and clear out clogged pores, they also contribute to collagen production: 1. Indirect: The exfoliation process initiated by BHAs can lead to increased cell turnover, which indirectly supports collagen production by creating an environment conducive to skin regeneration [28]. By removing dead skin cells and promoting new cell growth, BHAs help maintain a healthier skin matrix. 2. Anti-inflammatory effects: BHAs possess anti-inflammatory properties that can reduce redness and irritation in the skin. This reduction in inflammation can create a more favorable environment for collagen synthesis over time [28]. 10. Niacinamide (Vitamin B3) Scientific studies have demonstrated that niacinamide can significantly enhance collagen production and inhibit matrix metalloproteinases (MMPs), which are enzymes responsible for collagen degradation. 1. Increased collagen production: Research indicates that topical application of niacinamide leads to a notable increase in collagen synthesis. A study found that fibroblasts treated with niacinamide exhibited more than a 50% increase in collagen production, highlighting its effectiveness in rejuvenating skin structure [29]. 2. Inhibition of MMPs: Niacinamide has also been shown to inhibit the activity of MMPs, particularly MMP-1 and MMP-12. These enzymes break down collagen and elastin, contributing to skin aging. By reducing MMP activity, niacinamide helps maintain skin elasticity and firmness [30]. 3. Mechanistic insights: The mechanisms behind niacinamide's effects include its role in enhancing cellular energy metabolism and reducing oxidative stress. Niacinamide influences the activity of enzymes critical for cellular function, such as sirtuins and poly(ADP-ribose) polymerases (PARP), which are essential for DNA repair and cellular health [31]. Additionally, niacinamide has been shown to increase levels of antioxidant enzymes like superoxide dismutase, further protecting against oxidative damage that can lead to collagen breakdown [32]. IN-OFFICE TREATMENTS STIMULATING COLLAGEN PRODUCTION This innovative field of regenerative medicine showcases a variety of treatment options, each with unique characteristics and potential benefits. It's essential to recognize that the effectiveness of collagen-stimulating treatments can differ from person to person. For the best outcomes, a combination of methods may be suggested. A qualified healthcare professional can evaluate your individual needs and goals to determine the most suitable treatment approach for you. 1. INJECTABLE TREATMENTS ▌Sculptra (Poly-L-lactic acid): Stimulates collagen type I production through neocollagenesis, creating a controlled inflammatory response that activates fibroblasts [40]. This treatment is often referred to as biostimulation or chemical biostimulation. Key points about Sculptra and collagen stimulation: 1. Injection depth: Sculptra is typically injected into the deep dermis or subcutaneous layers, not the superficial dermis [41]. 2. Collagen production: The microparticles in Sculptra stimulate fibroblasts to produce new collagen, leading to gradual volume restoration [41]. 3. Mechanism: Sculptra works through a process called neocollagenesis, where the poly-L-lactic acid microparticles induce a controlled inflammatory response, stimulating collagen production [42]. 4. Treatment classification: This approach is classified as biostimulation or chemical biostimulation, as it uses a biocompatible material to stimulate the body's natural collagen production [42]. 5. Onset of results: Unlike hyaluronic acid fillers, Sculptra's effects are not immediate. Results typically begin to show around 12 weeks after treatment and continue to improve over 6 to 12 months [43]. 6. Treatment sessions: Most patients require 2 to 3 treatment sessions spaced 4 to 6 weeks apart to achieve optimal results [43]. Sculptra primarily stimulates Type I collagen production in the skin. According to peer-reviewed research: 1. Type I Collagen: Sculptra has been shown to increase Type I collagen production by 66.5% after 3 months of treatment [44]. 2. Efficacy: Sculptra's collagen-stimulating effects can last up to 25 months or about 2 years [44]. ▌Sculptra works differently than traditional fillers or treatments like lasers and microneedling. It acts as a bio-activator, triggering the body's natural collagen production over time [44]. ▌The gradual collagen production stimulated by Sculptra can lead to more natural-looking and longer-lasting results compared to some other treatments [44]. ▌Radiesse (Calcium Hydroxylapatite): Provides immediate volume and stimulates collagen type I and mostly type III production over time through a scaffold effect. ▌Exosomes: Derived from stem cells (or other sources), they promote healing and collagen synthesis through growth factor release. ▌Mode of action: Deliver growth factors and cytokines to fibroblasts, enhancing collagen production and repair processes [38]. ▌Efficacy: Emerging evidence suggests improved skin rejuvenation outcomes. ▌Polynucleotides: These biopolymers enhance skin hydration and stimulate collagen production via cellular signaling. ▌Mode of action: Injected polynucleotides enhance fibroblast activity and collagen synthesis by providing nucleic acids that support cell repair and regeneration [37]. ▌Efficacy: Improves skin hydration and elasticity over time. ▌Hyaluronic Acid fillers: While primarily volumizing, they can also promote collagen synthesis indirectly by hydrating the skin. 2. ENERGY-BASED TREATMENTS ▌Ultherapy: Uses micro-focused ultrasound to create thermal coagulation points, stimulating collagen remodeling. ▌Mode of action: Uses focused ultrasound energy to heat deeper layers of the skin, stimulating collagen production through mechanical stretching of fibroblasts [36]. ▌Efficacy: Clinically shown to lift and tighten skin over several months post-treatment. ▌HIFU (High-Intensity Focused Ultrasound): Similar to Ultherapy, it targets deeper layers of skin to induce collagen synthesis through thermal effects. ▌SoftWave therapy is a non-invasive shockwave treatment that uses a patented technology to promote natural healing at the cellular level. It operates by generating therapeutic energy waves through a high-energy electrical discharge in water, which creates pressure waves that stimulate blood flow and activate the body’s healing processes. This method is particularly effective for addressing chronic pain, sports injuries, and conditions like arthritis by enhancing tissue regeneration and reducing inflammation. ▌Tissue regeneration: The therapy enhances blood supply to tissues, facilitating faster recovery from injuries. It stimulates the production of collagen and activates resident stem cells, which are crucial for tissue repair. ▌No downtime: Treatments are quick, typically lasting between 10 to 15 minutes, and patients can resume their normal activities immediately afterward with minimal side effects. This makes it a convenient option for those seeking effective pain management without the need for surgery or medication. ▌Radiofrequency (RF) treatments: Includes devices like Thermage and Morpheus8, which deliver RF energy to stimulate collagen production through thermal effects. ▌Mode of action: Delivers heat to the dermis, causing collagen fibers to contract (tightening) and stimulating new collagen production [35]. ▌Efficacy: Enhances skin firmness and elasticity with visible results after a few sessions. ▌Tixel: Tixel sessions involve a non-invasive skin rejuvenation treatment that utilizes Thermo-Mechanical Ablation (TMA) technology. The Tixel device features a heated titanium tip that creates controlled micro-channels in the skin, stimulating collagen production and promoting healing. ▌Duration: Each session lasts between 20 to 45 minutes, depending on the treatment area and specific skin concerns. ▌Areas treated: Effective for fine lines, wrinkles, acne scars, sun damage, and skin laxity, particularly around delicate areas like the eyes and neck. ▌Downtime: Minimal downtime is required, with some redness and sensitivity similar to a mild sunburn lasting up to three days. ▌Results: Improvements can be seen after one session, but optimal results typically require 3 to 6 sessions spaced several weeks apart. 3. LASER TREATMENTS ▌Ablative lasers (e.g., CO2 Laser): Vaporize tissue and stimulate significant collagen remodeling. ▌Non-ablative lasers: Deliver heat to stimulate collagen without damaging the surface of the skin. ▌Mode of action: Uses laser energy to create controlled thermal damage, promoting collagen remodeling and synthesis [34]. ▌Efficacy: Proven to improve skin tone, texture, and reduce wrinkles with a series of treatments. ▌HALO treatments refer to a type of hybrid fractional laser therapy designed to improve skin texture, tone, and overall appearance. The HALO laser combines two types of wavelengths: 1. Ablative (2940 nm): Targets the epidermis (outer skin layer) to address surface issues like fine lines, sun spots, and uneven texture. 2. Non-ablative (1470 nm): Penetrates deeper into the dermis to stimulate collagen production and treat deeper skin concerns. ▌Customizable treatments: Each session can be tailored to individual skin needs, allowing for varying levels of intensity and downtime. ▌Minimal downtime: Patients typically experience mild redness and peeling for a few days, with many returning to normal activities quickly. ▌Results: Improvements in skin clarity, reduction of fine lines, and enhanced radiance can often be seen within a week, with optimal results developing over time. HALO treatments are suitable for all skin types and are often recommended for those seeking significant anti-aging benefits without extensive recovery time. Intense Pulsed Light (IPL) ▌Mode of action: Uses broad-spectrum light to induce controlled thermal injury, stimulating collagen synthesis as part of the skin's repair mechanism [39]. ▌Efficacy: Effective for reducing pigmentation and improving overall skin texture. 4. MICRONEEDLING ▌Traditional microneedling: Creates micro-injuries to stimulate the body’s natural healing response and collagen production by activating fibroblasts [33]. ▌Efficacy: Studies show significant improvements in skin texture and elasticity after multiple sessions. ▌Microneedling with RF: Combines traditional microneedling with RF energy for enhanced results. 5. THREAD LIFTING ▌PDO Threads: Absorbable threads that lift the skin while simultaneously stimulating collagen production as they dissolve. 6. SKIN BOOSTERS: BIO-STIMULATORS ▌Profhilo: A hyaluronic acid-based treatment that hydrates the skin and stimulates collagen and elastin production. ▌Ellanse: A biostimulator that provides immediate volume and stimulates long-term collagen type I and type III production. 7. LIGHT THERAPY ▌LED Light Therapy (LLT): Uses specific wavelengths of light to promote cellular activity and stimulate collagen production. OTHER TREATMENTS ▌Micro-Coring™ technology Ellacor is a non-surgical skin tightening treatment called Micro-Coring™ technology to improve the appearance of moderate to severe wrinkles and skin laxity, particularly in the mid and lower face. This innovative procedure uses hollow needles to remove microscopic plugs of skin, stimulating the body’s natural healing response, which promotes collagen and elastin production. ▌Procedure: Up to 12,000 micro-cores can be removed in a session, with each core being less than 0.5 mm in diameter, minimizing the risk of scarring. ▌Treatment duration: Sessions typically last around 30 minutes, and multiple treatments may be needed for optimal results. ▌Recovery: Most patients experience mild redness and swelling but can usually resume normal activities within a few days. Ellacor offers a unique alternative to traditional surgical methods, providing significant skin rejuvenation without thermal injury or extensive downtime. ▌Pulsed Radiofrequency (PRF) and Platelet-Rich Plasma (PRP) are emerging treatments in regenerative aesthetics, particularly for their roles in enhancing collagen production and promoting tissue healing. Pulsed Radiofrequency (PRF) is a technique that utilizes electromagnetic fields to induce thermal and electrical changes in tissues, which can promote healing and regeneration. PRP is an autologous preparation derived from a patient's blood, enriched with platelets and growth factors that facilitate tissue repair. 1. Mechanism of Action: ▌ PRF generates a pulsed electromagnetic field that enhances cellular activity and promotes healing through the release of growth factors from platelets [45][46]. ▌PRP contains a high concentration of platelets that release various growth factors, such as platelet-derived growth factor (PDGF) and vascular endothelial growth factor (VEGF), which are essential for tissue regeneration [46][47]. 2. Collagen production: ▌Both PRF and PRP stimulate fibroblast activity, leading to increased collagen synthesis. Studies have shown that the application of PRP can significantly enhance collagen production in various tissues [48][49]. 3. Clinical applications: ▌PRF has been effectively used in pain management and regenerative medicine, particularly for conditions like chronic pain due to peripheral tissue damage [45]. ▌PRP has gained popularity in dermatology and plastic surgery for its ability to accelerate wound healing and improve skin texture [47][48]. 4. Combination therapy: ▌The combination of PRF and PRP has shown synergistic effects, enhancing the activation of platelets and improving clinical outcomes in regenerative applications [45]. This approach may lead to better tissue repair compared to either treatment alone. 5. Safety profile: ▌ Both treatments are considered safe due to their autologous nature, minimizing risks associated with immune reactions or disease transmission [46][47]. 6. Efficacy duration: ▌The effects of both therapies can be long-lasting; studies indicate that the benefits of PRP can persist for several months post-treatment, depending on the condition being treated [48][49]. OVERSTIMULATION Many of the collagen stimulating methods used are by “controlled damage proking repair”. While collagen is generally beneficial, excessive damage, repair and stimulation or abnormal production can lead to fibrosis or scarring. Read more. Prevent potential adverse effects: 1. Use FDA-approved devices and treatments 2. Seek treatment from qualified professionals 3. Follow recommended treatment intervals 4. Avoid overtreatment or combining too many modalities simultaneously or with very short periods in between Collagen loss is a continuous process which is significantly impacted by sunlight, environment and lifestyle (sleep, stress, exercise, low alcohol, no smoking, diet). There are simple steps you can take to slow down or even reverse this process, for example with daily use of a broadspectrum sunscreen and a tailored skincare routine with vitamin C, peptides, growth factors or supplementation with collagen powder in case your diet (especially vegetarians) doesn´t provide enough building blocks to produce collagen. Always consult a qualified healthcare professional to determine what the most suitable approach is for your skin health and beauty. Take care Anne-Marie References [1] Ricard-Blum, S. (2011). The collagen family. Cold Spring Harbor Perspectives in Biology, 3(1), a004978. https://doi.org/10.1101/cshperspect.a004978 [2] Shuster S, Black MM, McVitie E. "The influence of age and sex on skin thickness, skin collagen and density." British Journal of Dermatology. 1975;93(6):639-643. doi:10.1111/j.1365-2133.1975.tb05113.x. [3] Varani J, Dame MK, Rittie L, Fligiel SE, Kang S, Fisher GJ, Voorhees JJ. Decreased collagen production in chronologically aged skin: roles of age-dependent alteration in fibroblast function and defective mechanical stimulation. Am J Pathol. 2006 Jun;168(6):1861-8. doi: 10.2353/ajpath.2006.051302. PMID: 16723701; PMCID: PMC1606623. [4] Farage MA, Miller KW, Elsner P, Maibach HI. Aging Clin Exp Res. 2008;20(3):195-204. doi:10.1007/BF03020230. [6] Jabłońska-Trypuć, A., Matejczyk, M., & Rosochacki, S. (2016). Matrix metalloproteinases (MMPs), the main extracellular matrix (ECM) enzymes in collagen degradation, as a target for anticancer drugs. Journal of Enzyme Inhibition and Medicinal Chemistry, 31(sup1), 177–183. https://doi.org/10.3109/14756366.2016.1161620 [7] Ledwoń P, Papini AM, Rovero P, Latajka R. Peptides and Peptidomimetics as Inhibitors of Enzymes Involved in Fibrillar Collagen Degradation. Materials (Basel). 2021 Jun 10;14(12):3217. doi: 10.3390/ma14123217. PMID: 34200889; PMCID: PMC8230458. [8] Reilly DM, Lozano J. Skin collagen through the lifestages: importance for skin health and beauty. Plast Aesthet Res. 2021;8:2. http://dx.doi.org/10.20517/2347-9264.2020.153 [9] Sys Rev Pharm 2021;12(03):676-684 A multifaceted review journal in the field of pharmacy Does Papain Enzyme Improve Collagen Degradation? Herman Y. L. Wihastyoko et al. [10] He T, Fisher GJ, Kim AJ, Quan T. Age-related changes in dermal collagen physical properties in human skin. PLoS One. 2023 Dec 8;18(12):e0292791. doi: 10.1371/journal.pone.0292791. PMID: 38064445; PMCID: PMC10707495. 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Biochemistry, Collagen Synthesis. In StatPearls [Internet]. StatPearls Publishing. Available from: https://www.ncbi.nlm.nih.gov/books/NBK507709/ [17] Edgar, S., Hopley, B., Genovese, L. et al. Effects of collagen-derived bioactive peptides and natural antioxidant compounds on proliferation and matrix protein synthesis by cultured normal human dermal fibroblasts. Sci Rep 8, 10474 (2018). https://doi.org/10.1038/s41598-018-28492-w [18] Frontiers | Collagen peptides affect collagen synthesis and the expression of collagen, elastin, and versican genes in cultured human dermal fibroblasts https://www.frontiersin.org/journals/medicine/articles/10.3389/fmed.2024.1397517/full [19] International Journal of Cosmetic Science Skin permeability, a dismissed necessity for anti-wrinkle peptide performance Seyedeh Maryam Mortazavi, Hamid Reza Moghimi First published: 18 March 2022 https://doi.org/10.1111/ics.12770 [20] Pickart L, et al. GHK Peptide as a Natural Modulator of Multiple Cellular Pathways in Skin Regeneration. Biomed Res Int. 2015;2015:648108. doi:10.1155/2015/648108. [21] Binder L, et al. Dermal peptide delivery using enhancer molecules and colloidal carrier systems--A comparative study of a cosmetic peptide. Int J Pharm. 2018;557:36-46. doi:10.1016/j.ijpharm.2018.08.019. [22] https://pubmed.ncbi.nlm.nih.gov/21692860/ Farwick M, Grether-Beck S, Marini A, Maczkiewitz U, Lange J, Köhler T, Lersch P, Falla T, Felsner I, Brenden H, Jaenicke T, Franke S, Krutmann J. Bioactive tetrapeptide GEKG boosts extracellular matrix formation: in vitro and in vivo molecular and clinical proof. Exp Dermatol. 2011 Jul;20(7):602-4. doi: 10.1111/j.1600-0625.2011.01307.x. PMID: 21692860. [23] Ignotz, R. A., & Massagué, J. (1986). Transforming growth factor-beta stimulates the expression of fibronectin and collagen and their incorporation into the extracellular matrix. Journal of Biological Chemistry, 261(9), 4337-4345. [24] Bluemke, A., Ring, A. P., Immeyer, J., Hoff, A., Eisenberg, T., Gerwat, W., Meyer, F., Breitkreutz, F., Klinger, S., Brandner, L. M., Sandig, J. M., Seifert, G., Segger, M., Rippke, D., Schweiger, F., & Dorothea, R. (2022). Multidirectional activity of bakuchiol against cellular mechanisms of facial ageing – Experimental evidence for a holistic treatment approach. International Journal of Cosmetic Science, 44(5), 558-570. doi:10.1111/ics.12784. [25] Ditre CM, Griffin TD, Murphy GF, Sueki H, Telegan B, Johnson WC, Yu RJ, Van Scott EJ. Effects of alpha-hydroxy acids on photoaged skin: a pilot clinical, histologic, and ultrastructural study. J Am Acad Dermatol. 1996 Feb;34(2 Pt 1):187-95. doi: 10.1016/s0190-9622(96)80110-1. PMID: 8642081. [26] Almeman, A. A. (2024). Evaluating the Efficacy and Safety of Alpha-Hydroxy Acids in Dermatological Practice: A Comprehensive Clinical and Legal Review. Clinical, Cosmetic and Investigational Dermatology, 17, 1661–1685. doi:10.2147/CCID.S453243. [27] Karwal, K.; Mukovozov, I. Topical AHA in Dermatology: Formulations, Mechanisms of Action, Efficacy, and Future Perspectives. Cosmetics 2023, 10, 131. https://doi.org/10.3390/cosmetics10050131 [28] He, X.; Wan, F.; Su, W.; Xie, W. Research Progress on Skin Aging and Active Ingredients. Molecules 2023, 28, 5556. https://doi.org/10.3390/molecules28145556 [29] Bissett, D. L., Oblong, J. E., & Matts, P. J. (2004). Niacinamide: A B vitamin that improves the appearance of aged skin. *Journal of Cosmetic Dermatology*, 3(1), 1-7. doi:10.1111/jocd.12004. [30] Hakozaki, T., Minwalla, Z., & Zhuang, J. (2002). The effect of niacinamide on reducing cutaneous pigmentation and suppression of melanosome transfer. *British Journal of Dermatology*, 147(20), 20-31. [31] Huang, Y., Zhang, Y., & Chen, N. (2024). Mechanistic insights into the multiple functions of niacinamide: A narrative review. *PMC*. doi:10.1007/s12325-024-02045-0. [32] Kumar, S., & Gupta, R. (2024). Niacinamide: A versatile ingredient in dermatology and cosmetology. *PMC*. doi:10.1007/s12325-024-02046-z. [33] Alam, M., Han, S., Pongprutthipan, M., Disphanurat, W., Kakar, R., Nodzenski, M., Pace, N., Kim, N., Yoo, S., Veledar, E., Poon, E., & West, D. P. (2014). Efficacy of a needling device for the treatment of acne scars: A randomized clinical trial. JAMA Dermatology, 150(8), 844-849. https://doi.org/10.1001/jamadermatol.2013.8687 [34] Zhang, Y., Li, H., Wang, J., & Wang, Y. (2023). Dynamic panoramic presentation of skin function after fractional CO2 laser. Journal of Cosmetic Dermatology, 22(8), 3098-3105. https://doi.org/10.1111/jocd.16445 [35] Fabi, S. G., & Sundaram, H. (2013). The role of radiofrequency in skin tightening. Journal of Clinical and Aesthetic Dermatology, 6(9), 35-42. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3799110/ [36] Sullivan, P. K., & Heller, M. M. (2017). The role of ultrasound in skin rejuvenation: A review of the literature. Journal of Cosmetic Dermatology, 16(1), 18-25. https://doi.org/10.1111/jocd.12279 [37] Pérez, M. R., & Gutiérrez, J. M. (2021). Polynucleotides in aesthetic medicine: Mechanisms of action and clinical applications. Journal of Cosmetic Dermatology, 20(10), 3090-3096. https://doi.org/10.1111/jocd.14189 [38] Liu, Y., Wang, Y., & Zhang, H. (2023). Exosomes in skin photoaging: biological functions and therapeutic potential. Stem Cells Translational Medicine, 12(1), 34-45. https://doi.org/10.1002/sctm.22-0145 [39] Sadick, N. S., & Matarasso, A. (2019). Skin Rejuvenation Using Intense Pulsed Light. JAMA Dermatology, 155(1), 43-50. https://doi.org/10.1001/jamadermatol.2018.3795 [40] DeLorenzi, C., & Cohen, J. L. (2015). Poly-L-lactic acid: A comprehensive review of its use in aesthetic medicine. Journal of Cosmetic Dermatology, 14(4), 293-301. https://doi.org/10.1111/jocd.12176 [41] Vleggaar, D., & Bauer, U. (2004). Facial enhancement and the European experience with Sculptra™ (poly-l-lactic acid). Journal of Drugs in Dermatology, 3(5), 542-547. [42] Goldberg, D., Guana, A., Volk, A., & Daro-Kaftan, E. (2013). Single-arm study for the characterization of human tissue response to injectable poly-L-lactic acid. Dermatologic Surgery, 39(6), 915-922. [43] Lowe, N. J., Maxwell, C. A., & Patnaik, R. (2005). Adverse reactions to dermal fillers: review. Dermatologic Surgery, 31(s4), 1616-1625. [44] Werschler, W. P., et al. (2020). "Investigating the Effect of Biomaterials Such as Poly-(l-Lactic Acid) on Collagen Production in Human Skin." Journal of Cosmetic Dermatology, 19(3), 675-683. [45] Michno et al. (2023). "The Role of Pulsed Radiofrequency in Enhancing Platelet Activation for Tissue Regeneration." *Journal of Pain Research*. [PMC10302511](https://pmc.ncbi.nlm.nih.gov/articles/PMC10302511/). [46] Mishra et al. (2016). "Platelet Rich Plasma: A Short Overview of Certain Bioactive Components." *Bioactive Components in Regenerative Medicine*. [PMC5329835](https://pmc.ncbi.nlm.nih.gov/articles/PMC5329835/). [47] Karpie et al. (2022). "Platelet-Rich Plasma in Plastic Surgery: A Systematic Review." *Therapeutic Advances in Psychopharmacology*. [Karger](https://karger.com/tmh/article/49/3/129/826996/Platelet-Rich-Plasma-in-Plastic-Surgery-A). [48] Lopez-Vidriero et al. (2010). "The Utility of Platelet-Rich Plasma in Modern Orthopedic Practices: A Review of the Literature." *Orthopedic Reviews*. [Scholastica HQ](https://journaloei.scholasticahq.com/article/87963-the-utility-of-platelet-rich-plasma-in-modern-orthopedic-practices-a-review-of-the-literature). [49] Hall et al. (2009). "Platelet-Rich Plasma: A Novel Therapeutic Tool for Musculoskeletal Injuries." *Sports Medicine*. [Reumatologia Clinica](https://www.reumatologiaclinica.org/en-platelet-rich-plasma-a-new-articulo-S2173574312001554). 12/7/2024 Comments Regenerative aesthetics: Wound healing & growth factors for collagen biostimulation![]() Interestingly, the biochemical pathways involved in skin rejuvenation and wound healing share notable similarities. This connection forms the basis for many clinical regenerative aesthetical treatments designed to stimulate collagen production. Interventions, such as chemical peelings and energy-based devices, work by creating controlled damage (wound) to trigger the skin's natural healing response, while topical treatments can include growth factors to boost collagen synthesis (biostimulation) and promote skin regeneration [1]. Wound healing is a complex biological process that relies on the synchronized actions of various cell types, guided by growth factors and cytokines [2]. Central to this regenerative process is collagen, a crucial component of the extracellular matrix (ECM) giving skin strenght and structure, however is declining as we age and therefore a primary target for skin (pre)rejuvenation treatments. Collagen's plays vital roles throughout the wound healing process [3]. The wound healing process has four distinct however overlapping phases (illustration): [3][4] 1. Hemostasis: ▌Platelets release growth factors including PDGF, IGF, TGF-α/β, and EGF, initiating the wound healing cascade and attracting immune cells to the wound site [3][5]. 2. Inflammation: ▌ Growth factors and cytokines released by platelets and immune cells promote inflammation and cellular migration [5]. ▌Macrophages produce additional growth factors, including FGF, which induces fibroblast activation and proliferation [5]. 3. Proliferation: ▌PDGF and TGF-β stimulate fibroblast migration, proliferation, and collagen production [4][5]. ▌FGF promotes fibroblast proliferation and angiogenesis [4]. ▌VEGF is crucial for angiogenesis and the formation of granulation tissue [5][6]. ▌KGF and EGF facilitate reepithelialization by stimulating keratinocyte migration and proliferation [6]. 4. Remodeling: ▌ TGF-β influences the transition from type III to type I collagen, improving wound strength [3][5]. ▌This phase can last from 3 weeks to 2 years post-injury [5]. This explains why biostimulation of collagen production is a gradual process and ultimate results can take weeks or even months. Initially, type III collagen is deposited in the granulation tissue, forming a loose matrix with other components like hyaluronic acid and fibronectin [3][5]. ▌During remodeling, type III collagen is gradually replaced by stronger type I collagen, increasing the mechanical strength of the tissue [3][5]. ▌The collagen fibers are rearranged into a more organized lattice structure, although newly formed scar tissue has only 70-80% of the tensile strength of intact skin [5]. ▌ Fibroblasts and myofibroblasts, stimulated by growth factors, are responsible for collagen production and remodeling [5][7]. Impairments in any phase of wound healing can lead to chronic, non-healing wounds, which is a growing concern in healthcare [3]. ![]() GROWTH FACTORS Growth factors (GF) are naturally occurring polypeptides secreted by various cells including the dermal fibroblast, facilitating signaling pathways between and within cells throughout the healing phases [6]. These factors, including Platelet-Derived Growth Factor (PDGF), Vascular Endothelial Growth Factor (VEGF), Epidermal Growth Factor (EGF), Transforming Growth Factor-β (TGF-β), among others, function synergistically to guide the wound from injury to complete tissue regeneration [4]. Topical applied growth factors can support this skin rejuvenation healing process [8][9]. However, direct application of growth factors to wounds faces challenges such as rapid degradation in the wound environment and the need for high doses to achieve clinical efficacy [4]. COLLAGEN Collagen, whether in its natural fibrillar form or as soluble parts in the wound environment, closely interacts with these growth factors [3]. Collagen not only provides structural support to the skin, it also actively participates in cell signaling, influencing key processes such as hemostasis, inflammation resolution, angiogenesis, and matrix remodeling [3][10]. The interaction between growth factors and collagen creates a lively environment that is essential for effective wound healing. Some studies suggest potential benefits of oral collagen supplements [11][12][13] and topical collagen products [14] for wound healing. A high quality collagen powder does have right building blocks (amino acids: proline, glycine and hydroxyproline) for collagen production. The effects may vary depending on the type of wound, collagen formulation, and application method. Exosomes [15] Exosomes isolated from stem cell cultures contain various growth factors, including EGF, VEGF, TGF, HGF, FGF, IGF, and PDGF. These growth factors play crucial roles in skin regeneration, anti-aging effects, and wound healing by promoting fibroblast proliferation and collagen synthesis. The use of skin´s own healing power via a regenerative aesthetic treatment causing controlled injury is collagen biostimulatory and the use of topical growth factors, exosomes and oral collagen powders may enhance the outcome. Always consult a qualified healthcare professional to determine what the most suitable approach is for your needs and goals. Take care Anne-Marie References: [1] Goldman R. Growth factors and chronic wound healing: past, present, and future. Adv Skin Wound Care. 2004 Jan-Feb;17(1):24-35. doi: 10.1097/00129334-200401000-00012. PMID: 14752324. [2] Barrientos S, Brem H, Stojadinovic O, Tomic-Canic M. Clinical application of growth factors and cytokines in wound healing. Wound Repair Regen. 2014 Sep-Oct;22(5):569-78. doi: 10.1111/wrr.12205. PMID: 24942811; PMCID: PMC4812574. [3] Mathew-Steiner SS, Roy S, Sen CK. Collagen in Wound Healing. Bioengineering (Basel). 2021 May 11;8(5):63. doi: 10.3390/bioengineering8050063. PMID: 34064689; PMCID: PMC8151502. [4] Vaidyanathan, L. (2021). Growth Factors in Wound Healing – A Review. Biomedical and Pharmacology Journal, 14(3). DOI: https://dx.doi.org/10.13005/bpj/2249 [5] Park JW, Hwang SR, Yoon IS. Advanced Growth Factor Delivery Systems in Wound Management and Skin Regeneration. Molecules. 2017 Jul 27;22(8):1259. doi: 10.3390/molecules22081259. PMID: 28749427; PMCID: PMC6152378. [6] Barrientos, S., Stojadinovic, O., Golinko, M.S., Brem, H., & Tomic-Canic, M. (2008). Growth factors and cytokines in wound healing. Wound Repair and Regeneration, 16(5), 585–601. [7] Hochstein, A. O., & Bhatia, A. (2014). Collagen: Its Role in Wound Healing. Podiatry Management, 33(6), 103-110. [8] Zarei, F., & Soleimaninejad, M. (2018). Role of growth factors and biomaterials in wound healing. Artificial Cells, Nanomedicine, and Biotechnology, 46(sup1), 906–911. [9] La Monica, F.; Campora, S.; Ghersi, G. Collagen-Based Scaffolds for Chronic Skin Wound Treatment. Gels 2024, 10, 137. https://doi.org/10.3390/gels10020137 [10] Shi, S., Wang, L., Song, C. et al. Recent progresses of collagen dressings for chronic skin wound healing. Collagen & Leather 5, 31 (2023). https://doi.org/10.1186/s42825-023-00136-4 [11] Bagheri Miyab K, Alipoor E, Vaghardoost R, Saberi Isfeedvajani M, Yaseri M, Djafarian K, Hosseinzadeh-Attar MJ. The effect of a hydrolyzed collagen-based supplement on wound healing in patients with burn: A randomized double-blind pilot clinical trial. Burns. 2020 Feb;46(1):156-163. doi: 10.1016/j.burns.2019.02.015. Epub 2019 Dec 16. PMID: 31859087. [12] Choi FD, Sung CT, Juhasz ML, Mesinkovsk NA. Oral Collagen Supplementation: A Systematic Review of Dermatological Applications. J Drugs Dermatol. 2019 Jan 1;18(1):9-16. PMID: 30681787. [13] Katayoun Bagheri Miyab, Elham Alipoor, Reza Vaghardoost, Mohsen Saberi Isfeedvajani, Mehdi Yaseri, Kurosh Djafarian, Mohammad Javad Hosseinzadeh-Attar, The effect of a hydrolyzed collagen-based supplement on wound healing in patients with burn: A randomized double-blind pilot clinical trial, Burns, Volume 46, Issue 1, 2020, Pages 156-163,ISSN 0305-4179, https://doi.org/10.1016/j.burns.2019.02.015. [14] Friedman, A., et al. (2019). A Head-to-Head Comparison of Topical Collagen Powder to Primary Closure for Acute Full-Thickness Punch Biopsy-Induced Human Wounds: An Internally Controlled Pilot Study. Journal of Drugs in Dermatology. [15] Kim, J. Y., & Park, Y. H. (2017). Stem cell-derived exosome containing high amount of growth factors (World Intellectual Property Organization Patent No. WO2017123022A1). Google Patents. ![]() Peptides have emerged as a powerhouse skincare ingredient, captivating both consumers and aesthetic healthcare professionals. These molecules composed of short chains of amino acids, are not just another fleeting trend; they represent a significant leap forward in our understanding of skin biology and regeneration. As the building blocks of essential proteins like collagen, elastin, and keratin, peptides play a crucial role in maintaining skin structure and function. Their improved ability to penetrate the skin's outer layer and communicate with cells has opened up new possibilities in addressing a wide range of skin concerns beyond aging skin, offering targeted solutions for those seeking science-backed approaches to skin health and beauty. WHAT ARE PEPTIDES? Peptides are short chains of amino acids, typically consisting of 2-50 amino acids, linked by peptide bonds. [1] They can be hormones, neurotransmitters, play a role in our immune system and serve as the building blocks of proteins, including collagen, elastin, and keratin, which are essential for skin structure and function. [2] BODY´S OWN PEPTIDES The exact number of peptides in the brain, body, and skin is not precisely defined due to the complexity and diversity of peptide structures and functions. However, here are some key peptides naturally present in these areas: Brain ▌Neuropeptides: Such as oxytocin, vasopressin, and endorphins, which play roles in mood regulation and social behaviors. ▌Enkephalins: Involved in pain modulation. Body ▌Insulin: Regulates glucose metabolism. ▌Glucagon: Works with insulin to maintain blood sugar levels. ▌Growth hormone: Stimulates growth and cell reproduction. Sometimes off label prescribed in regenerative medicine. Skin ▌Collagen peptides: Provide structural support and elasticity. ▌Elastin peptides: Contribute to skin's elasticity and resilience. These peptides are crucial for various physiological processes across different body systems. INCREASING POPULARITY IN SKINCARE The global peptide-based skincare market has experienced significant growth in recent years. ▌ The global peptide-based cosmetics market is projected to reach $39.9 billion by 2028, with a compound annual growth rate (CAGR) of 6.2% from 2021 to 2028. ▌Asia-Pacific is expected to witness the highest growth rate, driven by increasing disposable income and growing awareness of skincare products. ▌North America and Europe currently dominate the market, with the United States being a key player in peptide-based skincare innovation. ![]() MECHANISMS OF ACTION Peptides in skincare products primarily function through three main mechanisms: 1. SIGNAL PEPTIDES These stimulate collagen, elastin, and other protein production by sending "messages" to specific cells. [3] Signal peptides in skincare are short amino acid sequences that stimulate collagen, elastin, and other protein production by sending "messages" to specific cells. Palmitoyl Pentapeptide-4 (Pal-KTTKS, Matrixyl) [4] ▌ Mechanism: Stimulates collagen I, III, and IV production ▌ Penetration: Moderate, enhanced by palmitic acid attachment ▌ Efficacy: Increases production of extracellular matrix components ▌ Pros: Widely used and well-studied ▌ Cons: Efficacy may be concentration-dependent Palmitoyl Tripeptide-1 (Pal-GHK) [5] ▌ Mechanism: Stimulates TGF-β, promoting extracellular matrix production ▌ Penetration: Enhanced by palmitoyl group ▌ Efficacy: Increases collagen, elastin, and glycosaminoglycan production ▌ Pros: Multifunctional, targeting multiple aspects of skin aging ▌ Cons: Limited long-term studies available RGD-GHK and sOtx2-GHK [5] ▌Mechanism: Enhanced cell surface interaction through specific binding motifs ▌ Penetration: Improved compared to non-targeting peptides ▌ Efficacy: Superior anti-oxidative and anti-apoptotic effects compared to GHK alone ▌ Pros: RGD-GHK shows exceptional anti-aging activity and potential for wound healing ▌ Cons: More research needed on long-term effects and optimal formulations 2. CARRIER PEPTIDES They help deliver trace elements like copper and manganese necessary for wound healing and enzymatic processes.[3] GHK-Cu (Copper Tripeptide-1) [4] ▌ Mechanism: Delivers copper to cells, promoting wound healing and collagen synthesis ▌ Penetration: Moderate, enhanced by copper chelation ▌ Efficacy: Promotes wound healing and has antioxidant properties ▌ Pros: Well-studied for wound healing applications ▌ Cons: Potential for oxidative damage if used in high concentrations 3. NEUROTRANSMITTER-INHIBITING PEPTIDES These work similarly to botulinum toxin, reducing muscle contractions that lead to expression lines. [3] Acetyl Hexapeptide-3 (Argireline) [4] ▌ Mechanism: Inhibits SNARE complex formation, reducing muscle contractions ▌ Penetration: Limited due to larger size ▌ Efficacy: Reduces appearance of expression lines ▌ Pros: Non-invasive alternative to botulinum toxin ▌ Cons: Effects are temporary and may vary between individuals I would not want to compare the efficacy to botulinum toxin The challenge with peptides in skincare is their skin permeability. Most anti-wrinkle peptides are not ideal candidates for skin permeation, and enhancement methods are often necessary to increase their permeability and effectiveness. [5] Researchers are exploring ways to improve peptide delivery and efficacy, such as designing novel targeting peptide motifs to enhance the interaction between cosmetic peptides and the cell surface. [5] SOME OTHER PEPTIDES USED IN SKINCARE 4. Enzyme-inhibitor peptides: These block enzymes that break down collagen and other important skin proteins. 5. Antimicrobial peptides (AMPs): These are part of the immune response in living organisms and help defend against pathogens. 6. Antioxidant peptides: These help protect the skin from oxidative stress and free radical damage. BENEFITS OF PEPTIDES IN SKINCARE 1. Collagen stimulation: Certain peptides, such as palmitoyl pentapeptide-4, have been shown to stimulate collagen production, potentially reducing the appearance of fine lines and wrinkles. [6] 2. Improved skin barrier function: Peptides like palmitoyl tetrapeptide-7 may help reduce inflammation and improve skin barrier function. [7] 3. Antioxidant properties: Some peptides, including copper peptides, exhibit antioxidant properties, potentially protecting the skin from oxidative stress. [8] 4. Hydration: Peptides can act as humectants, helping to retain moisture in the skin. [9] COLLAGEN STIMULATING PEPTIDES Mode of Action: Collagen peptides potentially stimulate fibroblast proliferation and increase the expression of collagen and elastin genes, enhancing the structural integrity of the skin..[1][2] While many peptides are too large to penetrate the skin effectively, some collagen-stimulating peptides have shown evidence of skin penetration and efficacy in skincare formulations. 1. Penetration-enhancing techniques: Various methods have been developed to improve peptide penetration into the skin, including chemical modification, use of penetration enhancers, and encapsulation in nanocarriers. [10] Cell-Penetrating Peptides (CPPs) The discovery of cell-penetrating peptides (CPPs) is a significant advancement in drug delivery systems, particularly for large molecular cargoes. [11][12] Key features of CPPs include: 1. Composition: Rich in positively charged amino acids (arginine, lysine) [13] 2. Function: Ability to cross cell membranes [14] 3. Cargo capacity: Can transport large molecules into cells [15] 4. Potential applications: Delivery of therapeutic agents, including nucleic acids [12][15] 2. Specific evidence based peptides: ▌GHK (Glycyl-L-histidyl-L-lysine): This copper peptide has shown ability to penetrate the skin and stimulate collagen production. [3] ▌KTTKS (Lysine-threonine-threonine-lysine-serine): When modified with palmitic acid (palmitoyl pentapeptide-4), this peptide demonstrated improved skin penetration and collagen-stimulating effects. [3] ▌GEKG (Glycine-glutamic acid-lysine-glycine): Studies have shown this tetrapeptide can penetrate the skin when used with appropriate delivery systems. [6] GEKG significantly induces collagen production at both the protein and mRNA levels in human dermal fibroblasts. [7] GEKG is derived from extracellular matrix (ECM) proteins and has been shown to enhance gene expression responsible for collagen production up to 2.5-fold [7] boosts collagen, hyaluronic acid, and fibronectin production by dermal fibroblasts. [7] ▌Palmitoyl Pentapeptide Mode of Action: These peptides mimic the body's natural peptides that signal fibroblasts to produce more collagen. [1][2] Their efficacy can vary depending on the specific formulation, percentage and delivery method used. EVEN MORE PEPTIDES 1. Antifungal peptides (AFPs): These molecules defend organisms against fungal infections. 2. Neuropeptides: These peptides function as neurotransmitters or neuromodulators in the nervous system. 3. Cardiovascular peptides: These include peptides like adrenomedullin and angiotensin II, which play roles in cardiovascular function. 4. Endocrine peptides: These are hormone peptides that regulate various physiological processes, such as leptin, orexin, and growth hormone. 5. Anticancer peptides: These include molecularly targeted peptides, "guiding missile" peptides, and cell-stimulating peptides used in cancer treatment. 6. Plant peptides: These originate from plants and have various health benefits for humans. They can be incoroprated in skincare formulations. 8. Oligopeptides and polypeptides: These classifications are based on the number of amino acids in the peptide chain, also found in skincare. 9. Ribosomal and non-ribosomal peptides: These categories are based on how the peptides are synthesized. This diverse range of peptide types reflects their varied functions and applications in biological systems and therapeutic interventions. 10. Neurosensine is an acetyl dipeptide-1 cetyl ester composed of two amino acids: arginine and tyrosine [20]. Neurosensine works by stimulating the production of endorphins and enkephalins in keratinocytes, which are natural pain relievers. This action helps create a barrier that protects nerve endings in the skin, making it less prone to redness, dryness, irritation and itch. OS-01 [16][17] OS-01 from One Skin is a peptide designed to target cellular senescence, one of the 12 hallmark of skin aging. OS-01 works by reducing the accumulation of senescent cells—cells that have stopped dividing (also called zombie cells) and contribute to age-related deterioration. By decreasing the burden of these cells, OS-01 aims to improve skin appearance and function by boosting collagen and hyaluronic acid production, which are essential for skin elasticity and hydration. PEPTIDES FOR LONGEVITY ▌NAD+: A coenzyme that supports energy production, cellular repair, and longevity. It plays a role in DNA repair and declines with age. [18] ▌Epithalon: Regulates telomerase production, protecting against telomere degradation, which is crucial for cellular longevity. Research conducted by Khavinson et al. showed that Epithalon treatment significantly increased telomere lengths in blood cells of patients aged 60-65 and 75-80 years. ▌BPC157: Known for promoting healing and reducing inflammation, it also boosts collagen production, supporting skin health. [19] COLLAGEN PEPTIDE POWDERS. Bovine collagen peptides, extracted from cow hides, are rich in types I and III collagen. These types are prevalent in human skin, making bovine collagen a popular supplement, especially as they contain the building blocks for collagen production.. Research has shown that oral supplementation with bovine collagen peptides can improve skin elasticity and hydration. Marine collagen, derived from fish scales and skin, is primarily type I collagen with high bioavailability and absorption rate. Studies have demonstrated that marine collagen peptides can enhance skin hydration, reduce wrinkles, and improve wound healing. Additionally, marine collagen has shown promise in supporting bone health by potentially increasing bone mineral density. Plant-based collagen boosters, while not containing actual collagen, provide nutrients that support the body's natural collagen production. These supplements often include ingredients like vitamin C, silica, and various amino acids. Although not as extensively studied as animal-derived collagens, plant-based options cater to vegan consumers and those with dietary restrictions. In powder form they can easily be mixed into beverages or foods. The hydrolyzed nature of these peptides enhances their bioavailability. CHALLENGE Stability: Some peptides are unstable and may degrade quickly in formulations. Peptides, while very promising, are not straightforward ingredients in skincare products or oral supplementation. Their effectiveness depends on various factors, including formulation, delivery system, and individual skin characteristics. Always consult a qualified healthcare professional to determine what the most suitable approach is for your needs and goals. Take care Anne-Marie References: [1] Edgar, S., Hopley, B., Genovese, L. et al. Effects of collagen-derived bioactive peptides and natural antioxidant compounds on proliferation and matrix protein synthesis by cultured normal human dermal fibroblasts. Sci Rep 8, 10474 (2018). https://doi.org/10.1038/s41598-018-28492-w [2] Frontiers | Collagen peptides affect collagen synthesis and the expression of collagen, elastin, and versican genes in cultured human dermal fibroblasts [3] Pickart L, et al. GHK Peptide as a Natural Modulator of Multiple Cellular Pathways in Skin Regeneration. Biomed Res Int. 2015;2015:648108. doi:10.1155/2015/648108. [4] Draelos, Z. D. (2007). What are cosmeceutical peptides? Dermatology Times, 28(11). Retrieved from https://www.dermatologytimes.com/view/what-are-cosmeceutical-peptides [5] He B, Wang F, Qu L. Role of peptide-cell surface interactions in cosmetic peptide application. Front Pharmacol. 2023 Nov 13;14:1267765. doi: 10.3389/fphar.2023.1267765. PMID: 38027006; PMCID: PMC10679740. [6] Binder L, et al. Dermal peptide delivery using enhancer molecules and colloidal carrier systems--A comparative study of a cosmetic peptide. Int J Pharm. 2018;557:36-46. doi:10.1016/j.ijpharm.2018.08.019. [7] Farwick M, Grether-Beck S, Marini A, Maczkiewitz U, Lange J, Köhler T, Lersch P, Falla T, Felsner I, Brenden H, Jaenicke T, Franke S, Krutmann J. Bioactive tetrapeptide GEKG boosts extracellular matrix formation: in vitro and in vivo molecular and clinical proof. Exp Dermatol. 2011 Jul;20(7):602-4. doi: 10.1111/j.1600-0625.2011.01307.x. PMID: 21692860. [8] Bae, S. H., et al. (2020). "Copper peptides as a potential therapeutic agent for skin aging." Journal of Cosmetic Dermatology, 19(9), 2245-2252. doi:10.1111/jocd.13435. [9] Zhao, Y., et al. (2019). "Peptides and Proteins as Skin Moisturizers." Cosmetics, 6(3), 32. doi:10.3390/cosmetics6030032. [10] International Journal of Cosmetic Science Skin permeability, a dismissed necessity for anti-wrinkle peptide performance Seyedeh Maryam Mortazavi, Hamid Reza Moghimi First published: 18 March 2022 https://doi.org/10.1111/ics.12770 [11] Lindgren, M., Hällbrink, M., Prochiantz, A., & Langel, Ü. (2000). Cell-penetrating peptides. Trends in Pharmacological Sciences, 21(3), 99-103. [12] Tripathi, P. P., Arami, H., Banga, I., Gupta, J., & Gandhi, S. (2018). Cell penetrating peptides in preclinical and clinical cancer diagnosis and therapy. Oncotarget, 9(98), 37252-37267. [13] Chu, D., Xu, W., Pan, R., Ding, Y., Sui, W., & Chen, P. (2015). Rational modification of oligoarginine for highly efficient siRNA delivery: structure-activity relationship and mechanism of intracellular trafficking of siRNA. Nanomedicine: Nanotechnology, Biology and Medicine, 11(2), 435-446. [14] Frankel, A. D., & Pabo, C. O. (1988). Cellular uptake of the tat protein from human immunodeficiency virus. Cell, 55(6), 1189-1193. [15] Guidotti, G., Brambilla, L., & Rossi, D. (2017). Cell-Penetrating Peptides: From Basic Research to Clinics. Trends in Pharmacological Sciences, 38(4), 406-424. [16] Zonari, A., et al. (2023) "Double-blind, vehicle-controlled clinical investigation of peptide OS-01." Journal of Cosmetic Dermatology. doi:10.1111/jocd.16242. [17] Kirkland, J. L., et al. (2017). "Cellular Senescence: A Key Regulator of Aging." *Nature Reviews Molecular Cell Biology*, 18(7), 473-485. doi:10.1038/nrm.2017.30. [18] Fang, E. F., et al. (2019). NAD+ augmentation restores mitophagy and limits accelerated aging in Werner syndrome. Nature Communications, 10(1), 5284. [19] Chang CH, Tsai WC, Hsu YH, Pang JH. Pentadecapeptide BPC 157 enhances the growth hormone receptor expression in tendon fibroblasts. Molecules. 2014 Nov 19;19(11):19066-77. doi: 10.3390/molecules191119066. PMID: 25415472; PMCID: PMC6271067. [20] Resende, Diana I. S. P., Marta Salvador Ferreira, José Manuel Sousa-Lobo, Emília Sousa, and Isabel Filipa Almeida. 2021. "Usage of Synthetic Peptides in Cosmetics for Sensitive Skin" Pharmaceuticals 14, no. 8: 702. ![]()
Like epigenetics and exosomes, neurocosmetics represent a revolutionary approach for skin care incorporating neuroscience principles, leveraging the skin-brain connection to improve skin health and beauty. The term itself is a fusion of the words neuroscience and cosmetics. It differs from psychodermatology which like neurocosmetics connects the interaction between mind and skin, but in a different way. Some describe it as how simple sensory stimulation can improve our overall wellbeing and call it "mood beauty", however this doesn't do it justice as neurocosmetics go beyond mood boosting skincare.
DEFINITION NEUROCOSMETICS Dermatologist Professor Laurent Misery back in 2002 described that neurocosmetics are products which are supposed to modulate the neuro-immuno-cutaneous-system (NICS) function at an epidermal level. Skin cells can produce neuromediators, which are mediators for transmission of information between skin, immune and the nervous system. All skin cells express specific receptors for neuromediators and by binding of the neuromediator to its receptor, modulation of cell properties and skin functions are induced like cell differentiation and proliferation (renewal), pigmentation, etc. Hence, keratinocytes, Langerhans cells, melanocytes, endothelial cells, fibroblasts and the other cells of the skin are modulated and controlled by the nerves and in return skin is able to modulate neuronal activity and growth. [1] SKIN-BRAIN CONNECTION In an article from the International Journal of Novel Research and Developments, the skin-brain connection was described as a psychobiological concept that highlights how emotions, stress, and neurotransmitters impact skin health. Indicating that the skin acts as a neuroimmunoendocrine organ, emphasizing its sensitivity to neural signals and stress responses. [4] CUTANEOUS NERVOUS SYSTEM The skin a sophisticated sensory organ that allows you to interact with your environment through touch and feel. It contains a complex network of nerves that send information about sensations like pressure, pain, itch and temperature from the skin through the spinal cord to the brain [9]. The dynamic interactions between the skin and the nervous system is influenced by factors like stress and inflammation, which can impact skin health and ageing. [7] Nerves in the skin: These nerves are like tiny messengers that tell your brain about what your skin is feeling: pressure, heat or pain. Types of nerve fibers: Some are thick and wrapped in a protective coating, which helps them send messages quickly. Others are thin and slow but are very good at sending messages about pain or temperature changes. [3] Sensory receptors: These receptors can tell if something is touching the skin lightly or if there's a lot of pressure. They can also sense if something is hot, cold, or causing pain. [3] Autonomic nervous system: Part of the cutaneous nervous system helps control things that happen in the skin automatically, like sweating to regulate body temperature. [8] Nerve cells: There are about 20 different types of neurons in our skin. [10] The contribution of epidermal keratinocytes to NICS [3]
CUTANEOUS NEURO-AGEING Neuro-ageing is defined as the changes in the nervous system which cause continuous neurodegeneration due to oxidative stress, neuroinflammation or impaired neuromodulation. As skin ages, Aβ-toxin (increased by oxidative stress) accumulates at the nerve endings innervating the tissue, causing disrupted cellular communication, particularly affecting fibroblasts’ ability to produce collagen and extracellular matrix. On top there is a decrease of nerve growth factor (NGF) production, important for the development and maintenance of nerve cells. Different factors can lead to a drop in NGF production, resulting in malfunctioning keratinocytes and reduced lipolytic activity of adipocytes, visibly impacting skin hydration and firmness. [6] Skin nerve fibres are significantly reduced in number following UV irradiation and in ageing skin [5] and therefore neuro-protectors or targetting neurodegeneration can reduce stress manifestations and promote healthy cellular communication for optimal skin function. [3] Although not much is known regarding skin specific or topical neuroprotectors (most research was focussed on the brain), probably potent anti-oxidants, by significantly reducing oxidative stress from UV and blue light and anti-inflammatory ingredients may inhibit skin neuro-ageing and can be neuroprotective especially when combined with sunscreen and strengthening of the skin barrier. NEUROCOSMETIC VARIETY OF ACTIONS
THE FUTURE OF NEUROCOSMETICS The neurocosmetics market is booming, with a projected value of USD 2.69 billion by 2030. [11] The future of neurocosmetics holds promise for innovative ingredients and concepts that harness new neuroscientific insights to revolutionize skin care and sunscreen formulations, to cater to both physical and emotional aspects of skin health and beauty. Take care! Anne-Marie References
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Hair is a powerful factor in how we're perceived by others and even how we see ourselves. It plays a significant role in the perception of youth and attractiveness. Studies have shown that hair style, color, and quality can significantly affect how old we look and how attractive we're considered [1]. Research suggests that hair is one of the most defining characteristics of our appearance, with the potential to make us look years younger or older [1]. From an evolutionary perspective, lustrous hair has long been associated with youth, health, and fertility [1]. Culturally, hair has been a symbol of beauty and status across societies for centuries [2].
HAIR GENETICS BEYOND MATERNAL INHERITANCE We have approximately 5 million hair follicles distributed across our bodies, with only about 100,000 located on the scalp [3][4]. Contrary to popular belief, hair characteristics are not solely inherited from one's mother. Human genetic makeup consists of 23 pairs of chromosomes, including the sex-determining X and Y chromosomes [5]. Females typically have two X chromosomes (with one usually inactivated through a process called X-chromosome inactivation), while males have one X and one Y chromosome [6]. Our hair's characteristics, including texture, color, and growth patterns, are determined by about 600 genes [7]. Interestingly, only 11% of these genes are located on the X chromosome [8]. The majority of genes influencing hair traits are found on autosomes (non-sex chromosomes), contributing to the inheritance patterns observed in families [9]. For instance, genes like EDAR and FGFR2 have been associated with hair thickness in Asian populations, while TCHH has been linked to hair texture in individuals of Northern European ancestry [10]. Research has identified several genes on the X chromosome that play a role in male pattern baldness, including the androgen receptor (AR) gene. Telomere length in hair follicle stem cells correlates with hair growth capacity and may be a biomarker for hair follicle aging. The complexity of hair genetics extends beyond sex chromosomes, involving multiple autosomal genes, environmental factors, hence epigenetics, and this is great news as changes in epigenetic patterns are partially reversible! Epigenetics Epigenetics refers to heritable changes in gene expression that occur without alterations in the DNA sequence itself [11]. Environmental factors, diet, lifestyle, chronic stress, sleep, circadian rhythms, physical activity, aging and even social interactions can influence gene expression through four main epigenetic mechanisms:
These epigenetic mechanisms can significantly impact hair biology
Example of change in epigenetic pattern Ever wondered why hair starts growing in odd places as we age? It is a good example of epigenetic changes. As we get older, changes in our epigenome can cause regions of our DNA that are normally silent (due to histone modifications) to become readable. In essence, we're becoming more like our ancient ancestors! This is why some people start growing more hair in places like ears and noses as they age. Epigenetic changes can thus silence or activate hair growth-related genes, potentially contributing to hair loss or promoting regeneration. Thus, the future of our hair health is literally (at least partially) in our hands today!. Lifestyle changes and hair regrowth Lifestyle modifications have demonstrated impacts on hair regrowth, particularly in early stages of hair loss and for prevention. 1. Nutrition: A balanced diet rich in proteins, vitamins (especially biotin, vitamins A, C, and D), and minerals (iron, zinc) has been associated with improved hair growth [20]. Supplementation with these nutrients has shown benefits in treating telogen effluvium and other hair loss conditions [21]. 2. Stress Management: Chronic stress can lead to telomere shortening and premature hair follicle aging. Stress reduction techniques like meditation and yoga have been linked to increased telomerase activity, potentially benefiting hair growth. 3. Exercise: Regular physical activity improves blood circulation to the scalp, potentially enhancing nutrient delivery to hair follicles. A study found that moderate exercise was associated with increased expression of hair growth-related genes. 4. Sleep: Adequate sleep is crucial for maintaining healthy hair growth cycles. Sleep deprivation has been linked to increased oxidative stress and inflammation, which can negatively impact hair follicles. Studies have shown promising results in targeting epigenetic mechanisms for hair loss treatment
In office therapies 1. Low-Level Laser Therapy (LLLT): LLLT works by decreasing nitric oxide enzyme activity, leading to a beneficial "micro-stress" in mitochondria. This hormetic effect increases energy production, allowing stem cells to stay young and rejuvenate. Clinical studies have demonstrated improved hair density and thickness with LLLT in androgenetic alopecia patients. 2. Platelet-Rich Plasma (PRP) and exosomes: These regenerative therapies deliver growth factors and signaling molecules to hair follicles, potentially reversing miniaturization and promoting the anagen phase. PRP has shown promising results in multiple clinical trials for androgenetic alopecia. 3. HydraFacial Keravive scalp treatment: A 3-step process involving cleansing, exfoliating, and nourishing the scalp to improve hair follicle health. 4. Hair Transplantation: Includes techniques like Follicular Unit Extraction (FUE) and strip harvesting to transplant hair from donor areas to balding areas. 5. Scalp micropigmentation: A cosmetic tattooing procedure that creates the appearance of a fuller head of hair. 6. Corticosteroid Injections: Used primarily for treating alopecia areata by injecting steroids directly into affected areas of the scalp. 7. Microneedling: Uses small needles to create micro-injuries in the scalp, potentially stimulating hair growth when combined with topical treatments. 8. Scalp Reduction: A surgical procedure that removes bald areas of the scalp and stretches hair-bearing skin. 9. Mesotherapy: Involves injecting vitamins, minerals, and other nutrients directly into the scalp to nourish hair follicles. BALD AINT BAD (for men)
Always consult a qualified healthcare professional or dermatologist to determine what the most suitable approach is for your particular skin or hair condition. Take care! Anne-Marie
The picture I used for this post is from my lovely daughter, who is blessed with fabulous hair.
References
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If you've scrolled through Instagram, you may have caught a glimpse of dermatologists raving about LED masks emitting red light, the secret, evidenced based weapon behind skin rejuvenation known as photo biomodulation. It uses low-powered light within the red to near-infrared range (wavelengths from 632 to 1064 nm) to induce a biological reaction aka stimulate cellular processes. The wonders of red light, also known as LLLT (low-level laser therapy), PBM (red light photo-biomodulation), or PBMT (photo-biomodulating therapy), extend far beyond non-invasive skin rejuvenation. I am not a fan of devices for home use, mostly because of lacking safety and/or efficacy, PBM definitely earned it's prominent spot in my skincare routine.
A summary of the benefts of red light with and without near infrared light for skin Numerous studies have demonstrated the effectiveness of red and infrared light therapy for skin rejuvenation. A combination of red light and near IR light has proven to stimulate the production of collagen (I & III) plus elastin production (Li WH et al Int J Cosmet Sci 2021), enhance mitochondrial ATP production, cell signaling, growth factor synthesis, rebalance ROS (reactive oxidative species) and reduce inflammation. Stem cells can be activated allowing tissue repair and healing. Wrinkle and scar reduction was observed and it can reduce UV damage both as treatment and prophylactic measure. In pigmentary disorders such as vitiligo, it can increase pigmentation by melanocyte proliferation and reduce depigmentation by inhibiting autoimmunity (Pinar Avci et al. Semin Cutan Med Surg. 2013 & Mitchell J Winkie et al. Review Photodermatol Photoimmunol Photomed A focused review of visible light therapies for vitiligo 2024). It has the potential to activate both keratinocytes (epidermis) and fibroblasts (epidermal junction and dermis). With consistent use, you can expect a reduction of lines and wrinkles, improvement of skin tone and texture. PBMT (when done effective and safe) will compliment both your skin rejuvenating and regenerating at home skincare regimen and in-office procedures or even post-surgical skin recovery. ATP ATP (adenosine triphosphate) is the primary source of energy for cellular processes and plays a crucial role in various biological functions. When red light with specific wavelengths (630 nm to 638 nm and 810 nm) is absorbed by the skin cells, it stimulates the mitochondria, which are the powerhouses of the cells responsible for ATP synthesis. This increase in ATP production is providing cells with more energy to carry out their functions effectively and has several beneficial effects on the skin like boosting cellular metabolism, promoting more efficient nutrient uptake and waste removal. The increased ATP levels facilitate collagen synthesis by fibroblasts, a vital component for skin structure, elasticity and firmness and reduction of lines and wrinkles.. ATP aids in the repair and regeneration of damaged skin cells. It accelerates the healing process, making it beneficial for wound healing, post-surgical recovery, and addressing skin issues such as acne scars. ROS (Reactive Oxidative Species) By modulating ROS levels, red light therapy helps reduce oxidative stress and its detrimental effects on the skin. ROS are highly reactive molecules that are naturally produced by cells as byproducts of metabolic processes. While low levels of ROS play important roles in cellular signaling and immune responses, excessive ROS can lead to oxidative stress and damage to cells and tissues. Restoring the balance of ROS result in improved skin health, reduced inflammation, and enhanced skin rejuvenation. Red light therapy has been shown to modulate reactive oxidative species (ROS) levels in the skin by promoting antioxidant defense mechanisms and reducing oxidative stress:
The difference between LLLT and PBM LLLT refers specifically to the use of lasers, which produce coherent, focussed and an intense beam of monochromatic light, while PBM has a broader range of light sources, may include laser as well as light-emitting diodes (LEDs) and other non-laser devices. LEDs are often used in PBM because they are cost effective, versatile and have the ability to cover large treatment areas. LLT uses higher power densities with more energy and has a shorter treatment duration in comparison to PBM to achieve desired therapeutic effects. While there are similarities in terms of mode of action", there is a difference of light source, treatment application and parameters. Based on consensus, PBM and PBMT are considered the correct way to describe this photonic specialty for therapeutic applications. In this post I will focus on PBM and specifically LEDs. A home device claiming to use cold near infrared laser light or Low-Level Laser Therapy is called LYMA laser. It is sold for several thousand euro´s. LED masks and LED panels LED masks specifically produced by the brand Omnilux (FDA cleared) are currently very popular for very good reasons; they are safe and effective when the LEDs emit the right wavelengths and used in the recommended frequency. Omnilux combines 2 therapeutically effective and complimentary wavelengths: 633nm and near-infrared 830 nm. Both wavelengths (more precise 630nm + 850nm) I would recommend to minimally look for in any red LED device, which will disqualify most LED masks and panels in the market! I've include some (not affiliated) links to devices below. Both masks and panels can be effective, however most panels are stronger in comparison to masks 60 mW/cm² vs mW/cm²), hence have the benefit of a shorter treatment time to get a similar result. Intensity and power of red light therapy devices are typically measured in terms of irradiance (measured in milliwatts per square centimeter, mW/cm²) and radiant flux (measured in watts, W), which quantify the amount of light energy emitted by the device. Wearing a mask during a hot summer or in a warmer climate will make you sweat and depending on the materials of the mask and straps, they may be very uncomfortable to wear. Panels have the benefit that they give a more even distribution of emitted light as masks are worn on the face and thus the LED bulbs are pushed on a small skin surface area, panels can cover a larger area (depending on their size) and are more versatile in use, as area's like neck, décolletage, or knees are easier to treat with a panel. With a mask you may be more mobile, although I would not recommend walking around while using the mask. My personal preference would be a panel for the reasons mentioned before and panels are more suitable (more hygienic) for family sharing. My son can use it after an intense workout to speed up his recovery and I like to use it for purposes beyond photo-biomodulation or skin rejuvenation, for example to improve my sleep. With a panel I get more "bang for my buck". ![]()
Red light and NIR (Near Infra Red light) have the ability to penetrate varying depths of the skin, resulting in distinct benefits, thus combinations of wavelengths will provide complementary effects.
630 nm Wavelength This wavelength is often used for its skin rejuvenation benefits. It has a relatively shallow penetration depth and is absorbed closer to the surface of the skin primarily affecting the epidermis. 630nm light is associated with increased circulation, reduce inflammation, improved skin tone & texture, aiding in the delivery of nutrients and oxygen to skin cells, and stimulating the production of collagen, leading to improved skin elasticity and a reduction of the appearance of fine lines & wrinkles. 660 nm Wavelength At 660nm, red light can penetrate a little deeper into the skin, reaching the dermis. It is known for its ability to stimulate collagen production, enhance cellular metabolism, and promote anti-inflammatory effects, helping to reduce redness and inflammageing. It also promotes wound healing, making it beneficial for post-surgical or post-trauma skin recovery. 810 nm Wavelength Improve healing & recovery & accelerate wound healing. 830 nm Wavelength Accelerate healing, reduce infection, improve aesthetic outcome following plastic surgery, increase endorfines (mood-enhancing), improve bone repair and growth. 850 nm Wavelength Improve general inflammation body, enhance muscle recovery, improve wound healing, reduced fine lines, wrinkles and hyperpigmentation. Always consult a qualified healthcare professional or dermatologist to determine if and what the most suitable red light therapy approach is for your particular skin condition and rejuvenation goals. Take care! References: Hamblin, Michael R. "Mechanisms and applications of the anti-inflammatory effects of photobiomodulation." AIMS biophysics 4.3 (2017): 337-361. Barolet, Daniel. Regulation of Skin Collagen Metabolism In Vitro Using a Pulsed 660 nm LED Light Source: Clinical Correlation with a Single-Blinded August 2009Journal of Investigative Dermatology 129(12):2751-9 Wunsch A, Matuschka K. (2014). A controlled trial to determine the efficacy of red and near-infrared light treatment in patient satisfaction, reduction of fine lines, wrinkles, skin roughness, and intradermal collagen density increase. Journal of Cosmetic and Laser Therapy, 16(5), 232-237. Avci P, et al. (2013). Low-level laser (light) therapy (LLLT) in skin: stimulating, healing, restoring. Seminars in Cutaneous Medicine and Surgery, 32(1), 41-52. Links to some devices which combine 630 nm and 850 nm: FDA-approved devices ensure safety and regulatory compliance, however the panels are more powerful: Omnilux(tm) Mask (FDA clearance) Very affordable panel (no FDA clearance) Affordable panel (no FDA clearance) ![]()
Skin ageing is a biological degenerative process, marked by loss. The number of patients seeking nonsurgical rejuvenation of the face and the body is continuing to increase due to a growing ageing population concerned with physical appearance. Women wish to maintain a youthful appearance and attractiveness represent 92% of all cosmetic procedures.(1) Men are keen to maintain physical characteristics associated with virility.(2) Millennials are also increasingly concerned with preserving their beauty and youth.(3) Among the various treatment approaches, different minimally invasive techniques have been developed and dermal fillers currently come second after botulinum toxin type A (BTA).(3) Their use is increasing worldwide.
"The fear of looking done is the number 1 reason why patients don't seek treatment"* The range of fillers available for soft-tissue augmentation is constantly expanding. The latest advances in filler technology include bio-stimulators that exert their aesthetic effect by promoting predominantly collagenesis or biological stimulation of new collagen and sometimes also elastin production. Therewith they provide a biological answer to the skin ageing degeneration process, with gradual and often very natural results. Over the course of last years the knowledge on injectable bio-stimulators has grown, and therewith their safety and popularity as they provide subtle longer lasting results. Facial fillers can be broken into 3 main groups:
Bio-stimulating fillers promote the body’s natural production of some ECM components (mostly collagen) over a period of several months. Their differences are characterized by their property of inducing natural collagen production. SYNTHETIC BIOSTIMULATORS
Calcium Hydroxylapatite Calcium hydroxylapatite: Calcium hydroxylapatite is a type of mineral that is commonly found in human teeth and bones and in injectbales the calcium hydroxylapatite particles are suspended in a gel-like solution. The effects of this material last approximately 18 months with minimal inflammatory response. Radiesse is a biodegradable filler consisting of 30% synthetic CaHA microspheres (diameter of 25-45μm) suspended in a 70% aqueous carboxymethylcellulose gel carrier. The soluble carrier gel evenly distributes the Radiesse CaHA microspheres providing 1:1 correction and gradually dissipates leaving the microspheres at the injection site where they induce collagenesis (collagen type I and mostly collagen type III) by fibroblast activation. Animal studies have shown that this new collagen growth occurs as early as four weeks post-injection and continues for at least 12 months with an average duration of effect of 12 to 18 months, though some results have been noted 24 months post-injection. Radiesse provides both immediate (replacement volume) and long-lasting (collagen biostimulation) volume enhancement. (5) Poly-L-lactic acid PLLA is a biodegradable, bioresorbable biocompatible man-made polymer. This material has wide uses in absorbable stitches and bone screws. The effects of PLLA generally become increasingly apparent over time (over a period of several weeks) and its effects may last up to 2 years. There is an inflammatory response. PLLA is an alpha hydroxy acid polymer of the lactic acid L-enantiomeric structure that has been safely used in many applications and in medicine for more than 30 years. Its use has expanded worldwide, associated with good long-term aesthetic results thanks to its biostimulatory-collagen effect. PLLA-based fillers are supplied as a lyophilized powder to be reconstituted with sterile water. The collagen stimulatory properties were evidenced in human in subjects (n=14) who received PLLA injections (3 sessions, spaced 4 weeks apart) at the postauricular level by collagen histochemical determination on biopsies taken at different times. Increase of collagen type-I was shown at 3 and 6 months. This study opened the new class of collagen stimulators. The long duration of action was demonstrated in a first pivotal study comparing PLLA versus collagen (116/117 subjects, respectively); the long-term safety/efficacy was shown up to 25 months. The rationale for several sessions was first documented in a dedicated article; this modality allows the effect through collagen stimulation, a biological process to occur and avoids overcorrection. PLLA fillers are among the most clinically documented products. (6) Polymers, polycaprolactone The PCL-based collagen stimulator is composed of PCL microspheres suspended in a carboxymethyl-cellulose gel carrier providing immediate and sustained volumizing effects when injected; the morphology, the biocompatibility of the PCL microspheres embedded with the collagen fibers produced all contribute to the creation of a unique 3D scaffold for a sustained effect. Its safety has been investigated in clinical studies and vigilance surveys. It presents the advantage of a slower degradation than polylactic acid (PLLA) or polyglycolic acid (PGA), which both belong to the same chemical family. Both the S and M products induced collagen production. In animal, the M product induced collagen type-III and type-I at early stage (measure at 9 months), and later predominantly collagen type-I, that deposits around the PCL microspheres (measure at 21 months). Many fibroblasts were found near the PCL microspheres. Interestingly, new elastin fibers were also formed, and neovascularization with new capillaries observed as well. (7) NATURAL BIOSTIMULATORS 1. Platelet rich plasma 2. Platelet rich fibrin 3. Polynucleotides like Nucleofill or Nucleadyn 4. Exosomes 5. Alginate 6. Tropoelastin (precursor of elastin molecule) 7. Poly-y-glutamic acid Platelet-Rich Plasma (PRP): PRP treatments are produced by spinning a small volume of the patient’s own blood through a centrifuge. This separates and concentrates the blood’s components, including platelet-rich plasma and the “buffy coat,” a solution that contains immune cells. The provider combines these two components with a small amount of calcium chloride (which activates and keeps the PRP stable), then injects them into the treatment area. Over a period of months, PRP stimulates the body’s natural collagen production. Platelet-Rich Fibrin (PRF): PRF is produced using a process similar to PRP concentration. The active material is a fibrin matrix rich in platelets, stem cells, and immune cells. Like PRP, PRF treatment stimulates collagen production and is also implicated in tissue regeneration, though there’s less data on the durability of its effects. Because both treatments use material from the patient’s own body, so there’s no risk of rejection or similar complications. PRF and PRP effects are durable — typically lasting longer than 18 months. Polynucleotides: Polynucleotides are most often natural, highly purified DNA molecules extracted for example from trout gonads and activate specialised cells called myofibroblasts and adipocytes. PN containing devices act as short time temporary fillers thanks to the viscoelasticity of the long DNA fragments and improve skin well‐being (cell growth) and steady self‐repair (tissue regeneration). Read more Exosomes: The use of exosomes at the Aesthetic & Anti-Aging Medicine World Congress in Monaco was discussed during many session and some excellent results were presented. However their use is not yet approved and safety and long-term effect not yet established and largely depends on the source. Read more BOTULINUM TOXIN There is evidence that the neuromodulator or musclerelaxer Botinumtoxin after injection upregulated the expression of type I collagen, decreases the production of some MMPs in fibroblasts, preventing collagen degradation and improves collagen organisation. (8.9.) ENERGY BASED DEVICES Intense Pulsed Light/BroadBand Light, Radiofrequency Microneedling, lasers, High-Frequency Ultrasound, Electromagnetic Tec. stimulate collagen production via a controlled damage and repair mechanism. DERMO-COSMETICS WITH BIO-ACTIVES There are innovative dermo-cosmetic products containing bio-stimulating ingredients, working more superficial in comparison to in-office treatments and they therefor are potentially an excellent choice as adjunctive care for biological rejuvenation and revitalization for younger looking and acting skin. They are safe to use easy to apply over face, neck and décolletage. Unlike in-office treatments their effects are temporary (fully reversible as regulated), hence they require daily or twice daily application. Biostimulating active ingredients in skincare which have shown to particularly stimulate the fibroblast are for example:
VITAMIN C IS NEEDED FOR COLLAGEN SYNTHESES! Our skin needs Vitamin C to produce collagen and is not able to produce it, thus relies on external resources for supply. Therefore I highly recommend to either get enough Vitamin C from your diet or use a high quality topical product pre & post biostimulators. Read more BIOSTIMULATION FAT CELLS Renuva is an allograft adipose matrix injectable that offers a non-surgical solution for volume restoration in various areas of the body, including the face, hands, and areas with contour irregularities. It stimulates the growth of own fat cells, potentially providing longer-lasting results. Renuva is FDA-regulated. In skincare the ingredient Magnolol or Magnolia Bark Extract has shown to increase the number and size of adipocites or fat cells to counteract volume-loss. As the biological degeneration takes place in different layers of the skin and it's underlying structures, combining in-office treatments specifically targeting those layers in a series of treatments may provide longer lasting results and give higher patient satisfaction.(13) Safety and outcome rely on the qualification and experience of your cosmetic doctor, dermatologist or plastic surgeon. Take care Special thanks MD FAAD Hassan Galadari Jair Mauricio Cerón Bohórquez M.D. References: 1. American Society Plastic Surgeons. 2020 national plastic surgery statistics; 2020. 2. Wat H, Wu DC, Goldman MP. Noninvasive body contouring: a male perspective. Dermatol Clin. 2018;36(1):49–55. 3. Wang JV, Akintilo L, Geronemus RG. Growth of cosmetic procedures in millennials: a 4.5-year clinical review. J Cosmet Dermatol. 2020;19(12):3210–3212. 4. Evaluation of the biostimulatory effects and the level of neocollagenesis of dermal fillers: a review. Haddad S, Galadari H, Patil A, Goldust M, Al Salam S, Guida S International Journal of Dermatology, 29 Apr 2022 5. J Clin Aesthet Dermatol. 2015 Jan; 8(1): 38–49. Calcium Hydroxylapatite Over a Decade of Clinical Experience Jani Van Loghem, MD, Yana Alexandrovna Yutskovskaya, MD,b and WM. Philip Werschler, MDc 6. Clin Cosmet Investig Dermatol. 2022; 15: 997–1019. Collagen Stimulators in Body Applications: A Review Focused on Poly-L-Lactic Acid (PLLA) Marie-Odile Christen Read more 7. Clin Cosmet Investig Dermatol. 2020; 13: 31–48. Polycaprolactone: How a Well-Known and Futuristic Polymer Has Become an Innovative Collagen-Stimulator in Esthetics Marie-Odile Christen and Franco Vercesi 8. Oh SH, Lee Y, Seo YJ, Lee JH, Yang JD, Chung HY, Cho BC. The potential effect of botulinum toxin type A on human dermal fibroblasts: an in vitro study. Dermatol Surg. 2012 Oct;38(10):1689-94. 9. El-Domyati M, Attia SK, El-Sawy AE, Moftah NH, Nasif GA, Medhat W, Marwan B. The use of Botulinum toxin-a injection for facial wrinkles: a histological and immunohistochemical evaluation. J Cosmet Dermatol. 2015 Jun;14(2):140-4 10 EADV 2022 Inhibition of extracellular matrix degrading enzymes and bio-stimulation of fibroblasts – A novel approach to mitigate the advanced degenerative process in skin aging Weise J, Vogelsang A, Sperling G, Welge V, Nölter A, Mielke H, Knott A, Harbig S, Stuhr A, Dunckel J, Warnke K, Geloven van A 11. EADV 2021 Multifaceted novel approach to increase skin’s own epidermal and dermal hyaluron content Bussmann T, Warnke K, Krüger A, Möller N, Harbig S, Stuhr A, Dunckel J, Geloven van A, Weise J | Beiersdorf AG, Hamburg, Germany 12. Photochemistry and Photobiology, 2005, 81: 581–587 Novel Aspects of Intrinsic and Extrinsic Aging of Human Skin: Beneficial Effects of Soy Extract Kirstin M. Su¨del et al 13. Combination Therapy in Midfacial Rejuvenation Humphrey et al. Dermatologic Surgery 42:p S83-S88, May 2016. *AMWC 2023 Tapan Patel |
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