In a 2022 cosmetic science paper, purified freshwater sponge spicules loaded with a model flavonoid showed very high dermal absorption in ex vivo porcine (pig) skin of 73.4% of the dose in the dermis, while systemic/transdermal passage remained low, indicating that they can act as an effective local dermal delivery system, similar in concept to very superficial microneedling. However, the solid human clinical data are limited to small studies, mostly formula‑specific or manufacturer‑linked. 

One small Korean trial reportedly found better wrinkle/dermal density outcomes when growth factors were combined with spicules versus growth factors alone, but methodology and controls are not robust enough to be definitive. 

The “gimmick” part of spicules comes from mainly from marketing claims which come on top; of dramatic collagen induction, scar removal, or facelift‑like tightening, which are not backed by large, independent, long‑term human trials. Available data suggest modest improvements in texture and radiance at best, mainly by boosting penetration of real actives or mechnical exfoliation by the spicules themselves. When the formula itself is weak (without robust actives) spicules will not compensate. They should be seen as a delivery aid rather than a miracle ingredient.
​
Spicules are cosmetic-grade in EU/Korea (INCI: "Spongilla lacustris Spicule") but lack FDA monograph approval as drugs, limiting claims.​

USER EXPERIENCE

Spicule‑based peels and serums have been used in aesthetic practice for at least one to two decades, with traditional sponge‑powder applications going back much further, and modern K‑beauty “bio‑microneedling” formats expanding rapidly over the past 10–15 years to an estimated nine‑figure USD market, suggesting many millions of units sold worldwide.

Most reported reactions are transient stinging, erythema, tightness, and short‑lived dryness, however the intensity of discomfort depends strongly on spicule length and density: longer and more densely packed spicules create more microchannels and a sharper, more aggressive feel, whereas shorter or lower‑density systems are better tolerated. Subjectively, many users describe the sensation as similar to handling fiberglass or prickly pear spines; sharp, prickly, and aggravating rather than a mild “tingle” with this perception increasing as spicule size and concentration rise. Patting rather than rubbing tends to reduce discomfort while still providing a penetration benefit, so application technique is important for tolerability. Given the current lack of robust long‑term human safety data, spicule products are generally not ideal for very sensitive, rosacea‑prone, or barrier‑impaired skin, and high‑frequency use in these groups should be approached with caution.

SPICULE LENGHT
Most commonly spicules measure 100–300 μm in length, determining their skin penetration depth:

▌~100 μm: Superficial penetration, targeting the stratum corneum for very gentle exfoliation and enhanced absorption, suitable for regular at-home use
▌~300 μm: Deeper but still epidermal penetration, however still less deep compared to microneedling

Therefore, when you see 100 or 300 related to spicules, it’s a reference to their physical size and penetration depth, which determines their strength and function in skincare routines. This shallow range (100–300 μm) creates microchannels to enhance active absorption without reaching the dermis or causing significant trauma/downtime. Some brands like Mediheal and ClearDea use a very short spicules, which are more gentle, however also less effective as active penetration enhancers.

Classic microneedling needles penetrate from about 0.25 mm (250 μm) to 2.5 mm (2500 μm), much deeper than spicules. 

TYPES OF MICRONEEDLE TECHNOLOGIES – COMPARISON FROM MANUFACTURER

SPICULE CONCENTRATION CONFUSION

VT Reedle Shot, comes in various spicule concentrations (e.g., 50, 100, 300, 700), where higher numbers mean stronger micro-needling/exfoliation effects due to higher spicule density, not necessarily larger spicule size. Users report that higher concentrations like 300 or 700 have stronger exfoliating and penetrating sensations, while lower concentrations like 50 or 100 are milder. These concentration differences affect the intensity of the delivery effect and potential skin irritation. Higher concentrations create more microchannels but may increase tingling or prickling sensations and require less frequent use. Lower concentrations are gentler and can be used more regularly and are more suitable for sensitive or irritable skin.

VT describes its Cica Reedle™ spicules as “around fourteen times thinner than pores” and “smaller than pores,” without disclosing an exact micrometer size; typical facial pores are on the order of 200–300 µm in diameter, so this implies a very fine needle‑like structure. For Reedle Shot 300, VT and retailers report approximately 237,500 Cica Reedles per application, which, together with Cica Reedle’s small diameter, helps explain the pronounced “liquid microneedling” sensation and improved absorption, texture, pore visibility, and acne‑related roughness noted in marketing and user feedback. Classic Reedle Shot formulas pair Cica Reedle™ with Centella asiatica, multi‑weight hyaluronic acid, niacinamide, adenosine, propolis, and amino acids (CICA‑HYALON™ complex) for soothing, barrier support, and slow‑aging benefits. The Reti‑A Reedle Shot variants add a vitamin A complex (retinol and retinoid ester) plus bakuchiol on top of the Cica Reedle™ system, using the spicules to enhance retinoid delivery while the CICA‑HYALON™ base supports tolerability.

SPICULES + EXOSOMES
​
Medicube 1-Day Exosome Shot which is marketed as “microneedling in a bottle,” is available in 7,500 and 2,000 “microneedle” versions. 
▌7,500 spicules = Total hydrolysed sponge spicules delivered in one full application of the 7,500 version (typically 30ml bottle or single-use ampoule equivalent).
▌2,000 spicules = Total in the milder 2,000 version per application.
These are density/concentration markers for marketing and product differentiation. Key difference between both brands mentioned is that VT uses relative concentration (spicules/ml), while Medicube uses absolute count per treatment. Both scale intensity with higher numbers, but Medicube's 7,500 delivers far more spicules total despite similar density effects.

PAINLESS SPICULES
ClearDea is a brand that uses Collanetinal™ spicules of approximately 0.01 mm (11 μm) in length, i.e., very short. Because spicule length largely determines penetration depth, these collagen‑ and retinol‑coated spicules are expected to act predominantly in the very superficial layer(s) of the skin and to be gentler than longer, more prickling spicules. They are likely to be less efficient as active delivery enhancers. ​

SPICULES + CAPSULSES
​
In the SUNGBOON EDITOR gel‑cream, (tiny whitish) spicules are combined with separate capsules containing very low molecular weight (200 Da) collagen‑related ingredients, retinol, niacinamide, hyaluronic acid and panthenol in a gel-base. Spicules are designed to boost the bioavailability of the encapsulated actives by nudging them closer to the viable epidermis and superficial dermis, which may enhance visible results compared with a conventional cream of similar composition. The magnitude of this benefit, however, is tightly linked to spicule size (not disclosed for this product) and density. The formula contains 300.000 shots, which is a marketing way of saying that one jar contains approximately 300,000 individual spicules. The prickly, tingling feel from the spicules is frequently mentioned in reviews; some users enjoy it as a sign that the product is “doing something,” while others find it uncomfortable or briefly stinging. SUNGBOON recommends specifically for dry skin 2 part capsuls and 1 part gel, for oily skin 2 parts gel and 1 part capsule and for combination skin 1 part capsule and 1 part gel ratio.

​The concentration of active ingredients:
▌200 Da collagen: 1,100,000 ppb, which literally means 1,100,000 parts of a substance in 1,000,000,000 parts of the total mixture. In percentage terms, that is 0.11%. 
▌Niacinamide: 20,000,000 ÷ 1,000,000,000 = 0.02, which corresponds to 2%.
▌Retinol: 3000 ppb is 0.0003%. 
Retinol at just 0.0003% (3 ppm) barely penetrates skin: less than 1% gets through without help. Spicules' microchannels boost this 10x or more, making tiny doses far more effective. 

If SUNGBOON´S before‑and‑after photos truly reflect typical results, this product would be worth serious consideration. However, when used consistently and with appropriate skin tolerance, SUNGBOON EDITOR Deep Collagen Retinol can realistically be expected to modestly improve skin smoothness, hydration and fine lines rather than produce dramatic “filler‑like” changes. Some users experience more bouncy or firmer skin and even skin tone.

Similar, however not the same is the VT Reedle Shot 2‑step masks, which are bio‑microneedling sheet masks that combine a spicule “essence” with an occlusive mask to intensify penetration and skin benefits. In step 1, a concentrated ampoule containing natural micro‑spicules (Cica Reedle™ based on silica and Centella) is massaged onto cleansed skin, creating temporary microchannels and a characteristic tingling or prickling sensation while priming the surface.

Step 2 is a serum‑soaked sheet mask placed over this prepped skin for 15–30 minutes; it is typically loaded with humectants and barrier‑supporting actives such as hyaluronic acid, hydrolyzed collagen, peptides, niacinamide, centella, propolis, and amino acids, aiming to hydrate, improve elasticity, refine texture, and calm irritation.  Different versions (e.g., Mild 50, 100, 300) reflect increasing spicule density and intensity: lower numbers are gentler and better suited to sensitive or first‑time users, while higher numbers are positioned for concerns like rough texture, post‑acne marks, dullness, and fine lines, used no more than 1–2 times per week.

​Glutathione Vita Glow Spicule Shot
▌Focuses on radiance and tone uniformity, pairing 2,000 ppm glutathione with vitamin C derivatives in a spicule delivery base.
▌The spicule system provides a “microneedling effect” with tingling/micro‑stimulation while driving antioxidants deeper to enhance glow and transparency.
▌Clinical testing is claimed for improvements in brightness and overall skin tone.

Across these products, Genabelle positions spicules as an at‑home, low‑downtime alternative to procedural microneedling, designed mainly to boost delivery of brightening/antioxidant complexes while also addressing texture and early signs of aging, with suitability claims extending even to drier or more sensitive skin types but still with expected tingling on use.

SPICULES + PEPTIDES
Several brands deliberately pair peptides-molecules that typically show poor passive skin penetration with spicule‑based ‘bio‑microneedling’ systems, leveraging the micro‑channels created by spicules to substantially enhance peptide delivery into deeper epidermal and dermal layers, as proven by spicule‑based peptide delivery studies.

In a 2021 study, sponge spicules from Haliclona sp. (SHS) were incorporated into topical formulations containing insulin (hydrophilic peptide) and cyclosporine A (hydrophobic cyclic peptide). SHS increased insulin transdermal flux from 5.0 ± 2.2 ng/cm²/h (passive) to 457.0 ± 32.3 ng/cm²/h (about 90‑fold) and raised its deposition in deeper skin layers from 0.6% to roughly 55%. This enhancement was both spicule‑dose‑dependent and peptide‑dose‑dependent, supporting a true mechanistic effect of the spicules on peptide penetration.

DR.PEPTI Peptide Spicule Pore Solution Serum contains Hydrolyzed Sponge (3,000 ppm) as the spicule source plus an extensive peptide complex: acetyl hexapeptide‑8, acetyl octapeptide‑3, multiple tetra‑, tri‑, and dipeptides, copper tripeptide‑1, palmitoyl peptides, etc., alongside retinol, exosomes, bakuchiol, glutathione, tranexamic acid and sodium DNA. It is positioned for pore care, elasticity and anti‑aging, using spicules to drive the peptide blend deeper.

TONYMOLY Peptide Spicule Firming Ampoule  is described as an elasticity ampoule with peptide + bakuchiol + collagen‑coated spicules for firming sagging skin and fine lines. Here the spicules are directly linked to both collagen and peptide‑driven firming.

ALTUM™ PEPTIDE / PEPTAXEL™ programs (Skinzzo LAB) is a professional bio‑microneedling system where Raphitox™ spicules are bound to tripeptides, then released in the epidermis via glutathione; positioned as “5th‑generation spicules” specifically designed to deliver peptides for collagen stimulation. Altum™ Peptide (Raphitox‑bound tripeptides) compared a peptide‑only cream vs. spicules + peptides vs. Altum’s peptide‑spicule complex; the “spicules + peptides” combo outperforms peptides alone in improving skin density and wrinkles, supporting the delivery advantage.
​
Spicule Serum concept formulas (CTK): OEM “Spicule Serum” bases combine spicules + a 10‑peptide complex + collagen complex + panthenol, marketed for elasticity, lifting and hydration.

SOME NOTEWORTHY LESSER KNOWN BRANDS WHICH INCORPORATED SPICULE DELIVERY SYSTEMS:

▌Pepticule pairs spicules with acetyl hexapeptide-8 for “botulinumtoxin-like”anti-wrinkle effects via deep delivery. 
▌Pestlo Spicule Reborn Peeling Mask combines spicules with green tea and mugwort for brightening and even tone.
▌9wishes Pine Perfect Ampule Serum uses spicules alongside pine, licorice, and green tea extracts to target acne and renewal.
▌Isomers Diamond Peptide Spicule Body Cream blends spicules, diamond powder, alp rose stem cells, caffeine, and peptides to address body stretch marks, sagging, and texture.

REPRESENTATIVE SPICULE SKINCARE PRODUCTS OVERVIEW

VERDICT

“Do spicules work?”: yes, as a micro‑delivery technology, there is evidence that spicules enhance dermal delivery and can improve clinical skin parameters when paired with effective actives and when spicule length and density are sufficient. They likely also provide to some degree of mechanical exfoliation on application. Studies indicate that spicules can also help larger molecules, such as peptides and other macromolecules that usually penetrate the skin poorly in standard skincare, reach deeper skin layers more effectively when they are formulated together. 

“Are spicules a miracle?”: no; current scientific evidence is sparse, short‑term, and often industry‑linked, so they should be viewed as an adjunct delivery tool with potential, not a stand‑alone, clinically proven game‑changer. 

Worth a try”?: Alternative, more controlled options exist (e.g., microneedling, microstamping) that can provide similar or superior penetration or textural benefits without persistent mineral needles in the skin. Products containing “longer” spicules are potentially worth trying only for people with very resilient skin who are highly motivated and comfortable with discomfort and some uncertainty. For sensitive skin or risk-averse users, maybe the very short coated spicules are an option.

​Personally, I would recommend spicule‑based products only with caution at this stage, and limit use to a single product at a time whose active ingredients clearly match your main skin need r concern. The technology is exciting and promising, however more robust human safety data are needed before fully endorsing it, even though there is roughly 10–15 years of user experience without serious adverse effects reported. Daily use is not advisable. Spicules persist in the skin up to 72 hours, with no data on long-term accumulation, which could theoretically trigger granuloma formation from silica persistence as biogenic spicules may trigger foreign body reactions in long-term use, cause subclinical inflammation, or barrier impairment, changes that ultimately accelerate skin ageing.

Take care!
Anne-Marie

REFERENCES

▌Kim TG, Lee Y, Kim MS, Lim J. A novel dermal delivery system using natural spicules for cosmetics and therapeutics. J Cosmet Dermatol. 2022 Oct;21(10):4754-4764. doi: 10.1111/jocd.14771. Epub 2022 Feb 1. PMID: 35034416. 
▌Ha JM, Lim CA, Han K, Ha JC, Lee HE, Lee Y, Seo YJ, Kim CD, Lee JH, Im M. The Effect of Micro-Spicule Containing Epidermal Growth Factor on Periocular Wrinkles. Ann Dermatol. 2017 Apr;29(2):187-193. doi: 10.5021/ad.2017.29.2.187. Epub 2017 Mar 24. Erratum in: Ann Dermatol. 2017 Dec;29(6):828. PMID: 28392646; PMCID: PMC5383744.
▌Kim, H., Lee, H. J., Lee, H., Kim, S. N., & Park, E. S. (2021). Enhanced skin delivery of therapeutic peptides using sponge spicules in combination with flexible liposomes. Biomolecules & Therapeutics, 29(6), 707–716. https://doi.org/10.4062/biomolther.2021.166
▌Lee, N.E.; Kim, J.E.; Bang, C.Y.; Bang, O.Y. Nano-Encapsulated Spicule System Enhances Delivery of Wharton’s Jelly MSC Secretome and Promotes Skin Rejuvenation: Preclinical and Clinical Evaluation. Int. J. Mol. Sci. 2025, 26, 10024. https://doi.org/10.3390/ijms262010024
▌Udompataikul, M., Wongniraspai, M., Showpittapornchai, U., & Jariyapongsakul, A. (Year). The study on effects and safety of Spongilla lacustris in 3% hydrogen peroxide solution on rat skin. Journal Name, Volume(Issue), pages.
▌The Ultimate Guide To Spicules SkinCare: A Revolutionary Approach To Skincare https://spongespicule.com/the-ultimate-guide-to-spicule-skincare/

This post is based on my own, independently purchased products and personal research. It is intended for educational and informational purposes only, does not replace individual medical advice, and is not intended to diagnose, treat, cure, or prevent any disease. All opinions are my own; this content is not sponsored, and no affiliate links are used.

Skincare peptide innovation moves at lightning speed. New peptides, advanced delivery systems, and proprietary blends launch almost monthly, making it tough to separate breakthroughs from hype. Recently, I heard a TikTok claim that after age 40, we retain only 35% of our fibroblasts, dropping to 90% fewer receptors by the age of 80+, rendering peptides ineffective for mature skin. Let's unpack this scientifically as this is a bit oversimplified clickbait, even though it’s accurate that peptide efficacy varies.

BUSTING THE AGE MYTH [1-4]
Fibroblasts naturally decline as we age. Menopause speeds this up through estrogen loss (collagen drops 2.1%/year afterward). Cells shrink, divide less often, produce less collagen and other proteins, and release more wrinkle-causing enzymes like MMPs (Matrix metalloproteinases are enzymes that break down extracellular matrix proteins like collagen and elastin). Receptor responsiveness decreases (TGF-β signaling down 30-50% in 60+ skin).
 
Aging and menopause affect skin through:
▌ Senescence markers (p16/p21) increase, thus more “zombie cells”
▌ Reduced receptor signaling (TGF-β, estrogen receptors less responsive)
▌ Stiffer extracellular matrix
▌ Lower ceramides and hyaluronic acid from fibroblasts (thinner barrier, drier or dehydrated skin)
​
However, it's not a complete shutdown. Fibroblasts from 70-90-year-olds still respond to peptides in lab studies. Menopause mainly worsens skin barrier delivery.
 
5 REAL REASONS PEPTIDES VARY IN EFFICACY
Here's why the same formula or peptide might work for your bestie's skin but leave yours unchanged. 

​1. Receptor & signaling differences
Your fibroblasts' receptor density (TGF-β, integrins) varies by genetics, UV history, and inflammation. Photoaged skin shows 30-50% weaker responses. Senescent (zombie) cells prioritize survival over collagen production [1].

2. Skin barrier roadblocks
Compromised barriers (atopic, over-exfoliated, aged) reduce peptide delivery. Stratum corneum dysfunction limits penetration, especially in sensitive/aged skin [5].

3. Protease degradation
Skin enzymes chew up peptides before they reach targets. Inflamed or mature skin has higher protease activity, slashing bioavailability of peptides [6]. Read more about the proteasome.

4. Dose & vehicle mismatch
Lab studies use precise 0.005-3% concentrations with optimal pH/stability. Real products may underdose peptides or use unstable watery bases, reducing in vivo results. Efficacy depends on concentration, delivery system, and formulation stability [5].
​
5. Your damage profile
Your damage profile matters. Heavily UV‑exposed or smoker’s skin tends to benefit more from senotherapeutic peptides, which have been shown to reduce p16/p21 and overall senescence burden in aged or photo‑damaged skin models. Skin with milder, early aging changes often responds very well to matrikine peptides, which significantly increase collagen and other extracellular matrix components in vitro and improve wrinkles in clinical studies. A single peptide strategy rarely fits every skin type or damage pattern [1].

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 theoretically makes sense, as the producing cell called the dermal fibroblast is still very healthy and active, thus collagen stimulating treatments and care products give a "high return on investment". However, there is no direct scientific evidence that collagen stimulation is more effective in your twenties than in your sixties. 

Starting collagen stimulation <50 might 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. 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 is the highest achievable level. There is no need for "banking" collagen.

Starting collagen stimulation treatments <50 may help prevent further collagen loss and probably require less invasive and number of treatments. However, the best strategy at every age is to prevent collagen loss as much as possible with good lifestyle habits, diet, stress reduction, (topical) anti-oxidants and sunscreen, hence manage inflam-aging, photo-aging and chrono-aging. 
 
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. 

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].

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. 

1. It begins with the synthesis of procollagen in fibroblasts, where genes are transcribed into mRNA, which is then translated into polypeptide chains in the rough endoplasmic reticulum RER. 
2. These chains undergo hydroxylation of proline and lysine, a process dependent on vitamin C, and glycosylation [16]. 
3. The chains form a triple helix structure called procollagen, which is transported to the Golgi apparatus for further modifications before being secreted outside the cell.
4. Once outside, enzymes cleave procollagen to form tropocollagen, which assembles into collagen fibrils through covalent cross-linking facilitated by lysyl oxidase. 
5. These fibrils aggregate to form collagen fibers, providing structural integrity to tissues like skin, bones, and tendons [16]. 

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
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, with daily use of a broadspectrum sunscreen and a tailored skincare routine which supports skin barrier health, prevents inflammation / irritation, and incorporation of collagen stimulating ingredients for example vitamin C, peptides, growth factors and supplementation with collagen powder, especially for vegetarians, when your regular diet 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 quality and longevity.


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.
Age-related changes in dermal collagen physical properties in ... https://pmc.ncbi.nlm.nih.gov/articles/PMC10707495/
[11]Trujillo, J., & Galligan, J. J. (2024). An overview on glycation: molecular mechanisms, impact on biomolecules, and related diseases. Glycoconjugate Journal. https://doi.org/10.1007/s10719-024-10254-y
[12]Sadowska-Bartosz, I., & Bartosz, G. (2022). Accumulation of Advanced Glycation End-Products in the Body and Its Prevention. Nutrients, 14(19), 4072. https://doi.org/10.3390/nu14194072
[13] Sadowska-Bartosz, I., & Bartosz, G. (2015). Prevention of protein glycation by natural compounds. Molecules, 20(2), 3309-3334.
[14] Uribarri, J., et al. (2015). Dietary advanced glycation end products and their role in health and disease. Advances in Nutrition, 6(4), 461-473.
[15] Guilbaud, A., et al. (2016). How can diet affect the accumulation of advanced glycation end-products in the human body? Foods, 5(4), 84.
[16] Wu, M., Cronin, K., & Crane, J. (2023). 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).

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 function as hormones, neurotransmitters and immune messengers, and they also appear as fragments of structural proteins such as collagen, elastin, and keratin, which are essential for skin structure and function. This dual role - structural and signalling - is what makes peptides so attractive as cosmeceutical ingredients. [2] 

BODY´S OWN PEPTIDES: BRAIN, BODY AND SKIN
The exact number of endogenous peptides in the brain, body, and skin is unknown, but we know they form dense communication networks across multiple systems. In the brain, neuropeptides such as oxytocin, vasopressin, endorphins, and enkephalins are involved in mood regulation, social behaviour, and pain modulation. In the rest of the body, hormone peptides like insulin, glucagon, and growth hormone regulate glucose metabolism, energy balance, growth, and tissue repair, and are even explored off‑label in some regenerative medicine settings.

In the skin, collagen peptides provide structural support and elasticity, while elastin peptides contribute to elasticity and resilience; together with cytokine‑like peptides and antimicrobial peptides (AMPs), they help coordinate barrier function, immune defence, pigmentation, and wound healing. This endogenous peptide “language” is what cosmetic peptide design tries to mimic or amplify.
 
INCREASING POPULARITY IN SKINCARE
The global peptide‑based cosmetics market has grown steadily and is projected to continue this trend, driven by demand for more targeted, “active” skincare and by advances in peptide synthesis and delivery. Asia‑Pacific is expected to show especially strong growth, while North America and Europe currently lead in innovation and early adoption. From an R&D point of view, peptides are attractive because they combine high specificity and relatively low immunogenicity with the ability to be fine‑tuned at the sequence level.

POTENTIAL 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]

MECHANISMS OF ACTION
Most cosmetic peptides are grouped by their function in the skin rather than their origin. The main classes are signal (messenger/matrikine) peptides, carrier peptides, neurotransmitter‑inhibiting/neuromodulating peptides, enzyme‑inhibitory and antimicrobial/antioxidant peptides, plus several emerging subgroups.

1. SIGNAL PEPTIDES
Signal peptides (including matrikines) send biochemical “instructions” to cells, particularly fibroblasts, to make more extracellular matrix (ECM) components or remodel damaged tissue. [3] Many are fragments of collagen or other matrix proteins that naturally appear during injury or remodelling and tell the skin it is time to repair. 

Palmitoyl pentapeptide‑4 (Pal‑KTTKS, Matrixyl)  [4]
▌Mechanism: Mimics a collagen fragment and stimulates collagen I, III, and IV synthesis.
▌Penetration: Palmitoylation increases lipophilicity and improves skin penetration.
▌Efficacy: Increases ECM components in vitro and improves wrinkles clinically when used at effective concentrations.

Palmitoyl tripeptide‑1 (Pal‑GHK) [5]
▌Mechanism: Collagen‑derived matrikine that activates TGF‑β signalling and promotes ECM production (collagen, elastin, GAGs).
▌Penetration: Enhanced by the palmitoyl group.
▌Efficacy: Multifunctional, targeting several aspects of skin ageing, though long‑term independent data are still relatively limited.
​
Palmitoyl tetrapeptide‑7
▌Mechanism: Reduces IL‑6 to help suppress inflammation and prevent collagen breakdown, while promoting laminin IV/V and collagen VII synthesis at the dermal–epidermal junction.
▌Penetration: Good, due to palmitoylation and moderate size.
▌Efficacy: In vitro IL‑6 reduction and clinical data showing less redness and improved firmness, especially in combination formulas such as Matrixyl 3000.

Matrixyl 3000 (Pal‑GHK + Palmitoyl tetrapeptide‑7)
▌Mechanism: A patented matrikine complex that signals fibroblasts to boost collagen I and IV, fibronectin, and GAGs while suppressing IL‑6‑driven inflammation.
▌Efficacy: In vitro collagen increases up to several‑fold and clinical trials showing meaningful wrinkle reduction after a few months.

Palmitoyl tripeptide‑5
▌Mechanism: Mimics a thrombospondin‑1 sequence to activate TGF‑β, stimulating collagen I/III synthesis and inhibiting MMP‑1 and MMP‑3, thereby combining ECM build‑up with protection against enzymatic degradation.
▌Efficacy: In vitro data show strong ECM increases; clinical studies report wrinkle reduction after around 12 weeks.

Palmitoyl tripeptide‑38
▌Mechanism: A next‑generation matrikine that stimulates multiple ECM components at the dermal–epidermal junction, including collagens I, III, IV, fibronectin, hyaluronic acid, and laminin‑5.
▌Efficacy: In vitro increases in these components after 7 days and clinical improvements in wrinkles and elasticity after around 8 weeks.

Hexapeptide‑9
▌Mechanism: A hybrid neuro/signal peptide that mimics collagen fragments to stimulate collagen I, III, IV, laminin‑5 and integrins, improving dermal–epidermal junction cohesion and firmness.
▌Efficacy: Clinical studies report wrinkle reduction and elasticity improvements after about 4–8 weeks of use.

GEKG (Gly‑Glu‑Lys‑Gly) [7] 
▌Mechanism: A tetrapeptide derived from ECM proteins that significantly induces collagen production at both protein and mRNA level in human dermal fibroblasts.
▌Efficacy: Shown to boost collagen, hyaluronic acid, and fibronectin and up‑regulate genes responsible for ECM formation up to ~2.5‑fold.

RGD‑GHK and sOtx2‑GHK [5]
▌Mechanism: GHK derivatives with additional binding motifs (e.g. RGD) that enhance cell‑surface interaction and receptor targeting.
▌Efficacy: Show superior anti‑oxidative and anti‑apoptotic effects compared with GHK alone, with promising activity for anti‑ageing and wound healing.

Palmitoyl hexapeptide‑12
▌Mechanism: Supports dermal matrix regeneration and firmness, and is associated with activation of longevity‑related genes (Klotho, SIRT1) and autophagy pathways while promoting collagen synthesis and ECM remodelling.
▌Evidence: Preclinical longevity data in fibroblast and ageing models are still relatively early but conceptually interesting.

Oligopeptide‑20
▌Mechanism: Growth‑factor‑mimicking and enzyme‑modulating peptide used especially in K‑beauty to support epidermal renewal and brightening.
 
​2. CARRIER PEPTIDES
Carrier peptides bind and deliver trace metals that are essential cofactors for enzymatic reactions involved in antioxidant defence and tissue repair. [3]​

GHK‑Cu (Copper tripeptide‑1) [3][4] 
▌Mechanism: Chelates copper and transports it into cells, where it supports collagen and elastin synthesis, angiogenesis, antioxidant enzyme activity, and wound healing.
▌Efficacy: Well‑studied in wound healing and increasingly used in anti‑ageing skincare; it also has antioxidant properties, although at high or imbalanced levels copper can be pro‑oxidative.
 
3. NEUROTRANSMITTER-INHIBITING PEPTIDES
These peptides act on neuromuscular or sensory pathways to soften expression lines or reduce stinging, burning, and itch. [3]

Acetyl hexapeptide‑3/8 (Argireline) [4]
▌Mechanism: Inhibits SNARE complex formation at the neuromuscular junction, reducing acetylcholine release and thereby decreasing muscle contraction that contributes to expression lines.
▌Efficacy: Offers modest softening of dynamic wrinkles as a non‑invasive topical option; its effects are temporary and depend on concentration and compliance. Is often compared to botulinum toxin (mode of action), however it´s efficacy isn´t comparable.

Neurosensine (acetyl dipeptide‑1 cetyl ester)
A dipeptide of arginine and tyrosine linked to a cetyl ester.
▌Mechanism: Stimulates the production of endorphins and enkephalins in keratinocytes, which act as natural pain relievers, and modulates TRP‑mediated neurogenic inflammation.
▌Efficacy: Helps create a more protective micro‑environment around nerve endings, making skin less prone to redness, dryness, irritation, and itch, especially in sensitive or reactive skin.

4. ENZYME INHIBITORY, ANTIMICROBIAL AND ANTI-OXIDANT PEPTIDES
Several peptides primarily exert their effects by blocking enzymes, defending against microbes, or modulating oxidative stress.

▌Oligopeptide‑20 (as above) is often positioned as a growth‑factor‑mimic and enzyme‑inhibiting peptide that supports epidermal renewal and brightening.
▌Antimicrobial peptides (AMPs) are part of the innate immune system and help defend against bacteria, fungi, and viruses; synthetic or biomimetic versions are being investigated for acne‑prone and microbiome‑disrupted skin.
▌Antifungal peptides (AFPs) are specialised AMPs that target fungal pathogens and may be relevant for scalp or body care in predisposed individuals.
▌Antioxidant peptides include sequences that directly scavenge reactive oxygen species or up‑regulate endogenous antioxidant systems; copper peptides are a key example, combining carrier and antioxidant functions.

5. SPECIALIZED AND EMERGING PEPTIDE TYPES
Several specialised peptide families that sit at the interface of skincare, regenerative medicine, and longevity.

▌Cell‑penetrating peptides (CPPs) are short, usually cationic peptides rich in arginine and lysine [13] that can cross cell membranes [14] and carry cargo such as proteins, peptides, and nucleic acids into cells. [12][15] This makes them highly attractive as delivery tools for future topical and transdermal actives. [11][12] 
 ▌OS‑01 / Peptide‑14 (senotherapeutic peptide) is designed to target cellular senescence, one of the key hallmarks of skin ageing. In 2D cultures, 3D skin equivalents from older donors, and ex vivo human skin, OS‑01 reduces markers of senescence (including p16 and SASP‑related genes), increases epidermal thickness and collagen expression, and lowers DNA‑methylation‑based biological age of skin by about 2.6 years on average. These data support classifying OS‑01 as a senotherapeutic - more precisely a senomorphic - peptide that helps prevent cells from progressing to a late, pro‑inflammatory senescent state. [16][17]
▌Epithalon is a tetrapeptide associated with telomerase activation and telomere length maintenance in systemic studies; in work by Khavinson et al., Epithalon treatment increased telomere length in blood cells of older patients, positioning it within longevity research rather than classical topical cosmetics.
▌BPC‑157 is a pentadecapeptide known from experimental work in tendon and gut repair; it enhances growth hormone receptor expression in fibroblasts and supports collagen production, with growing interest in broader tissue regeneration and potential skin benefits. [19] 
▌NAD+ is not a peptide but a central coenzyme for energy production, DNA repair, and cellular resilience whose levels decline with age; NAD+ augmentation is explored as a complementary longevity strategy.  [18]

BARRIER, SENSITIVE SKIN AND TEXTURE-FOCUSED PEPTIDES 
Some peptides are best understood through their barrier and sensory effects.

Palmitoyl tetrapeptide‑10
▌Mechanism: A synthetic tetrapeptide acylated with palmitic acid that increases expression of corneodesmosin and filaggrin in reconstructed human epidermis, improving corneocyte adhesion and terminal differentiation.
▌Efficacy: Associated with improved barrier function and reduced perceived sensitivity; supplier data also suggest increased firmness and a “soft‑polish” effect, though independent clinical data on the isolated peptide are still limited.
Neurosensine 
▌Especially relevant for sensitive or redness‑prone skin due to its effects on keratinocyte‑derived endorphins, enkephalins, and neurogenic inflammation pathways.

COLLAGEN-STIMULATING PEPTIDES AND ORAL COLLAGEN 
Topically, signal peptides such as Pal‑KTTKS [3], Pal‑GHK [3], GEKG and complexes like Matrixyl 3000 modulate fibroblast activity and increase the expression and synthesis of collagen and other extracellular matrix components, which can improve the structural integrity and appearance of the skin. 
[1][2] Orally, specific collagen‑derived peptides from bovine and marine sources are absorbed as small di‑ and tripeptides, reach the skin via the circulation, and have been shown to stimulate dermal fibroblasts and increase expression of collagen and other ECM‑related genes in experimental models. Clinical studies report improvements in skin hydration, elasticity and wrinkle parameters after several weeks of oral collagen peptide supplementation. Bovine collagen peptides are typically rich in types I and III, while marine collagen provides mainly type I and is often reported to have high bioavailability; plant‑based “collagen boosters” do not contain collagen but supply co‑factors such as vitamin C, silica and amino acids that support the body’s own collagen synthesis. In powder form, hydrolysed collagen peptides are easy to mix into foods or beverages and show better absorption than intact gelatin.
   
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. 
 
PEPTIDE FLOODING
“Peptide flooding” is used on social media to describe layering several peptide serums or very high peptide concentrations in one routine, assuming that more products mean more results. In reality, cosmetic peptides act via specific receptors and signalling pathways and have optimal concentration windows; once these targets are engaged, extra layers mostly add formulation load, not extra biology. Penetration and cell‑surface interaction are usually the limiting factors, and these are shaped by peptide sequence, charge, lipid modification (e.g., palmitoylation), and delivery system rather than the sheer number of bottles used. Current evidence supports well‑designed multi‑peptide products that combine complementary mechanisms (e.g., matrikines, which are tiny signal/messenger peptides that tell your skin to repair itself, for extracellular matrix support; senotherapeutic peptides for high‑senescence; anti‑inflammatory or barrier peptides for sensitivity) within a barrier‑supportive vehicle, instead of stacking multiple peptide serums. [21] 
​
CHALLENGES 

One of the challenges with peptides in skincare is their skin permeability. For example, 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] Various methods have been developed to improve peptide penetration into the skin, including chemical modification, use of penetration enhancers, and encapsulation in nanocarriers. [10]  

Peptides are powerful tools, but they’re not “easy” ingredients. How well they work depends on the exact sequence of amino acids, the formula around them, how stable they are, the dose, how they are delivered into the skin, and the person’s own skin biology. Many peptides can break down quickly (for example by oxidation or skin enzymes), so they need smart formulation, protective packaging, and careful manufacturing, which is still challenging for some of the more complex types.

For users, the key questions are: which peptide(s), in what vehicle (formula), at what dose, for which skin concern. When used thoughtfully in this way, peptides can meaningfully contribute to skin regeneration, barrier health, comfort, and visible ageing outcomes. 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.
[21] Badilli U, Inal O. Current Approaches in Cosmeceuticals: Peptides, Biotics and Marine Biopolymers. Polymers (Basel). 2025 Mar 18;17(6):798. doi: 10.3390/polym17060798. PMID: 40292641; PMCID: PMC11946782.