Unveiling the power of topical growth factors

Dr Dev Patel considers revolutionising skin health and aesthetic practices

DR DEV PATEL

Dr Dev Patel is aglobally reputed aesthetic physician, speaker and trainer and winner of multiple industry awards. His skin clinic Perfect Skin Solutions has also won over 10 awards including Best Clinic Southeast England 2024 (Aesthetic Medicine Awards). He is also founder of skincare brand, CellDerma which focuses on growth factor technology. CellDerma has already won several awards including ‘Most Sustainable Company’ (CCR 2023), ‘Best Multi-tasking Serum’ (Marie Claire Skincare Awards 2024 -Youth Restore), ‘Most Innovative Green Ingredient’ (the Global Green Beauty Awards 2024 -GF5 Next Generation) and ‘Best New Dermatological Treatment/Product 2024’ (Pure Beauty Awards –GF5 Next Generation).

Topical growth factors have emerged as transformative tools in dermatology, offering unparalleled potential for skin health and rejuvenation. Their role spans wound healing, regenerative skincare, and integration into pre-and post-procedural protocols, making them a cornerstone of modern aesthetic practices. This article explores their mechanisms of action, benefits, and applications, while also addressing how these growth factors are manufactured for cosmetic use and the legal frameworks governing their use.

UNDERSTANDING THE SCIENCE: KEY ROLE IN WOUND HEALING

Wound healing is a dynamic process driven by a complex interplay of cellular and molecular events. At the core of this process are growth factors—bioactive molecules that regulate essential aspects of tissue repair.1 Epidermal growth factor (EGF), insulin-like growth factor-1(IGF-1), and fibroblast growth factors (bFGF and aFGF) play critical roles in orchestrating wound healing, while vascular endothelial growth factor (VEGF) supports angiogenesis.2 These are just a select few of many different growth factors that play a role in maintaining skin health.

EGF stimulates keratinocyte and fibroblast proliferation, promoting epidermal renewal and dermal regeneration.3 IGF-1enhances cellular growth and survival, supporting collagen synthesis and tissue strength.4 bFGF and aFGF accelerate fibroblast proliferation and extracellular matrix production, contributing to faster wound closure.5 VEGF stimulates the formation of new blood vessels, ensuring efficient delivery of oxygen and nutrients to the regenerating skin.6 Together, these growth factors coordinate the sequential phases of wound healing, ensuring efficient tissue repair and restoration of skin integrity.7

REGENERATIVE BENEFITS: FROM WOUND HEALING TO ANTI-AGEING STRATEGIES

Beyond wound healing, topical growth factors have profound applications in anti-ageing skincare. By stimulating collagen synthesis, elastin production, and epidermal turnover, they improve skin texture, firmness, and radiance i.e., all key parameters of skin health.8 Their antioxidant properties neutralise free radicals and mitigate oxidative stress, counteracting photoageing and enhancing skin resilience.9,10

Topical growth factors serve as powerful tools for preventing premature ageing and preserving youthful skin by addressing cellular repair mechanisms and environmental damage.11

MECHANISMS OF ACTION

Growth factors, being polypeptides, are relatively large molecules with molecular weights typically ranging between 5,000 and 50,000 daltons.12 For topical applications, the general rule is that molecules must be less than 500 daltons to penetrate the skin barrier effectively.13 There are numerous published studies demonstrating the effects of topical growth factors. So, how do they exert their effects when applied topically?

OVERCOMING THE SIZE BARRIER

Although growth factors are too large to penetrate the skin’s intact stratum corneum directly, they act via indirect mechanisms. When applied topically, they interact with receptors on epidermal cells or within micro-abrasions caused by treatments such as microneedling, laser resurfacing, or chemical peels, which temporarily compromise the skin barrier.14 This enhanced permeability allows growth factors to reach deeper layers, where they stimulate enhanced repair and regeneration.15 In fact, most patients seen in clinic will have a degree of compromise to their skin barrier which aids penetration of the growth factors.

Fig 1: 24-day result using only a home topical growth factor serum, twice daily.

THE DOUBLE PARACRINE EFFECT

A particularly important mechanism is the double paracrine effect (especially when considering use in healthy intact skin), where topically applied growth factors stimulate epidermal keratinocytes to secrete secondary growth factors, such as VEGF, IGF-1, and EGF.16 These secondary growth factors act in a paracrine manner, signalling nearby fibroblasts in the dermis to initiate collagen production, angiogenesis, and extracellular matrix remodelling.17 This cascade amplifies the effect of the initial growth factor application, ensuring that even limited penetration can result in substantial biological activity.18

KEY INTRACELLULAR PATHWAYS

1. Ras/MAPK pathway: Growth factor receptors recruit adaptor proteins like Grb2, leading to activation of the Ras/MAPK cascade. This pathway promotes cellular proliferation and differentiation, critical for skin rejuvenation.19

2. PI3K/Akt pathway: Activation of PI3K generates PIP3, which activates Akt, enhancing cell survival and protein synthesis. This pathway is integral to skin barrier repair (20) .

3. JAK/STAT pathway: Ligand binding activates STAT proteins, which translocate to the nucleus to regulate genes involved in proliferation and immune responses.21

HOW GROWTH FACTORS ARE MADE FOR THE COSMETIC INDUSTRY

The growth factors used in cosmetic products are manufactured through three primary methods:

1. Human-derived growth factors: Historically, some growth factors were derived from human cells or tissues. This process involves culturing fibroblasts or keratinocytes and harvesting the secreted growth factors. However, current EU and UK cosmetic regulations prohibit the use of human-derived cells or tissues in cosmetic products, as outlined in Regulation (EC) No 1223/2009, Annex II.22 Despite this, some companies illegally market products containing human-derived growth factors, breaking these laws.

2. Animal-derived growth factors: Some growth factors are extracted from animal tissues, such as bovine or porcine sources. While still used in some regions, these sources raise ethical concerns and carry risks of contamination, leading to a decline in their use in favour of synthetic alternatives.23

3. Synthetic growth factors (Biofermentation): Most modern growth factors are produced synthetically through biofermentation. In this method, genetically engineered microorganisms such as bacteria or yeast are used to produce growth factors identical to their natural counterparts. These growth factors are often denoted by the prefix “sh-”(synthetic human) in the INCI (International Nomenclature of Cosmetic Ingredients) list. 24

Fig 2: 2nd degree burns - seven days of a topical growth factor serum, twice daily.

Fig 3: 48 hours of topical growth factors post-laser resurfacing with coring.

Fig 3: 48 hours of topical growth factors post-laser resurfacing with coring.

APPLICATIONS IN PREAND POST-PROCEDURAL SKINCARE

Topical growth factors are invaluable in pre- and post-procedural skincare regimens. Pre-treatment with growth factors primes the skin, enhances resilience, and accelerates wound healing by promoting collagen synthesis and reducing postoperative complications.25

Post-procedural application mitigates inflammatory responses, reduces downtime, and promotes angiogenesis and tissue repair. This ensures optimal outcomes, particularly in procedures such 26, 27 as laser resurfacing, micro-needling, and chemical peels.

ENHANCED COLLAGEN PRODUCTION THROUGH OPTIMISED HEALING

1. Growth factors promote effective healing: Topical growth factors enhance healing by accelerating cellular repair and regeneration. Rather than reducing collagen production, they enable more efficient and higher-quality collagen synthesis. Key growth factors such as IGF-1, EGF, and bFGF stimulate fibroblast activity and promote collagen production, which is vital for skin 28, 29 repair and rejuvenation.

2. Reduced risk of excessive inflammation: Prolonged inflammation can lead to excessive collagen deposition, increasing the risk of fibrosis or scarring. By modulating and controlling the inflammatory response, growth factors create a balanced healing environment, leading to a more uniform and desirable collagen matrix.30

3. Patient comfort and satisfaction: Faster resolution of inflammation reduces downtime, discomfort, and risks such as hyperpigmentation. This enhances patient satisfaction and supports optimal recovery outcomes, indirectly contributing to superior collagen formation.31

CONCLUSION

Topical growth factors represent a pivotal advancement in dermatology, offering multifaceted benefits for skin health and aesthetic outcomes. Their ability to promote wound healing, enhance anti-ageing regimens, and optimise procedural recovery underscores their transformative potential.

Moreover, incorporating growth factors into clinical practice fosters greater trust from patients. By reducing risks, enhancing safety, and improving procedural outcomes, we provide a more positive and satisfying experience. For some, growth factors as a stand-alone treatment offer a cost-effective, simple solution for improving skin health without the need for invasive procedures. This strengthens the therapeutic relationship and reinforces patient confidence in modern aesthetic care.

GLOSSARY OF TERMS

1. EGF (epidermal growth factor) A growth factor that stimulates cell growth, proliferation, and differentiation by binding to its receptor (EGFR). It is critical for skin regeneration and repair.

2. IGF-1(insulin-like growth factor-1) A hormone-like growth factor that promotes cell growth, survival, and collagen production, contributing to tissue repair and skin health.

3. bFGF (basic fibroblast growth factor) A growth factor that supports fibroblast proliferation, extracellular matrix production, and angiogenesis, essential for wound healing and tissue repair.

4. aFGF (acidic fibroblast growth factor) A growth factor involved in cell proliferation, differentiation, and angiogenesis, with applications in tissue regeneration and skin repair.

5. VEGF (vascular endothelial growth factor) A signalling protein that promotes the formation of new blood vessels (angiogenesis), ensuring adequate oxygen and nutrient supply during skin regeneration.

6. Ras/MAPK pathway (mitogen-activated protein kinase pathway) A key intracellular signalling pathway that regulates cell growth, proliferation, and differentiation. It is activated by growth factor receptors like EGFR.

7. PI3K/Akt pathway (phosphoinositide 3-kinase/protein kinase B pathway) A signalling pathway involved in promoting cell survival, metabolism, and growth. It is essential for skin barrier repair and anti-apoptotic processes.

8. JAK/STAT pathway (janus kinase/signal transducer and activator of transcription pathway) A pathway activated by cytokines and growth factors, regulating immune responses, cell proliferation, and survival.

9. Stratum corneum The outermost layer of the epidermis, composed of dead skin cells and lipids, serving as the primary barrier to external substances.

10. Paracrine effect A form of cell signalling where cells release molecules that affect nearby cells, such as growth factors acting on adjacent skin cells.

11. Double paracrine effect A mechanism where topically applied growth factors stimulate keratinocytes to release secondary growth factors, which then signal fibroblasts to initiate repair processes.

12. Extracellular matrix (ECM) A network of proteins and carbohydrates, including collagen and elastin, that provides structural and biochemical support to cells.

13. INCI (international nomenclature of cosmetic ingredients) The standardised naming system for ingredients used in cosmetics and personal care products.

14. Biofermentation A process where genetically engineered microorganisms (e.g., bacteria or yeast) produce synthetic growth factors identical to natural human growth factors. 15. Dalton (Da) A unit of molecular mass, where 1 Dalton equals the mass of a single hydrogen atom. Molecules under 500 Daltons typically penetrate the skin.

16. Regulation (EC) No 1223/2009 A European law governing the safety and composition of cosmetic products. It prohibits the use of human-derived cells or tissues in cosmetics.