Epidermal growth factor (EGF)

EGF is a single polypeptide of 53 amino acid residues which is involved in the regulation of cell proliferation. EGF is a message telling cells that they have permission to grow. This molecule can stimulates fibroblasts to synthesize increased amount of pro-angiogenesis factors ) VEGF and HGF( and also increase keratinocyte and fibroblast proliferation [1]. EGF (by activating MAPK pathway) can influence the keratinocyte migration machinery that determines the speed of re-epithelialization and keratinocyte contraction [2]. EGF, formulated in skin care product assessed to show the ability of fibroblast cytokine production [1].  Figure 1. Show the effect of barely, human liked EFG serum in the clinical study on 29 women, aged 39-75 with mild to severe wrinkle, fine and course rhytids, photodamage, and pigmentation. The results indicated significant improvement in the appearance of fine lines and rhytids, skin texture, pore size, and various dyschromatic conditions apparent within the first month of use [3].

Fig.1. viable anti-wrinkle effect after 30 day of use topical barely EGF serum

Different clinical studies in various clinical conditions like scar [4], senile purpura and dermatoporosis [5], hyperpigmentation[6], photo damage [7, 8], under-eye wrinkle and bag [9], radiation dermatitis in cancerous patient [10], leprosy [11] and even non-healing wound [12, 13] showed the beneficial use of topical EGF.

Fig.2. Improvement in under-eye bags and wrinkle after 12 weeks of twice daily infraorbital EGF serum application

IGF

Insulin-like growth factor (IGF)-1 is a growth factor that can influence fibroblast functioning, with effects including the inhibition of collagenases and the induction of collagen expression. The graph in below show result of clinical study on 617 subjects, perceived age and skin wrinkling were assessed from facial photographs, and IGF-1 were measured in serum. Skin wrinkling decreased when the ratio of IGF-1 increased [14].

FGF2

The basic FGF (FGF-2) reduces and prevents expression lines and wrinkles through the activation of new skin cells and stimulates the proliferation of cells of mesodermal, ectodermal, and endodermal origin, mainly fibroblasts and keratinocytes. In recent years, topical and injectable growth factors have emerged as an intriguing therapeutic modality that can be harnessed for esthetic and medical purposes. A group of researchers, who also studied FGFs, aimed to evaluate an in vivo method for aged skin rejuvenation through direct injection of intradermal FGF-2. The following rejuvenating effects were observed: improvement of skin smoothness, atrophied skin thickness, and improved viscoelasticity. The changes of viscoelasticity pre- and post-treatment were comparable to an age difference of more than 20 years [15].

Fig2. A 50-year-old female treated on the dorsal surface of the right hand. (a) Pre-treatment. (b) Post-treatment 9 months. (c) Post-treatment 31 months

VEGF:

Vascular endothelial growth factor (VEGF) is a signaling protein that promotes the growth of new blood vessels. VEGF forms part of the mechanism that restores the blood supply to cells and tissues when they are deprived of oxygenated blood due to compromised blood circulation. VEGF, Is the most frequent stem cell (SC) growth factor secretion and play important role in angiogenesis to recover injuries. Topical application of cream contains mixture of growth factors including VEGF, PDGF-A, G-CSF, HGF, IL-6, IL-8, and TGF-beta (1) on 20 subjects for facial rhytides showed significant success between baseline and 3-month scores [16].

Fig.4. clinical result of rough skin texture with periotbital rhytides, VS smoother and significant improvement in the appearance of fine lines.

Extracellular matrix proteins: Collagen, Fibronectin and Elastin

Collagens are the most abundant components of the extracellular matrix and many types of soft tissues. Elastin is another major component of certain soft tissues, such as arterial walls and ligaments. Many other molecules, though lower in quantity, function as essential components of the extracellular matrix in soft tissues. Fibronectin with its muldomain structure plays a role of “master organizer” in matrix assembly as it forms a bridge between cell surface receptors, e.g., integrins, and compounds such collagen, proteoglycans and other focal adhesion molecules. It also plays an essential role in the assembly of fibrillin-1 into a structured network. They all contribute to the structure of the extracellular matrix (ECM) and modulate cellular functions such as adhesion, differentiation, migration, stability of phenotype, and resistance towards apoptosis [17]. Figure.5. in below show the clinical result of topical cream formulated with multiple growth factors, antioxidants, and a collagen-building peptide—ingredients that have been shown to increase collagen levels and provide long-term aesthetic benefits

Fig.5. Visible improvements in periocular wrinkles

Sodium hyaluronate:

Hyaluronic acid (HA) acts as a biologic humectant, thus retaining water in the skin, making HA useful as a topical moisturizing ingredient. HA is a valuable ingredient to improve facial appearance in women with poor skin plumpness, decreased skin hydration, and photoaging. It has been used both topically and orally for appearance improvement. HA is multifunctional, even possessing a role in immune modulation in disease and as a post-procedure treatment in facial resurfacing. Changes occur in HA with aging such that a HA-based moisturizer might improve facial appearance through topical application. Hyaluronic acid has two salt forms: sodium hyaluronate and potassium hyaluronate. As the name suggests, sodium hyaluronate is the sodium salt version. The current formulation contains hydrolyzed 50 kDa HA and 10–1000 kDa sodium hyaluronate. This size of the HA allowed it to penetrate into and through the stratum corneum [18]. These humectant ingredients produced an immediate increase in the water-holding capacity of the skin, as demonstrated in fig.6 by the investigator assessments in clinical study on forty females 30–65 years of age.

Fig.6. A. Percent improvements from baseline immediately after application and at week 2, week 4, and week 6 are shown. B. In vitro study. C. This African-American female demonstrated increased light reflection from the face, especially from the medial cheeks, improving overall skin tone after 6 week

Multi peptides Miracle:

Although the effect of each ingredients explained above, different studies showed the synergic effect of application multiple growth factors like a mixture along with some specific materials like HA, ……. To boost the effect on skin by co-stimulation, especially for person plus forty. Topical application of human sourced of 5 GFs contain IGF1, KGF, EGF, SOD1 and bFGF with HA and combination of stem cell conditioned medium on 23 Korean women, show in fig.7 and demonstrate significant improved in periobital wrinkles assessed by visiometer [19].

Fig.7. Improvement of periorbital wrinkles (a, b) – Changes in wrinkles were analyzed by the Skin Visiometer SV 600 after 4 and 8 weeks’ treatment. R1, skin roughness; R2, maximum roughness; R3, average roughness; R4, smoothness depth; and R5, arithmetic average roughness.

The before and after clinical study by using bone marrow derived stem cell conditioned medium serum on 40 Indian women aged 35 to 60 showed improvement in fine lines, wrinkles, crow’s feet, evenness of skin tone, skin firmness / laxity, hydration of skin, homogeneity of age spots, and visible pores. this study was followed for 90 days and no adverse effect was reported [20].

Fig.9. Improvement in fine lines and wrinkles was felt by 73.68% subjects (p = 0.0018); Improvement in skin tone was felt by 65.79% subjects (p = 0.0258); Improvement in skin hydration was felt by 94.74% subjects (p < 0.0001); Improvement in visible pores was felt by 63.14% (p = 0.0524) and 65.79% (p = 0.0258)

Photographs taken (a) 3 days after treatment, (b) 10 days after treatment, and (c) 3 weeks after treatment. The right side of face was the study group, and the left side of face was the control group. (d) The regions treated with the MGF cream-applied showed significantly less edema than those treated with the control cream at each visit. *signifies a statistically significant difference [21].

1. Yamamoto, A., Ohno, H. and Kuroyanagi, Y. , Evaluation of Epidermal Growth Factor Incorporating Skin Care Product in Culture Experiment Using Human Fibroblasts. . Open Journal of Regenerative Medicine, 2016. 5
2. 44-54.
3. Haase, I., et al., Regulation of keratinocyte shape, migration and wound epithelialization by IGF-1- and EGF-dependent signalling pathways. J Cell Sci, 2003. 116(Pt 15): p. 3227-38.
4. Schouest, J.M., T.K. Luu, and R.L. Moy, Improved texture and appearance of human facial skin after daily topical application of barley produced, synthetic, human-like epidermal growth factor (EGF) serum. J Drugs Dermatol, 2012. 11(5): p. 613-20.
5. Zoumalan, C.I., et al., Safety and Efficacy of a Scar Cream Consisting of Highly Selective Growth Factors Within a Silicone Cream Matrix: A Double-Blinded, Randomized, Multicenter Study. Aesthet Surg J, 2019. 39(3): p. 319-330.
6. McKnight, B., R. Seidel, and R. Moy, Topical Human Epidermal Growth Factor in the Treatment of Senile Purpura and the Prevention of Dermatoporosis. J Drugs Dermatol, 2015. 14(10): p. 1147-50.
7. Kalasho, B.D., et al., Evaluating the Safety and Efficacy of a Topical Formulation Containing Epidermal Growth Factor, Tranexamic Acid, Vitamin C, Arbutin, Niacinamide and Other Ingredients as Hydroquinone 4% Alternatives to Improve Hyperpigmentation: A Prospective, Randomized, Controlled Split Face Study. J Cosmet Sci, 2020. 71(5): p. 263-290.
8. Mehta, R.C., et al., Reduction in facial photodamage by a topical growth factor product. J Drugs Dermatol, 2008. 7(9): p. 864-71.
9. Watson, R.E., et al., Repair of photoaged dermal matrix by topical application of a cosmetic ‘antiageing’ product. Br J Dermatol, 2008. 158(3): p. 472-7.
10. Seidel, R. and R.L. Moy, Reduced appearance of under-eye bags with twice-daily application of epidermal growth factor (EGF) serum: a pilot study. J Drugs Dermatol, 2015. 14(4): p. 405-10.
11. Kong, M. and S.E. Hong, Topical use of recombinant human epidermal growth factor (EGF)-based cream to prevent radiation dermatitis in breast cancer patients: a single-blind randomized preliminary study. Asian Pac J Cancer Prev, 2013. 14(8): p. 4859-64.
12. Prakoeswa, C.R.S., et al., The efficacy of topical human amniotic membrane-mesenchymal stem cell-conditioned medium (hAMMSC-CM) and a mixture of topical hAMMSC-CM + vitamin C and hAMMSC-CM + vitamin E on chronic plantar ulcers in leprosy:a randomized control trial. J Dermatolog Treat, 2018. 29(8): p. 835-840.
13. Tuyet, H.L., et al., The efficacy and safety of epidermal growth factor in treatment of diabetic foot ulcers: the preliminary results. Int Wound J, 2009. 6(2): p. 159-66.
14. Hanft, J.R., et al., Phase I trial on the safety of topical rhVEGF on chronic neuropathic diabetic foot ulcers. J Wound Care, 2008. 17(1): p. 30-2, 34-7.
15. Noordam, R., et al., Serum insulin-like growth factor 1 and facial ageing: high levels associate with reduced skin wrinkling in a cross-sectional study. Br J Dermatol, 2013. 168(3): p. 533-8.
16. Ono, I., A Study on the Alterations in Skin Viscoelasticity before and after an Intradermal Administration of Growth Factor. J Cutan Aesthet Surg, 2011. 4(2): p. 98-104.
17. Ehrlich, M., et al., Improvement in the appearance of wrinkles with topical transforming growth factor beta(1) and l-ascorbic acid. Dermatol Surg, 2006. 32(5): p. 618-25.
18. Halper, J. and M. Kjaer, Basic components of connective tissues and extracellular matrix: elastin, fibrillin, fibulins, fibrinogen, fibronectin, laminin, tenascins and thrombospondins. Adv Exp Med Biol, 2014. 802: p. 31-47.
19. Draelos, Z.D., et al., Efficacy Evaluation of a Topical Hyaluronic Acid Serum in Facial Photoaging. Dermatol Ther (Heidelb), 2021. 11(4): p. 1385-1394.
20. Lee, D.H., et al., Improvement in skin wrinkles using a preparation containing human growth factors and hyaluronic acid serum. Journal of Cosmetic and Laser Therapy, 2015. 17(1): p. 20-23.
21. Sachdev, M., et al., A Single Arm, Monocentric, Prospective, Open Label Study to Evaluate Anti-Ageing Efficacy of Human Growth Factors and Cytokines Containing Cosmetic Skin Serum in Indian Female Population. Journal of Cosmetics, Dermatological Sciences and Applications, 2017. 07: p. 118-132.
22. Shin, S., et al., The effects of a multigrowth factor-containing cream on recovery after laser treatment: a double-blinded, randomized, split-face controlled study. J Cosmet Dermatol, 2017. 16(1): p. 76-83.