Epidermal Growth Factor:

EGF is a 6 kDa polypeptide growth factor that has been of particular interest because of its ability to promote wound and ulcer healing when applied topically (1). Twenty healthy volunteers aged 33 to 54 years were enrolled in a randomized, controlled, split-face study. For 4 weeks, a periocular wrinkle was treated daily with either a soluble MS-EGF cream or a cream containing EGF alone. MS-EGF group showed statistically significant increase of dermal depth and density compared to EGF alone group after 4 and 8 weeks. In addition, there was a marked improvement shown in clinical and 3-dimensional skin image in MS-EGF group. The treatments were well-tolerated; no significant side-effect was note (2)

Fig 1) The Effect of Micro-Spicule Containing Epidermal Growth Factor (MS-EGF) and Epidermal Growth Factor (EGF) on Periocular Wrinkles

Insulin Growth Factor:

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. In the skin, IGF-1 is produced by dermal fibroblasts, where it stimulates these fibroblasts to proliferate and provide loose connective tissue. Also, it acts on epidermal keratinocytes stimulating their proliferation resulting in acanthosis, hyperkeratosis and sometimes papillomatosis, hence forming ST lesions (3).

Basic-Fibroblast growth factor (bFGF)


FGF basic ( or bFGF ) is a member of the fibroblast growth factor (FGF) family. FGF family members are heparin-binding multifunctional proteins and are involved in a variety of biological processes including angiogenesis, wound healing, and embryonic development. FGF2 which is highly expressed in skin tissue, has pro-angiogenesis and pro-migratory effect (4),  and increase survival and proliferation, migration and differentiation potential of stem cells (5). FGF2 treatment enhanced the activity of c-Jun N-terminal kinase (JNK), a key regulator of fibroblast cell migration (6). Fig.3. Show the clinical result of topical application human fibroblast growth factor twice daily for 6 months. Improvement in fine rhytids and mottled hyperpigmentation is seen (7).

Fig.2) Improvement in fine rhytids and mottled hyperpigmentation after topical application human fibroblast growth factor


Vascular endothelial growth factor (VEGF)


Vascular endothelial growth factor (VEGF), a key mediator of angiogenesis, plays a key role in physiological processes and is a major contributor to several diseases including cancer and psoriasis. VEGF and HGF are known to be the most potent cytokines for the promotion of wound angiogenesis(8). 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 (9).

Fig.3) 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

Within the dermal ECM, aging is associated with a thickening of collagen fibrils and disorganization of total collagen content, mainly due to decreased collagen I synthesis and increased fibril fragmentation. In addition, skin aging is associated with increased levels of matrix metalloproteinases, which can break down collagen and elastin fibers, combined with impaired transforming growth factor (TGF)-β signaling, which may reduce collagen deposition (10) (fig.5). Figure.4. in below show the clinical result of eight female patients between the ages of 35 to 60 years with Fitzpatrick skin types III to IV and mild-to-moderate photodamage, skin laxity, fine lines, and wrinkles (Fitzpatrick Wrinkle Scale: 3–6) were enrolled to receive the 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 (11).

fig.4) Skin texture and wrinkles on the periorbital area A) before treatment and B) improvement seen after treatment

fig.5) As the skin ages, several changes occur in the epidermis and dermis. In the epidermis, corneocytes (terminally differentiated keratinocytes) accumulate, giving the skin a rough and dull appearance. In the dermis, the collagen content decreases and collagen and elastin fibers become disorganized and fragmented. This weakens the structure underlying the epidermis, leading to wrinkles. Illustration: © Kleinhans RED, source: www.skin-care-forum.basf.com.

Multi peptides Miracle:

Growth factors are not growth hormones. They are natural substances made by the skin cells that support the repair of damaged skin, as a result of ageing or environmental factors. They promote the formation of collagen and elastin to provide firmness and elasticity. Cells in ageing skin make fewer growth factors than cells in youthful skin. One approach to support the levels of skin rejuvenation is to regularly use skin care products with a high concentration of stable growth factors. Daily use of skin care products containing growth factors is known to help reduce the appearance of fine lines, wrinkles and improve skin tone and texture. Advances in biotechnology over the past decade have created multiple sources of growth factors. They can be derived from several different human cells grown in a laboratory (skin cells, bone marrow stem cells, fat stem cells), extracted from one’s blood (PRP – Platelet Rich Plasma), or bioengineered from non-human sources such as snails and some plants. However, fat stem cells are likely to produce growth factors that help the functioning of fat cells, and bone marrow stem cells are likely to produce growth factors that improve the functioning of the bone marrow. Ideal growth factors for the skin would be produced by fibroblasts.

Combination of hyaluronic acid with a mixture of human growth factors in conjunction with the micro laser peel procedure for skin rejuvenation twice daily for one month, 15 female volunteers between 35 to 65 years of age with demonstrable facial wrinkling, the subjects reapplied the test products for another month. In the large majority of subjects, erythema or edema, crusts or erosions, and transitory stinging or burning sensations after the micro laser peel were minimal or mild when the skin was treated with the serum followed by the cream. The products helped to significantly improve hyperpigmentation, wrinkles, and texture as compared to before treatment (12).

Fig.6. Example of subject demonstrating reduced signs of skin aging when using a 1% hyaluronic acid serum in combination with a skin cream containing a mixture of proprietary human growth factors and cytokines as a pre- and postprocedural skin care regimen

  1. Hardwicke J SD, Boyce D, Thomas D. Epidermal growth factor therapy and wound healing – past, present and future perspectives. Surgeon. 2008;6(3):172–177.
  2. Ha JM, Lim CA, Han K, Ha JC, Lee HE, Lee Y, et al. The Effect of Micro-Spicule Containing Epidermal Growth Factor on Periocular Wrinkles. Annals of dermatology. 2017;29(2):187-93.
  3. Bosseila M SOTteoI-LGFI-iaJEwDS.
  4. Jin S, Yang C, Huang J, Liu L, Zhang Y, Li S, et al. Conditioned medium derived from FGF-2-modified GMSCs enhances migration and angiogenesis of human umbilical vein endothelial cells. Stem Cell Research & Therapy. 2020;11(1):68.
  5. Khan S, Villalobos MA, Choron RL, Chang S, Brown SA, Carpenter JP, et al. Fibroblast growth factor and vascular endothelial growth factor play a critical role in endotheliogenesis from human adipose-derived stem cells. Journal of Vascular Surgery. 2017;65(5):1483-92.
  6. Song YH, Zhu YT, Ding J, Zhou FY, Xue JX, Jung JH, et al. Distribution of fibroblast growth factors and their roles in skin fibroblast cell migration. Molecular medicine reports. 2016;14(4):3336-42.
  7. Fabi S, Sundaram H. The potential of topical and injectable growth factors and cytokines for skin rejuvenation. Facial Plast Surg. 2014;30(2):157-71.
  8. Akiko Yamamoto HO, Yoshimitsu Kuroyanagi. Evaluation of Epidermal Growth Factor-Incorporating Skin Care Product in Culture Experiment Using Human Fibroblasts. Open Journal of Regenerative Medicine. 2016;5 (2).
  9. Ehrlich M, Rao J, Pabby A, Goldman MP. Improvement in the appearance of wrinkles with topical transforming growth factor beta(1) and l-ascorbic acid. Dermatologic surgery : official publication for American Society for Dermatologic Surgery [et al]. 2006;32(5):618-25.
  10. Aldag C NTD, Leventhal PS. Skin rejuvenation using cosmetic products containing growth factors, cytokines, and matrikines: a review of the literature. Clin Cosmet Investig Dermatol. 2016;9:411-419, https://doi.org/10.2147/CCID.S116158.
  11. Pamela RD. Topical Growth Factors for the Treatment of Facial Photoaging: A Clinical Experience of Eight Cases. J Clin Aesthet Dermatol. 2018;11(12):28-9.
  12. Gold MH, Katz BE, Cohen JL, Biron J. Human growth factor cream and hyaluronic Acid serum in conjunction with micro laser peel: an efficient regimen for skin rejuvenation. J Clin Aesthet Dermatol. 2010;3(12):37-42.
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