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   Table of Contents     
REVIEW ARTICLE  
Year : 2021  |  Volume : 14  |  Issue : 2  |  Page : 137-146
Epidermal growth factor in aesthetics and regenerative medicine: Systematic review


1 Pan-American Institute of Scientific Professionals (IPPC), México City, Mexico
2 Department of Investigation, Dental Research Center, University of Los Andes (ULA), Mérida, Venezuela
3 Department of Restorative Dentistry, Dental Research Center, University of Los Andes (ULA), Mérida, Venezuela

Click here for correspondence address and email

Date of Web Publication10-Aug-2021
 

   Abstract 

Introduction: Epidermal Growth Factor (rhEGF) is a promising skin antiaging agent that successfully promotes skin wound repair, and it has been investigated in the past decade for these purposes. However, there are no updated systematic reviews, in English or English, that support the efficacy of rhEGF as a regenerative skin treatment or systematic reviews that compile the uses of rhEGF as facial aesthetic therapy and regenerative medicine. Aim: To describe the current state of facial aesthetic and regenerative medicine treatments in which rhEGF has been effectively used. Materials and Methods: An exhaustive search was carried out in “Medline” (via “PubMed”), “Cochrane,” “Bireme” through the Virtual Health Library (VHL), “Elsevier” via “Science Direct,” “Springer,” “SciELo,” “ResearchGate,” and Google Scholar. Studies related to the use of rhEGF in addressing skin disorders or skin aging are included. Results: Overall, 49 articles were found, which described the use of rhEGF for skin regeneration and restructuring. Efficacy in the regeneration of skin wounds was verified through the intradermal and topical application of formulations with rhEGF. Most clinical trials in aesthetics point to an effective inversion of skin aging. However, uncontrolled or randomized trials abound, so that does not represent enough evidence to establish its efficiency. There are transient adverse effects for both cases. Conclusion: The rhEGF considers an effective therapeutic alternative for patients with recalcitrant skin wounds and skin aging, as it is a potent and specific mitogenic factor for the skin.

Keywords: Epidermal growth factor, facial aesthetics, regenerative medicine, skin aging, skin ulcers

How to cite this article:
Miller-Kobisher B, Suárez-Vega DV, Velazco de Maldonado GJ. Epidermal growth factor in aesthetics and regenerative medicine: Systematic review. J Cutan Aesthet Surg 2021;14:137-46

How to cite this URL:
Miller-Kobisher B, Suárez-Vega DV, Velazco de Maldonado GJ. Epidermal growth factor in aesthetics and regenerative medicine: Systematic review. J Cutan Aesthet Surg [serial online] 2021 [cited 2022 Jan 17];14:137-46. Available from: https://www.jcasonline.com/text.asp?2021/14/2/137/323554





   Key messages: Top


  • Similarities exist between the aging skin and wound healing, and mostly they involve the same oxidation and repair mechanisms


  • In both cases, it is necessary to biostimulate fibroblasts and keratinocytes, inducing dermal restructuring.


  • The EFG is more effectively applied by intradermal injections and using transdermal patches, thereby reducing the rhytids, folds, and hyperpigmentation and accelerating wound healing.



  •    Introduction Top


    In recent years, Epidermal Growth Factor (EGF) has been an important innovation .[1] It is a mitogenic polypeptide that is responsible for the maintenance and protection of the epithelia.[2] Thanks to genetic recombination, effective and clinically safe recombinant EGF (rhEGF) is available.

    On the other hand, there are striking similarities between oxidative events that promote skin aging and the oxidation seen in delayed wound healing. In both cases, the skin’s repair mechanisms are overwhelmed, as the production of growth factors slows down, including the production of EGF.[3]

    In both cases, it is necessary to biostimulate fibroblasts and keratinocytes, inducing the replacement of collagen and elastin and the extracellular matrix.[3] The success of the use of growth factors as a strategy to reverse photoaging lies in understanding its role in wound healing.[4] Therefore, the new cosmetic assets with recombinant growth factors as the rhEGF pursue this restructuring.[5],[6],[7]

    The rhEGF has been investigated in the past decade as a treatment of facial photoaging.[8] However, the literature review revealed that there are no systematic reviews, in Spanish or English, about the efficacy of rhEFG as facial and regenerative therapy.

    Given the lack of this information and the clinical potential of this factor, this systematic review aims at describing the current state of facial aesthetic and regenerative medicine treatments in which rhEGF has been effectively used with an emphasis on cutaneous restructuring.


       Materials and Methods Top


    Search strategy

    The search was started in health databases: Medline (via PubMed), Lilacs (via Bireme), Science Direct, Cochrane Library Virtual Health Library (VHL), SciELO, Medigraphic, and Google Scholar. To delimit the number of papers to select, the search was filtered by preferred languages (English and Portuguese) and the period 2001–2019 (since the information published in the past five years was not enough).

    The logical AND operator was used to combine the following descriptors for the search:

    • — English (MeSH): facial antiaging therapeutics; skin rejuvenation; EGF recombinant; epidermal growth factor; tissue regeneration; EGF, rhEGF.


    • — Portuguese: Fator crescimento ou recombinant epidermal carcinoma; rejuvenescimento gives peel; redensificação dermal; com faciais therapies fatores of crescimento; EGF, rhEGF.


    Selection of clinical studies

    The following inclusion criteria were considered:

    • — Preclinical and clinical trials related to the use of the rhEGF in skin disorders or skin aging


    • — Texts that undergo a rigorous evaluation process (peer-reviewed publications and texts from renowned publishers)


    Duplicated publications were removed. Literature reviews, case reports, incomplete publications or those did not comply with methodological rigor criteria (e.g. biases selection of participants or biases analysis of information), clinical treatment guidelines, and other irrelevant studies were excluded.

    By utilizing skimming and scanning as analysis strategies for information, irrelevant items were discarded by title and abstract. Once the exhaustivity of the search had been confirmed (by depletion of publications of each source consulted), the veracity of the information was confirmed by each author by methodological analysis and the content analysis of each publication.


       Results Top


    Seven sources of information were consulted, resulting in 75,986 publications that included the descriptors; of these, only 133 articles were directly related to the subject and they were examined by their title and abstract, and 73 articles were excluded because they did not meet the selection criteria. After reading the full text of the remaining 60 articles, taking into consideration the analysis criteria, 11 articles were removed, leaving a total of 49 articles [Figure 1] with a total sample of 821 patients.
    Figure 1: Flowchart of literature search. Source: Prepared by the authors from the study results

    Click here to view


    The results indicate that most of the publications on rhEGF applications were led by Korea, followed by the United States and Japan. The years in which it was most published in this regard were 2015 and the period between 2017 and 2019.

    Publications were classified according to the information source where they were located [Table 1]. Medline via Pubmed was the source that hosted major related scientific evidence.
    Table 1: Corpus according to sources and number of papers selected

    Click here to view


    Likewise, 46 studies corresponded to original research articles, and they are predominantly clinical trials (24 articles) over preclinical trials and case series; also, 13 articles are review articles, 9 are traditional reviews, 2 are systematic reviews, and 2 are meta-analyses [Table 2].
    Table 2: Corpus according to the type of study and number of articles found

    Click here to view


    Epidermal growth factor has been used basically in two major areas: regenerative medicine and aesthetic medicine. In aesthetics, there are three emerging categories: its application in hyperpigmentation, skin restructuring, and facial rejuvenation.

    The rhEGF in regenerative medicine

    Growth factor promotes wound healing,[9],[10] employing the intralesional administration of 75mg lyophilized powder thrice per week; gel 150g / g or spray rhEGF topically twice a day until complete healing.[11]

    Of the 21 publications in regenerative medicine, only 14 are clinical or preclinical trials [Table 3]. Korea is the country that has most investigated rhEGF in regeneration and the year in which it was most published was 2013.
    Table 3: Research designs under which rhEGF studies were conducted in the area of regenerative medicine

    Click here to view


    The main clinical uses of rhEGF in regenerative medicine include the treatment of alopecia and dermatitis after chemotherapy, burns, diabetic foot ulcers, postsurgical ulcers, oral mucositis, pharyngeal ulcers, and tympanic membrane perforation. This evidence is summarized in [Table 4] next.
    Table 4: Applications of the rhEGF in regenerative medicine

    Click here to view


    In alopecia treatment, the topical EGF-liposomal solution by transfollicular route favored primary hair recovery via the dystrophic anagen pathway.[12] In this regard, the mechanism of action consists of EGF, promotes the proliferation and migration of hair follicle outer root sheath cells, and modulates the expression of several follicle-regulatory genes via Wnt/β-catenin signaling.[13]

    The rhEGF in aesthetic medicine

    From fibroblast cell cultures with rhEGF, it was determined that rhEGF promotes the migration and contractility of aged fibroblasts[10] and increases the production of hyaluronic acid and the synthesis of collagen.[11] Hence, it possesses potential as a regenerator of skin aging.

    Peptides with rhEGF that penetrate the skin when applied topically have been developed[11]; cosmeceuticals with rhEGF that prevent or improve rhytids and hydrate the skin without significant side effects are being formulated.[26]

    Of the 28 publications in Aesthetic Medicine, 23 are clinical or preclinical trials [Table 5] with a higher level of evidence in aesthetics than in regenerative medicine. The country that has researched this matter the most is Korea, followed by the United States, and the periods of greatest publication were 2015 and 2017.
    Table 5: Research designs under which rhEGF studies were conducted in the area of aesthetics

    Click here to view


    The rhEGF to treat hyperpigmentation

    The EGF is a noninvasive and effective treatment for melasma. Topical serum twice a day for 8 weeks decreased melasma in 73.4% cases of the experimental group without any side effects.[27]

    The EGF acts on the melanocytes by reducing the expression of melanogenesis‐associated proteins (e.g. tyrosinase/MITF microphthalmia-associated transcription factor), in consequence inhibiting or regulating melanin synthesis.[28] It is also effective in preventing postinflammatory hyperpigmentation after fractional carbon dioxide laser treatment; its daily application resulted in significant stimulation of healing with slight pruritus.[29] Other research confirmed that rhEGF prevents inflammatory hyper pigmentation by laser treatment at 3, 7, and 35 days after its use.[30]

    The rhEGF for restructuring the skin

    The EGF contributes to restructuring the skin tissue; it improves facial acne, both inflammatory and noninflammatory, when it is applied as an rhEGF cream for 6 weeks. It also decreases sebum production and increases hydration, whereby the topical rhEGF may be an effective and safe adjuvant treatment option for mild to moderate vulgar acne.[31]

    The EGF also restructures the skin with stretch marks; it is being used as a complementary treatment to the ablative fractional carbon dioxide laser, twice a day until one month after the last session, showing significant improvements in stretch marks. Skin biopsy revealed an increased epidermal thickness and a decrease in elastic fragmentation.[32]

    The rhEGF to treat skin aging

    Most clinical trials reported the efficacy of rhEGF to reverse signs of skin aging,[33],[34] such as rhytids, grooves, hyper pigmentation and other senile pigmentations, hydration loss, and a decrease in epidermal and dermal thickness; test topical formulations such as cream, serum, and gel, either as a single therapy applied daily at home or as a complementary treatment after other treatments for facial rejuvenation such as the ablative laser.

    Only a few recent publications have studied its incorporation with classic injections of mesotherapy or through the use of patches with microspicles for the transdermal release of the factor.[35],[36] Clinical applications of the EGF factor in facial aesthetics are shown in [Table 6].
    Table 6: Applications of the rhEGF in aesthetic medicine

    Click here to view



       Discussion Top


    A skin wound is similar to skin aged by inflammation mediated by reactive oxygen species.[48] Besides, in wound healing there is angiogenesis and replacement of extracellular matrix, leading to re-epithelialization, but it is in the final phase that the collagen fibers are remodeled and elastin is restructured.[49] This last phase is characterized by antiaging treatments, and the use of growth factors evokes such dermal restructuring.[50]

    When topical or injectable growth factors are administered, the depleted levels are replenished and the activity of the cells responsible for dermal remodeling is regulated, reversing skin aging.[48],[51],[52] The rhEGF replenishes this balance and facilitates wound healing and dermatological conditions, as evidenced in some studies.[53]

    In 1972 Savage et al.[54] completed the sequentiation of EGF for the first time. In 1995 Parries et al.[55] they worked into their isolation and purification. Since this, the mass production of rhEGF has become a formidable task.

    From 2002, a heterologous protein such as EGF with an adequate molecular size (6kDa) started being produced in large quantities based on recombinant DNA technology. This placed an increased impetus on the development of more effective and economical methods for industrial purposes.[56],[57] Taking advantage of this technology, in the past two decades, the EGF has been produced and exploited in the cosmetic industry for the purpose of skin treatment.[58]

    For some authors, it is controversial that a growth factor that is applied topically can rejuvenate the skin; however, due to its large molecular size (> 15,000Da), its ability to penetrate the stratum corneum and to reach viable keratinocytes in the basal stratum is limited.[59],[60] This limitation was overcome from 2002 onward, because since then the majority of dermatologically and cosmetically commercialized formulations contain an rhEGF of 6kDa (or 6,000Da) with excellent potential for topical penetration into the stratum corneum.[61],[62]

    The rhEGF entry into the skin is through hair follicles and sweat glands. Also, it may be possible to improve their penetration by chemical modification with lipophilic molecules or by facilitating their diffusion by compromised skin, for example, after using microneedling or laser resurfacing,[63] as observed in all studies cited earlier, in which the EGF exhibits a low molecular size.

    The evidence is clear as to the success or effectiveness of rhEGF for facial rejuvenation; however, quasi-experimental, uncontrolled, or randomized clinical trials still abound. The studies assessed its effects while it was applied topically, but the greatest efficiency of the EFG was obtained intradermally, with a greater reduction of rhytids, folds, and a longer response over time. Besides, to guarantee its effectiveness, a possible route of entry for this molecular size is through intradermotherapy.

    In regenerative medicine, the EGF has been studied under preclinical trials and clinical trials, mostly quasi-experimental ones that are not uniform in terms of the route of administration, dose, and therapeutic regimen, which indicates the need to shield studies in this area by promoting the control and randomization to give more precise results on the resounding efficacy of the factor in wound regeneration.


       Conclusions Top


  • Products with EGF are an important topical therapeutic modality to treat aging skin efficiently and to treat hyper-pigmentation, rhytids, dryness, and laxity.


  • The EGF is effective in the advanced healing of skin wounds, according to the results of multiple investigations in severe cases, although studies are required to establish concentrations and indications of use for each case.


  • Injected rhEGF exerts a higher antiaging effect, inducing collagen, elastin, and hyaluronic acid, which are responsible for skin elasticity and turgor. However, more controlled, randomized, and long-term follow-up clinical trials are needed to specify the dose and therapeutic protocol to ensure its efficacy.


  • Financial support and sponsorship

    Nil.

    Conflicts of interest

    There are no conflicts of interest.



     
       References Top

    1.
    Esquirol Caussa J, Herrero Vila E. [Epidermal growth factor, innovation and safety]. Med Clin (Barc) 2015;145:305-12.  Back to cited text no. 1
        
    2.
    Esquirol-Caussa J, Herrero-Vila E. Factor de Crecimiento Epidérmico (EGF) y geles de silicona en el abordaje de heridas, quemaduras y cicatrices: Revisión de la literatura. Cir Plást Iberolatinoam [Internet] 2017;43:387-94. doi: http://dx.doi.org/10.4321/s0376-78922017000500009.  Back to cited text no. 2
        
    3.
    Sundaram H, Mehta RC, Norine JA, Kircik L, Cook-Bolden FE, Atkin DH, et al. Topically applied physiologically balanced growth factors: A new paradigm of skin rejuvenation. J Drugs Dermatol 2009;8:4-13.  Back to cited text no. 3
        
    4.
    De Araújo R, Lôbo M, Trindade K, Silva DF, Pereira N. Fibroblast growth factors: A controlling mechanism of skin aging. Skin Pharmacol Physiol 2019;32:275-82. doi: 10.1159/000501145  Back to cited text no. 4
        
    5.
    Rozman P, Bolta Z. Use of platelet growth factors in treating wounds and soft-tissue injuries. Acta Dermatovenerol Alp Pannonica Adriat 2007;16:156-65.  Back to cited text no. 5
        
    6.
    Fitzpatrick RE, Rostan EF. Reversal of photodamage with topical growth factors: A pilot study. J Cosmet Laser Ther 2003;5:25-34.  Back to cited text no. 6
        
    7.
    Zeka K, Ruparelia KC, Sansone C, Macchiarelli G, Continenza MA, Arroo RRJ. New hydrogels enriched with antioxidants from saffron crocus can find applications in wound treatment and/or beautification. Skin Pharmacol Physiol 2018;31:95-8.  Back to cited text no. 7
        
    8.
    Park JW, Hwang SR, Yoon IS. Advanced growth factor delivery systems in wound management and skin regeneration. Molecules 2017;22:E1259. doi: 10.3390/molecules22081259.  Back to cited text no. 8
        
    9.
    Breederveld RS, Tuinebreijer WE. Recombinant human growth hormone for treating burns and donor sites. Cochrane Database Syst Rev 2014;9:CD008990. doi: 10.1002/14651858.CD008990.pub3  Back to cited text no. 9
        
    10.
    Kim D, Kim SY, Mun SK, Rhee S, Kim BJ. Epidermal growth factor improves the migration and contractility of aged fibroblasts cultured on 3D collagen matrices. Int J Mol Med 2015;35:1017-25.  Back to cited text no. 10
        
    11.
    Jeon YJ, Kim YH, Jeon YJ, Lee WW, Bae IG, Yi KW, et al. Increased synthesis of hyaluronic acid by enhanced penetration of CTP‐EGF recombinant in human keratinocytes. J Cosmet Dermatol2019;18:1539-45.  Back to cited text no. 11
        
    12.
    Paik SH, Yoon JS, Ryu HH, Lee JY, Shin CY, Min KH, et al. Pretreatment of epidermal growth factor promotes primary hair recovery via the dystrophic anagen pathway after chemotherapy-induced alopecia. Exp Dermatol 2013;22:496-9.  Back to cited text no. 12
        
    13.
    Zhang H, Nan W, Wang S, Zhang T, Si H, Yang F, et al. Epidermal growth factor promotes proliferation and migration of follicular outer root sheath cells via wnt/β-catenin signaling. Cell Physiol Biochem 2016;39:360-70.  Back to cited text no. 13
        
    14.
    Niiyama H, Kuroyanagi Y. Development of novel wound dressing composed of hyaluronic acid and collagen sponge containing epidermal growth factor and vitamin C derivative. J Artif Organs 2014;17:81-7.  Back to cited text no. 14
        
    15.
    Yamamoto A, Shimizu N, Kuroyanagi Y. Potential of wound dressing composed of hyaluronic acid containing epidermal growth factor to enhance cytokine production by fibroblasts. J Artif Organs 2013;16:489-94.  Back to cited text no. 15
        
    16.
    Esquirol-Caussa J, Herrero-Vila E. Human recombinant epidermal growth factor in skin lesions: 77 cases in epitelizando project. J Dermatolog Treat 2019;30:96-101.  Back to cited text no. 16
        
    17.
    Martínez-Peñalver I, Cuevas-Pérez I. Efecto del factor de crecimiento epidérmico humano (EGF) recombinante sobre fístulas faríngeas y faringostomas. Rev Cubana Oncol 1998;14:77-8. Available from: http://imbiomed.com/1/1/articulos.php?method=showDetail&id_articulo=15298&id_seccion=473&id_ejemplar=1574&id_revista=74.  Back to cited text no. 17
        
    18.
    Kim JW, Kim MG, Lee HJ, Koh Y, Kwon JH, Kim I, et al. Topical recombinant human epidermal growth factor for oral mucositis induced by intensive chemotherapy with hematopoietic stem cell transplantation: Final analysis of a randomized, double-blind, placebo-controlled, phase 2 trial. PLoS One 2017;12:e0168854. doi: 10.1371/journal.pone.0168854.  Back to cited text no. 18
        
    19.
    Shi HX, Lin C, Lin BB, Wang ZG, Zhang HY, Wu FZ, et al. The anti-scar effects of basic fibroblast growth factor on the wound repair in vitro and in vivo. Plos One 2013;8:e59966.  Back to cited text no. 19
        
    20.
    Lee JH, Bae IH, Choi JK, Park JW. Evaluation of a highly skin permeable low-molecular-weight protamine conjugated epidermal growth factor for novel burn wound healing therapy. J Pharm Sci 2013;102:4109-20.  Back to cited text no. 20
        
    21.
    Kong M, Hong SE. 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;14:4859-64.  Back to cited text no. 21
        
    22.
    Hwang IG, Kang JH, Oh SY, Lee S, Kim SH, Song KH, et al. Phase II trial of epidermal growth factor ointment for patients with erlotinib-related skin effects. Support Care Cancer 2016;24:301-9.  Back to cited text no. 22
        
    23.
    Hernández-Cañete CM, Jácome-Ruiz R, Iturralde-Mc Farlen L, Sánchez-Montiel ME. Resultados y reacciones adversas en pacientes tratados con Heberprot-P® en la comunidad. Revista Cubana de Angiología 2017;18:35-42. Available from: http://scielo.sld.cu/scielo.php?script=sci_arttext&pid=S1682-00372017000100004.  Back to cited text no. 23
        
    24.
    Kahraman M, Misir A, Kizkapan TB, Ozcamdalli M, Uzun E, Mutlu M. The long-term outcomes following the application of intralesional epidermal growth factor in patients with diabetic foot ulcers. J Foot Ankle Surg 2019;58:282-7.  Back to cited text no. 24
        
    25.
    Lou Z. The effect of epidermal growth factor on the pseudo-healing of traumatic tympanic membrane perforations. Braz J Otorhinolaryngol 2021;87:53-8.  Back to cited text no. 25
        
    26.
    Vivó-Sesé I, Plá Miralles MD, Carbonell-Ripoll C, Ricarte-Amorós P, López-Cacho JM, Russo G, et al. Estudio de eficacia del producto factor de crecimiento epidérmico + ácido hialurónico fórmula. Actual Med 2015;100:76-80. doi: 10.15568/am.2015.795.or03  Back to cited text no. 26
        
    27.
    Lyons A, Stoll J, Moy R. A randomized, double-blind, placebo-controlled, split-face study of the efficacy of topical epidermal growth factor for the treatment of melasma. J Drugs Dermatol 2018;17:970-3.  Back to cited text no. 27
        
    28.
    Austin E, Nguyen JK, Jagdeo J. Topical treatments for melasma: A systematic review of randomized controlled trials. J Drugs Dermatol 2019;18:S1545961619P1156X. PMID: 31741361  Back to cited text no. 28
        
    29.
    Techapichetvanich T, Wanitphakdeedecha R, Iamphonrat T, Phothong W, Eimpunth S, Jane Hidajat I, et al. The effects of recombinant human epidermal growth factor containing ointment on wound healing and post inflammatory hyperpigmentation prevention after fractional ablative skin resurfacing: A split-face randomized controlled study. J Cosmet Dermatol 2018;17:756-61.  Back to cited text no. 29
        
    30.
    Park GH, Rhee do Y, Moon HR, Won CH, Lee MW, Choi JH, et al. Effect of an epidermal growth factor-containing cream on postinflammatory hyperpigmentation after Q-switched 532-nm neodymium-doped yttrium aluminum garnet laser treatment. Dermatol Surg 2015;41:131-5.  Back to cited text no. 30
        
    31.
    Kim HK, Yeo IK, Li K, Kim BJ, Kim MN, Hong CK. Topical epidermal growth factor for the improvement of acne lesions: A randomized, double-blinded, placebo-controlled, split-face trial. Int J Dermatol 2014;53:1031-6.  Back to cited text no. 31
        
    32.
    Disphanurat W, Kaewkes A, Suthiwartnarueput W. Comparison between topical recombinant human epidermal growth factor and aloe vera gel in combination with ablative fractional carbon dioxide laser as treatment for striae alba: A randomized double-blind trial. Lasers Surg Med 2020;52:166-75.  Back to cited text no. 32
        
    33.
    Barone F, Bashey S, Woodin FW.Jr Clinical evidence of dermal and epidermal restructuring from a biologically active growth factor serum for skin rejuvenation. J Drugs Dermatol 2019;18:290-5.  Back to cited text no. 33
        
    34.
    Seidel R, Moy RL. Improvement in atrophic acne scars using topical synthetic epidermal growth factor (EGF) serum: A pilot study. J Drugs Dermatol 2015;14:1005-10.  Back to cited text no. 34
        
    35.
    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. Ann Dermatol 2017;29:187-93. doi: https://doi.org/10.5021/ad.2017.29.2.187.  Back to cited text no. 35
        
    36.
    An JH, Lee HJ, Yoon MS, Kim DH. Anti-wrinkle efficacy of cross-linked hyaluronic acid-based microneedle patch with acetyl hexapeptide-8 and epidermal growth factor on Korean skin. Ann Dermatol 2019;31:263-71. Available from: https://synapse.koreamed.org/search.php?where=aview&id=10.5021/ad.2019.31.3.263&code=0140AD&vmode= PUBREADER#!po=73.5294.  Back to cited text no. 36
        
    37.
    McKnight B, Seidel R, Moy R. Topical human epidermal growth factor in the treatment of senile purpura and the prevention of dermatoporosis. J Drugs Dermatol 2015;14:1147-50. PMID: 26461827  Back to cited text no. 37
        
    38.
    Kwon SB, An S, Kim MJ, Kim KR, Choi YM, Ahn KJ, et al. Phytosphingosine-1-phosphate and epidermal growth factor synergistically restore extracellular matrix in human dermal fibroblasts in vitro and in vivo. Int J Mol Med 2017;39:741-8.  Back to cited text no. 38
        
    39.
    Schouest JM, Luu TK, Moy RL. 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;11:613-20.  Back to cited text no. 39
        
    40.
    Gawdat HI, Tawdy AM, Hegazy RA, Zakaria MM, Allam RS. Autologous platelet-rich plasma versus readymade growth factors in skin rejuvenation: A split face study. J Cosmet Dermatol 2017;16:258-64.  Back to cited text no. 40
        
    41.
    Draelos ZD. The effect of a combination of recombinant egf cosmetic serum and a crosslinked hyaluronic acid serum as compared to a fibroblast-conditioned media serum on the appearance of aging skin. J Drugs Dermatol 2016;15:738-41. PMID: 27272082  Back to cited text no. 41
        
    42.
    Lee DH, Oh IY, Koo KT, Suk JM, Jung SW, Park JO, et al. Improvement in skin wrinkles using a preparation containing human growth factors and hyaluronic acid serum. J Cosmet Laser Ther 2015;17:20-3.  Back to cited text no. 42
        
    43.
    Ruri DP. Topical growth factors for the treatment of facial photoaging: A clinical experience of eight cases. J Clin Aesthet Dermatol 2018;11:28-9. PMCID: PMC6334836  Back to cited text no. 43
        
    44.
    Kim J, Jang JH, Lee JH, Choi JK, Park WR, Bae IH, et al. Enhanced topical delivery of small hydrophilic or lipophilic active agents and epidermal growth factor by fractional radiofrequency microporation. Pharm Res 2012;29:2017-29.  Back to cited text no. 44
        
    45.
    Park B, Kong JS, Kang S, Kim YW. The effect of epidermal growth factor on autogenous fat graft. Aesthetic Plast Surg 2011;35:738-44.  Back to cited text no. 45
        
    46.
    Draelos ZD, Karnik J, Naughton G. The anti-aging effects of low oxygen tension generated multipotent growth factor containing serum. J Drugs Dermatol 2017;16:30-4. PMID: 28095530  Back to cited text no. 46
        
    47.
    Yamamoto A, Ohno H, Kuroyanagi Y. Evaluation of epidermal growth factor-incorporating skin care product in culture experiment using human fibroblasts. Open J Regenerative Med 2016;5:44-54. doi: 10.4236/ojrm.2016.52004.  Back to cited text no. 47
        
    48.
    Fabi S, Sundaram H. The potential of topical and injectable growth factors and cytokines for skin rejuvenation. Facial Plast Surg 2014;30:157-71.  Back to cited text no. 48
        
    49.
    Carvalho MR, Silveira IA, Oliveira BGRB. Treatment of venous ulcers with growth factors: Systematic review and meta-analysis. Rev Bras Enferm 2019;72:200-10.  Back to cited text no. 49
        
    50.
    Yamakawa S, Hayashida K. Advances in surgical applications of growth factors for wound healing. Burns Trauma 2019;7:10.  Back to cited text no. 50
        
    51.
    Dreher F. Topical growth factors for skin rejuvenation. In: Farage M, Miller K, Maibach H, editors. Textbook of aging skin. Berlin, Heidelberg: Springer; 2016. doi: 10.1007/978-3-642-27814-3_100-3  Back to cited text no. 51
        
    52.
    Alcaraz-Rubio J, Oliver-Iguacel A, Sánchez-López JM. Plasma rico en factores de crecimiento plaquetario. Una nueva puerta a la Medicina regenerativa. Rev Hematol Mex 2015;16:128-42. Available from: https://www.medigraphic.com/cgi-bin/new/resumen.cgi?IDARTICULO=59346.  Back to cited text no. 52
        
    53.
    Berlanga-Acosta J, Mendoza-Mari Y, Garcia-Ojalvo A, Fernandez-Mayola M, Guillen-Nieto G. Epidermal growth factor therapy impact on scar tissue resilience of diabetic lower limbs ulcers-an enlightening hypothesis. J Diabetes Metab 2018;9:798. doi: 10.4172/2155–6156.1000798  Back to cited text no. 53
        
    54.
    Savage CR Jr, Inagami T, Cohen S. The primary structure of epidermal growth factor. J Biol Chem 1972;247:7612-21.  Back to cited text no. 54
        
    55.
    Parries G, Chen K, Misono KS, Cohen S. The human urinary epidermal growth factor (EGF) precursor. Isolation of a biologically active 160-kilodalton heparin-binding pro-EGF with a truncated carboxyl terminus. J Biol Chem 1995;270:27954-60.  Back to cited text no. 55
        
    56.
    Heo JH, Won HS, Kang HA, Rhee SK, Chung BH. Purification of recombinant human epidermal growth factor secreted from the methylotrophic yeast hansenula polymorpha. Protein Expr Purif 2002;24:117-22.  Back to cited text no. 56
        
    57.
    Lee YS, Suh CW, Park SK, Lee EK. Purification of soluble human epidermal growth factor (hegf) from recombinant escherichia coli culture broth by using expanded-bed adsorption chromatography. Biotechnol Appl Biochem 2003;38:9-13.  Back to cited text no. 57
        
    58.
    Wong WKR, Ng KL, Lam CC, Hu XH, Lai NCY, et al. Review article: Reasons for underrating the potential of human epidermal growth factor in medical applications. J Anal Pharm Res 2017;4:00101. doi: 10.15406/japlr.2017.04.00101.  Back to cited text no. 58
        
    59.
    Aldag C, Nogueira Teixeira D, Leventhal PS. Skin rejuvenation using cosmetic products containing growth factors, cytokines, and matrikines: A review of the literature. Clin Cosmet Investig Dermatol 2016;9:411-9.  Back to cited text no. 59
        
    60.
    Mehta RC, Fitzpatrick RE. Endogenous growth factors as cosmeceuticals. Dermatol Ther 2007;20:350-9.  Back to cited text no. 60
        
    61.
    Yang Q, Zhang Y, Yin H, Lu Y. Topical recombinant human epidermal growth factor for diabetic foot ulcers: A meta-analysis of randomized controlled clinical trials. Ann Vasc Surg 2020;62:442-51.  Back to cited text no. 61
        
    62.
    Shen C, Sun L, Zhu N, Qi F. Kindlin-1 contributes to EGF-induced re-epithelialization in skin wound healing. Int J Mol Med 2017;39:949-59.  Back to cited text no. 62
        
    63.
    Schaefer H, Lademann J. The role of follicular penetration. A differential view. Skin Pharmacol Appl Skin Physiol 2001;14:23-7. doi: 10.1159/000056386  Back to cited text no. 63
        

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    Correspondence Address:
    Dubraska V Suárez-Vega
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    DOI: 10.4103/JCAS.JCAS_25_20

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