EGF

Dosing from the Literature

Published for skin: creams, ointments and serums applied twice a day for 6 weeks to 3 months in trials of 9 to 36 people with acne, acne scars or aging skin, mostly without a stated strength (Kim et al., 2014; Seidel & Moy, 2015; Kim et al., 2022; Schouest et al., 2012). Not published: a trial of EGF for hair, or an agreed cosmetic strength (Draelos, 2016).

The table records amounts as each source gave them, applied to the face unless noted; the last three rows are other uses. They are doses from research, not recommendations.

What It Is

EGF, epidermal growth factor, is a human protein of 53 amino acids held in shape by three internal disulfide bonds (UniProt P01133). The body cuts it out of a precursor of 1,207 amino acids, made in the kidney, salivary glands, brain and prostate (UniProt P01133). Its international nonproprietary name is nepidermin; older papers call it urogastrone, and cosmetic labels call it sh-Oligopeptide-1 (FDA’s substance registry, GSRS). At about 6,220 Da it is roughly 12 times heavier than the 500 Da that a widely cited review proposed as the limit for molecules passing through the skin’s outer layer (FDA’s substance registry; Bos & Meinardi, 2000).

Stanley Cohen found it in 1962 in mouse salivary glands, as a protein that made newborn mice open their eyelids and erupt their incisors early (Cohen, 1962). He named it for its effect on cells of the skin and cornea, and in 1975 he and Carpenter isolated the human form from urine and showed that it too made newborn mice open their eyes early (Nobel Assembly at the Karolinska Institute, 1986; Cohen & Carpenter, 1975). Cohen shared the 1986 Nobel Prize in Physiology or Medicine with Rita Levi-Montalcini “for their discoveries of growth factors” (Nobel Assembly at the Karolinska Institute, 1986).

Made today in bacteria, yeast or plants, recombinant EGF became a medicine outside the US (European Commission CosIng; Cho et al., 2022; Schouest et al., 2012). In South Korea, the drug regulator approved Daewoong’s Easyef, an EGF solution now supplied as a spray, in 1997; it is a prescription medicine, now labelled for diabetic foot ulcers in people whose blood sugar is poorly controlled, and the regulator approved an Easyef ointment with 1 µg of EGF per gram as a non-prescription medicine in 2010 (MFDS drug database). Cuba’s Center for Genetic Engineering and Biotechnology (CIGB) developed Heberprot-P, injected into diabetic foot ulcers; it was registered in Cuba in 2006, approved for marketing there in 2007 and, by 2013, registered in 15 other countries, by the developer’s account (Berlanga et al., 2013). A gel sold as Regen-D 150 contains 150 µg of EGF per gram (Yamakawa & Hayashida, 2019). In the US, Drugs@FDA holds no application for EGF, and FDA’s orphan-drug database lists three designations from 1984 to 1987, for corneal healing and burns, none of which led to an approval (FDA orphan designations). The only recombinant growth factor FDA has approved for use on the skin is a different one: becaplermin (Regranex), a platelet-derived growth factor first approved in 1997 (Yamakawa & Hayashida, 2019; Drugs@FDA; Regranex label).

In cosmetics, EGF made in E. coli from a synthetic copy of the human gene is listed in the European Commission’s CosIng database as sh-Oligopeptide-1, a skin-conditioning ingredient (European Commission CosIng, searched October 5, 2026). PubMed returns 101,977 records for “epidermal growth factor” (October 5, 2026), but only 28,546 of them make no mention of its receptor or HER2; 329 name “recombinant human epidermal growth factor,” and 3 name sh-Oligopeptide-1 (searched October 5, 2026).

Mechanism of Action

The findings below come almost entirely from cells. How much EGF from a cream reaches living skin cells has not been measured: the one human study that looked sampled only the outer, dead layer (Wyganowska et al., 2026).

• EGF receptor (EGFR) and its tyrosine kinase — EGF docks onto the outer part of the EGF receptor, and two EGF-bound receptors then pair up, as the crystal structure of the human complex shows (Ogiso et al., 2002). In membranes of A-431 human carcinoma cells, EGF switched on the receptor’s enzyme, which adds phosphate to tyrosine (Ushiro & Cohen, 1980); the Nobel Assembly called that finding a breakthrough in how signals reach the inside of a cell, and noted that one cancer gene codes for a protein resembling the EGF receptor (Nobel Assembly at the Karolinska Institute, 1986).
• Keratinocyte growth and migration — In culture, EGF extended the life of epidermal cells from newborns from 50 to 150 generations, by keeping them further from final differentiation, and not necessarily by speeding their growth (Rheinwald & Green, 1977). Colonies of epidermal keratinocytes spread outward 8 times faster with EGF, because the dividing cells at the rim migrated faster (Barrandon & Green, 1987).
• Fibroblasts and collagen: sources disagree — In cultured human skin fibroblasts, recombinant human EGF at 2–10 ng/mL stimulated growth but cut collagen production by 60%, mostly type I collagen, at the level of its genes (Kurata & Hata, 1991). In a 36-patient split-face acne trial, skin biopsies taken before and after 12 weeks of treatment showed more collagen types 1 and 3, elastin and TGF-β1 afterwards, and less of several inflammatory markers; the abstract compares before with after, not the EGF side with the vehicle side, and does not say how many patients were biopsied (Kim et al., 2022).
• Getting through the skin — Formulating EGF is hindered by low delivery through the skin and by the protein’s instability in common cosmetic emulsions (Eskens & Amin, 2021). In 20 healthy women using a cream with 25 µg of EGF per gram, the EGF recovered from the outermost, dead layer of the skin rose over the first three weeks and then held steady (Wyganowska et al., 2026). The authors note that tape stripping samples only that layer, that their figures are concentrations in the fluid used to wash the tape strips, not in the skin, and that the results are not evidence of penetration into living layers (Wyganowska et al., 2026). One trial delivered EGF with dissolving microneedles instead (An et al., 2019).

What the Research Shows

The results below are in animals; the human results follow in the next section.

• The founding observation, in newborn mice — A protein from mouse salivary glands made newborn mice open their eyelids and erupt their incisors early (Cohen, 1962), and human EGF from urine did the same for eyelid opening (Cohen & Carpenter, 1975).
• Skin wounds in pigs — Recombinant EGF applied daily to partial-thickness wounds on pigs’ backs sped the regrowth of skin across the wound, thickened the new dermis, and thickened granulation tissue in step with the dose (Nanney, 1990).
• Hair: EGF stopped wool growth and sent follicles into regression — In Merino sheep, mouse EGF infused under the skin at 0.25 mg per kg^0.75 or more for 7–28 hours stopped wool growth wholly or partly 2–4 weeks later; a complete break formed in the fleece, which was shed, while lower doses left only a weak zone in the wool (Moore et al., 1982). In mice, an EGF liposome solution on the skin pushed hair follicles into a catagen-like stage, the hair cycle’s regressing phase, which protected them from damage by the chemotherapy drug cyclophosphamide (Paik et al., 2013). No study has tested EGF alone for hair growth in people (PubMed, searched October 5, 2026).

Human Data

On skin, this section covers 18 published studies of 9 to 60 people, at least 11 of them randomized, and two meta-analyses, one of them pooling Chinese trials of up to 128 people (Zhou et al., 2026); for other uses, placebo-controlled trials in diabetic foot ulcers and a Cuban stroke program with GHRP-6 (PubMed, searched October 5, 2026). One registered facial-serum study has posted results without a paper (ClinicalTrials.gov NCT05724589), and no trial of EGF itself is recruiting (ClinicalTrials.gov, searched October 5, 2026).

• Skin wounds: two trials disagree — In a randomized, double-blind trial in 12 patients needing skin grafts, the donor site treated with silver sulfadiazine cream containing EGF (10 µg/mL) healed faster in all 12 than the paired site on the cream alone, by about one day to 25% and 50% healing and about 1.5 days to 75% and 100% (P < 0.02) (Brown et al., 1989). A later trial made matched wounds on both flanks of 17 healthy volunteers and found no significant difference in healing time; its authors questioned the first trial’s mix of patients and wounds (Cohen et al., 1995).
• Acne: two split-face trials — In 20 Korean adults with mild to moderate acne, rhEGF cream on one half of the face and vehicle on the other, twice a day for 6 weeks, inflamed spots fell 33.5% and non-inflamed lesions 25.4% on the EGF side, while non-inflamed lesions on the vehicle side increased; no severe side effects (Kim et al., 2014). In 36 patients over 12 weeks, single-blind, acne and acne scars improved on the EGF-ointment side and not on the vehicle side (Kim et al., 2022).
• Acne scars, serum alone: open pilots — Synthetic EGF serum twice a day for 12 weeks: in 9 adults (8 finished), a blinded rater picked the after-photo in 5 of 8 pairs (Seidel & Moy, 2015); in 12 adults with darker skin (11 finished), 9 of 11, and 81% rated their scars “good” to “excellent” improved (Stoddard et al., 2017). Neither had a control group.
• Acne scars, after laser — In a randomized split-face trial of 23 adults (21 finished), EGF twice a day for 7 days after each of three monthly fractional CO2 laser sessions gave 27.40% scar-volume improvement at three months against 21.28% on the placebo side (P = 0.01); the authors reported no funding (Ratanapokasatit & Sirithanabadeekul, 2022). In a 15-patient split-face trial, an rhEGF spray after laser did not significantly improve the scars beyond laser alone, though scabs shed sooner, 4.33 against 5.85 days (Peng et al., 2024). A 2026 review of 12 Chinese trials of 15 to 128 patients each, 1,044 in all, pooled 7 of them (586 patients) for a scar score: laser plus rhEGF lowered it 11.14 points more than laser alone, evidence the review’s grading table rated very low in certainty (Zhou et al., 2026).
• Aging skin — Open study: 29 women aged 39–75 using a barley-made EGF serum twice a day for 3 months improved on investigator ratings of fine lines, texture, pores and pigment (Schouest et al., 2012). In 60 women over 12 weeks, an EGF serum used with a hyaluronic-acid serum was preferred by the blinded investigator to a fibroblast-conditioned-media serum, while participants rated both highly (Draelos, 2016). In a randomized, double-blind trial in 52 Korean women, a dissolving microneedle patch made with 0.005% EGF in its hyaluronic-acid base, worn once a week, improved deep wrinkles around the eyes by 12.9% against 3.5% for the plain patch at day 5, with no difference at the nasolabial folds (An et al., 2019). In 20 women aged 50–65, investigator ratings of texture and firmness favored a recombinant EGF serum over a human-derived growth-factor serum at week 8, but the difference was not statistically significant at week 12, the end of the study; wrinkle ratings barely changed in either group; the study was funded by the recombinant serum’s maker (Abud et al., 2026).
• Skin barrier: one cream study in young women — In 20 healthy women aged 20–40, water loss through the skin fell 37% over four weeks where a cream with 25 µg of EGF per gram was used, around the eyes, and 24% where the plain base cream was used, on every volunteer’s forehead; the authors say this design cannot separate the creams’ effects from the facial areas’, and scaliness rose 13.4% with the EGF cream (Wyganowska et al., 2026).
• A facial serum study without a control group (registry results) — At Thailand’s Institute of Dermatology, 28 adults aged 40–65 used an EGF serum twice a day for two months; over 16 weeks there was no statistically significant change in hydration, water loss through the skin, elasticity, wrinkles or melanin, no adverse events, and most participants said they were satisfied (ClinicalTrials.gov NCT05724589, results posted). Two dermatologists rating photos at week 16 placed 22 and 17 of 27 participants in the scale’s improvement grades, most of them in its lowest (under 25%), and 5 and 10 in “worse”; the scale has no “unchanged” grade, and no statistical test was run on these ratings (ClinicalTrials.gov NCT05724589). No paper has been published from it (PubMed, searched October 5, 2026).
• Pigment and healing after laser — In 19 adults, an rhEGF ointment after fractional CO2 laser did no better than petrolatum on healing, redness or later dark marks (52.6% against 57.9%) (Techapichetvanich et al., 2018). In 30 adults treated with a Q-switched laser, an EGF cream did not prevent dark marks (26.7% against 20% on placebo), though participants were more satisfied (Wattanakrai et al., 2022). In 40 adults with sun spots in South Korea (30 finished), an ointment with 1 µg rhEGF per gram after laser left dark marks in 7.14% at 8 weeks against 37.5% on petrolatum (p = 0.014) (Kim et al., 2021). Pooling 7 trials of 169 patients, EGF lowered the melanin index at one month but did not significantly reduce dark marks, redness or skin-barrier damage (Ying et al., 2024).
• Skin side effects of cancer treatment — In 40 breast cancer patients having radiotherapy after surgery, an rhEGF cream group had grade 3 radiation dermatitis in 15% against 40% on general skin care (p = 0.068, or 0.035 after adjustment) (Kong & Hong, 2013). In an open, uncontrolled Phase II in 52 Korean patients on erlotinib, an EGF ointment downgraded the drug’s skin rash in 69.2% (Hwang et al., 2016; NCT01593995).
• Diabetic foot ulcers: the approved use abroad — In Cuba’s placebo-controlled trial of 149 patients with deep ulcers, granulation covering at least half the ulcer at 2 weeks came in 44 of 53 on 75 µg and 34 of 48 on 25 µg against 19 of 48 on placebo; ulcers closed in 40 of 53 on 75 µg, but in 25 of 48 on 25 µg, the same as on placebo (25 of 48) (Fernández-Montequín et al., 2009). In 1,788 patients treated after approval, 76% of ulcers granulated fully in a median of 5 weeks and 12% needed an amputation (Yera-Alos et al., 2013). In a six-center Phase III of a 0.005% spray in 167 patients, funded by Daewoong, 73.2% healed fully against 50.6% on saline (P = .001) (Park et al., 2018). Pooling 9 trials of 720 patients, rhEGF raised complete healing (odds ratio 2.79) (Zhao et al., 2020); a Cochrane review of 28 growth-factor trials in diabetic foot ulcers found all of them underpowered and at high risk of bias (Martí-Carvajal et al., 2015).
• Stroke, given with GHRP-6 — In an open-label Phase I/II in Cuba, 36 patients within 12 hours of an ischemic stroke received 75 µg EGF with 3.5 or 5 mg GHRP-6 into a vein twice a day for 7 days, or standard care; serious adverse events occurred in 9 of 16 controls and 5 of 20 treated patients; two serious events in one treated patient, and adverse events in 7 of the 20, were attributed to the treatment, against none in the controls (Hernández-Bernal et al., 2024). The open-label Phase III that followed, 188 patients, missed its main goal: disability, daily function and survival did not differ across all patients; a subgroup of 27 with severe strokes did better, which the authors say calls for further study (Hernández-Bernal et al., 2026).

The evidence meter on the EGF card reads “Controlled trials”: it counts published human data on EGF itself, for skin, and randomized trials against a placebo, vehicle or plain patch are published (Kim et al., 2014; An et al., 2019; Ratanapokasatit & Sirithanabadeekul, 2022). Controlled is not the same as consistent: several of those trials found no benefit on their main measures (Cohen et al., 1995; Techapichetvanich et al., 2018; Wattanakrai et al., 2022), and most were small: the largest, a Chinese laser trial, had 128 people (Zhou et al., 2026).

Reconstitution & Storage

There is nothing to reconstitute in the skin-care use: EGF comes already mixed into creams, serums, ointments, sprays and patches. Heberprot-P, the injected ulcer medicine, is a freeze-dried powder of 75 or 25 µg per vial, given by injection in Cuban hospitals and clinics (Yera-Alos et al., 2013).

• Strengths in the studies — An ointment with 1 µg per gram (Kim et al., 2021), a cream with 25 µg per gram (Wyganowska et al., 2026), a microneedle patch molded from a hyaluronic-acid solution containing 0.005% (w/w) EGF, with no amount per patch given (An et al., 2019), a 0.005% spray (Park et al., 2018), a gel with 150 µg per gram (Yamakawa & Hayashida, 2019), and 10 µg/mL in a wound cream (Brown et al., 1989). Many of the cosmetic studies on this page state none in the abstracts or texts read (Kim et al., 2014; Kim et al., 2022; Seidel & Moy, 2015); the author of a 2016 EGF serum study wrote that the lack of dosing standards holds cosmetic science back (Draelos, 2016).
• One consumer listing — DailyMed, the National Library of Medicine’s database of labels filed with FDA, holds one listing that names nepidermin: a cream mask listed in 2021 as an over-the-counter product in the marketing category “unapproved drug other”, at 0.00000001 g per 100 g, which is 0.1 ng per gram (DailyMed, 2021): ten thousand times less than the 1 µg per gram ointment above.
• Stability — EGF is a protein, and its instability in common cosmetic emulsions is one of the main obstacles to putting it in skin care (Eskens & Amin, 2021).
• Storage — The Cuban Phase I/II stroke trial kept its freeze-dried EGF at 2–8 °C throughout (Hernández-Bernal et al., 2024), and South Korea’s labels for the Easyef spray and ointment list storage in a refrigerator at 2–8 °C (MFDS drug database). No document read for this page gives storage conditions for cosmetic EGF products.
• Laboratory vials — Laboratory suppliers sell freeze-dried recombinant human EGF made in E. coli, in vials of 10 µg to 1 mg, for cell-culture work, labelled “For Research Use Only” (a supplier’s product sheet, searched October 5, 2026).

→ Peptide Calculator — vial-to-syringe math

Side Effects & Risks

• On the skin, in trials — Side effects were few where reported: no severe ones in the 20-person acne trial (Kim et al., 2014), no allergic reactions after laser (Ratanapokasatit & Sirithanabadeekul, 2022), none in the sun-spot trial (Kim et al., 2021), no serious adverse events in a 20-woman serum trial (Abud et al., 2026), and no adverse events in the 28-adult serum study (ClinicalTrials.gov NCT05724589). A review of growth-factor creams in general found a low risk of adverse events (Quinlan et al., 2023).
• Injected into ulcers — In 1,788 Cuban patients given Heberprot-P, 47% had adverse events; pain and burning where it was injected, shivering and chills made up 87% of them, and more than 85% were mild or moderate (Yera-Alos et al., 2013). There were 31 serious adverse events, and 15 of them were deaths, 12 from heart attacks and other heart and circulation causes, including one stroke; the investigators judged 2 of the 31, both deaths, unrelated to treatment and the other 29, including 13 deaths, “conditional or possible”: linked in time, with other explanations available (Yera-Alos et al., 2013). Of the 14 serious heart and circulation events, 13 were in patients who already had high blood pressure, coronary heart disease or an irregular heartbeat, and the authors write that there is not enough information to relate those events and the deaths to treatment; local infection made up 32% of the serious events (Yera-Alos et al., 2013). In all, 352 of the 1,788 patients (20%) died during treatment or follow-up, most often of heart and circulation disease (Yera-Alos et al., 2013). In the placebo-controlled trial, most adverse events were mild and none was a drug-related severe reaction (Fernández-Montequín et al., 2009).
• Into a vein, with GHRP-6 — In the stroke Phase III, severe adverse events occurred in 30 of 95 treated patients and 18 of 93 on standard care (odds ratio 1.92, 95% CI 0.981–3.767, not statistically significant); none was judged treatment-related (Hernández-Bernal et al., 2026). In the Phase I/II before it, adverse events in 7 of the 20 treated patients, and two serious events (vomiting and shortness of breath) in one of them, were attributed to the treatment, against none in the controls (Hernández-Bernal et al., 2024).
• Cancer: a theoretical risk — EGF makes cells divide, and in experimental cancer models it did not start cancers but showed “tumour promotion”; animals given EGF into the body for long periods developed dose-dependent, reversible overgrowth of lining tissues (Berlanga-Acosta et al., 2009, a review by Heberprot-P’s developers). The same review found no report linking clinical use of EGF with cancer, and cites a Cuban survey, 15 years after burns were treated with or without EGF, in which cancer rates were comparable (Berlanga-Acosta et al., 2009). After Heberprot-P, 42 patients were found with new cancers during follow-up, none at the treated site, and cancer was not related to the amount of EGF received (Yera-Alos et al., 2013). A 2023 review calls the long-term risks of cosmetic EGF unknown (Martínez-Carpio, 2023).
• A growth-factor precedent — The only recombinant growth factor FDA has approved for use on the skin, becaplermin (Regranex), a platelet-derived growth factor (Yamakawa & Hayashida, 2019), carries a cancer warning: in a follow-up of 491 trial patients, cancers were diagnosed in 8 of 291 on becaplermin and 2 of 200 on vehicle or standard of care, all remote from the treated site (Regranex label). It is a different growth factor, and EGF has no US label.
• What has not been tested — The cosmetic studies on this page applied EGF for about three months, one with an optional extension to six (Schouest et al., 2012; Abud et al., 2026). No study of topical EGF in pregnancy turned up (PubMed, searched October 5, 2026). Whether cosmetic EGF reaches living skin cells is unknown: the one human measurement sampled only the outer, dead layer (Wyganowska et al., 2026).
• WADA — EGF is not named on the 2026 Prohibited List. Section S2.3 prohibits at all times named growth factors and “other growth factors or growth factor modulators affecting muscle, tendon or ligament protein synthesis/degradation, vascularisation, energy utilization, regenerative capacity or fibre type switching”; the List does not say whether that covers EGF (World Anti-Doping Agency, 2026). S0 does not apply, because Cuba has registered EGF as a medicine (Berlanga et al., 2013).

Bloodwork & Monitoring

No monitoring guidance for EGF has been published outside the trials. The trials measured these:

• Skin measures — Acne lesion counts, investigator and scar grades, sebum, hydration and skin biopsies (Kim et al., 2014; Kim et al., 2022); melanin and erythema indexes and water loss through the skin after laser (Kim et al., 2021).
• Ulcer outcomes and cancer follow-up — Granulation, wound closure, amputations and adverse events; in Cuba, a cross-search of the national cancer and mortality registries for new cancers after treatment (Yera-Alos et al., 2013).
• Stroke trials — Adverse events, vital signs and ECG monitoring during the hospital stay, with disability scales at 3 and 6 months (Hernández-Bernal et al., 2024).
• Which tests fit a given person — A question for a licensed healthcare provider. This page can’t answer it.

Commonly Stacked With

EGF has been tested with a laser, in a hyaluronic-acid microneedle patch and, by IV, with GHRP-6 (Ratanapokasatit & Sirithanabadeekul, 2022; An et al., 2019; Hernández-Bernal et al., 2024). No study has tested it together with GHK-Cu, Matrixyl, Argireline, BPC-157 or TB-500 (PubMed, searched October 5, 2026); one 2019 trial tested EGF and acetyl hexapeptide-8, Argireline’s ingredient, in separate groups, not together (An et al., 2019).

→ Peptide Calculator — vial-to-syringe math

Legal Status

Related Compounds

People researching EGF often also look at these:

Next Steps

References

1. UniProt Consortium. UniProtKB P01133 (EGF_HUMAN): pro-epidermal growth factor, 1,207 amino acids; chain 971–1023, epidermal growth factor (alternative name urogastrone), with disulfide bonds 976–990, 984–1001 and 1003–1012; expressed in kidney, salivary gland, cerebrum and prostate. rest.uniprot.org/uniprotkb/P01133. Read October 5, 2026.
2. FDA. Global Substance Registration System: Nepidermin, UNII TZK30RF92W (protein, 53 amino acids, NSDSECPLSHDGYCLHDGVCMYIEALDKYACNCVVGYIGERCQYRDLKWWELR; 3 disulfide links; molecular weight 6,220 Da, calculated; names include nepidermin [INN], urogastrone, human epidermal growth factor and SH-OLIGOPEPTIDE-1; CAS 62253-63-8). gsrs.ncats.nih.gov. Read October 5, 2026.
3. Cohen S. Isolation of a mouse submaxillary gland protein accelerating incisor eruption and eyelid opening in the new-born animal. J Biol Chem. 1962;237:1555-1562. PMID: 13880319.
4. Cohen S, Carpenter G. Human epidermal growth factor: isolation and chemical and biological properties. Proc Natl Acad Sci U S A. 1975;72(4):1317-1321. PMID: 1055407. DOI: 10.1073/pnas.72.4.1317.
5. Nobel Assembly at the Karolinska Institute. Press release: The Nobel Prize in Physiology or Medicine 1986, awarded jointly to Stanley Cohen and Rita Levi-Montalcini “for their discoveries of growth factors.” nobelprize.org/prizes/medicine/1986/press-release/. Read October 5, 2026.
6. European Commission. CosIng, the cosmetic ingredient database: SH-OLIGOPEPTIDE-1 (substance ID 87479; function: skin conditioning; status: active), “a single chain recombinant human peptide, produced by fermentation in E. coli … identical to the human gene which codes for Epidermal Growth Factor.” ec.europa.eu/growth/tools-databases/cosing. Read October 5, 2026.
7. Bos JD, Meinardi MM. The 500 Dalton rule for the skin penetration of chemical compounds and drugs. Exp Dermatol. 2000;9(3):165-169. PMID: 10839713. DOI: 10.1034/j.1600-0625.2000.009003165.x.
8. Ushiro H, Cohen S. Identification of phosphotyrosine as a product of epidermal growth factor-activated protein kinase in A-431 cell membranes. J Biol Chem. 1980;255(18):8363-8365. PMID: 6157683.
9. Ogiso H, Ishitani R, Nureki O, Fukai S, et al. Crystal structure of the complex of human epidermal growth factor and receptor extracellular domains. Cell. 2002;110(6):775-787. PMID: 12297050. DOI: 10.1016/s0092-8674(02)00963-7.
10. Rheinwald JG, Green H. Epidermal growth factor and the multiplication of cultured human epidermal keratinocytes. Nature. 1977;265(5593):421-424. PMID: 299924. DOI: 10.1038/265421a0.
11. Barrandon Y, Green H. Cell migration is essential for sustained growth of keratinocyte colonies: the roles of transforming growth factor-alpha and epidermal growth factor. Cell. 1987;50(7):1131-1137. PMID: 3497724. DOI: 10.1016/0092-8674(87)90179-6.
12. Kurata S, Hata R. Epidermal growth factor inhibits transcription of type I collagen genes and production of type I collagen in cultured human skin fibroblasts in the presence and absence of L-ascorbic acid 2-phosphate, a long-acting vitamin C derivative. J Biol Chem. 1991;266(15):9997-10003. PMID: 2033086.
13. Eskens O, Amin S. Challenges and effective routes for formulating and delivery of epidermal growth factors in skin care. Int J Cosmet Sci. 2021;43(2):123-130. PMID: 33354795. DOI: 10.1111/ics.12685.
14. Wyganowska ML, Tyliszczak F, Marzec M, Klewin-Steinböck S, Nowak I. Instrumental In Vivo Assessment of Cosmetic Emulsions Containing Platelet-Rich Fibrin (PRF) or Recombinant Epidermal Growth Factor (EGF): A Pilot Compatibility Study. Pharmaceuticals (Basel). 2026;19(3):394. PMID: 41901242. DOI: 10.3390/ph19030394.
15. Nanney LB. Epidermal and dermal effects of epidermal growth factor during wound repair. J Invest Dermatol. 1990;94(5):624-629. PMID: 2324518. DOI: 10.1111/1523-1747.ep12876204.
16. Moore GP, Panaretto BA, Robertson D. Inhibition of wool growth in merino sheep following administration of mouse epidermal growth factor and a derivative. Aust J Biol Sci. 1982;35(2):163-172. PMID: 6982038. DOI: 10.1071/bi9820163.
17. Paik SH, Yoon JS, Ryu HH, Lee JY, et al. Pretreatment of epidermal growth factor promotes primary hair recovery via the dystrophic anagen pathway after chemotherapy-induced alopecia. Exp Dermatol. 2013;22(7):496-499. PMID: 23800066. DOI: 10.1111/exd.12182.
18. Brown GL, Nanney LB, Griffen J, Cramer AB, et al. Enhancement of wound healing by topical treatment with epidermal growth factor. N Engl J Med. 1989;321(2):76-79. PMID: 2659995. DOI: 10.1056/NEJM198907133210203.
19. Cohen IK, Crossland MC, Garrett A, Diegelmann RF. Topical application of epidermal growth factor onto partial-thickness wounds in human volunteers does not enhance reepithelialization. Plast Reconstr Surg. 1995;96(2):251-254. PMID: 7624397. DOI: 10.1097/00006534-199508000-00001.
20. Kim HK, Yeo IK, Li K, Kim BJ, et al. Topical epidermal growth factor for the improvement of acne lesions: a randomized, double-blinded, placebo-controlled, split-face trial. Int J Dermatol. 2014;53(8):1031-1036. PMID: 24962549. DOI: 10.1111/ijd.12488.
21. Kim DH, Yang JH, Cho SI, Yoon JY, et al. Clinical and Histological Effects of Topical Epidermal Growth Factor on Acne and Acne Scars. Dermatology. 2022;238(5):837-845. PMID: 35078198. DOI: 10.1159/000521294.
22. 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(9):1005-1010. PMID: 26355620.
23. Stoddard MA, Herrmann J, Moy L, Moy R. Improvement of Atrophic Acne Scars in Skin of Color Using Topical Synthetic Epidermal Growth Factor (EGF) Serum: A Pilot Study. J Drugs Dermatol. 2017;16(4):322-326. PMID: 28403265.
24. Otto MA. Acne scars improved with topical epidermal growth factor serum. Dermatology News (MDedge), September 11, 2015. mdedge.com/edermatologynews/article/102564/aesthetic-dermatology/acne-scars-improved-topical-epidermal-growth. Read October 5, 2026. (A news report on Seidel & Moy, 2015: the serum “was supplied by its maker,” and “Dr. Moy owns stock in [the company] and is the company’s scientific adviser”; the company is not named here. The journal’s own disclosure section sits behind a login and was not read.)
25. 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(5):613-620. PMID: 22527430.
26. 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(6):738-741. PMID: 27272082.
27. 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(3):263-271. PMID: 33911590. DOI: 10.5021/ad.2019.31.3.263. (Full text at PMC7992733, read October 5, 2026: three randomized groups, plain patch, patch with acetyl hexapeptide-8 and patch with EGF, each ingredient at 0.005% w/w in the hyaluronic-acid solution the patch was molded from; no amount per patch given.)
28. Abud B, McGinn L, Cawthon E, Pankey A, et al. A Randomized, Double-Blinded Pilot Study Comparing Synthetic Versus Human-Derived Topical Epidermal Growth Factor for Facial Rejuvenation and Psychosocial Perception. J Cosmet Dermatol. 2026;25(5):e70927. PMID: 42152512. DOI: 10.1111/jocd.70927. (Full text at PMC13184420, read October 5, 2026: funded by the maker of the recombinant serum.)
29. Ratanapokasatit Y, Sirithanabadeekul P. The Efficacy and Safety of Epidermal Growth Factor Combined with Fractional Carbon Dioxide Laser for Acne Scar Treatment: A Split-Face Trial. J Clin Aesthet Dermatol. 2022;15(7):44-48. PMID: 35942017. (Full text at PMC9345195, read October 5, 2026.)
30. Peng H, Ran X, Yang X, Zhou G, et al. Efficacy of a Combination Treatment of Ablative Fractional Carbon Dioxide Laser Therapy and Recombinant Human Epidermal Growth Factor for Atrophic Acne Scars. J Cosmet Dermatol. 2024;23(12):3986-3992. PMID: 39212099. DOI: 10.1111/jocd.16552.
31. Zhou S, Guo C, Zhai J, Zhang Y. Efficacy and safety of recombinant human epidermal growth factor combined with fractional carbon dioxide laser for facial atrophic acne scars: a systematic review and meta-analysis of randomized trials. Lasers Med Sci. 2026;41(1). PMID: 42168448. DOI: 10.1007/s10103-026-04881-w.
32. Techapichetvanich T, Wanitphakdeedecha R, Iamphonrat T, Phothong W, 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(5):756-761. PMID: 29956440. DOI: 10.1111/jocd.12691.
33. Kim HO, Kim HR, Kim JC, Kang SY, et al. A Randomized Controlled Trial on the Effectiveness of Epidermal Growth Factor-Containing Ointment on the Treatment of Solar Lentigines as Adjuvant Therapy. Medicina (Kaunas). 2021;57(2):166. PMID: 33668564. DOI: 10.3390/medicina57020166. (Full text at PMC7918714, read October 5, 2026: ointment with 1 μg rhEGF per gram; 40 enrolled, 30 finished.)
34. Wattanakrai P, Sindhusen S, Ploydaeng M. Effectiveness of an epidermal growth factor-containing cream on postinflammatory hyperpigmentation after 1064-nm Q-switched neodymium-doped yttrium aluminum garnet laser treatment of acquired bilateral nevus of Ota-like macules (Hori’s nevus) in Asians: A split-face, double-blinded, randomized controlled study. J Cosmet Dermatol. 2022;21(5):2031-2037. PMID: 35066982. DOI: 10.1111/jocd.14765.
35. Ying J, Zhang Y, Qiu Y, Xiang W. The role of epidermal growth factor-containing topical products on recovery and post-inflammatory hyperpigmentation prevention after laser surgeries: A systematic review and meta-analysis. J Cosmet Dermatol. 2024;23(2):382-390. PMID: 37853844. DOI: 10.1111/jocd.16007.
36. Quinlan DJ, Ghanem AM, Hassan H. Topical growth factor preparations for facial skin rejuvenation: A systematic review. J Cosmet Dermatol. 2023;22(7):2023-2039. PMID: 37222303. DOI: 10.1111/jocd.15644.
37. Martínez-Carpio PA. Topical application of sh-oligopeptide-1 and clinical trials with cosmetic preparations: risk or fraud? Cutan Ocul Toxicol. 2023;42(4):190-197. PMID: 37452558. DOI: 10.1080/15569527.2023.2234020.
38. 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(8):4859-4864. PMID: 24083759. DOI: 10.7314/apjcp.2013.14.8.4859.
39. Hwang IG, Kang JH, Oh SY, Lee S, et al. Phase II trial of epidermal growth factor ointment for patients with Erlotinib-related skin effects. Support Care Cancer. 2016;24(1):301-309. PMID: 26041481. DOI: 10.1007/s00520-015-2783-9.
40. Fernández-Montequín JI, Valenzuela-Silva CM, Díaz OG, Savigne W, et al. Intra-lesional injections of recombinant human epidermal growth factor promote granulation and healing in advanced diabetic foot ulcers: multicenter, randomised, placebo-controlled, double-blind study. Int Wound J. 2009;6(6):432-443. PMID: 20051095. DOI: 10.1111/j.1742-481X.2009.00641.x.
41. Berlanga J, Fernández JI, López E, López PA, et al. Heberprot-P: a novel product for treating advanced diabetic foot ulcer. MEDICC Rev. 2013;15(1):11-15. PMID: 23396236. DOI: 10.37757/MR2013V15.N1.4.
42. Yera-Alos IB, Alonso-Carbonell L, Valenzuela-Silva CM, Tuero-Iglesias AD, et al. Active post-marketing surveillance of the intralesional administration of human recombinant epidermal growth factor in diabetic foot ulcers. BMC Pharmacol Toxicol. 2013;14:44. PMID: 24004460. DOI: 10.1186/2050-6511-14-44. (Full text at PMC3844572, read October 5, 2026.)
43. Park KH, Han SH, Hong JP, Han SK, et al. Topical epidermal growth factor spray for the treatment of chronic diabetic foot ulcers: A phase III multicenter, double-blind, randomized, placebo-controlled trial. Diabetes Res Clin Pract. 2018;142:335-344. PMID: 29902542. DOI: 10.1016/j.diabres.2018.06.002. (Funder in the publisher’s Crossref record and in Europe PMC, read October 5, 2026: Daewoong Pharmaceutical Co.)
44. Zhao DY, Su YN, Li YH, Yu TQ, et al. Efficacy and safety of recombinant human epidermal growth factor for diabetic foot ulcers: A systematic review and meta-analysis of randomised controlled trials. Int Wound J. 2020;17(4):1062-1073. PMID: 32343054. DOI: 10.1111/iwj.13377.
45. Martí-Carvajal AJ, Gluud C, Nicola S, Simancas-Racines D, et al. Growth factors for treating diabetic foot ulcers. Cochrane Database Syst Rev. 2015;2015(10):CD008548. PMID: 26509249. DOI: 10.1002/14651858.CD008548.pub2.
46. Cho KH, Kim JH, Nam HS, Kang DJ. Efficacy Comparison Study of Human Epidermal Growth Factor (EGF) between Heberprot-P® and Easyef® in Adult Zebrafish and Embryo under Presence or Absence Combination of Diabetic Condition and Hyperlipidemia to Mimic Elderly Patients. Geriatrics (Basel). 2022;7(2):45. PMID: 35447848. DOI: 10.3390/geriatrics7020045. (Full text at PMC9028627, read October 5, 2026: Heberprot-P’s EGF made in yeast, Easyef’s in E. coli; Easyef “purchased from a local hospital under prescription.”)
47. MFDS (Ministry of Food and Drug Safety, South Korea). Drug database, nedrug.mfds.go.kr: product records for Daewoong Pharmaceutical’s Easyef. Easyef SOLN 0.005% (item 199700704, permit 349): recombinant human EGF made in E. coli, a biological product in a two-compartment pump spray, approved March 4, 1997, prescription (rare-disease) medicine, indicated for diabetic foot ulcers in patients with poorly controlled blood sugar (fasting glucose 140 mg/dL or more, or HbA1c above 8%), refrigerated storage at 2–8 °C. Easyef Oint. (item 201002496, permit 656): 1 µg per gram, approved April 2, 2010, non-prescription medicine, indicated as an adjunct for wounds and skin ulcers, refrigerated storage at 2–8 °C. Easyef Dermal Solution 0.005% (permit 596): approved July 25, 2008, withdrawn October 27, 2023. Read October 5, 2026.
48. Yamakawa S, Hayashida K. Advances in surgical applications of growth factors for wound healing. Burns Trauma. 2019;7:10. PMID: 30993143. DOI: 10.1186/s41038-019-0148-1.
49. Hernández-Bernal F, Estenoz-García D, Gutiérrez-Ronquillo JH, Martín-Bauta Y, et al. Combination therapy of Epidermal Growth Factor and Growth Hormone-Releasing Hexapeptide in acute ischemic stroke: a phase I/II non-blinded, randomized clinical trial. Front Neurol. 2024;15:1303402. PMID: 38638315. DOI: 10.3389/fneur.2024.1303402.
50. Hernández-Bernal F, Subirós-Martínez N, Gutiérrez-Ronquillo JH, Colina-Ávila E, et al. Phase III Open-Label, Randomized Clinical Trial of Epidermal Growth Factor and Growth Hormone Releasing Hexapeptide in Acute Ischemic Stroke. J Clin Neurosci. 2026;152:112195. PMID: 42462342. DOI: 10.1016/j.jocn.2026.112195.
51. Berlanga-Acosta J, Gavilondo-Cowley J, López-Saura P, González-López T, et al. Epidermal growth factor in clinical practice - a review of its biological actions, clinical indications and safety implications. Int Wound J. 2009;6(5):331-346. PMID: 19912390. DOI: 10.1111/j.1742-481X.2009.00622.x.
52. Regranex (becaplermin) gel 0.01% prescribing information, LRM Therapeutics, LLC (BLA103691): section 5.1 Risk of Cancer and section 6.1 Clinical Trials Experience. DailyMed set ID 377b3021-13d7-96d5-e063-6394a90a8ca3, effective May 8, 2026 (openFDA). dailymed.nlm.nih.gov. Read October 5, 2026.
53. DailyMed (National Library of Medicine). Over-the-counter listing of a cream mask naming nepidermin (UNII TZK30RF92W) among its active ingredients at 0.00000001 g per 100 g; marketing category “unapproved drug other”; set ID 2ad6a3f7-c3ba-4faa-9a28-9e37e57f5783, version 1, effective October 27, 2021, published October 29, 2021 (maker not named here). dailymed.nlm.nih.gov. Read October 5, 2026.
54. ClinicalTrials.gov. Registrations of EGF: NCT05724589 (one-group study of an EGF facial serum, 28 adults, primary completion June 5, 2024; results posted); NCT01593995 (EGF ointment for erlotinib skin effects, 52, primary completion December 2013, completed October 2014); NCT04704245 (EGF ointment after laser for solar lentigines, 40, completed 2018); NCT05219461 (Phase 1 of rhEGF eye drops in 48 healthy men, completed 2019; no results posted); NCT04886726 (Phase 1, urine-derived hCG containing EGF after stem-cell transplant, recruiting, primary completion estimated November 2028). clinicaltrials.gov, API v2. Read October 5, 2026.
55. FDA. Orphan Drug Designations and Approvals database: urogastrone, designated November 1, 1984 (corneal epithelial regeneration after corneal transplant surgery; designation 1684); epidermal growth factor (human), designated March 6, 1985 (cutaneous wound healing in extreme burn treatment; designation withdrawn or revoked; 5485); epidermal growth factor (human), designated October 5, 1987 (non-healing corneal defects; 14386); none approved for the orphan indication. accessdata.fda.gov/scripts/opdlisting/oopd. Read October 5, 2026.
56. FDA. Drugs@FDA through openFDA (api.fda.gov/drug/drugsfda.json): searches for nepidermin, epidermal growth factor and urogastrone, October 5, 2026 (no records); becaplermin: BLA103691, Regranex, first approved December 16, 1997. European Medicines Agency. Medicines data table (ema.europa.eu, medicines-output-medicines_json-report), searched for epidermal growth factor, nepidermin and urogastrone, October 5, 2026 (no entry; becaplermin as Regranex, withdrawn, and Gemesis, refused).
57. Code of Federal Regulations. 21 CFR 600.3(h), Biological product, and (h)(6): “A protein is any alpha amino acid polymer with a specific, defined sequence that is greater than 40 amino acids in size.” ecfr.gov (current version). Read October 5, 2026.
58. Code of Federal Regulations. 21 CFR 216.23, Bulk drug substances that can be used to compound drug products in accordance with section 503A of the Federal Food, Drug, and Cosmetic Act, and 21 CFR 216.24, Drug products withdrawn or removed from the market for reasons of safety or effectiveness. ecfr.gov. Read October 5, 2026: neither names EGF, nepidermin or urogastrone.
59. FDA. Bulk Drug Substances Nominated for Use in Compounding Under Section 503A of the Federal Food, Drug, and Cosmetic Act (categories 1–3). Updated May 14, 2026. fda.gov/media/94155/download.
60. FDA. Bulk Drug Substances Nominated for Use in Compounding Under Section 503B of the Federal Food, Drug, and Cosmetic Act (categories 1–3). Updated March 21, 2025. fda.gov/media/94164/download.
61. World Anti-Doping Agency. Prohibited List 2026 (in effect January 1, 2026). S0, Non-approved substances; S2.3, Growth factors and growth factor modulators. wada-ama.org.
62. Searches of October 5, 2026: PubMed, “epidermal growth factor” (101,977 records; 28,546 without “epidermal growth factor receptor”, EGFR, HER2 or “receptor 2”), “recombinant human epidermal growth factor” (329), “sh-oligopeptide-1” (3), Heberprot-P (14), nepidermin (0); EGF with wrinkle, photoaging and rejuvenation terms (18), with acne and scar terms (71), with laser and split-face or randomized terms (32), with alopecia or hair-growth terms (no trial of EGF alone for hair), with pregnancy and topical or cosmetic terms (0), with cosmetic content or stability terms (no independent analysis of products on sale), and with GHK-Cu, Matrixyl, BPC-157, TB-500 or Argireline (no study testing the combination; one trial testing EGF and acetyl hexapeptide-8 in separate groups); PubMed, NCT05724589 (0, no paper); Europe PMC, “sh-oligopeptide-1” and nepidermin; ClinicalTrials.gov, interventions “epidermal growth factor,” EGF, rhEGF, Heberprot and nepidermin with open statuses (no open trial of EGF itself); a laboratory supplier’s product sheet for recombinant human EGF, 10 µg to 1 mg vials, “For Research Use Only” (supplier not named); MFDS drug database, Easyef (3 product records); Crossref and Europe PMC records of Park et al., 2018 (funder); Crossref reference list of Martínez-Carpio, 2023 (31 references).

Related Research

• GHK-CuCopper tripeptide — skin and hair serums
• MatrixylPalmitoyl pentapeptide — anti-aging serums
• ArgirelineAcetyl hexapeptide — wrinkle creams
• GHRP-6Growth hormone releasing peptide — given with EGF in Cuban stroke trials