Factor de Crecimiento Epidérmico

Epidermal Growth Factor (EGF)

1. Identity: Chemical Nature, Names, Sources, and Preparations

Chemical and Biological Identity

Epidermal growth factor (EGF) is a protein that stimulates cell growth and differentiation by binding to its receptor, EGFR. Human EGF is 6 kDa and has 53 amino acid residues and three intramolecular disulfide bonds. In humans, EGF has 53 amino acids with a molecular mass of around 6 kDa, and contains three disulfide bridges (Cys6–Cys20, Cys14–Cys31, Cys33–Cys42). This sequence contains 6 cysteine residues that form three intramolecular disulfide bonds. Disulfide bond formation generates three structural loops that are essential for high-affinity binding between members of the EGF family and their cell-surface receptors.

Epidermal Growth Factor (EGF) is a small mitogenic polypeptide (~6 kDa) present in many mammalian species and distributed throughout a wide number of tissues and body fluids. Human and mouse EGFs are very similar, but not identical in their physical and chemical properties. Of the 53 amino acid residues comprising each of the two polypeptides, 37 are common to both molecules, and three disulfide bonds are formed in the same relative positions.

Alternative Names

Initially, human EGF was known as urogastrone. EGF was independently discovered in human urine under the name "urogastrone" due to its ability to inhibit gastric acid secretion, and the two molecules were later confirmed to be identical. Urogastrone, which suppresses stomach acid secretion from the intestinal mucosa, was originally isolated in urine and eventually identified as EGF.

Natural Sources in the Body

EGF was originally described as a secreted peptide found in the submaxillary glands of mice and in human urine. EGF has since been found in many human tissues, including platelets, submandibular gland (submaxillary gland), and parotid gland. EGF is a polypeptide of 53 amino acids that is secreted by platelets, macrophages, and fibroblasts. EGF is produced by salivary glands, Brunner's glands of the duodenum, the kidney, and other tissues.

Salivary EGF, which seems to be regulated by dietary inorganic iodine, also plays an important physiological role in the maintenance of oro-esophageal and gastric tissue integrity. The biological effects of salivary EGF include healing of oral and gastroesophageal ulcers, inhibition of gastric acid secretion, stimulation of DNA synthesis, as well as mucosal protection from intraluminal injurious factors such as gastric acid, bile acids, pepsin, and trypsin, and from physical, chemical, and bacterial agents.

Common Forms and Preparations

Because naturally occurring Epidermal Growth Factor and Urogastrone are available in only minute quantities naturally, synthetic methods, including genetic engineering methods, are now utilized to produce these materials. The principal commercial forms encountered in research, medicine, and the supplement/cosmeceutical marketplace include:

• Recombinant human EGF (rhEGF): The rhEGF was developed through recombinant DNA technology and has been produced by biotechnological methods in a Saccharomyces cerevisiae yeast line. Recombinant human EGF has been obtained from a transformed Saccharomyces cerevisiae strain and may contain a mixture of the EGF1–51 and EGF1–52 forms.
• Plant-derived (barley seed) EGF: Chemists have discovered a way to synthesize EGF using genetically modified barley seeds.
• Yeast-derived EGF: An EGF/urogastrone-related material designated as yeast Epidermal Growth Factor (yEGF) is produced by extraction from various forms of yeast which, with their peptide reduction products in compatible pharmaceutical formulas, are claimed as useful medicinal agents.
• Mouse salivary gland EGF: Mouse salivary gland-sourced EGF has a molecular weight of approximately 6.1 kDa and is used extensively as a laboratory reagent.
• Pharmaceutical injectable (Heberprot-P): Heberprot-P is a parenteral formulation in a lyophilized powder vial presentation containing 75 μg of recombinant Epidermal Growth Factor (rhEGF) for local (intralesional) application.
• Topical cosmeceutical formulations: Peptides with rhEGF that penetrate the skin when applied topically have been developed; cosmeceuticals with rhEGF that prevent or improve wrinkles and hydrate the skin without significant side effects are being formulated.

2. Historical Context and Discovery

In 1962, epidermal growth factor (EGF) was discovered by Dr. Stanley Cohen while studying nerve growth factor (NGF). Stanley Cohen discovered epidermal growth factor (EGF) during studies of nerve growth factor as a side effect of other experiments. The first indication of epidermal growth factor was observed in newborn mice injected with a crude extract from the mouse salivary gland. The salivary gland is an abundant source of nerve growth factor (NGF), and was used by Cohen and Levi-Montalcini to characterize NGF. The extract of mouse nerve growth factor led to "side effects" in mice: their eyelids opened and teeth erupted earlier than normal. This effect was not seen in purifications of nerve growth factor, so Cohen decided to look for an epidermal growth factor in the other fraction of the salivary gland extract.

Cohen published the initial discovery of EGF in 1960. The term "epidermal growth factor" was not used until 1965 when in vitro studies demonstrated that the growth factor directly stimulated epidermal tissue. This work led to the 1986 Nobel Prize in Physiology or Medicine awarded to Cohen and Rita Levi-Montalcini.

It was soon recognized that EGF is the prototypical member of a family of peptide growth factors that activate the EGF receptors, and that the EGF/EGF receptor signaling pathway plays important roles in proliferation, differentiation, and migration of a variety of cell types, especially in epithelial cells.

There is no documented history of deliberate traditional use of EGF as a discrete ingredient in any pre-modern medical tradition. EGF is an endogenous human protein identified by modern biochemical science; no historical pharmacopeia or ethnobotanical record describes its isolation or purposeful administration before the 20th century. The first systemic administration of EGF dates back to 1975, in patients with Zollinger–Ellison syndrome. EGF topical administration has been used since 1989 to enhance the healing process of a variety of peripheral tissue wounds (16 clinical reports), as well as its intravenous, oral, and rectal administration for gastrointestinal damages (11 clinical reports).

3. Key Constituents and Molecular Structure

The epidermal growth factor (EGF) is one of the earliest known polypeptide growth factors and the founding member of the EGF-like family. This class of proteins has highly similar structural and functional characteristics, promotes mitogenic activity, and typically uses the same receptors for response triggering.

EGFR is activated by several ligands, including EGF, transforming growth factor α (TGFα), epiregulin, epigen, betacellulin, heparin-binding EGF-like growth factor, and amphiregulin. These all constitute the broader EGF family of ligands.

The ErbB family comprises four receptors, which include EGFR (ErbB-1/HER1), ErbB-2 (Neu, HER2), ErbB-3 (HER3), and ErbB-4 (HER4). Four ErbB (HER) family receptor tyrosine kinases, including EGFR/ErbB1, ErbB2, ErbB3, and ErbB4, mediate responses to EGF family members.

4. Mechanisms of Action

Receptor Binding and Dimerization

EGF, via binding to its cognate receptor, results in cellular proliferation, differentiation, and survival. Epidermal growth factor receptor (EGFR) is the first discovered and prototypical member of the receptor tyrosine kinase (RTK) family of receptors. It is activated by various ligands in the extracellular milieu and transmits the cellular response to mediate various cellular activities, including cell proliferation, cell survival, growth, and development.

EGF activation of the EGFR induces receptor dimerization and transphosphorylation of the C-terminal domain. The phosphorylated C-terminal domain binds SHC and GRB2, along with PLC-γ1 at Y992.

Downstream Signaling Cascades

EGFR signaling pathways leading to G1/S cell cycle progression are activated by EGF. Depicted among these are the RAS-RAF-MEK-ERK MAPK and PI3K-AKT-mTOR pathways. The GRB2 SH3 domain recruits the proline-rich domains of SOS or GAB1 to initiate ERK MAPK or AKT signaling respectively. SOS is also recruited to the plasma membrane by the interaction of its PH domains with PIP2 and PA. SOS catalyzes the conversion of GDP to GTP of RAS.

EGFR signaling is fine-tuned intracellularly via multiple coordinated mechanisms including regulation mediated by phosphatases, feedback from the downstream components in the signaling pathway, endocytosis, and intracellular transport.

Cellular Outcomes

Chemotaxis, mitogenesis, motogenesis, and cytoprotection are common cellular events involved in both tumourigenesis and tissue repair, which appear amplified upon growth factor exposure. Epidermal growth factor promotes these events in epithelial and mesenchymal cells through the binding to a specific tyrosine kinase receptor.

Some of the cellular outcomes of EGFR signaling involve alterations of specific aspects of cellular metabolism. EGFR regulates cell metabolism, including by modulation of gene expression and protein function leading to control of glucose uptake, glycolysis, biosynthetic pathways branching from glucose metabolism, amino acid metabolism, lipogenesis, and mitochondrial function.

EGF, along with many other growth factors and cytokines, directly affects collagen, elastin, and extracellular matrix (ECM) biosynthesis, but its binding and signalling are reduced with age.

EGF is also found to have a cytoprotective effect, stimulating migration of a cell toward a wound in vivo, or toward a gap introduced in a monolayer of cells in culture, to promote wound healing.

5. Scientific Evidence by Area of Use

5.1 Wound Healing — Peripheral and Cutaneous Wounds

Epidermal growth factor (EGF) participates in dermal wound healing through stimulation, proliferation, and migration of keratinocytes, endothelial cells, and fibroblasts, and facilitates dermal regeneration. Early clinical trials showed that topical administration of EGF increased epithelialization and shortened healing time in skin grafts, venous ulcers, and diabetic foot ulcers, but the lack of data demonstrating a significant benefit from its application, along with data indicating that EGF plays an important role in cancer development, significantly hampered further therapeutic use.

A landmark early human clinical trial was published in the New England Journal of Medicine in 1989. A prospective, randomized, double-blind clinical trial was conducted using skin-graft donor sites to determine whether epidermal growth factor would accelerate the rate of epidermal regeneration in humans. Paired donor sites were created in 12 patients who required skin grafting for either burns or reconstructive surgery. One donor site from each patient was treated topically with silver sulfadiazine cream, and one was treated with silver sulfadiazine cream containing epidermal growth factor (10 μg per milliliter). The donor sites treated with silver sulfadiazine containing epidermal growth factor had an accelerated rate of epidermal regeneration in all 12 patients. This was an early, small, proof-of-concept study.

Epidermal growth factor (EGF) is a growth factor that plays a pivotal role in wound healing and maintaining tissue homeostasis by regulating cell survival, proliferation, migration, and differentiation. Exogenous administration of bioidentical human recombinant epidermal growth factor (rhEGF) has been known to promote skin wound healing, although rhEGF is increasingly being used in drug delivery systems and nanotechnology.

Despite considerable attention being focused on the potential clinical applications of rhEGF in several dermatological conditions beyond wound healing, the number of studies still remains relatively low.

5.2 Diabetic Foot Ulcers — Strongest Evidence Base

The most robustly studied clinical application of EGF is in diabetic foot ulcers (DFUs), where diabetic patients have decreased growth factor concentrations in their tissues, particularly epidermal growth factor. Growth factor shortage impairs wound healing, which leads to chronic nonhealing wounds and sometimes eventual amputation.

Many trials were performed to evaluate the effect of recombinant human epidermal growth factor (rhEGF) in healing DFUs. A meta-analysis was performed to synthesize the evidence of rhEGF treatment in DFUs in comparison to placebo. Databases included PubMed, EMBASE, the Cochrane Library, Web of Science, EBSCOhost, ScienceDirect, and Scopus. A total of six studies involving 530 patients were eligible for analysis. The combined OR (intralesional injection and topical application) was 4.005 (95% CI: 2.248–7.135, p < 0.001).

Heberprot-P is an innovative Cuban product containing recombinant human epidermal growth factor for peri- and intra-lesional infiltration; evidence reveals it accelerates healing of deep and complex ulcers, both ischemic and neuropathic, and reduces diabetes-related amputations. Clinical trials of Heberprot-P in patients with diabetic foot ulcers have shown that repeated local infiltration of this product can enhance healing of chronic wounds safely and efficaciously. As a result, Heberprot-P was registered in Cuba in 2006, and in 2007 was included in the National Basic Medications List and approved for marketing. It has been registered in 15 other countries, enabling treatment of more than 100,000 patients.

Patients in clinical trials were treated with intralesional injections of a lyophilised formulation of Heberprot-P containing 75 μg (one vial) of EGF, three times a week on alternate days up to complete wound healing. The effect of topical EGF formulation can be abated, especially in high-grade wounds, since an increased protease activity has been identified. Direct intralesional administration of an EGF-based formulation (Heberprot-P) can overcome this limitation, as has been confirmed in a randomised, double-blinded, placebo-controlled phase III trial.

EGF is not approved as a standalone pharmaceutical product by the FDA. However, the FDA has authorized Phase III clinical trials of Heberprot-P. Recombinant EGF is used as a component in some FDA-cleared wound care products and is available in cosmetic skincare formulations (regulated as cosmetics, not drugs). Topical EGF preparations are approved or available for wound healing and corneal repair in several Asian countries, including South Korea and Japan, where rhEGF-containing products have established clinical use.

Evidence strength for DFU: Moderate-to-strong — supported by multiple randomized, placebo-controlled trials, a systematic review and meta-analysis, and regulatory approval in over 15 countries for intralesional use.

5.3 Skin Aging and Aesthetic Applications

In vitro studies have shown that rhEGF promotes the migration and contractility of aged fibroblasts and increases both hyaluronic acid and collagen synthesis. Based on this experimental background, several preclinical and clinical studies on the effect of rhEGF on photoaged skin have been conducted.

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 EGF was obtained intradermally, with a greater reduction of wrinkles, folds, and a longer response over time.

A study published in Cosmetics (2026) examined an EGF-loaded elastosome formulation. Following two weeks of product application, significant enhancements were observed in skin elasticity (R7 value) with a 9.87% increase, wrinkle reduction (Ra) with an 8.97% decrease, and skin lifting. The results of clinical trials confirmed significant efficacy in anti-aging, moisture, skin barrier improvement, and hyperpigmentation reduction. This is a small-scale industry-funded study and its results should be interpreted cautiously.

A study in the Journal of Drugs in Dermatology evaluated a combination of recombinant EGF cosmetic serum and crosslinked hyaluronic acid serum. A blinded investigator noted a statistically significant preference for the EGF/RHA combination at week 2 in terms of smoothness (P = 0.003) and firmness (P = 0.003). This improvement continued into weeks 4 and 8.

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.

Evidence strength for skin aging: Preliminary to moderate. In vitro data are robust, and small clinical studies show positive signals, but large, well-controlled, long-term RCTs are lacking.

5.4 Radiation- and Chemotherapy-Related Skin Damage

In one study evaluating topical application of rhEGF-containing cream in 20 breast cancer patients, the severity of radiation dermatitis decreased significantly compared with supportive skin care alone.

A pilot phase 3 trial of rhEGF for treating EGFR inhibitor-induced skin toxicities showed that rhEGF ointment significantly improved skin lesions and patients' quality of life when compared with a placebo.

Evidence strength: Preliminary; small sample sizes, few controlled trials specifically for this indication.

5.5 Oral Mucositis

A phase 2, randomized, double-blind, placebo-controlled trial evaluated rhEGF oral spray for chemotherapy-induced oral mucositis (OM). In this phase 2 study, patients were randomized to either rhEGF (50 μg/mL) or placebo in a 1:1 ratio. The primary endpoint was incidence of National Cancer Institute (NCI) grade ≥2 OM. A total of 138 patients were enrolled in this study. In the intention-to-treat analysis, rhEGF did not reduce the incidence of NCI grade ≥2 OM (p = 0.717) nor reduce its duration (p = 0.725). Secondary endpoints including the day of onset and duration, the incidence of NCI grade ≥3 OM, and patient-reported quality of life were also similar between the two groups.

Evidence strength for chemotherapy-induced oral mucositis: Negative Phase 2 result for primary endpoint. Evidence does not currently support this indication via the oral spray route in HSCT patients.

5.6 Gastrointestinal Applications

A placebo-controlled, multicenter, randomized, and double-blind study was conducted to evaluate oral human recombinant EGF in the treatment of duodenal ulcers. Treatment groups were: (A) placebo solution, (B) 10 μg/mL of human recombinant (hr)-EGF, and (C) 50 μg/mL of hr-EGF, three times daily during 6 weeks. Patients 15–65 years old with a duodenal ulcer >4 mm were eligible. Oral hr-EGF was effective in the treatment of duodenal ulcer at a 50 μg/mL dose every 8 hours but not at 10 μg/mL.

Chronic administration of intraluminal EGF enhanced colonic mucosal growth both in a rodent model and in humans. In a randomized, placebo-controlled trial of IV recombinant EGF in premature infants with necrotizing enterocolitis, 6-day continuous IV administration of EGF improved gut mucosal thickness by 54% over baseline as early as day 4 of therapy. No significant infusional or other systemic adverse effects from EGF administration were noted in this trial.

Evidence strength for GI applications: Preliminary. Small, isolated studies; no systematic review or guideline-level evidence supports routine GI use of exogenous EGF.

5.7 Corneal Wound Healing

Epidermal Growth Factor has been found to be very effective in the healing of wounds, and particularly wounds resulting from corneal transplants and cataract surgery. This application has been studied primarily in animal models and small clinical reports; large RCT-level evidence in humans is limited.

5.8 Bone and Dental Tissue

EGF plays an enhancer role on the osteogenic differentiation of dental pulp stem cells (DPSCs) because it is capable of increasing extracellular matrix mineralization. Evidence for this application is primarily in vitro and preclinical.

5.9 Hair Growth

Topical application of rhEGF promoted primary hair recovery through the dystrophic anagen pathway in a mouse model of cyclophosphamide-induced alopecia. As the evidence for this is currently weak, further research will be necessary to understand the exact roles of EGF in hair follicle morphogenesis and cycling, as well as their therapeutic potential for reducing hair loss.

Evidence strength for hair growth: Very preliminary — animal model only; insufficient human data.

6. Body Systems Associated with EGF

• Integumentary system (skin): Wound healing, skin aging, radiation dermatitis, atopic dermatitis, photoprotection, hyperpigmentation.
• Gastrointestinal system: Biological effects of salivary EGF include healing of oral and gastroesophageal ulcers, inhibition of gastric acid secretion, stimulation of DNA synthesis, and mucosal protection from intraluminal injurious factors.
• Musculoskeletal/dental: Osteogenic differentiation, corneal regeneration, periodontal wound repair.
• Cardiovascular and renal systems: EGFR is widely expressed and many studies reveal a multitude of tissue-specific EGFR functions, including key roles in cardiovascular physiology, kidney, and the nervous system.
• Endocrine/metabolic: EGFR regulates cell metabolism, including modulation of gene expression and protein function, leading to control of glucose uptake, glycolysis, biosynthetic pathways, amino acid metabolism, lipogenesis, and mitochondrial function.

7. Dosage Forms and Reported Dosages

Dosages reported in clinical literature vary substantially by indication and route of administration. The following are sourced directly from published studies:

• Topical wound healing (skin grafts, burns): Silver sulfadiazine cream containing epidermal growth factor at 10 μg per milliliter was used topically on skin-graft donor sites in a 1989 NEJM clinical trial.
• Intralesional injection (diabetic foot ulcers — Heberprot-P): Patients were treated with intralesional injections of Heberprot-P containing 75 μg (one vial) of EGF, three times a week on alternate days up to complete wound healing.
• Intralesional dose-response (diabetic foot ulcers): Heberprot-P Phase II trials evaluated 25 μg versus 75 μg intralesional doses administered three times weekly. The 75 μg dose was selected for commercial development based on superior granulation response and the lowest amputation rate.
• Oral administration (duodenal ulcers): Treatment groups received placebo, 10 μg/mL of human recombinant EGF, or 50 μg/mL of hr-EGF, three times daily during 6 weeks. Oral hr-EGF was effective at the 50 μg/mL dose every 8 hours but not at 10 μg/mL.
• Oral spray (oral mucositis): In a phase 2 study, patients were randomized to rhEGF oral spray at 50 μg/mL or placebo.
• IV continuous infusion (necrotizing enterocolitis, neonates): A 6-day continuous IV administration protocol was evaluated in a placebo-controlled trial.

Note on oral supplement bioavailability: EGF is a polypeptide and as such is subject to gastrointestinal proteolysis when taken orally. The clinical oral studies above used it as a mucosal contact agent or gastrointestinal luminal agent, not as a systemic supplement absorbed across the gut. No peer-reviewed clinical data were identified establishing systemic bioavailability of orally ingested EGF in healthy adult humans as a dietary supplement.

8. Safety Considerations and Interactions

Tumor Promotion Concern

In experimental oncology settings, EGF does not initiate malignant transformation but exhibits "tumour promotion." These observations have raised doubts on the clinical use of EGF despite solid demonstrations of efficacy in experimental conditions and clinical trials.

The epidermal growth factor receptor (EGFR) is a receptor tyrosine kinase that is commonly upregulated in cancers such as in non-small-cell lung cancer, metastatic colorectal cancer, glioblastoma, head and neck cancer, pancreatic cancer, and breast cancer. EGF, as the primary ligand for EGFR, binds to the receptor to initiate downstream signaling cascades that promote tumor cell proliferation, survival, angiogenesis, and metastasis, while EGFR dysregulation — via overexpression, mutation, or ligand-dependent activation — makes this axis a critical therapeutic target.

Endogenous Regulatory Mechanisms

EGF bioavailability is tightly controlled by local peptidases. Receptor downregulation occurs rapidly after ligand binding, reducing sensitivity to prolonged stimulation. PKC-mediated counter-regulation of tyrosine kinase activity provides an additional brake on excessive signaling. These built-in safety mechanisms mean that exogenous EGF application in healthy tissue does not result in uncontrolled proliferation.

Clinical Safety Data

There has been no evidence that any of these therapeutic interventions has led to long-term adverse events. However, the number of clinical interventions, patients included, and follow-up periods described fall short of achieving definitive safety conclusions.

Tentative evidence shows improved wound healing with recombinant EGF. Safety has been poorly studied.

Contraindications and High-Risk Populations

In many human epithelial tumors, the EGFR is amplified or overexpressed with deregulated signaling. In this context, any therapy with EGF or any other growth factor is absolutely contraindicated. This includes active cancers, pre-cancerous lesions (such as severe actinic keratoses), and situations where the skin contains genetically damaged cells from extensive UV exposure or other carcinogen exposure.

Interaction with EGFR-Targeted Cancer Therapies

EGFR inhibitors (EGFRis) have become a therapeutic option for the treatment of cancer. Therapies targeting EGF/EGFR are useful for the treatment of both cutaneous wounds and cancer. EGFR inhibitor drugs induce dermatological toxicity, a papulopustular rash that is pruritic and painful; chronic use may negatively impact wound healing. Conversely, exogenous EGF would be pharmacologically antagonistic to therapeutic EGFR blockade and is contraindicated in patients receiving anti-EGFR cancer treatment.

Skin Irritation

Primary skin irritation tests on EGF-loaded cosmeceutical formulations have classified evaluated products as non-irritants. However, the broader safety profile across diverse formulations and long-term exposures has not been systematically characterized in large-scale human studies.

Regulatory Status

EGF is not approved as a standalone pharmaceutical product by the FDA. However, the FDA has authorized Phase III clinical trials of Heberprot-P. Recombinant EGF is used as a component in some FDA-cleared wound care products and is available in cosmetic skincare formulations (regulated as cosmetics, not drugs). EGF-containing cosmetic products are commercially available in the European Union. Pharmaceutical EGF products would require marketing authorization through the EMA.

References

• Wikipedia — Epidermal Growth Factor
• Embryo Project Encyclopedia — Epidermal Growth Factor
• PMC — Epidermal growth factor, from gene organization to bedside (2014)
• PubMed — Epidermal growth factor, from gene organization to bedside (2014)
• PMC — Epidermal growth factor in clinical practice: a review of its biological actions, clinical indications and safety implications
• PMC — The use of epidermal growth factor in dermatological practice (2023)
• PMC — Epidermal Growth Factor and EGFR: The Yin and Yang in the Treatment of Cutaneous Wounds and Cancer
• NEJM — Enhancement of Wound Healing by Topical Treatment with Epidermal Growth Factor (1989)
• PMC — Epidermal Growth Factor is Effective in the Treatment of Diabetic Foot Ulcers: Meta-Analysis and Systematic Review
• PMC — Intralesional administration of epidermal growth factor-based formulation (Heberprot-P) in chronic diabetic foot ulcer
• PubMed — Heberprot-P: a novel product for treating advanced diabetic foot ulcer
• PMC — Topical rhEGF for Oral Mucositis Induced by Intensive Chemotherapy: Phase 2 Trial
• PubMed — A multicenter, randomized, double-blind clinical trial examining oral recombinant EGF on the healing of duodenal ulcers
• PMC — Epidermal Growth Factor in Aesthetics and Regenerative Medicine: Systematic Review
• MDPI Cosmetics — Development of an EGF Loaded Elastosome Formulation for Enhanced Skin Penetration and Anti-Aging Effects (2026)
• International Journal of Cosmetic Science — Challenges and effective routes for formulating and delivery of EGF in skin care (2021)
• MDPI Cancers — Epidermal Growth Factor Receptor Cell Proliferation Signaling Pathways (2017)
• PubMed — Epidermal growth factor receptor: mechanisms of activation and signalling (2003)
• ScienceDirect — Control of cell metabolism by the epidermal growth factor receptor (2022)
• ScienceDirect Topics — Epidermal Growth Factor Overview
• PMC — Enhanced Skin Wound Healing Through Chemically Modified mRNA Encoding EGF (2025)
• Burns & Trauma — Clinical guideline on topical growth factors for skin wounds (2020)
• Journal of Drugs in Dermatology — Effect of Recombinant EGF Cosmetic Serum and Crosslinked HA Serum on Aging Skin (2016)
• PubMed — Growth factors for treating diabetic foot ulcers (Cochrane-related review, 2015)