Table 4.

Applications of the rhEGF in regenerative medicine

Authors and year of publication	Type of study	Country of origin	Number of participants	Intervention protocol	Follow-up period	Results	Adverse effects
Jeon YJ et al 2019[11]	In vitro preclinical trial	Korea	Dermal cultures	Skin penetration study of CTP-EGF recombinant protein using fluorescent imaging techniques and synthesis of hyaluronic acid study by immunoblotting and ELISA	Between 6 and 48 hours according to the corresponding laboratory test	CTP-EGF has superior ability, compared with EGF alone, to penetrate the skin and induce hyaluronic acid synthesis and collagen formation.	-
Paik SH et al.2013[12]	In vivo preclinical trial	Korea	24 Mice	Four days before chemotherapy, topical pretreatment with EFG was performed on hair follicles.	Days 2 and 4 after chemotherapy	EGF is effective as an anagen inducer protecting against chemotherapy-induced alopecia.	-
Niiyama H And Kuroyanagi Y, 2014[14]	Invitro preclinical trial	Japan	Cell cultures	EGF wound dressing, wound dressing with Vit. C, and dressing with EGF + Vit. C have probed into cytokine production. Fibroblasts were assessed in vitro and cultured.	7 Days for cell culture	The dressing with EGF and Vit. C improved the production of vascular endothelial growth factor (VEGF) and hepatocyte growth factor (HGF) compared with the dressing without EGF.	-
Yamamoto A et al 2013[15]	In vitro preclinical trial	Japan	40 Mice	The effectiveness of wound dressings with EGF, Vit. C, and EGF + Vit. C was assessed in diabetic mice.	1 Week (clinical and histologic assessment)	The dressing with EGF promoted best granulation tissue and major angiogenesis being more effectively than the other wound dressings..	No report
Esquirol-Caussa J and Herrero-Vila E. 2019[16]	Quasi-experimental clinical trial	Spain	77 Patients	Ulcers are cured by gel using rhEGF gel once per day.	7 Weeks	The surrounding skin improved in 93.5% of cases. The appearance of the wound improved by 92.2%. The size of the wound was reduced from 66.7% in 43.3% in 4 weeks.	They were not found.
Martínez -Peñalver I and Cuevas -Pérez I. 1998[17]	Quasi-experimental clinical trial	Cuba	12 Patients	Topical application twice a day until healing or improvement that would allow successful reoperation	7 Weeks	8 cases of complete cicatrization and 4 partial closures. Closures are completed in 34 days. The EGF is an option for patients who cannot undergo pharyngoplasty or where it has not been effective.	They were not found.
Kim JW et al. 2017[18]	Clinical trial	Korea	138 Patients	Spray rhEGF (experimental) or placebo was applied in oral mucosa twice a day from the day of chemotherapy until oral mucositis resolved.	28 Days	The spray does not reduce grade 2 of oral mucositis in patients receiving chemotherapy. However, the oral spray reduces pain induced by mucositis.	Transient nausea
Shi HX, et al. 2013[19]	In vitro and in vivo preclinical trial	China	30 Rats	1ml of EFG every 2 days in skin wounds; the control group received saline at 0.9%	14 Days	EGF regulated the synthesis and degradation of the extracellular matrix. EGF regeneration was promoted in animals and in human cells in vitro.	-
Lee JH et al.2013[20]	In vivo preclinical trial	Korea	40 Animals	Once the burn was induced 14 days after laser irradiation, the gel was started with EFG once a day.	22 Days	EGF stimulated granulation tissue with accelerated wound closure and minimization of scars, compared with the group without treatment.	It was not observed
Kong Mand Hong SE.2013[21]	Clinical trial	Korea	40 Patients	EFG cream in the irradiated area thrice a day from the start of radiotherapy until 2 weeks after completion of radiotherapy	Weekly during radiotherapy and 6 weeks after completion	Cream with EGF has a beneficial role in preventing or minimizing radiation dermatitis in patients with breast cancer.	They were not recorded
Hwang IG et al 2016[22]	Clinical trial	Korea	52 Patients	Cream twice a day in skin lesions (ERSEs or skin-related effects of erlotinib)	8 Weeks	It is effective in improving all types of ERSEs, regardless of the dose of erlotinib	They were not reported
Hernández-Cañete CM et al 2017[23]	Quasi-experimental clinical trial	Cuba	17 Patients	Intralesional application thrice a week until complete granulation or healing	-	EGF avoided amputation in Wagner grade 4 diabetic foot ulcers, and 100% evolved to healing.	Muscle spasms
Kahraman M et al 2019[24]	Quasi-experimental clinical trial	Turkey	34 Patients	Intralesional injections thrice per week for 8 weeks or until healing	8 Weeks or until healing follow-up to 5 years	Wound closure in 87.9% of injuries. It is effective in reducing the recurrence of long-term ulcers.	Burning pain
Lou Z.2019[25]	Quasi-experimental clinical trial	China	24 Patients	Tympanic membrane application once a day	Twice per week for 6 months or until the closure of the tympanic perforation	The closing rate was 100% in 6 days	They were not recorded.

Source: Prepared by the authors from the study results.