Cosmetic Upgrade of EGF: Genetically Modified Probiotic-Derived Cell-Free Supernatants Containing Human EGF Protein Exhibit Diverse Biological Activities

Although epidermal growth factor (EGF) has potential wide applications in the cosmetic industry, it still has limitations, such as a costly purification process and low stability in the surrounding environment. To overcome these limitations, we developed genetically modified Pediococcus pentosaceus CBT SL4, which can secrete EGF protein in growth media, thereby producing probiotic-derived PP-EGF culture medium supernatant (PP-EGF-SUP). Even at low EGF concentrations, PP-EGF-SUP exhibited EGF activities, such as cell scratch wound healing, tyrosinase inhibition, and improvements in anti-wrinkle factors, similar to or stronger than those of recombinant human EGF (rhEGF), which was used as a positive control. PP-EGF-SUP exhibited strong additional biological activities, such as antioxidant, anti-inflammatory, and anti-microbial activities, even though rhEGF did not have such properties. PP-EGF-SUP could be easily transformed to PP-EGF-SUP dried powder (PP-EGF-DP) using the freeze-drying method, and it could also be well resolved in water up to 20 mg/mL; furthermore, it still maintained its bioactivity after the manufacturing process. To determine melasma improvement efficacy, a human application test was performed using melasma ampoules containing 1% or 5% PP-EGF-DP formulations for four weeks. When comparing the melasma values before and after treatment, it was found that the light melasma value statistically decreased by 3.38% and 3.79% and that the dark melasma value statistically decreased by 1.74% and 2.93% in the test groups applying the 1% and 5% PP-EGF-DP melasma ampoules, respectively. In addition, the melasma area also decreased by 21.21% and 29.1%, while the control group showed no statistical difference. During the study period, no significant adverse skin reactions were observed due to the application of the PP-EGF-DP melasma ampoule. In conclusion, PP-EGF-DP may offer unique advantages in the cosmetic ingredient market, such as safety (as a probiotic derivative), stability (postbiotics protect EGF activity), and diverse bioactivities (activity potentiation and postbiotic-derived biological activities).