Reactive Oxygen Species (ROS)‐Assisted Nano‐Therapeutics Surface‐Decorated with Epidermal Growth Factor Fragments for Enhanced Wound Healing

• Published in: Macromolecular bioscience 2024-02, Vol.24 (2), p.e2300225-n/a
• Main Authors: Lee, Miso, Bui, Hoai‐Thuong Duc, Pham, Lan, Kim, Songrae, Yoo, Hyuk Sang
• Format: Article
• Language: English
• Subjects: Cell migration; Disinfection; Epidermal growth factor; Epidermis; Gene expression; Growth factors; Hydrogen peroxide; In vivo methods and tests; Mechanical milling; nanofiber; Oxygen; Reactive oxygen species; thioketal; Wound healing
• ISSN: 1616-5187; 1616-5195
• DOI: 10.1002/mabi.202300225

In this study, stimuli‐responsive liberation of an epidermal growth factor fragment (EGFfr) is accomplished using nanofibrous meshes to improve wound healing effects. Electrospun nanofibers are fragmented by mechanical milling, followed by aminolysis to fabricate powdered nanofibrils (NFs). EGFfrs are covalently immobilized on NFs via thioketal linkers (EGFfr@TK@NF) for reactive oxygen species (ROS)–dependent liberation. EGFfr@TK@NF exhibits ROS‐responsive liberation of EGFfr from the matrix at hydrogen peroxide (H2O2) concentrations of 0–250 mm. Released EGFfr is confirmed to enhance the migration of HaCaT cell monolayers, and keratinocytic gene expression levels are significantly enhanced when H2O2 is added to obtain the released fraction of NFs. An in vivo study on the dorsal wounds of mice reveals that EGFfr‐immobilized NFs improve the expression levels of keratin1, 5, and 14 for 2 weeks when H2O2 is added to the wound sites, suggesting that the wounded skin is re‐epithelized with the original epidermis. Thus, EGFfrs‐immobilized NFs are anticipated to be potential nanotherapeutics for wound treatment in combination with the conventional disinfection process with H2O2. An ROS‐responsively liberated epidermal growth factor fragment (EGFfr) is synthesized using thioketal‐conjugated in nanofibrous meshes (EGFfr@TK@NF) to enhance wound healing. EGFfr released from EGFfr@TK@NF is dependent on H2O2 concentration. In vitro and in vivo studies confirm that EGFfr@TK@NF increases keratins and collagens gene expression, and the retention of EGFfr on the wounds, suggesting a promising strategy for wound treatment.